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TAO Bonan, WANG Yonglan, HONG Lan, YUAN Lin
2024,34(1):1-7, DOI: 10. 3969 / j.issn.1671-7856. 2024. 01. 001
Abstract:
Objective To study the cGAS/ STING signaling pathway and investigate the potential effect of emodin(EMD) on autophagy of human rheumatoid arthritis fibroblast synovial cells (MH7A). Methods CCK-8 method was used to detect MH7A cell proliferation, and the experimental concentration of EMD was screened according to cell survival rate. Then, autophagy inhibitor 3-MA was added to further verify the effect of EMD on autophagy. Autophagy of MH7A cells was detected via the monodansylcadaverine staining method. Protein expression levels of cGAS, STING, p-STING, LC3-I, LC3-II, P62 and Beclin-1 were detected by Western blot. Results Monodansylcadaverine staining indicated that EMD enhanced the autophagy of MH7A cells. Western blot indicated that EMD decreased the expression of autophagy related proteins cGAS, STING, p-STING and P62, and increased that of LC3-II and Beclin-1 in MH7A cells. After addition of the autophagy inhibitor 3-MA, the expression of P62 protein in MH7A cells increased, while that of LC3-II and Beclin-1 decreased. Conclusions EMD may accelerate autophagy and inhibit MH7A cell proliferation by down-regulating cGAS/ STING signaling pathway proteins.
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WU Xuehai, YANG Yiyan, WANG Xiaotang, CHEN Wenlu, SONG Xiaona, WANG Tian, SONG Guohua
2024,34(1):8-17, DOI: 10. 3969 / j.issn.1671-7856. 2024. 01 002
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Objective To analyze the effects of miR-181a-5p overexpression on metabolites in the small intestines of mice with subcutaneous oral cancer by detecting changes in metabolites and metabolic pathways. Methods Three groups were included in study: Control group, negative control and miR-181a-5p overexpression group. To establish a subcutaneous oral cancer model in mice, variously treated cell suspensions were subcutaneously injected into the upper right of the groin in female M-NSG severely immunodeficient mice. Changes in pathology and small intestinal tissues were assessed by HE staining. Changes in mouse body weight were also assessed. Tandem orbitrap mass spectrometry and ultrahigh performance liquid chromatography-tandem time-of-flight mass spectrometry, were used to examine metabolites in the small intestines. By pre-analyzing the original data and quality rating sample data, XCMS was able to assess which metabolites were different among the groups. To identify unique metabolic pathways, KEGG enrichment analysis was used. Results A total of 170 distinct metabolites were found in the small intestinal tissues of Control and NC groups. Choline metabolism, alanine, aspartate, and glutamate metabolism, GABA synaptic metabolism, glycerophospholipid metabolism, cAMP signaling route, cancer center carbon metabolism, and niacin and niacin amine metabolic pathways were important signaling pathways for metabolite enrichment. In the NC group, 16 distinct metabolites with VIP values larger than 2 were found in the small intestines compared with the OE group overexpressing miR-181a-5p. Glycerin phosphorylcholine, palmitic acid, 3-hydroxybutyl carnitine, and β-hydroxybutyric acid were among the metabolites that significantly varied. The primary enhanced metabolic pathway was the choline pathway. Conclusions Mouse small intestines underwent slight changes from subcutaneous oral cancer with the greatest effect on metabolites critical for energy metabolism. The choline metabolic pathway was the pathway that selected absolutely metabolites in mouse small intestines with subcutaneous grafts of oral cancer.
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LI Jiaxian, LIANG Lina, XU Kai, LI Yamin, HUANG Ziyang, LI Xiaoyu, ZHOU Wei, JIN Yu
2024,34(1):18-33, DOI: 10. 3969 / j.issn.1671-7856. 2024. 01. 003
Abstract:
Objective To evaluate the quality of animal studies into acupuncture for glaucoma using SYRCLE’s risk of bias tool, ARRIVE 2. 0 guidelines, and the GSPC checklist. Methods Databases from CNKI, VIP, Wanfang, Sinomed, PubMed, Web of Science, Embase and Cochrane Library were searched to find animal research articles on acupuncture for glaucoma. Risk of bias was assessed for the included studies using the SYRCLE’ s tool, and reporting quality was evaluated using the ARRIVE 2. 0 guidelines and GSPC checklist. Statistical analysis was performed by Excel and SPSS software. Results Thirty articles met the inclusion/ exclusion criteria and were included in the final analysis. Six of the 10 items of the SYRCLE’s tool had a low-risk rate of <50%, and the non-low-risk items focused on selectivity bias, implementation bias and measurement bias. Twelve of the 22 essential sub-items of the ARRIVE 2. 0 guidelines had a low-risk rate of <50%; 9 of the 16 recommended sub-items had a low-risk rate of <50%; and 12 of the 19 subentries of the GSPC list had a low-risk rate of <50%. Randomization, blinding, ethical statements, housing and husbandry, animal care and monitoring, and protocol registration were the non-low-risk items in the ARRIVE 2. 0 guidelines and GSPC list. Conclusions The quality of the methodology and experimental reporting of animal studies into acupuncture for glaucoma are generally low, and the description of several items is not yet complete, which affects the readers’ judgment on whether the result of animal studies can be translated to clinical studies. It is advisable to further promote the use of SYRCLE’s tool and reporting guidelines for animal experiments to enhance the design, performance, and reporting of animal experiments; ensure the reproducibility of experiments and result ; and provide reliable evidence for the translation of result to the clinic.
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WANG Baojie, SU Liqing, ZHANG Zhiyong, YAN Lei, WANG Zhiguang, BAO Suya, SHAO Guo
2024,34(1):34-39, DOI: 10. 3969 / j.issn.1671-7856. 2024. 01. 004
Abstract:
Objective To investigate the effect of 5-Aza-CdR on Notch1 pathway and neural regeneration and to explore the effects of 5-Aza-CdR on learning memory ability in mice by exploring active avoidance behavior. Methods Sixty 6~8-week-old SPF-grade ICR male mice were divided into two groups. 5-Aza-CdR was administered to one group of mice via lateral ventricular injection, while the control group was injected with bovine serum albumin. Notch1 and HES1 mRNA and protein expression levels were detected by Real-time PCR and Western blot 24 hours after injection; 5-bromo-2’-deoxyuridine-positive cells were observed by laser confocal microscopy, and Notch1 expression in hippocampal dentate gyrus was viewed with laser confocal microscopy. Notch1 methylation changes were detected by ethylation-specific PCR, and learning and memory behaviors of mice were assessed by passive avoidance tests and shuttle avoidance assays. Results Injection of 5-Aza-CdR increased hippocampal Notch1 pathway activity, promoted neuronal regeneration in the DG region, decreased methylation levels in the Notch1 promoter region, and enhanced the ability of mice to perform active avoidance behavior. Conclusions The effect of 5-Aza-CdR on active avoidance behavior may be related to the influence of hippocampal neural regeneration through the Notch1 pathway.
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SONG Mengyu, GUO Yijun, ZHAO Xuerong, BAI Jing, ZHOU Zijuan, WANG Jingyu
2024,34(1):40-51, 113, DOI: 10. 3969 / j.issn.1671-7856. 2024. 01. 005
Abstract:
Objective Explore differences in the cognitive abilities of socially different Labradors. Methods The dog mentality assessment (DMA) test created by the Swedish Working Dog Association was modified to employ 12 behavioral variables from five subtests of the DMA test, social contact, play Ⅰ, distance-play, ghosts and play Ⅱ, to assess sociability of the dogs. In accordance with the scoring criteria, 49 labradors provided by the China Guide Dog Training Centre in Dalian were scored on the social behavioral variables and classified into high (n= 15) and low (n= 34) sociability groups by cluster analysis. A new system to test canine cognitive ability was developed using the dog cognitive development battery, which tests various domains of cognitive ability such as social cue use, unsolvable task, inhibitory control, cognitive flexibility, working memory, and multistep problem solving task. The dogs’ behavioral performance and duration of the test were also recorded. Statistical analysis was performed to determine assess differences in the cognitive abilities of socially diverse dogs. Results Dogs in the high and low social subgroups differed significantly in behavioral variables of the unsolvable task, inhibitory control test, and multistep problem solving task. In the unsolvable task, dogs in the high social group looked at people for significantly longer than dogs in the low social grouping (P= 0. 008) and looked at people with significantly less latency time than dogs in the low social group (P= 0. 0001). In the inhibitory control, dogs in the high social group chose significantly more correctly than dogs in the low social group (P= 0. 034) and chose for significantly less time than dogs in the low social group (P= 0. 039). In the multistep problem solving task, for dogs in the high social group. successfully completed number of stakes was significantly higher than for dogs in the low social group (P= 0. 044). The percentage of operation pale time was significantly lower than for dogs in the low social group (P= 0. 05). The average latency time to solve the bone task was significantly higher than for dogs in the low social group (P= 0. 037). Moreover, the percentage of operation bone time was significantly lower than for dogs in the low social group (P= 0. 038). In tests involving a manipulable apparatus, dogs in the high social group spent more time looking at people than dogs in the low social group and less time manipulating the apparatus than dogs in the low subgroup, but no statistically significant differences were observed (P> 0. 05). Conclusions Highly sociable labradors have a greater cognitive ability, they are more able to suppress impulses during tests, more able to complete the multistep problem solving task, and more inclined to change strategies to seek new cues from people rather than obsessing over manipulating the apparatus when they are unable to solve a problem.
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PENG Dongdong, CHEN Xiangchi, TANG Zining, LIU Xuewu, YUAN Xiangzhong, LI Meng, LI Qiao, ZHANG Zeheng
2024,34(1):52-59, DOI: 10. 3969 / j.issn.1671-7856. 2024. 01. 006
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Objective A model for studying oral ulcers induced by betel nut-extract was constructed in rats. Changes in the structure and diversity of oral flora were observed to explore the involvement of oral flora and local inflammatory factors in the pathogenesis of oral ulcers induced by betel nut-extract and to provide theoretical support for the prevention and treatment of oral ulcers in the clinic. Methods Thirty SD rats were randomly divided into normal, model and intervention groups (Guilin watermelon cream, 8 mg/ d for 7 days), with 10 rats/ group. The oral mucosa of rats was subcutaneously injected with 10 g/ mL of betel nut-extract to generate an oral ulcer model. The histomorphological changes were observed, and ulcer area and ulcer scores were assessed. Local oral tissue tumor necrosis factor-α (TNF-α), interleukin (IL)-2 and IL-8 levels were determined. Oral mucosal tissues were sampled for HE staining and analyzed for the structural distribution of oral flora and the diversity of microbial communities using high-throughput sequencing method. Results Compared with rats in the normal group, those in the model group had an increased ulcer area, significantly increased ulcer scores (P< 0. 01), and significantly increased levels of TNF-α, IL-2 and IL-8 in the oral mucosal tissues (P< 0. 01). The amount Streptococcus (P< 0. 05) and Veillonella (P< 0. 001) in the oral saliva of the model group rats was significantly reduced. The model group rats showed oral mucosal epithelial cell hyperplasia or focal necrosis, mucosal lamina propria edema, and hemorrhage accompanied by mass neutrophil and monocyte infiltration. Compared with the model group rats, the intervention group rats had significantly reduced ulcerated area (P< 0. 05, P< 0. 01) and ulcer scores (P< 0. 05). And oral mucosal tissue levels of TNF-α(P< 0. 01), IL-2(P< 0. 05) and IL-8 (P< 0. 05), as well as significantly increased Streptococcus (P< 0. 001) and Veillonella (P< 0. 01) and significantly reduced Staphylococcus (P< 0. 01) in the oral saliva. The degree of lesions in the oral mucosal tissues was significantly improved in the intervention group. Conclusions Betel nut-extract can be used to successfully reproduce a rat model of oral ulcer, and it is speculated that the development of oral ulcers after exposure to betel nut-extract may be related to an imbalance in the oral flora and local tissue inflammatory mediators.
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CHEN Yuanyuan, ZENG Yanan, DU Xiaolang, MU Zejing, LIAO Chengdong, ZHANG Changhua, CAO Lan
2024,34(1):60-68, DOI: 10. 3969 / j.issn.1671-7856. 2024. 01. 007
Abstract:
Objective To explore the effect of compound active tea of Lithocarpus litseifolius on uric acid levels and kidney function of mice with hyperuricemia nephropathy and to provide an experimental basis for the development of hyperuricemia nephropathy drugs and functional food. Methods A mouse model of hyperuricemia nephropathy was established by administering potassium oxazinate with adenine. Mice were randomly divided into common, model, positive drug (10 mg/ (kg·d)) and compound active tea of Lithocarpus litseifolius high-, middle-and low-dose groups (10 g/ (kg·d), 3. 33 g/ (kg·d) and 1. 11 g/ (kg·d), respectively). One hour after the last gavage, urine protein (UP) was measured by CBB method, urea nitrogen (UUN) was measured by urease method. Orbital blood pampling, blood was collected for uric acid (UA) analysis by enzyme ratio method, urea nitrogen (BUN) was measured by urease method. The serum contents of interleukin 6 (IL-6) and tumor necrosis factor (TNF-α) were measured by ELISA. Take kidney tissue, levels of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) were measured by quantitative fluorescence, kidney histopathological changes were observed by HE stainning. Results Compared with the control group, the model group’s levels of UP, UUN, UA, BUN, IL-6, URAT1, ULUT9 and TNF-α were significantly increased (P< 0. 01, P< 0. 05), and the renal tissue structure was normal. Compared with the model group, the positive group’s levels of UP, UUN, UA, BUN, IL-6 and TNF-α were significantly decreased (P< 0. 01, P< 0. 05), there was little glomerular atrophy or deformation in the kidneys, kidney tubular dilatation was occasionally seen, but there was no inflammatory cell infiltration. Compared with the model group, the high-dose compound active tea of Lithocarpus litseifolius group’s UP, UUN, UA, BUN, IL-6, URAT1, TNF-α and GLUT9 levels were significantly decreased(P< 0. 01, P< 0. 05). The middle-dose compound active tea of Lithocarpus litseifolius group’s UP, UUN, UA content, IL-6, URAT 1, GLUT9, BUN and TNF-α were significantly decreased (P< 0. 01, P< 0. 05). The low-dose compound active tea of Lithocarpus litseifolius group’s UP, UUN, UA, IL-6, URAT1, BUN, TNF-α and GLUT9 levels were significantly decreased (P< 0. 01, P< 0. 05). Conclusions Compound active tea of Lithocarpus litseifolius can reduce uric acid in mice with hyperuricemia nephropathy and has a certain protective effect on the kidneys. The mechanism may be related to the inhibition of uric acid reabsorption, and the specific mechanistic details should be further investigated.
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LI Yihui, PENG Hao, XU Yuchun, GUO Rong, GONG Wei
2024,34(1):69-79, DOI: 10. 3969 / j.issn.1671-7856. 2024. 01. 008
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Objective Because of the poor prognosis of colon adenocarcinoma (COAD), it is necessary to screen prognosis-related genes in COAD patients and establish a new prognostic risk assessment model. Methods COAD-related data from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) were used as training and validation sets, respectively. Weighted gene co-expression network analysis (WGCNA), a Cox regression model and least absolute selection and shrinkage operator (LASSO) regression analysis were used to screen prognosis-related genes of COAD and establish a prognostic model. A receiver operating characteristic (ROC) curve was combined with a survival curve to verify the model accuracy, and a nomogram was constructed. Patients were divided into two groups by the median risk score. The immune cell proportion score (IPS) was used to evaluate the immunotherapy response of the two groups. Results A total of 15 feature genes were screened. The area under the ROC curve in the predictive model of COAD patients was >0. 6, and the survival rate of the high-risk group was significantly lower than that of the low-risk group (P< 0. 05), suggesting a good distinguishing ability for high- and low-risk COAD patients. Patients in the low-risk group had a higher IPS (P= 0. 026), indicating a better response to immunotherapy. Conclusions The model developed for COAD in this study has a good ability to predict the survival of patients at high and low risk of COAD.
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DU Xiaoshuang, LIU Ping, DENG Ying, YANG Hongqiu, DU Yu
2024,34(1):80-87, DOI: 10. 3969 / j.issn.1671-7856. 2024. 01. 009
Abstract:
Objective To investigate the therapeutic effect of licorice zinc on melasma. Methods Thirty-six BALB/ c mice were equally divided into blank group, model group, licorzinc low-dose group, licorzinc medium-dose group, licorzinc high-dose group and tranexamic acid group. Melasma was induced by 100 mJ/ cm2 UVB irradiation combined with 15 mg/ kg progesterone injection. Mice were treated with tranexamic acid (0. 065 g/ kg) and low (0. 65 g/ kg), medium(1. 3 g/ kg), or high (2. 6 g/ kg) doses of zinc licorice for 14 days. Skin was taken for HE and Masson-Fontana staining and measurement of SOD, MDA, GSP-Px, TNF-α, IL-1β, IL-6, plasma protein Nrf-2, nuclear protein Nrf-2 and HO-1 expression levels. Results Compared with model group, high-dose licorice zinc group showed decreased melanocyte formation, collagen cell necrosis, and inflammatory infiltration (P< 0. 01); decreased MDA, IL-6, IL-1β, TNF-α and plasma protein Nrf-2 expression (P< 0. 01); and increased GSP-Px, SOD and nuclear protein Nrf-2 and HO-1 expression (P< 0. 01). Conclusions Zinc licorice activates the Nrf-2/ HO-1 pathway to initiate high expression of HO-1, SOD and GSP-Px and fight oxidative stress, thereby reducing melanogenesis.
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WU Xuying, CHEN Min, TIAN Yushu, LI Bin, ZHANG Wenming, LIU Yunbo
2024,34(1):88-95, DOI: 10. 3969 / j.issn.1671-7856. 2024. 01. 010
Abstract:
Objective To explore the effects of different types of drinking water on the growth and fecal flora of mice. Methods Specific pathogen-free NIH mice were randomly divided into five groups, 32 mice each group,with half males and half females in each group. The group were given either purified water (control group), acidified water, alkalized water, weakly acidic water or solid water. Diet and body weight were monitored continuously for 20 days. After the experiment, animal fecal samples were collected, and the V3-V4 region was amplified with bacterial 16S rDNA universal primers. An Illumina Miseq high-throughput sequencing platform was used for high-throughput sequencing, and microbial community, α diversity and β diversity were analyzed by bioinformatics method. Results The body weight of female mice given different pH values of weakly acidic water was higher, while the weight of the other groups was lower, than that of the control group (P> 0. 05). The body weight of male mice in the acidified water group was higher, while that of other groups was lower, than that of control group, but there was no statistical difference between the groups (P> 0. 05). The body weights of male and female mice in the solid water group were lower than those in the control group (P< 0. 05). The food and water intake of the female animals in the alkaline water group and the water intake of female animals in the solid water group were lower than those of the other groups. OTU clustering analysis showed that the data volume of the sequencing was reasonable, and the fecal flora species of NIH mice were divided into five phyla, among which Bacteroides and Firmicutes were dominant. Unclassified Pseudopurpuromonas, Lactobacillus and Alistipes were the main genera. There were differences in fecal flora abundance and diversity among the mice given the five drinking water types. α analysis showed that the acidified water group had the highest flora abundance and diversity, while the solid water group had the lowest flora diversity. β analysis showed that the fecal flora composition in the solid water group was the closest to that of the control group, followed by the alkalized water group, acidified water group and weakly acidic water group. Conclusions Through an exploration of the effects of consuming different forms of water, this study revealed that solid water consumption had the greatest effects on body weight, feed intake, water consumption, and fecal flora of mice. The abundance and diversity of fecal flora in mice were affected by different pH values of drinking water, especially acidified water.
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YE Qianchen, XU Dan, WEN Fuqiang, CHEN Jun, WANG Tao
2024,34(1):96-102, DOI: 10. 3969 / j.issn.1671-7856. 2024. 01. 011
Abstract:
Objective Optimizing the preparation method to improve the quality of mouse lung cryosections to help enhance the specificity of immunofluorescence staining and obtain more accurate and reliable experimental result. Methods C57BL/6 mouse lung tissue was used to make cryosections via the traditional post-freezing fixation method, prefreezing fixation method, and a modified perfusion pre-freezing fixation method. A laser-scanning confocal microscope was used to observe lung tissue immunofluorescence staining. Whole areas of mouse lung slices were scanned by fluorescence microscope, and the numbers of intact airways per unit area of lung tissue were calculated. Results In the lung cryosections made via the traditional post-freezing fixation method, the alveoli structure was damaged, the airway wall was seriously disrupted, and there was non-specific staining. Lung cryosections made via the pre-freezing fixation method showed relatively intact alveolar and airway structures but collapsed alveoli and several destroyed airways. In the lung cryosections obtained via the modified perfusion pre-freezing fixation method, the structure and morphology of the alveoli and airways were intact and clear. Additionally, the locations of multiple proteins targeted with immunofluorescence staining were accurate. The number of intact airways (diameter ≥100 μm) per unit area in the lung cryosections obtained via the modified perfusion pre-freezing fixation method was higher than that from cryosections made using the pre-freezing fixation method ((0. 66±0. 15) / mm2 vs (0. 33±0. 14) / mm2, P< 0. 05) and was also significantly higher than that from sections made using the traditional post-freezing fixation method ((0. 66 ± 0. 15) / mm2 vs (0. 02 ± 0. 04) / mm2, P< 0. 01). Conclusions The modified perfusion pre-freezing fixation method for cryosections is conducive to maintaining the integrity of mouse lung tissue morphology and obtaining high-quality multiplex immunofluorescence staining result.
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2024,34(1):103-113, DOI: 10. 3969 / j.issn.1671-7856. 2024. 01. 012
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As the intelligence level gradually improves in domestic laboratory animal facilities, a large amount of valuable data have been accumulated. These data have not been fully exploited because of the lack of analytical method. In the context of big data, machine learning has achieved remarkable result in biomedicine, building science, and other fields, and provides a reference for its application in laboratory animal facility management. In this article, the contents, methods and models of machine learning applied to various systems of laboratory animal facilities at home and abroad are reviewed and discussed.
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2024,34(1):114-120, DOI: 10. 3969 / j.issn.1671-7856. 2024. 01. 013
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Based on the development history that the modern medicine and laboratory animal science have long been hindered by animal welfare groups and animal-rights activists in Western countries, and considering the relevant circumstance in China, the author appeals and recommends that the laboratory animal practitioners and biomedical researchers, the scientific community in China should recognize and identify the boundaries of our professional activities. Firstly, do not participate in the activity related to so called “World (Lab) Animal Day” that is said in some Chinese websites, to originate from NAVS, an antivivisection society Ltd. , London. Secondly, do not participate in the activity related to so called “animal memorial stone” that was originated in Japan. These movements have nothing to do with biomedicine and laboratory animal sciences, and fundamentally are antiscientific and are incompatible to traditional Chinese culture. Thirdly, distinguish the standpoints of laboratory animal science from various viewpoints of animal welfare/ rights activists, promote scientific management of the institutional animal care and use for better supporting biomedical research in China.
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2024,34(1):121-124, DOI: 10. 3969 / j.issn.1671-7856. 2024. 01. 014
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As the basic carrier and key condition for research in the fields of life science, medicine and pharmacy, laboratory animals have played an extremely important role in the development of modern science. Animal welfare ethics is built on the moral foundation of human civilization and is a product of social and economic development to a certain stage. From a scientific point of view, treating animals well is both a humanitarian need and a need for scientific experiments. This paper elaborates the role and significance of laboratory animal welfare from the aspects of the development of laboratory animal welfare ethics and the content of regulations and policies, whether and how to establish a memorial day and monument for laboratory animals, and calls on experimental personnel to follow the “3R” principle and enhance their sense of responsibility and awareness of norms.
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2024,34(1):125-126, DOI: 10. 3969 / j.issn.1671-7856. 2024. 01. 015
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This review clarifies that laboratory animal welfare and ethics in life science research should be humancentered, positive and responsible through the understanding of the connotation of laboratory animal welfare.
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2024,34(1):127-129, DOI: 10. 3969 / j.issn.1671-7856. 2024. 01. 016
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In the practice of laboratory animal ethics and welfare, 3R is the core of contents. As the subject in this process, individuals working in laboratory animal field play a leading role and should take corresponding responsibility. In this article, the author discussed the function, realized route, and significance of subject responsibility in the practice of laboratory animal ethics and welfare by following aspects: proposal of subject responsibility, requirements of responsibility in the implementation of ethics and welfare regulation, in the application of ethics and welfare technique and method, in the development of ethics and welfare products, in the management and monitoring of ethics and welfare application, as well as establishing an anniversary and cenotaphs to embody subject responsibility.
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SANG Jiala, LI Shanshan, CUI Xin, REN Qingqing, HOU Ruiling, PAN Xingfang, WANG Shenjun, ZHAO Meidan
2024,34(1):130-138, DOI: 10. 3969 / j.issn.1671-7856. 2024. 01. 017
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Depression is a major cause of disability and has adverse effects. Despite the many types of antidepressants, clinical treatments of depression remain poor. Therefore, novel anti-depressant mechanisms need to be explored. The beneficial effects of irisin on the nervous system are gradually being elucidated, and studies have found that irisin has an anti-depressant effect, which may become a new treatment for depression. This study explored the mechanism of irisin and its upstream and downstream anti-depressants by reviewing the existing studies explaining the link between irisin and depression, and proposes that SIRT1/ PGC-1α may mediate FNDC5/ irisin to regulate BDNF to promote neurogenesis and improve depression, which provides a new idea to study irisin and its upstream and downstream antidepressants.
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ZHU Ziyue, WANG Lu, YAO Junpeng, LIU Huilin, LI Yanqiu, LI Ying, ZHANG Wei
2024,34(1):139-145, 157, DOI: 10. 3969 / j.issn.1671-7856. 2024. 01. 018
Abstract:
Diabetic peripheral neuropathy is a common diabetic complication. Presently, our understanding of its pathogenesis is incomplete, and there are no effective treatment options. In-depth research requires the use of animal experiments. The criteria for modeling success and the evaluation method for peripheral nerve function recovery are critical for carrying out animal experiments into type 2 diabetic peripheral neuropathy. However, but there has been a lack of systematic interrogation and analysis of the evaluation method used with type 2 diabetic peripheral neuropathy models. Therefore, the author reviewed the recent data, summarized and analyzed the evaluation method used for animal models of type 2 diabetic peripheral neuropathy of small and large nerve fibers, and proposed future directions for development, providing a reference for related research.
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2024,34(1):146-150, DOI: 10. 3969 / j.issn.1671-7856. 2024. 01. 019
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Pyroptosis is a programmed mode of cell death. Activated caspase-1 can induce the occurrence of pyroptosis, promote the release of inflammatory factors, and trigger a violent inflammatory response. Depending on the type of caspase involved, pyroptosis can be divided into a caspase-1-mediated typical inflammasome pathway and a human caspase-4/5 (or mouse caspase-11)-mediated atypical inflammasome pathway. In recent years, studies have found that pyroptosis is closely related to the occurrence, development, and prognosis of atherosclerosis. This article reviews the roles and mechanisms of endothelial cells, vascular smooth muscle cells, and macrophage cells in the occurrence and development of atherosclerosis, with the aim of promoting new ideas for research into the pathogenesis, diagnosis, and treatment of atherosclerosis.
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HU Lingfeng, LIU Jie, FAN Shengtao
2024,34(1):151-157, DOI: 10. 3969 / j.issn.1671-7856. 2024. 01. 020
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Non-human primates (NHP) are becoming increasingly important laboratory animals, especially in the field of neuroscience, where many significant breakthroughs have been made, including research on brain development, neurodegenerative diseases, and psychiatric disorders. However, as their breeding and use grows, biosafety and animal ethics issues should be considered. This review summarizes the application and challenges of NHP laboratory animals in the neuroscience field from the aspects of an NHP overview, feeding and operation, biosafety, and animal ethics.
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2024,34(1):158-164, DOI: 10. 3969 / j.issn.1671-7856. 2024. 01. 021
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Exosomes are small endosomally derived extracellular vesicles with a lipid bilayer structure, and they contain substances, such as proteins, lipids, DNA, RNA, micro(mi)RNA, and long non-coding(lnc)RNA. Exosomes participate in pathogen recognition, antigen presentation, autophagy regulation, immune activation and immunosuppression in bacterial infections. Studies have shown that miRNA, lncRNA, and proteins in exosomes play important roles in regulating antibacterial reactions in organisms. We reviewed the immunomodulatory effects of exosomes on several intracellular and extracellular bacterial infections to provide a reference for those studying the interactions between exosomes and bacterial infections.
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REN Qunli, LUO Qian, LIU Huaqian, WU Faming, HE Yuqi, LIU Jianguo, WANG Qian
2024,34(1):165-170, DOI: 10. 3969 / j.issn.1671-7856. 2024. 01. 022
Abstract:
Ardisia Crenata Radix is a traditional Chinese medicinal plant that belongs to the Myrsinaceae family, and its main active components are coumarins, saponins, flavonoids, and volatile oil. Bergenin, ardisicrenoside A, ardisicrenoside B, ardisiacripin A, ardisiacripin B, and embelin were identified as active anticancer compounds in in-depth studies into the anti-tumor effects of Ardisia Crenata Radix. They show high therapeutic potential in oral cancer, nasopharyngeal carcinoma, liver cancer, colon cancer, bladder cancer, cervical cancer, and leukemia, mainly by inducing tumor cell apoptosis, increasing tumor cytotoxicity, inhibiting cell proliferation, inhibiting tumor cell metastasis and migration, and inducing cell regulatory enzyme cascade reactions. However, most preclinical experimental data on cinnabar root’s anti-tumor mechanism have not been verified in high-quality, multi-sample, and repeated randomized controlled trials, and there are a lack of clinical research data on tumor prognosis, pharmacodynamics, and pharmacokinetics. Accurate research experiments and clinical trials should be designed to further explore the pharmacological effects of Ardisia Crenata Radix.
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WU Xueliang, FAN Jianchun, GUO Fei, ZHANG Qi, XUE Jun, WANG Ximo, SUN Guangyuan, LIU Jianling, HAN Lei, GAO Shuquan
2024,34(1):171-176, DOI: 10. 3969 / j.issn.1671-7856. 2024. 01. 023
Abstract:
Tumor-associated macrophages (TAMs) are the predominant cell group in the tumor microenvironment(TME) and are the most important regulatory cells of immune system suppression and tumor cell proliferation in TIME. Src homology-2 domain-containing protein tyrosine phosphatase 2 (SHP-2) is a non-receptor protein tyrosine phosphatase that plays an important role in the transmission of signals from the cell surface to the nucleus. SHP-2 is a key intracellular regulatory factor mediating cell proliferation and differentiation and is involved in a variety of growth factor and cytokine signaling pathways linking the cell surface to the nucleus. Recent studies have shown that SHP-2 is a key enzyme in determining the function of TAMs, but because of its variable function, it plays different or even opposite roles in different solid TMEs. This paper reviews the function of SHP-2 in TAMs and related solid tumors to provide a comprehensive reference for tumor immunity and targeted therapy research.
Volume 34,2024 Issue 1
Volume 34,2024 Issue 1
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Lipidomics driven biomarker discovery in chronic lung disease
Zhang Ang, Liu Xinguang, Du Yan, Xie Yang
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Chronic lung diseases (CLD) include chronic obstructive pulmonary disease, asthma, idiopathic pulmonary fibrosis, etc. Studies have shown that CLD is closely related to the disorder of lipid metabolism. Therefore, lipids, as biomarkers of CLD, may be of great value in the diagnosis, prevention and monitoring of disease treatment.This review mainly discusses four aspects of lipidomics, selection of clinical samples for lipidomics, discovery of biomarkers for CLD, and differentiation of TCM syndromes for CLD.
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Establishment of WHBE rabbit knee osteoarthritis model and intervention study of platelet-rich fibrin releasates
Huang Jun-jie, Chen Min-li, Zhu Ke-yan, Jiang Jing-ao, Zhang Jing-hui, Jiang Chao, Pan Yong-ming
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Objective WHBE rabbit KOA model was established by excision of medial collateral and partial patellar ligaments and intervention with platelet-rich fibrin release solution (PRFr). To investigate the mechanism of cartilage injury and inflammation in WHBE rabbit KOA model and the effect of PRFr intervention on KOA process. Methods Twenty-four WHBE rabbits were randomly divided into three groups: normal control (NC) group (n=6), KOA group (n=12) and PRFr group (n=6). The KOA group and PRFr group injected 0.5 mL of saline and PRFr into both joint cavities on the 7th and 14th postoperative days, respectively. At 4 and 8 weeks of modeling, knee joint grade score, X-ray imaging observation and gross score were performed. Serum levels of IL-1β, TNF-α and MMP-13 were detected by ELISA. Pathological sections were made after decalcification, and then HE staining, toluidine blue staining, safranin o-fast green staining and immunohistochemical expression of TGF-β, BMP3 and NF-κB were detected. Results Lequesne MG behavioral score, Mankin's score and Pelletier score of WHBE rabbits after the operation were significantly increased vs NC group (P<0.01); Pathological observation shows surface defects of cartilage and partial loss of chondrocytes; These results above indicated that the KOA model was established successfully. In KOA rabbits, knee joint swelling, joint pain stimulation and movement limitation were obvious, and X-ray showed high-density soft tissue shadow, indicating more joint effusion, and rough articular surface in general. After PRFr treatment, the levels of serum inflammatory factors (IL-1β, TNF-α, MMP-13) in KOA model rabbits were significantly reversed (P<0.05, P<0.01), and the surface of cartilage became smooth, and most of the chondrocytes were neatly distributed. At the same time, the expression levels of TGF-β, BMP3 and NF-κB induced by KOA were significantly decreased(P<0.01). Conclusion This study successfully established the KOA model of WHBE rabbits, and PRFr can improve the cartilage injury and inflammation of WHBE rabbits KOA model through TGF-β/BMP and NF-κB pathways.
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Potential risks of biosafety and prevention strategies in medical and pharmaceutical research laboratories
Chen Mo, Tao Jiayi, Wang Hongxu, Zhang Qingjian
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Medical and pharmaceutical research laboratory usually involves wide range of study aspects. The materials used in the laboratory are various, including animals, microorganisms and nano-particles and other kinds. Meanwhile, with the production of more and more waste, more biosafety risks would be created. Here, we outlined the potential safety risks related with gene amplification, gene recombination, pathogenic microorganism research, nanotechnology, animal experiments, genetically altered animals, and experimental waste, etc. It also proposed preventive measures for laboratory biosafety risks, which mainly associate with developing strict legal frameworks, bettering hardware infrastructure, strengthening safety awareness, and enhancing education and training programs.
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Research progress on related complications after snake bite
LI Yumei, YANG Yue, YI Jun, YAN Zhangren, WANG Wanchun, DONG Degang
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Snake bite is a common clinical emergency, which has the characteristics of acute onset, rapid changes in condition, high disability and mortality rates. In addition to the common systemic and local tissue damage, snake envenomation can also cause significant complications, including immediate and delayed effects. These complications are also the main causes of disability and even death caused by snake bite, which seriously affect the long-term prognosis and quality of patients’ life. This paper summarizes the symptoms, diagnosis and treatment of snakebite complications from the aspects of blood system, nervous system, motor system, endocrine system, reproductive system and other aspects, in order to provide references for effective and precise treatment of snake bite in clinical practice.
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Research progress of ferroptosis in the mechanism of cerebral ischemia reperfusion injury
jianghuan, BAI Wenya, SHAO Jianlin
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Ferroptosis is a newly cell death mode discovered in recent years, involving in a variety of pathophysiological processes, such as ischemia reperfusion injury, neurodegenerative diseases and tumors, etc. At present, there is a lack of effective methods to prevent and treat ischemic stroke worldwide, and ferroptosis which is involved in cerebral ischemia reperfusion injury. 50 articles were included in this paper after searching the related literature, which published in databases such as PebMed, Wanfang, CNKI and VIP in recent years. Discussing theIorn metabolism and the concept, mechanism and regulation of ferroptosis, the role of ferroptosis in the mechanism of cerebral ischemia reperfusion injury, and the methods of inhibiting ferroptosis, this paper attempts to provide reference for finding a new potential treatment for ischemic stroke from the direction of inhibiting ferroptosis.
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Research progress on MHC function and transgenic mouse models
CAO Xiangwen, LI Min, YIN Qi, HAN Xueliang, WANG Yuan, ZHAO Guangyu
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The major histocompatibility complex (MHC) is closely related to immune regulation, and not only has genetic polymorphisms, but also has species differences in MHC restriction. The construction of humanized MHC transgenic mouse models is an important strategy to break through the differences of MHC species and simulate the characteristics of human immune response. MHC transgenic mice are mainly divided into MHC I or MHC II. single transgenic mouse models and MHC I and MHC II double transgenic mouse models. At present, the strategy of knocking out H-2Kb and H-2Db or knocking out murine β2m is adopted to eliminate the competitive inhibition of HLA I molecules by endogenous H-2 class I molecules, and the construction of HLA II transgenic mouse model is to knock out the β strand of murine origin and transfer it to HLA II. class genes.With the optimization of construction strategies, MHC transgenic mouse models have been applied to epitope vaccine development, tumor treatment, and disease genetic association studies, becoming a powerful tool for preclinical trials. In this paper, we summarize the relevant data of MHC transgenic mouse models, and summarize the construction strategies of MHC transgenic mouse models and their application progress in vaccine development and disease treatment.
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Advances in the study of glucose metabolic reprogramming in the pathogenesis of Alzheimer's disease
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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by widespread dementia. Despite extensive research on the pathogenesis of AD over the past fifty years, the underlying mechanisms responsible for AD-related cellular damage and cognitive impairment remain elusive. Currently, multiple studies have confirmed alterations in glucose metabolism patterns within nerve cells in individuals with AD. This metabolic transition plays a crucial role in cell survival and disease progression, even occurring decades before pathological changes and cognitive dysfunction manifest. This article provides an overview of potential mechanisms through which glucose metabolism reprogramming contributes to AD development in various types of nerve cells and brain regions, as well as their interplay, aiming to establish a foundation for further investigation into AD while offering insights and ideas for the development of novel preventive and therapeutic approaches.
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Analysis of animal model of psoriatic arthritis based on the characteristics of Chinese medicine and Western medicine
Shi Yajin, LI Hanbing, LI Genlin, WU Suhui
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Purpose: In recent years, with the incidence of psoriatic arthritis gradually increasing and incurable in China, it has become a major problem in the medical career. Therefore, In this study, we actively explored the pathogenesis of psoriatic arthritis based on the characteristics of Chinese and Western medicine clinical evidence, summarized the currently available animal models and analyzed and evaluated them. Methods: Literature detected in line with this topic was collated and summarized, and the existing models were given an agreement score through the study of the etiology and pathogenesis of psoriatic arthritis in Chinese and Western medicine, the diagnostic criteria of Chinese and Western medicine, and the analysis of the characteristics of the animal models and their degree of agreement with the clinic. Results: This thesis found that the human leukocyte antigen transgenic mouse model, the multiple hybridization transgenic mouse model, and the mannan-induced mouse model had the highest fit scores. Conclusion: Since psoriatic arthritis is mostly seen in Europe, the preparation methods of animal models are mostly imported from abroad, and there are very few animal models prepared with the characteristics of Chinese medicine, therefore, the model agreement scores of western diagnosis are higher than those of Chinese medicine diagnosis as a whole. It is hoped that in the future, we can combine the unique diagnosis and treatment methods of Chinese medicine to further improve the types of animal models of psoriatic arthritis, so as to provide a basis for the construction of more ideal animal models for the treatment of psoriatic arthritis by combining traditional Chinese medicine and Western medicine.
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Research progress of mitochondrial quality control in respiratory diseases
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Respiratory diseases (lung inflammation, pulmonary fibrosis) are a serious threat to human health. As organelles unique to eukaryotic cells, mitochondria not only have important functions in energy production, biosynthesis and maintenance of intracellular homeostasis, but also act as diverse signaling organelles involved in inflammation, proliferation, differentiation, cell repair and other processes. The mitochondrial quality control system includes mitochondrial biogenesis, mitochondrial dynamics, and mitochondrial autophagy. It has been found that certain pathological mechanisms of respiratory diseases such as oxidative stress and inflammation are closely related to dysregulation of mitochondrial quality control. Therefore, this paper summarizes the research progress of mitochondrial quality control dysregulation in respiratory diseases (chronic obstructive pulmonary disease, pulmonary fibrosis, acute lung injury, asthma and bacterial pneumonia), in order to seek new ideas for the prevention and treatment of respiratory diseases from the perspective of mitochondria.
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Neuro-pathological study of the intrathalamic neurovirulence test of poliomyelitis vaccine in rhesus macaques
YU Pin, XU Yan-feng, HAN Yun-lin, ZHAO Wen-jie, QIN Chuan
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Objective To study the effect and pathological mechanisms of the neuro-immune response of viral encephalomyelitis caused by the virulence reversion of the intrathalamic neurovirulence test of poliomyelitis vaccine in rhesus macaques. Methods The stock solution (not less than 7000 lgCCID50?L-1) of the inactivated polio vaccine (Vero cells) of type I, type II and type III Sabin strains and 10-1 dilution of each type of polio vaccine were carried out using intrathalamic neurovirulence test. We observed the pathological changes of polio. Via immunohistochemical method, the distribution of receptor CD155 and CD4+ T lymphocytes, CD20+ B lymphocytes and CD68+ microglia were detected. Results Lesions were observed on the virulence reverted polio case. Inflammatory cells infiltrating, neuronal degeneration and necrosis, satellite phenomenon, perivascular cuffing and glial cell proliferation were observed in the spinal cord. The inflammatory cells were mainly CD4+ T lymphocytes, CD20+ B lymphocytes, and CD68+ microglia in perivascular cuffing and proliferative glial nodules. There is no significant difference on distribution of poliovirus receptor CD155 in neurons and glial cells of monkeys with and without polio, while no expression was observed in vascular endothelial cells. Conclusion Polio caused by virulence reversion of the intrathalamic neurovirulence test is viral encephalomyelitis.
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Effects and mechanism of Five-elements music on the social behavior of offspring from Stress-Injured pregnant rats
WU Yongye, YANG Liping, ZHAO Jiajia, SONG Qi, HOU Junlin, WANG Yaohui, LI Xiaolin
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Objective To investigate the effects and mechanism of Five-element music on the social behavior of Pregnant Children with Allergic Stress during Pregnancy, in order to provide a basis for the early prevention and treatment of clinical fetogenic affective disorders. Methods Forty-five pregnant mice were randomly divided into three groups: a blank group, a model group, and a Five Element Music group. In the model and Five Element Music groups, the model was induced using the bystander electric shock method. Additionally, the Five Element Music group was exposed to Palace Tune Five Element Music daily from 17:00 to 19:00 during pregnancy. On the 19th day of pregnancy, ELISA was employed to assess the levels of adrenocorticotropin (ACTH) and cortisol (CORT) in the serum of pregnant mice in each group for modeling evaluation. The offspring were subsequently grouped with their mother mice and underwent an 8-week-old three-box social experiment to observe social behavior. We utilized the immunofluorescence double-labeling method to detect glutamatergic neuron activity in the mPFC region of the offspring mice. Furthermore, high-performance liquid chromatography was employed to measure the total glutamate (Glu) content in the mPFC region of the offspring mice, while Gorky staining was used to observe changes in dendritic spines of mPFC neurons in the offspring mice.Results Compared to the blank group, the model group exhibited a significant increase in the levels of ACTH and CORT in the serum of pregnant mice, alongside a significant decrease in the social interaction time and social novelty preference index of the offspring mice. Additionally, there was a significant decrease in the activity of glutamate neurons, glutamate content, and neuronal dendritic spines.In contrast, when compared to the model group, the Wuxing Music group demonstrated a reduction in the levels of ACTH and CORT in the serum of pregnant mice, as well as improvements in the social behavior, glutamate neuron activity, glutamate content, and the condition of neuronal dendritic spines in the offspring. Conclusions The intervention of Five-element music effectively ameliorates offspring"s social behavior disorder resulting from prenatal fear stress, with its mechanism potentially linked to enhancing glutamate neuron activity in the mPFC region.
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Immune cell composition analysis of CAST/EiJ mice
LIUQI, HOU Yongzhi, LI Na, ZHANG Jingjing, LU Jiahan, CONG Zhe, ZHU Lin, XUE Jing
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Objective To explore the possible causes of susceptibility to multiple pathogens in CAST/EiJ mice, immune cell phenotypes in the peripheral blood and spleen of CAST/EiJ mice were analyzed to clarify the immune cell composition of CAST/EiJ mice. Methods Classical dendritic cells (cDCs), natural killer (NK) cells, B lymphocytes, T lymphocytes and their subsets in peripheral blood and spleen of CAST/EiJ mice and C57BL/6J mice were detected by flow cytometry using the cell surface markers CD3, CD4, CD8, CD11b, CD11c, CD19, CD27, CD49b and TCRβ. Results There was no significant difference in the proportion of cDCs between CAST/EiJ and C57BL/6J mice, but the cDC1 cell subset was low. The proportion of NK cells (mainly mature NK cell subsets) and T lymphocytes (mainly CD8+ T cells) were both lower in CAST/EiJ mice than in C57BL/6J mice, while the proportion of B cells in CAST/EiJ mice were higher than those in C57BL/6J mice. Conclusion The proportion of NK and T lymphocytes in CAST/EiJ mice was lower than those in C57BL/6J mice.
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Evaluation of an animal model of chronic fatigue syndrome based on data mining
Li Ya-qing, Wang Can, miaomingsan
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Objective To study the application of the animal model of chronic fatigue syndrome, and to provide reference for its animal experimental methods and model improvement. Methods Using "chronic fatigue syndrome, animal model" and "chronic fatigue syndrom, animal model" as search terms, we searched in China Knowledge, Wanfang and PubMed databases. Literature on animal models of chronic fatigue syndrome was compiled from July 2000 to July 2023, and experimental animals, modeling methods, positive drugs, and detection indexes were sorted out, and a database was established for statistics and analysis. Results A total of 155 articles were included; the most experimental animals were male SD rats of SPF grade and 6-8 weeks of age, with weights of 180-220g; the most used mice were male KM mice of 18-22g and 6-8 weeks of age; the most used positive drug was ginseng saponin tablets; the most used modeling method was the method of "forced cold water swimming + chronic restraint"; the most used modeling method was the method of "forced cold water swimming + chronic restraint"; the most used modeling method was the method of "forced cold water swimming + chronic restraint". +The most widely used modeling method is the "forced cold water swimming" method, and the modeling cycle is mostly concentrated in 14 days, and most of them adopt the method of intervention while modeling; the testing indexes are mainly behavioral, which mainly include the exhaustion swimming experiment, the open field experiment, the rat-tail suspension experiment, the Morris water maze experiment, and the observation of the general state of the animals, and the second is the serum biochemical indexes, and the most frequently detected indexes are serum MDA, SOD, TNF-alpha, IOD, and IBP, TNF-α, IL-1β, CORT, IL-2, IFN-γ, ACTH, GSH-Px, IgG, IgA, IL-6, etc. The rest of the indicators were selected according to the research purpose, including the indexes of spleen, thymus, etc., the morphological indicators detected by HE staining and ultrastructural electron microscopy, the immunohistochemistry-related indicators, the CRH and Smilax detected by fluorescence PCR, the CRH, the Smilax, the Smilax, and the Smilax. The mRNA expression indexes of CRH, Smad4, BDNF, CREB, IFN-γ, NRF-1, TFAM, Tlr4, etc., and the protein expression indexes of BDNF, CREB, ERK, Bmal1, Clock, NGF, PGC-1α, SIRT1, Smad4, Caspsae-3, etc., were determined by Western blot method. and other related protein expression indicators. Conclusion At present, the pathogenesis of chronic fatigue syndrome is still unclear, and the animal model is mainly based on the stress modeling method of "forced cold water swimming + chronic restraint", which simulates the physical and mental fatigue state of human beings; there is no uniform regulation on the criteria for the formation of animal models, and the evaluation of the model is based on the application of a variety of behavioral experiments individually or in combination, and the objective evaluation indexes are mostly used to argue the etiology of the disease and evaluate the effectiveness of interventions. The objective evaluation indexes are mostly used to prove the conjecture of etiology and evaluate the effectiveness of interventions; the results of the application of various test indexes show that chronic fatigue syndrome may be related to inflammatory response, neurological dysfunction, and mitochondrial dysfunction, and there may be abnormalities in the pathogenesis of immune function, energy metabolism, cell proliferation, and cell death, which is expected to provide reference for the application of the model, and to provide ideas for the model"s refinement. The excavated content is expected to provide reference for the application of the model and provide ideas for the improvement of the model.
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Application and prospect in experimental animal model of chronic stress
YUE Xiaoqi, Li Yuting, JIANG Miao, ZHAO Zigang, NIU Chunyu
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The effect and mechanism of chronic stress on psychosomatic diseases is a hot topic in the field of stress research. The establishment of animal models to simulate human chronic stress state is of great significance in the principle of stress response, the pathogenesis of related diseases, clinical treatment and drug development. In this paper, the commonly used animal models of chronic stress at home and abroad were reviewed, the classification of stressors, animal selection, model construction, pathological manifestations and evaluation indexes were summarized, and the advantages and disadvantages and application progress of various models were discussed, hoping to provide references for the study of model selection of chronic stress response.
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Technological advances in the study of post-stroke neural loop
Chenyanxi, Xuzhidong, Liutingting, Maliansu, Sunfangling, Wangwen
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Neural loops are formed by interconnections between neurons through synaptic structures, Which are the basic units of information transmission and processing in the brain and play an important role in the regulation of neural functions. After Stroke, the neural connections between the infarcted area and the peri-infarct region and the remote area are damaged, resulting in patients at risk for neurological dysfunction or even disability. However, with advances in detection technology, more and more studies have demonstrated that patients with stroke can produce some functional recovery during the chronic phase, possibly related to the re-establishment of synaptic connections and neural circuits. Therefore, the development of specific technology to identify and manipulate neuronal activity patterns, as well as the use of high temporal and spatial resolution imaging strategies to decipher these neurological processes allows us to understand the whole-brain network dynamics of stroke recovery and the mechanisms by which neural loop reestablishment occurs. Furthermore, we could neurobiologically comprehend the closed-loop relationships that underlie the development of stroke pathology to behavioral outcomes. Current technology for studying neural circuits focus on optogenetics, chemical genetics, in vivo calcium imaging, and functional magnetic resonance imaging technology. This article will introduce the working principles of these four major technologies, focus on summarizing the results of their respective applications in resolving neural remodeling after stroke, and briefly analyze the application scenarios, advantages and disadvantages, and future development trends of each technique. This paper will help clinical and basic researchers to to utilize these technologies in discovering new therapeutic strategies as well as evaluating the effectiveness of rehabilitation strategies.
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Analysis of the Role of Brain Plasticity in Improving Depression by Exercise
Chen Xianghe, LU Pengcheng, SHEN Ziming, LIU Chi, ZENG Xinyu, YIN Rongbin
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The research on the mechanism of depression is currently a focus in the field of neuroscience, degeneration of brain plasticity (decrease in volume, structural degradation, and functional disorder of the hippocampus, PFC, CG, etc.) leads to depression. Exercise is an important means of improving depression. Current research has confirmed the important mechanism of improving the volume, structure, and function of the hippocampus, PFC, CG, etc. in this process, but related research results only focus solely on changes in a certain brain volume or connectivity function, lacking a comprehensive understanding Systematic analysis of the mechanism of improving brain plasticity in exercise antidepressant effects. Therefore, this study aims to explore the role of brain plasticity in the occurrence of depression and the improvement of depression through exercise. This helps to comprehensively understand the role of brain plasticity in the occurrence of depression, and will also provide new ideas for exercise intervention in depression.
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Construction and application of patient-derived pancreatic tumor organoid model
LI Peng, HUANG Minli, TAN Dengxu, ZHANG Caiqin, ZHANG Yongbin, SHI Changhong
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Objective To construct a patient-derived pancreatic tumor organoid (PDO) and evaluate its effectiveness. Methods Collect fresh surgical specimens from pancreatic cancer patients for PDO culture; Compared the pathological and genetic characteristics of the PDO model with the primary tumors; Using the PDO model to evaluate the efficacy of clinical chemotherapy drugs and evaluate the effectiveness of the model. Results A PDO model of pancreatic cancer was successfully established. Histomorphological analysis displayed that the PDO model basically maintained the pathological characteristics of the primary tumor. Whole-exon sequencing showed that both organoids and original tumor tissue remained consistent in the gene mutation type and characteristics. Drug screening tests have exhibited that the PDO model had good sensitivity to gemcitabine and irinotecan. Conclusion A case of pancreatic cancer PDO was successfully constructed, which can reflect the histological and genetic characteristics of the original tumor, and can be used for drug sensitivity experiments in vitro, which proves the effectiveness of PDO model and is expected to imply precision medicine.
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Advances in the study of epigenetic regulatory mechanisms of astrocytes
xu liuqing, zhaopeiyuan, liuxihong, duxiaodan, fangmengyang, yuchenyang, houjunlin
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Astrocytes (AS) are the most abundant glial cells in the central nervous system and are involved in many physiology and pathology processes in the nervous system. Alterations in their phenotype are particularly important for the health of the CNS. Epigenetic mechanisms, including DNA methylation, histone modification, non-coding RNA regulation and chromatin remodeling, are closely linked to alterations in AS proliferation, differentiation, inflammation and other phenotypic features, but how these mechanisms function still needs to be explored and summarized. By reviewing the recent advances in the role of epigenetic mechanisms in AS under different physiological and pathological states, aim to provide new ideas for the understanding and treatment of related diseases.
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Experimental study of ursolic acid to ameliorate pancreatic β-cell injury in type 1 diabetic rats based on the TLR4/NF-κB pathway and Th17/Treg cell balance
songyu, zhangxiaoli, chenhuanhuan, tangcong
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[abstracts] Objective To investigate the effects of ursolic acid (UA) on TLR4/NF-κB signaling pathway and Th17/Treg cells in type 1 diabetes (T1DM) rats. Mmthods The T1DM rat model was prepared by intraperitoneal injection of streptozotocin, and randomly divided into blank (Control group) group, model group (Model group), metformin group (MET group) and UA group. General conditions such as body weight and blood glucose were recorded, and peripheral blood and pancreatic tissues were collected after six weeks of gavage to assess insulin intervention. Immunohistochemistry was used to observe the pathological changes in pancreatic tissues; horseshoe crab reagent was used to detect the changes in serum LPS content; qRT-PCR was used to detect the expression of pancreatic TLR4, MyD88, IκBα, and NF-κB p65 mRNAs, as well as the expression of the transcription factors RORγt and Foxp3 mRNAs; and Western blot was used to detect the expression of pancreatic TLR4, MyD88, IκBα , NF-κB p65 protein expression, and transcription factors RORγt, Foxp3 protein expression; flow cytometry to detect changes in the ratio of peripheral blood Th17, Treg cells; ELISA to detect changes in serum TNF-α, IL-6, IL-1β levels. Results After STZ-induced diabetic rats were treated by gavage for 6 weeks, compared with the Model group, fasting blood glucose (FBG) decreased significantly in both the MET and UA groups, and body weights increased; inflammatory infiltration of pancreatic β-cells was reduced; and the expression of TLR4, MyD88, IκBα, NF-κB p65, RORγt mRNA and protein expression was significantly decreased; LPS content was significantly decreased; IκBα, Foxp3 mRNA and protein expression was significantly increased; Th17/Treg ratio was significantly decreased; and TNF-α, IL-6, and IL-1β content was significantly decreased. Conclusion UA can improve the symptoms of rats by reducing LPS shift, inhibiting TLR4/NF-κB pathway, down-regulating RORγt and up-regulating Foxp3 expression to correct the imbalance of Th17/Treg cell ratio in T1DM rats.
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Effects of Shaoyao Gancao granule on hair growth, behavior and hypothalamic pituitary adrenal axis in mice with alopecia areata
QU Baoquan, LYU Shuying, LIN Wenjun, YANG Dingquan
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Objective To explore the effects of Shaoyao Gancao granule on hair growth, behavior and hypothalamic pituitary adrenal (HPA) axis in mice with alopecia areata (AA). Methods Forty-two C3H/HeJ mice were randomly divided into control, model, Shaoyao Gancao granule, corticotropin-releasing hormone receptor 1 (CRHR1) antagonist, and compound glycyrrhizin tablet (CGT) group. Photography, dermoscopy photography, weight weighing, behavioral measurement were taken, as well as corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), cortisol, glucocorticoid receptor (GR), and brain derived neurotrophic factor (BDNF) were assessed. Results Compared with the model group, high-dose Shaoyao Gancao granules could improve hair regeneration and weight gain (P<0.05), increase the percentage of total exercise distance and central area exercise distance in the open field experiment (P<0.05), reduce the immobility time in the forced swimming experiment and tail suspension experiment (P<0.05), reduce peripheral blood CRH, ACTH, Cortisol levels (P<0.05), and increase the expression of GR and BDNF in the hippocampus (P<0.05). Conclusions Shaoyao Gancao granule can promote hair growth and improve behavioral performance in mice with AA. The effects may be related to downregulating the levels of CRH, ACTH, and Cortisol, upregulating the expression of GR and BDNF, and inhibiting excessive activation of the HPA axis.
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Advances in the study of CAV1 in digestive tract tumors
Wu Zhihang, Pan Haibang, Tang mingzheng, lixiaofeng, rong yao, cuiyan
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[Abstract] Digestive tract tumour is currently one of the most common types of cancer in the world, including esophageal cancer, gastric cancer, hepatocellular carcinoma, pancreatic cancer and colorectal cancer, etc. Their prognosis is not good and the treatment still needs further improvement. Caveolin-1（CAV1）has a dual regulatory effect in digestive tract tumors, which is both a tumor suppressor and a carcinogen. CAV1 plays an important role in cell proliferation, invasion, metastasis, angiogenesis and drug tolerance of digestive tract tumors, the regulation of CAV1 protein and its related signaling pathways may become one of the strategies for the treatment of digestive tract tumors. Therefore, the review analyzes the relationship between CAV1 and digestive tract tumors in terms of structure, function, expression regulation, regulation of epithelial-mesenchymal transition（EMT）and drug resistance in digestive tract tumors in order to provide new ideas for the diagnosis and treatment of clinical digestive tract tumors.
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Advances of Programmed Cell Death in Post-stroke Cognitive Impairment
sunkexin, xiaoyuqian, wanjun, chenshuying, chenlimin, wangyan, baiyanjie
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Post-stroke cognitive impairment (PSCI) is one of the common complications after stroke, which has a significant impact on the quality of life of stroke patients. However, the pathogenesis has not been fully explained. More and more evidence shows that the mechanism of programmed cell death (PCD) is related to PSCI, including apoptosis, necrotic apoptosis, pyroptosis, generalized apoptosis, PARP-1 dependent cell death and iron death. Therefore, it is crucial to have a clear understanding of various mechanisms of PCD and their relationship with PSCI, and to elucidate the role of PCD in the pathogenesis of diseases. The article reviews six PCD pathways related to PSCI, summarizes their mechanisms of action in PSCI, and elucidates the possible crosstalk between different pathways, in order to provide data basis for clinical targeting of regulatory factors in the PCD pathway for the treatment of PSCI.
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Experimental study on the health hazards of brake pad particles and their main component antimony sulfide respiratory exposure in mice
LI Yanhong, XIU Jinghui, ZHOU Li, GUO Jianguo
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Objective To study the potential harmful effects of brake source particles. Methods Grind the brake pad particles or antimony sulfide particles. Subsequently, the mice were exposed through tracheal perfusion for 1 month to observe pathological changes in in the lungs, heart, and liver, and flow cytometry was used to analyze the changes in peripheral blood macrophages and regulatory T cells (Treg). Results After exposure, there was deposition of foreign substances in the alveolar wall of mice, with obvious infiltration of inflammatory cells around blood vessels, which worsened with increasing exposure concentration. In addition, pathological changes such as vascular inflammation and microthrombosis in the heart, and hepatocyte swelling in the liver were observed. Treg cells in peripheral blood decreased and macrophages increased in the antimony sulfide group and low-dose brake pad particles group, while the proportion of M2-type macrophages decreased. Conclusions Exposure to brake pad particles and their component antimony sulfide particles has varying degrees of toxic effects on the lung, heart, and liver of mice, and has a impact on the immune system, indicating the potential health hazards of brake-derived air pollution.
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Effect of Sanjie Quban Recipe on the Keloid Model of BALB/C Nude Mice and Influence on Transforming Growth Factor-β1
Huang ChuHan, Yang DingQuan, Zhong ShiYi, Wu RuiYing, Yang ZhiShan, Fang HuiJuan, Liu QingWu
Abstract:
Objective This study aimed to investigate the therapeutic efficacy of the Sanjie Quban Recipe on a keloid nude mice model and its impact on Transforming Growth Factor-β1 (TGF-β1). Methods Keloid tissue after surgical resection was transplanted into the subcutaneous back of healthy SPF BALB/C female nude mice aged 6-8 weeks, and the keloid nude mice model was established. The mice were randomly divided into 3 groups, 5 in each group. They were respectively treated with Sanjie Quban Recipe, Asiaticoside tablet and sterile pure water. After 28 days of continuous gavage, keloid tissue was exfoliated and weighed, HE staining, Masson staining, and immunohistochemical staining (TGF-β1). The difference of keloid weight between the three groups before and after treatment was compared, and the difference of collagen fiber, fibroblast number and TGF-β1 expression between the three groups after treatment was also compared. Results The weight difference of keloid in the Asiaticoside tablet group was greater than that in the control group, and the weight difference before and after keloid treatment was the largest in the Sanjie Quban Fang group compared with the Asiaticoside tablet group and the control group (P < 0.01). Compared with the control group, the collagen fibers in Sanjie Quban Fang group were loose and the number decreased. The number of fibroblasts decreased. The expression of TGF-β1 in Sanjie Quban Formula group was decreased compared with control group (P < 0.01). Conclusion Sanjie Quban Recipe has certain therapeutic effect on keloid, the mechanism may be through reducing the expression of TGF-β1 in keloid tissue, thereby reducing the proliferation of fibroblasts and the synthesis of extracellular matrix. This study provides experimental basis and theoretical basis for the clinical treatment of keloid with Chinese medicine.
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MiR-379-5p inhibits proliferation, invasion and migration of mouse breast cancer 4T1 cells
Song Yanmei, Sun Ningxin, Liu Chen, Song Yifen, Li Hongli, Yin Chonggao
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By investigating the effects of miR-379-5p on the proliferation, invasion and metastasis of mouse breast cancer 4T1 cells, we provide new therapeutic targets for clinical inhibition of breast cancer proliferation, invasion and metastasis. Methods After plasmid transfection, 4T1 cells were utilized to detect the expression of miR-379-5p using real-time fluorescence quantitative polymerase chain reaction (qRT-PCR); 5-ethynyl-2' doxyuridine (5-ethynyl-2'-deoxyuridine, EdU) cell proliferation assay and Transwell assay to detect changes in proliferation and invasion ability of 4T1 cells in each group; Migration ability of 4T1 cells after overexpression and knockdown of miR-379-5p was examined by scratch healing assay; BABL/c mice were used to establish the transplanted tumor model of breast cancer mice, and the tumor growth in vivo after miR-379-5p overexpression was observed.The transplanted tumor model of breast cancer was established in BABL/c mice, and the effects of overexpression of miR-379-5p on tumor growth and the number and size of lung metastases were observed . Results EdU results showed that knockdown of miR-379-5p enhanced the proliferation ability of cells compared with the control group, and miR-379-5p overexpression reduced the capacity of breast cancer cells to proliferate (p<0.05). Transwell and wound healing assays showed that knockdown of miR-379-5p enhanced the invasion and migration ability of breast cancer cells, and overexpression of miR-379-5p significantly inhibited the invasive and migratory ability of cells (p<0.01). In vivo tumorigenesis experiment of BABL/c mice showed that overexpression of miR-379-5p could significantly slow down the growth rate of tumor (p<0.05) and inhibit lung metastasis (p<0.01 ).In vivo experiments demonstrated that overexpression of miR-379-5p significantly slowed tumor growth (p<0.05). Conclusions miR-379-5p plays the role of tumor suppressor gene in breast cancer and inhibits the proliferation, invasion and migration of mouse breast cancer 4T1 cells.
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Study on pathogenesis and animal model building mechanism of ovarian dysfunction
yangzhihui, Hu Yang, Zong Zheng, Sun Xiangming, Song Hui, Chen Yingxiang, Xu Beilei, Zhang Wenjun, Chen Luning, Li Wenlan
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Premature ovarian insufficiency (POI), also known as "ovarian insufficiency", has a high incidence of 1%-5%, and has been on the rise in recent years, which has seriously affected women's physical and mental health and quality of life. At present, the cause and mechanism of POI are still unclear, and the methods and applications of model construction are also confusing, and most models have some shortcomings in pertinence and stability. This also greatly limits the related research and clinical diagnosis and treatment of POI. Therefore, this paper summarizes and discusses the etiology and pathogenesis of POI and the construction of POI animal models, in order to provide more reference for the study of POI etiology and pathogenesis and the selection and construction of models.
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The effect of AIM in inflammatory reaction and lipid metabolism diseases
Zhang Fan, Tian Chun yu, Wang Jingcun, La Xiaojin
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Apoptosis inhibitor of macrophage (AIM), belongs to the group B of scavenger receptor cysteine rich-super family (SRCR-SF). AIM is a soluble protein secreted by macrophages. The expression of this protein is controlled by the liver X receptor (LXR), and it plays an important role in the immune response of the body. AIM, as a secreted protein of macrophages, plays a broad role. It not only inhibits the apoptosis of macrophages, but also participates in the regulation of macrophage polarization. In addition, relevant studies have revealed that AIM is involved in various physiological and pathological processes such as inflammation, obesity, atherosclerosis and cancer; It was used as a biological diagnosis marker for diseases such as tuberculosis, liver cirrhosis and the like; Besides, it can promote lipolysis of adipose cells by inhibiting the activity of fatty acid synthase (FAS), playing an important role in the regulation of lipid homeostasis, lipid metabolism and autoimmune diseases. In this paper, we reviewed the molecular characteristics of AIM and its effects on inflammation, lipid metabolism and other related diseases, showing multiple functional characteristics of AIM to provide the basis for relevant medical research.
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Autophagy and Neurological Diseases
Liang YuYing, Huang Yong, Liu JunSheng, Ou YiLin, Li YiWen, Zhang Rui, Li Zheng, Zhang Zhi Nan
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Autophagy is the main degradation and recycling pathway of abnormal aggregates and damaged organelles in cells, which maintain the normal metabolic balance and material renewal of cells. Autophagy has neuroprotective effects and can affect the functional state of the nervous system by regulating the homeostasis, development, apoptosis and other physiological processes of neurons and glial cells. In recent years, a large number of studies have shown that nervous system diseases are closely related to abnormal autophagy, and inhibition or overactivation of autophagy affects the occurrence and development of depression, neurodegenerative diseases and schizophrenia. Understanding the mechanism of autophagy in nervous system diseases is of great significance for the prevention and treatment of related diseases. This review mainly reviews the current research progress of autophagy and the above diseases of nervous system, in order to provide reference for further research of these diseases.
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Research progress in the effects of Δ9-tetrahydrocannabinol on the blood-brain barrier
Zhang Qianyao, CHENG Hao, HUANG Yi-zhen, TENG Han-xin, ZHANG Yue, ZAHNG Rui-lin
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The psychoactive properties of cannabinoids are well known, and there has been controversy about whether cannabinoids can be used for therapeutic purposes worldwide.Δ9-tetrahydrocannabinol(tetrahidrocannabinol, THC), the main psychoactive substance in cannabis, its neurological mechanism has not been discovered until recently, and its neurological mechanism of action is still not fully understood. The blood-brain barrier(blood-brain barrier, BBB) is a very important barrier structure to protect the brain and is the first line of defense against foreign substances entering the brain. THC's lipophilic nature and its interaction with the endocannabinoid system make it more likely to act on the BBB. In this paper, we review the neurotoxic effects of THC, focusing on the effect and mechanism of THC on the BBB, and provide a theoretical basis for elucidating the neural mechanism of THC.
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Establishment and evaluation of animal model of Varicocele and Erectile dysfunction
lujie, liqunsheng, zhoulei, lidongrun, shenzhennan, lininghua, zhufanyu, chendong, tangwenping, yangwentao
Abstract:
Objective By surgery inducing Varicocele(VC) in SD rats and Apomorphine Test(APO Test),we screened the rats with Erectile dysfunction(ED) after VC,and explored the method of establishing VC and ED model.Methods Randomly divide 60 rats into control group,sham group,and model group,with 20 rats in each group.Referring to the Turner method,partially ligate the left renal vein to induce left VC.And conduct three APO Tests to screen rats with ED after inducing VC,observe and record the number of erection,genital grooming,and yawning.Measuring the diameter of spermatic vein.Weighing both testises and kidneys.HE staining and observing the pathological changes in the penis and left testis.The success rate of modeling was calculated in the model group.Results 15 out of 20 rats in the model group were successfully established VC and ED model,with a success rate of 75%.After modeling,the diameter of the left spermatic vein in the model group increased significantly and were significantly higher than before-modeling,and the diameter of the right spermatic vein in the model group increased and were higher than before-modeling.The weight of the left testises in the model group significantly decreased compared to the right testises.There was no significant difference between or within groups in the comparison of bilateral kidney weight. In the model group,the number of erections,yawning and genital grooming decreased significantly,and decreased with the time of modeling.The pathological changes of the left testis and penis were significant in the model group.Conclusions Turner method can induce the increase of the diameter of spermatic vein in rats,causing testis injury and weight loss,and APO Test can screen the rats with ED after VC induction.The combination of the two methods is suitable for establishing an animal model with VC and ED status similar to human.
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Establishment and evaluation of hyperuricemia mouse model based on triple method
ni jianyu, bai ningning, liu xianli, gong lihong, shou qiyang
Abstract:
Objective: To investigate whether a stable and reliable hyperuricemia model can be established in mice with ICR background by triple modeling method (combined with potassium oxazine, hypoxanthine and 30% yeast paste), and to evaluate the modeling method with positive drug febuxoesta. Methods: The hyperuricemia model of ICR mice was established by using potassium oxazine, hypoxanthine and 30% yeast paste diet, respectively, and the serum uric acid, creatinine, xanthine oxidase (XOD), uric acid oxidase (UOX) and other indicators were detected to evaluate the success of hyperuricemia model.Results: The serum uric acid level of ICR mice was not significantly changed by potassium oxazinate alone, which showed an increasing trend but no significant difference with that of 30% yeast paste diet and hypoxanthine combined groups, while the serum uric acid level in triple administration group was significantly increased at 7 days (P<0.01). After 14 days of dynamic monitoring, blood uric acid level of triple dose induced ICR mice peaked at 7 days. Meanwhile, the activity of XOD enzyme was increased, while that of UOX enzyme was decreased (P<0.001). In addition, triple-dose induced hyperuricemia in ICR mice was sensitive to the positive drug febuxoat, with a significant decrease in blood uric acid levels (P<0.001). Conclusion: The hyperuricemia model of ICR mice can be stably induced by triple administration at 7 days.
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Optimization and evaluation of an acute obstructive suppurative cholangitis model in rats
yukui, Liangxiaoqiang, hanmian, zhangjingzhe
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Objective A stable model of acute obstructive suppurative cholangitis in rats was established to detect its pathophysiological indexes and provide a stable and reliable standardized animal model for the study of acute cholangitis and cholestasis.Methods SPF grade male SD rats were selected and the model was constructed by injection of toxoid into the lower bile duct and ligation of the common bile duct, and the changes in body weight, mortality, major indexes of liver function and histopathological changes in the liver were evaluated before and after modeling.Results After modeling, the body weight of rats in the model group decreased significantly; the number of rats died was less; the main indexes of liver function and liver pathology showed obvious changes of cholestasis and liver function damage.Conclusion In this study, a rat acute obstructive suppurative cholangitis model was successfully established, which has the advantages of easy operation, low damage, low mortality and high successful modeling rate, and can provide a standardized experimental animal model for the study of the mechanism of many common diseases and drug development.
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Research progress of pyroptosis in renal ischemia-reperfusion injury
sunhaojie, zhujunlei, liwei, wangsuogang
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Pyroptosis is a programmed cell death mediated by cysteine proteases, which is characterized by mitochondrial participation, inflammasome assembly, plasma membrane perforation, and inflammatory release. As an important mechanism mediating the body's inflammatory response, pyroptosis plays a key role in renal ischemia-reperfusion injury (RIRI). This article reviews the molecular mechanism of pyroptosis, the mechanism of pyroptosis in RIRI and the research progress of therapeutic drugs in recent years, aiming to provide theoretical reference for the early treatment of RIRI.
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Research progress of mitochondria function regulation by TRP channels and its relationship with cardivascular diseases
Abstract:
TRP channel is a non-selective cation channe. In recent years, a large number of studies have found that TRP channels take participate in variety of cardiovascular diseases, and the study on mitochondrial function regulation by TRP channel and its relationship with cardiovascular diseases has become a research hotspot. Up to date, the relative references are mainly focused on TRPV, TRPM and TRPC channels. This review focuses on above TRP channels in the regulation of mitochondrial function and their relationship with cardiovascular diseases.
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Exploration of mouse model construction of breast cancer complicated with depression induced by using method of 4T1 breast cancer cell line inoculation combined with chronic restraint stress
liu yan, pengmengwei, Liu gaoyuan, Yang Tiezhu, Zhang wenxian, Wuyaosong, Chen Yulong
Abstract:
【Abstract】Objective To study the core behavioral symptoms, biological indicators and pathological changes of the mouse model construction of breast cancer complicated with depression induced by using method of 4T1 breast cancer cell line inoculation combined with chronic restraint stress (CRS). Methods BABL/c mice were randomly divided into control group, stress group, tumor group and stress combined with tumor group (S T). 4T1 cell lines were inoculated into the underarm of mice in tumor and S T groups. After tumor formation, mice in the stress and S T groups were subjected to CRS for 21 days. Body weight and food intake of each group were monitored during modeling. After the experiment, depression-like behavior of mice in each group was evaluated by sucrose preference test, open field test, elevated plus-maze test, and forced swimming test. After the mice were decapitated, the weight and volume of mouse tumor were measured. Serum tumor markers including carbohydrate antigen (CA199), carcinoembryonic antigen (CEA), vascular endothelial growth factor (VEGF) and related neurotransmitters including 5-hydroxytryptamine (5-HT), norepinephrine (NE) and corticosterone (CORT) were determined by using Elisa method. HE staining was used to observe the histopathological changes of hippocampus and tumor of mice. Results In mice of S T group, the body weight and food intake were significantly decreased, tumor weight and volume were significantly increased, serum tumor markers (CA199, CEA, VEGF) levels were significantly increased, pleasure and desire to explore the new environment were weakened, stress and despair behaviors were significantly increased, serum neurotransmitters 5-HT and NE levels were significantly decreased, and CORT levels were significantly increased. In addition, the cell arrangement of tumor tissue was loose, the interstitial was reduced, the pathological nuclear classification phase was increased, the arrangement and morphology of neurons in the CA3 region of hippocampus were disordered, and the nuclear vacuolation-like changes were obvious. Conclusion The mouse model of breast cancer complicated with depression induced by 4T1 breast cancer cell line inoculation combined with chronic restraint stress showed the dual typical symptoms and biological indicators of breast cancer and depression, which can provide a good model reference for the experimental study of breast cancer complicated with depression.
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Study on the effect of Buyang Huanwu Decoction in reducing oxidative stress and protecting cerebral ischemia-reperfusion injury in rats' blood-brain barrier
Abstract:
Objective To explore the mechanism of Buyang Huanwu Decoction (BYHWD) in reducing oxidative stress levels to protect the blood-brain barrier (BBB) in cerebral ischemia/reperfusion injury (CIRI) rats. Methods: Middle cerebral artery occlusion / reperfusion （MCAO/R）model was established by wire embolization method in rats, and PeriCam PSI laser speckle flow imaging system was applied to detect whether the model establishment was successful. The neurological deficits of rats were evaluated by Zea longa score; The histopathological changes in the rat brain were observed by HE staining; The degree of brain edema was detected by dry and wet weight method; The BBB permeability was detected by Evansblue (EB) staining; Ultrastructural changes of BBB were observed by transmission electron microscopy; The levels of ROS, MDA, and SOD activities, which are related to oxidative stress, were detected by kits; The expression levels of MMP-9 were detected by immunohistochemical staining and Western blot; The protein expression levels of Occludin, ZO-1, and Claudin-5 in TJP were determined by double staining of immunofluorescence and Western blot. Results:BYHWD can reduce neurological deficit scores, alleviate the brain histopathological damage, alleviate the disruption of blood-brain barrier structure, prolonged the dense region of tight junction structure, attenuated the edema of the brain in the ischemic side, and reduce the BBB permeability in MCAO / R rats. BYHWD can decrease the levels of ROS and MDA, increase the activity of SOD, decrease the expression levels of matrix metalloproteinase-9 （MMP-9）, and increase the protein expression levels of Occludin, Claudin-5, and ZO-1. Conclusions: BYHWD can increase BBB tight junction protein expression levels, reduce the permeability of the BBB, protect the ultrastructure of the BBB, and reduce brain edema, and its mechanism may be related to the antioxidant stress of BYHWD and inhibition of MMP-9 activation.
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Effects of decoction of Euphorbia fischeriana Steud. and jujuba against breast cancer of different molecular phenotypes via PI3k/Akt pathway
maliwei, YAO Hongyu, CHEN Zhe, NI Shiyu, CHEN Song, LI Jing, LIU Jicheng
Abstract:
Objective To explore the effect of decoction of Euphorbia fischeriana Steud. and jujuba (DEFSJ) against estrogen receptor (ER) negative (-) and ER positive (+) of breast cancer via PI3k/Akt pathway, and to provide reference for targeted treatment of breast cancer. Methods DEFSJ extract was prepared and analysed by using UHPLC-Triple Quad. DEFSJ containing serum (CS) was prepared by a method of serumal pharmacology. Different concentrations of DEFSJ-CS were applied to (ER-) MDA-MB-453 cells and (ER ) MCF-7 of breast cancer in vitro for 48 h. Flow cytometry was used to detect the distribution of cellular cycle，DNA ladder assay was used to assess the degree of apoptosis，and Western blot was used to detect the expression of PI3k/Akt pathway-related proteins. The expressions of FoxO3a, FoxO1a and Bim mRNA were detected by a real-time quantitative polymerase chain reaction (qrt-PCR) method. Nuclear translocation of FoxO3a protein was detected by a confocal laser microscopy. Results Five batches of the DEFSJ extract were analysed by using UPLC, and the results showed that the preparation technology was feasible and the quality was controllable, ensuring the accuracy of pharmacological experiments results. DEFSJ-CS can block cells in G2/M phase (P<0.05，P<0.01). The cells treated with DEFSJ-CS emerged the typical apoptotic ladder in DNA ladder experiment. Compared with negative control group, DEFSJ-CS can decrease the proteins expression of p-PI3k，p-Akt，p-FoxO3a and p-FoxO1a (P<0.05, P<0.01) and can increase the proteins expression of Bim (P<0.05, P<0.01), and can decrease the mRNAs expression of FoxO3a and FoxO1a (P<0.05, P<0.01) and can increase the mRNA expression of Bim (P<0.05, P<0.01), and can enhance nuclear translocation of FoxO3a protein in the cells. Besides, these datas all showed that DEFSJ-CS had better effect on (ER-) MDA-MB-453 cells than (ER ) MCF-7 cells. Conclusion The regulatory effect of the DEFSJ extract on anti-breast cancer is involves the PI3k/Akt pathway, and the effect is varies with phenotypic differences.
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To explore the effect of Bufei Jianpi Formula on mitochondrial damage of skeletal muscle in COPD rats based on IRS-1/PI3K signaling axis
shentingting, lisuyun, liya, xuanyinshuang, lijingmei, Ligaofeng, hanbingyang
Abstract:
Objective To explore the effects of Bufei Jianpi Formula (BJF) on mitochondrial damage of skeletal muscle in COPD rats by regulating IRS-1/PI3K signaling axis. Methods 60 SPF SD rats were randomly divided into blank group, model group (COPD stable stage group), BJF group, pioglitazone group (PIO group), BJF PIO group and aminophylline group, with 10 rats per group. The stable COPD rat model was established by the method of smoking and nasal drip (Klebsiella pneumoniae). The samples were taken from the 9th week to the end of the 20th week, and the weight of the rats was measured every week. Routine sections and HE staining were performed on lung tissue and skeletal muscle tissue respectively, and the corresponding pathological changes were observed under light microscope. Lung function of rats was observed by whole body plethysmography (WBP) at week 0, 8 and 20, including tidal volume (VT) and peak expiratory flow, respectively. PEF), 50% tidal volume expiratory flow (EF50). The mRNA expression of IRS-1, Leptin, PGC1-α and PI3K in rat skeletal muscle was detected by qPCR. The expression of PGC-1α, TFAM, IRS-1, PI3K, AKT, p-AKT and Leptin in rat skeletal muscle tissue was detected by WB technique. Results Compared with the Control group, there were a large number of inflammatory cells infiltrated in the alveolar interstitium and bronchus in the Model group, some alveolar walls were broken and fused to form air cavities, and the fibrous network was destroyed. Compared with Model group, the rupture of alveolar wall and destruction of fibroid network were improved in all groups after medication treatment, and the inflammatory cell infiltration in bronchus was reduced, especially in BJF group and Am group. Compared with the Model group, the skeletal muscle pathology of each group after medication treatment could improve the arrangement space, atrophy and fracture of muscle fibers in different degrees, and the cytoplasmic staining of muscle cells was uneven, among which the BJF group had a more significant effect. Compared with Control group, PEF, VT and EF50 in Model group were significantly decreased from week 8 (P<0.01), while PEF and EF50 in BJF, BJF PIO and Am groups were significantly increased (P<0.01). Compared with Control group, mRNA expression levels of IRS-1, PGC1α and PI3K in Model group were significantly decreased(P<0.01), while Leptin mRNA expression level was significantly increased (P<0.01). Compared with Model group, Leptin mRNA expression levels in four medication groups were significantly decreased (P<0.01), while IRS-1 mRNA expression levels in BJF, PIO and BJF PIO groups were significantly increased (P<0.01). The mRNA expression level of PGC-1α in BJF and BJF PIO groups was significantly higher than that in Model group (P<0.01). Compared with Model group, the expression level of PI3K mRNA in BJF, BJF PIO and Am groups was significantly increased (P < 0.01). Compared with Control group, the protein expression levels of PGC-1α, IRS-1 and PI3K in Model group were significantly decreased (P<0.01), while the protein expression level of Leptin was significantly increased (P<0.01). Compared with Model group, the expression level of PGC-1α protein in BJF group was significantly increased (P<0.05), and the expression level of IRS-1 protein in BJF PIO and BJF groups was significantly increased compared with Model group (P<0.05, P<0.01). The expression level of PI3K protein in Am, BJF and BJF PIO groups was significantly higher than that in Model group (P<0.01), especially in BJF PIO group. Compared with Control group, the protein expressions of TFAM and P-Akt in quadriceps femoris tissue of Model group were significantly decreased, while the protein expressions of TFAM and P-Akt were increased in all treatment groups, but there was no statistically significant difference (P>0.05).Conclusion By regulating IRS-1/PI3K signaling axis, Bufei Jiempi can improve the mitochondrial damage of skeletal muscle, increase the expression of mitochondrial coactivator PGC-1α and mitochondrial transcription factor TFAM, enhance mitochondrial biosynthesis, and reduce the pathological damage of lung and skeletal muscle tissue.
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LIMK1 promotes the progression of cervical cancer by up-regulating the ROS/Src pathway
Jia Yajing, Du Naiyi, Zhao Wei, Li Yongping, Liu Yakun
Abstract:
Abstract: Objective To explore the effect of LIMK1 on the progression of cervical cancer (CC). Methods LIMK1-overexpressed human cervical cancer HeLa cells were constructed and inoculated subcutaneously in nude mice. The tumor volume was observed and the expressions of NOX2, NOX4, p-Src, p-RUNX3, RUNX3, and MMP-9 proteins in the tumor cells were detected by Western blot assay. LIMK1-overexpressed HeLa cells were cultured under 5%O2 and added with antioxidants. The protein expressions of LIMK1, NOX4, p-Src, p-RUNX3, RUNX3, and MMP-9 in the cells were detected by Western blot assay. The cell migration ability was detected by scratch assay. Transwell assay was used to detect cell migration and invasion ability. Monoclonal proliferation assay was used to detect cell proliferation ability. Results The tumor volume of nude mice inoculated with LIMK1-overexpressed HeLa cells increased significantly, and NOX2, NOX4, p-Src, p-RUNX3, and MMP-9 proteins increased, while RUNX3 protein expression decreased. In LIMK1-overexpressed HeLa cells, the protein expressions of LIMK1, NOX4, p-Src, p-RUNX3, and MMP-9 were increased, RUNX3 protein expression was decreased, while the cell migration, invasion, and proliferation ability were increased. However, after adding antioxidants, the expression levels of NOX4, p-Src, p-RUNX3, RUNX3, and MMP-9 proteins, and the ability of cell migration, invasion, and proliferation were not different from those of HeLa cells with normal expression of LIMK1. Conclusion LIMK1 promotes the progression of cervical cancer by promoting the ROS/Src pathway, thereby promoting the migration, invasion, and proliferation ability of cervical cancer cells.
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Research progress of SHP2 in digestive system tumors
WANG Peng, FAN Jianchun, JIA Juming, DIAO Qingfei, WU Xueliang, Xue Jun
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【Abstract】 Currently malignant tumors have become one of the major diseases threatening human health,with disability and mortality rates increasing year by year.Protein tyrosine phosphatase 2 (SHP2) of Src homology 2, an important member of the PTP family, is a tyrosine phosphatase with a wide range of functions,whose expression is elevated in a wide range of solid tumors,and plays a important regulatory role in invasion,metastasis,proliferation,apoptosis and drug resistance.A large number of studies have shown that SHP2 plays a very important role in the genesis and development of many solid tumors,but there is no systematic report on the role of SHP2 in digestive system tumors.Based on this paper,we reviewed the biological functions and clinical significance of SHP2 in seven different tumors of the digestive system,explored its roles and mechanisms in different cancer development stages,and summarized and looked forward to the development of SHP2 inhibitors,to further search for potential targets for effective early diagnosis and gene therapy,which is of great significance for the improvement of cancer patients' survival rate.
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Research progress on the relationship between regulatory cell death and Dilated cardiomyopathy
Abstract:
Dilated cardiomyopathy (DCM) is one of the common primary diseases of heart failure and arrhythmias. With the continuous deepening of research in recent years, the intrinsic molecular mechanism of regulatory cell death (RCD) has gradually become clear. Researchers have found that RCD plays a very important role in the occurrence and development of DCM. RCD mainly includes apoptosis, necrotic apoptosis, Pyroptosis, Ferroptosis, autophagy, etc. They have certain correlation and can interact and regulate each other. This article provides an overview of the current research status on the mechanisms of the five RCD modes involved in DCM, in order to provide reference for future related experiments and clinical studies.
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Research progress on the interaction between gut microbiota and microRNA in inflammatory bowel disease
KONG Binghui, BAI Longzhou, YANG Li
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Inflammatory bowel disease (IBD) is a chronic intestinal disorder characterized by an immune response to factors in the intestinal environment. Dysregulation of the intestinal flora may lead to the development of inflammation. Studies suggest that fecal transplants, probiotics, prebiotics, and dietary interventions may play a potential role in reshaping the intestinal flora and treating the disease. MicroRNAs (miRNAs) participate in physiological processes, including cell development, proliferation, and apoptosis. In addition, miRNAs are important in inflammatory processes and play a role in regulating pro- and anti-inflammatory pathways. MiRNA profiles may serve as a diagnostic tool for IBD and prognostic markers for the disease. The relationship between miRNAs and intestinal flora has not been fully elucidated, and recent studies have demonstrated their roles in regulating the intestinal flora and inducing ecological dysbiosis. In turn, the flora can regulate miRNA expression and improve intestinal homeostasis. It is important to continue exploring this relationship. Therefore, the purpose of this review is to analyze the relationship between gut microbiota and miRNAs in IBD and identify possible precision-targeted therapies for IBD.
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Study on the effects of various herbs and different proportions of herbs in Huidu Yinhua Powder on methicillin-resistant Staphylococcus aureus
LI Yufen, JIANG Shuang, SONG Wu, JIANG Tao, LIU Chang, ZHOU Haofang, TANG Yating, SU Xin
Abstract:
Objective: To study the inhibitory ability of Huidu Yinhua Powder, from “Orthodox Manual of External Medicine”, on methicillin?resistant staphylococcus aureus (MRSA) as well as the inhibitory effect of virulence factor α-hemolysin (Hla) activity and biofilm formation, and at the same time, to explore the optimal ratios of Huidu Yinhua Powder, to provide experimental support for the new use of the ancient formula. Methods: The inhibitory effects of Huidu Yinhua Powder and the herbs in the formula on USA300 were analyzed by minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and disk diffusion assay (K-B method). Hemolysis assay, neutralization assay, Oligomerization assay, Western Blot (WB) to verify in which form the drug inhibits the activity of the virulence factor alpha-hemolysin (Hla). The biofilm assay was performed to evaluate the inhibitory effect of Huidu Yinhua Powder on biofilm, while finally orthogonal experiments were performed to explore the optimal ratios of Huidu Yinhua Powder. Results: Huidu Yinhua Powder inhibited the MRSA strain with a MIC90 of 64 mg/mL and an MBC of 256 mg/mL, with antibacterial circle diameter of 7.50±0.50 mm. Huidu Yinhua Powder inhibits Hla activity by inhibiting Hla secretion and the minimum effective concentration (MEC) was 16 mg/mL, while the MEC of biofilm was 8 mg/mL. In Huidu Yinhua Powder, Honeysuckle and Astragalus only affected the hemolytic activity of MRSA and the formation of biofilm without inhibiting the growth of bacteria, the hemolytic activity MEC and the biofilm MEC of both of them were 32 mg/mL. Glycyrrhiza had a strong bacterial inhibitory capacity, with a MIC90 of 8 mg/mL and a biofilm MEC of 1 mg/mL, without showing inhibitory hemolytic activity at subinhibitory concentrations. The final orthogonal experiment showed that when the ratio of honeysuckle: astragalus: glycyrrhiza in Huidu yinhua Powder was 1:2:4, the MIC90 was 16 mg/mL, the hemolytic activity MEC was 8 mg/mL, and the biofilm MEC was 4 mg/mL, all of which were the lowest among the nine groups. Conclusion: Huidu Yinhua Powder affects the hemolytic activity and biofilm formation of MRSA at sub inhibitory concentrations, with the optimal ratio of honeysuckle, astragalus, and glycyrrhiza being 1:2:4.
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Effect of vitamin D on the structure and diversity of intestinal flora in spontaneously diabetic rats
chen lin, tan hong xing, hao li ping, li yan yan
Abstract:
[Abstract] Objective To investigate the effect of vitamin D (VD) on intestinal flora in spontaneously diabetic rats. Methods Zucker diabetic fatty rats (ZDF rats) were randomly divided into control group (Con), VD control group (VD), model group (T2DM) and VD intervention group (VD+T2DM). Fasting blood glucose profile and oral glucose tolerance level were detected in rats in each group. The 16S rDNA sequencing technology was used to detect the changes in rat intestinal flora, and OTU analysis (Venn diagram), Alpha diversity analysis (chao1, observed species, PD whole tree, shannon and simpson), Beta diversity analysis [principal coordinate analysis (PCoA)], flora structure and colony species variability analysis [linear discriminant analysis and influence factor (LEfSe) analysis]. Results VD intervention significantly improved fasting blood glucose levels and insulin resistance in T2DM rats (P<0.05).Alpha diversity results showed no significant differences in chao1, observed species, PD whole tree, shannon and simpson indices between T2DM and VD+T2DM groups (P>0.05) ; Beta diversity analysis showed that the VD+T2DM group had more species similarity with the Con group compared with the T2DM group. The dominant bacteria of rat intestinal flora in each group were significantly different; compared with the T2DM group, the VD+T2DM group showed decreased abundance of Bacteroidetes and increased abundance of Firmicutes and Clostridium XIVa. Conclusion VD improved fasting glucose elevation and insulin resistance in T2DM rats; VD improved the structure of intestinal flora, decreased Bacteroidetes, and elevated Firmicutes and Clostridium XIVa abundance in T2DM rats.
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Overview of in vitro skin models of transdermal drug delivery system
LiuYan, HuXiaolei, XuKeHong, ZhaoHaiRong, WuXiuMei, YangZiZhong, ZhangChengGui, ZhaoYu, GaoPengFei
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Skin modeling of transdermal drug delivery systems refers to the experimental models which can mimic the structure and function of human skin to explore and evaluate the absorption, penetration and efficacy of medicines in transdermal drug delivery. It provides alternative to traditional human skin experiments and reducing the utility of human skin in medicines research, which is convenient, controllable, and cost-effective . For the skin models of transdermal drug delivery systems, this paper introduces commonly used animal skin models, artificial skin models, and recombinant human skin models from the perspective of the transdermal absorption pathway of medicines, and analyzes its advantages and disadvantages as well as its applications, so as to provide references for the research and development of transdermal formulations and topical therapies and so on.
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AMPK: Diverse Regulatory Mechanisms and New Perspectives for Disease Treatment
Ning Jinghua, zhang xin, zhang Yuzhe
Abstract:
The AMP-activated protein kinase (AMPK) is a conserved cellular energy Adenosine monophosphate, plays an important role in regulating cell growth, proliferation, differentiation, autophagy, phosphorylation, crosstalk, and glucose and lipid metabolism. AMPK is activated when the body is low in energy or under certain extreme conditions, and it's suppressed when there's an excess of nutrients to maintain the energy balance. In addition, the regulatory mechanism of AMPK signaling pathway mediating ferroptosis also reflects its unique role. AMPK plays a special regulatory function in different organelles, which provides a new direction for disease therapy. It is also a therapeutic target for the prevention of diseases such as reproductive system diseases, aging, cancer, inflammation and cardiac dysfunction. This article reviews the damage of cellular energy imbalance to the body's microenvironment. AMPK stimulates its potential therapeutic potential in diseases and drugs through diverse signal regulatory mechanisms, it provides a new way of treatment for different system diseases. This review summarizes the diverse regulatory mechanisms of AMPK signaling pathway, and provides theoretical reference for cancer therapy and other diseases therapy targeting AMPK.
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Discussion on the Mechanism of "Brain-Spleen Inflammation Coupling" in Rat Model of Acute Ischemic Stroke Stasis Toxin Syndrome
dongyilei, Liu Yue, Li Junyuan, Fu Jianhua, Zhang Yunling, Yao Mingjiang
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【Abstract】Objective: To investigate the correlation between brain injury and spleen damage in rat models of acute ischemic stroke and stasis interaction, and its effect on the signal axis of MCP-1/CCR2 chemokine, and to provide experimental basis for the mechanism of "brain-spleen inflammatory coupling" in spleen lesions caused by acute ischemic stroke. Methods: Forty male SD rats were randomly divided into sham group, carrageenan/yeast stasis syndrome group (Carrageenan/Yeast, CA/Y), middle cerebral artery occlusion group (MCAO), middle cerebral artery occlusion (MCAO), middle cerebral artery stasis syndrome group (MCAO CA/Y), 10 rats in each group. The CA/Y group and the MCAO CA/Y group were injected with 10 mg穔g-1 carrageenan, 10 mg穔g-1 intraperitoneally on the first day of molding, and 2 mg穔g-1 of dry yeast suspension were injected subcutaneously on the second day, and the MCAO group and MCAO CA/Y group were established by wire embolism on the second day. 24 h after cerebral infarction model, the neurological deficit score was performed on each group of rats, the percentage of cerebral infarction area was observed by TTC staining, the spleen weight was determined, and the correlation between the percentage of cerebral infarction area and spleen weight was further analyzed by Spearman correlation coefficient, the pathological morphology of brain tissue and spleen tissue was observed by hematoxylin-eosin (HE) staining, and monocyte-1 (monocyte) was detected in rat plasma by enzyme-linked immunosorbent assay (ELISA). chemotactic protein 1, MCP-1), interferon-γ γ (IFN-γ) content, western blot method to detect ischemic side brain tissue chemokine C-C-motif receptor 2 (CCR2) protein expression. Results: Compared with the ham group, the neurological deficit score, cerebral infarction area, MCP-1 and IFN-γ content in plasma were significantly increased (P<0.01), spleen weight decreased significantly (P<0.01), and the expression of CCR2 protein in brain tissue was also significantly up-regulated (P<0.05) in the MCAO group and the MCAO CA/Y group. The area of cerebral infarction increased significantly (P<0.01), the weight of the spleen decreased significantly (P<0.01), and the expression of CCR2 protein in brain tissue and spleen tissue was also significantly up-regulated (P<0.05), compared with the MCAO group, the area of cerebral infarction in the MCAO CA/Y group was significantly increased (P<0.01) and the weight of the spleen decreased significantly (P<0.05). Spearman correlation analysis showed that spleen weight was negatively correlated with the percentage of cerebral infarction area (P<0.01, r=-0.9711). The pathological morphological observation results showed that the pathological changes in the MCAO CA/Y group were the most serious, cerebral liquefaction necrosis foci could be seen in the brain tissue cortex, the arrangement of neuronal cells in the lesions was sparse, disordered, volume atrophy, a small number of vacuoles and nuclear solidification, most of the neuronal cells were red degeneration and necrosis, microglia hyperplasia was obvious, small blood vessels were significantly increased, and interstitial lipid degeneration was superb; The density of periarterial lymph sheath cells in part of the spleen tissue is reduced, and the marginal area is widened. Conclusion: A correlation between brain and spleen injury could be found after acute ischemic stroke with stasis and toxins syndrome, and the chemokine signaling axis of MCP-1/CCR2 might be involved in the mechanism of "brain-spleen inflammation coupling".
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Effect of lidocaine regulating Hippo-YAP signal pathway on ischemia-reperfusion injury in orthotopic liver transplantation rats
Liu Yue, Akbar Nurmaimaiti, Ye Jian-rong
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Objective: To explore the effect of lidocaine (LID) on ischemia-reperfusion injury in orthotopic liver transplantation (OLT) rats and to analyze its mechanism of action. Methods: 60 rats were randomly divided into control group, model group, low-dose LID group, medium-dose LID group, high-dose LID group, and Verteporfin group, with 10 rats in each group, except for the control group, and other rats were used to construct OLT models. The pathological changes in liver tissue was observed by hematoxylin-eosin (HE) staining, the serum aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin (TBIL) and lactate dehydrogenase (LDH) activities were detected by automatic biochemical analyzer, the liver tissue inflammatory factor tumor necrosis factor-α (TNF-α), interleukin (IL) -6, IL-1β and IL-10 levels were detected by enzyme-linked immunosorbent assay (ELISA), the reactive oxygen species (ROS) was detected by fluorescence probe method, the malondialdehyde (MDA) was detected by thiobarbituric acid colorimetric method, the superoxide dismutase (SOD) was detected by nitrogen blue tetrazole colorimetry, the glutathione peroxidase (GSH-Px) was detected by spectrophotometer method, the apoptosis of liver histiocyte was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) , and the expression of mammalian STE20 like protein kinase (MST1), phosphorylation (p) - MST1, large tumor suppressor factor 1 (LATS1), p-LATS1, Yes associated protein (YAP), p-YAP, as well as apoptosis related proteins B-cell lymphoma 2 (Bcl-2) and Bcl-2 related X protein (Bax) were detected by western blotting (WB). Results: Compared with control group, the liver tissue in model group rats showed injury, liver cells necrosis and a large number of inflammatory cells infiltration, the cell apoptosis rate, serum AST, ALT, TBIL, LDH activity, liver tissue TNF-α, IL-6, IL-1β, MDA, ROS, and Bax levels significantly increased, the liver tissue IL-10, SOD, GSH-Px, Bcl-2, p-MST1/MST1, p-LATS1/LATS1 and p-YAP/YAP proteins expression levels were significantly reduced (P<0.05). Compared with model group, the liver tissue injury was reduced in low-dose LID group, medium-dose LID group, and high-dose LID group, the cell apoptosis rate, serum AST, ALT, TBIL, LDH activity, liver tissue TNF-α, IL-6, IL-1β, MDA, ROS and Bax levels were significantly reduced, the liver tissue IL-10, SOD, GSH-Px, Bcl-2, p-MST1/MST1, p-LATS1/LATS1, and p-YAP/YAP proteins expression levels were significantly increased (P<0.05). Hippo-YAP signaling pathway inhibitor Verteporfin reversed the improvement effect of LID on ischemia-reperfusion injury in OLT rats (P<0.05). Conclusion: LID may activate the Hippo-YAP pathway, which reduce inflammatory response, oxidative stress, and liver cell apoptosis, and improve liver ischemia-reperfusion injury in OLT rats.
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Overview of the research of Q fever in animal models
Abstract:
Q fever is a zoonotic disease caused by Coxiella burnetii infection, which is widely spread in nature. Animal models are important tools to study the etiology and pathogenesis of infectious diseases and evaluate the effectiveness of vaccines. In recent years, a variety of animal models such as invertebrates, rodents and non-human primates have been used to study Q fever. This paper summarizes the research status of different Q fever animal models, discusses the advantages and disadvantages of these models, and summarizes the requirements and standards of future modeling work.
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Advances in the application of laser speckle contrast imaging in animal models of chronic cerebral hypoperfusion
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Laser speckle contrast imaging technology can be used to dynamically measure microcirculation blood flow in tissues or organs in a visual and quantifiable way. Because of its advantages of in vivo detection, real-time imaging and simple operation, it has been applied in many fields of microcirculation detection.The animal model of chronic cerebral hypoperfusion is mainly constructed by reducing the bilateral common carotid artery blood flow to the brain, which can cause long-term insufficient cerebral blood supply. Laser speckle contrast imaging technology can observe and analyze the cortical cerebral blood flow, collateral circulation opening, neurovascular coupling response, etc., in the animal model of chronic cerebral hypoperfusion , so as to judge the success of animal model modeling and the therapeutic effect of intervention methods. In this paper, the application and advantages and disadvantages of laser speckle contrast imaging technology in the animal model of chronic cerebral hypoperfusion were summarized in order to provide new ideas for clinical treatment and scientific research.
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Research progress of berberine in the field of neuroprotection in ischemic stroke
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Berberine is a natural Isoquinoline alkaloid, which can be initially used as a broad-spectrum antibacterial agent in clinical treatment of enteritis, peptic ulcer, chronic gastritis, pneumonia and other diseases. In recent years, with the in-depth study of the pharmacological effects of Berberine, more and more evidence shows that Berberine has neuroprotective effects on ischemic stroke. In this review, we introduced the intervention of Berberine on risk factors of ischemic stroke, and discussed the neuroprotective effects of Berberine in different mechanisms of ischemic stroke in detail, aiming to provide some reference for clinical and basic research in this field.
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Advances in Research on Mechanisms Related to Myocardial Regeneration in Neonatal Rats
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Cardiovascular disease is a health hazard to humans and systolic heart failure due to myocardial infarction is a major cause of death. It was previously thought that myocardial cells of adult mammalian heart possess a limited ability to proliferate and renew themselves, and that after ischemic injury, a large number of myocardial cells are lost and eventually replaced by non-contractile scar tissue. In contrast, it has been widely reported that mammals have the ability to regenerate myocardium which is restricted to early postnatal life, and that it is strong enough to repair damaged heart tissue. The discovery of myocardial regeneration in neonatal heart has provided an ideal animal model to investigate the mechanisms that affect myocardial cell proliferation, and subsequently many mechanisms that can reverse myocardial cell cycle arrest and promote myocardial cell proliferation have been revealed. In this paper, we review the factors affecting myocardial regeneration gene expression (ncRNAs, transcription factors, etc.), myocardial regeneration-related signaling pathways, and the regulation of myocardial regeneration by non-myocardial cells (extracellular matrix, immune response, epicardium, etc.), so as to provide directions for achieving myocardial regeneration after myocardial injury in adult mammals.
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Establishment of genetic monitoring methods for experimental quail
heyang, zhangxiulin, zhangqiuyu, zhangxiaolu, fubo, wangwendong, duxiaoyan, chenzhenwen, lichanglong
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Objective To establish a genetic monitoring method for laboratory quails. Methods Quail microsatellite loci were screened through literature search, and microsatellite DNA loci suitable for quail were screened by interspecific transfer method in quail closely related species, chickens and ducks. Quail liver tissue DNA was extracted as a template, and the corresponding loci were screened by PCR amplification and agarose gel electrophoresis. Finally, based on the amplification of the selected microsatellite loci, the number of alleles, and polymorphism, microsatellite loci combinations for quail genetic quality detection were selected and detection methods were established. Results We preliminary determined 23 microsatellite loci for genetic monitoring of closed-colony laboratory quails. Conclusion A genetic monitoring method for laboratory quails is preliminary established.
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Innovation and exploration of Medical Laboratory Animal Science teaching based on smart teaching environment
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Objective In the traditional laboratory zoology lecture environment, there is less teacher-student interaction, less student interest and less engagement in learning.In order to further improve the teaching quality of laboratory zoology, Methods this teaching and research department based on the different teaching environment of multimedia classroom and intelligent classroom, the theoretical course teaching of Medical Laboratory Zoology as the research ,object, the course lecture format, teaching mode, teaching methods and other aspects of innovation and exploration. The study used questionnaires to understand changes in student engagement in learning and preferences for smart classroom use, and NVivo qualitative analysis software to code student classroom behaviour. Results The smart teaching environment resulted in higher student interest and more frequent teacher-student interaction in the classroom. At the same time, students are significantly more engaged in learning than in traditional teaching, with higher correct rates on in-class and post-lesson exercises and a better grasp of concepts related to laboratory zoology. Conclusions In summary, the smart teaching environment can bring students a better feeling and experience, improve their interest in laboratory zoology, increase classroom learning engagement and achieve good teaching results.
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Progression of tripterygium wilfordii polyglycoside in mice with premature ovarian insuffici-ency model at different time points
马林纳, makun, fanxiaodi, luojie, lijiani, zhanghan
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Objective The changes of relevant indexes in the mice model of early-onset ovarian insufficiency caused by tripterygium wilfordii polyglycoside were discussed, and the best time point for intervention was determined. Methods Forty female ICR mice were randomly divided into blank group, A, B, C, and D model groups, with 8 mice in each group. The blank group was given gavage purified water for 14d (0.01ml/10g), and the remaining groups were given tripterygium wilfordii polyglycoside suspension (80mg/kg, 0.01ml/10g) for 1d (A model group), 3d (B model group), 7d (C model group), 14d (D model group), and the materials were taken in batches. Weigh the body weight, wet weight uterus and bilateral ovaries of mice in each group; Serum FSH, LH, E2, P, AMH, INH-B and T contents were detected by enzyme-linked immunoassay. HE staining observed the number and development status of follicles and corpus luteum at all levels of mice in each group. TUNEL fluorescence staining method detected the apoptosis area in the ovaries of mice in each group. The IHC method detected the positive expression of VEGFA, CD34 and EPO proteins in the ovaries of mice in each group. The mRNA expression of HIF-1α, SDF-1 and CXCR4 in each group of mice was detected by PCR. Results Compared with the blank group, the changes of indicators in model A did not meet the POI modeling standard. The ovarian index, uterine index and body weight of mice in the B model group decreased significantly (P<0.01), the weight of the C model group decreased significantly (P<0.01), and the ovarian index of the D model group decreased significantly (P<0.05). The serum indexes of the B, C and D model groups increased the contents of FSH and LH (P<0.01 or P<0.05), and the contents of E2, PROG, AMH, INH-B and T decreased (P<0.01). The number of basal follicles, presinus follicles, sinusoidal follicles, antral follicles, preovulatory follicles and corpus luteum decreased significantly (P<0.01 or P<0.05) and the number of atresia follicles increased significantly (P<0.01) in the B, C and D model groups. The apoptosis area of TUNEL fluorescent staining in A, B, C, and D model groups increased significantly (P<0.01 or P<0.05). The positive expression of CD34, VEGFA and EPO in the B, C and D model groups decreased significantly (P<0.01 or P<0.05). The expression of mRNA in the A and B model groups of HIF-1α, SDF-1 and CXCR4 was significantly increased (P<0.01 or P<0.05). Compared with the B model group, the relevant indexes of the C and D model groups changed significantly, indicating that the C and D models were more serious and tended to develop POF. Conclusion The B model group is the turning point of ovarian function from impaired POI to irreversible POF, suggesting that 3d administration of tripterygium wilfordii polyglycoside is the best time to induce POI disease model and effective drug intervention.
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Research progress of noncoding RNA in methamphetamine-induced addiction and neurotoxicity
zhang shu wei, cheng hao, wang hao wei, miao lin, li yi, guan li na, zeng xiao feng
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Methamphetamine (METH) is highly addictive and neurotoxic, which can cause cognitive and memory dysfunction in abusers. The harm of METH lies not only in its own toxicity, but also in the high physical and mental dependence of drug addicts, often causing mental disorders and causing violent behavior, bringing great safety risks to society. Non-coding RNA (ncRNA) does not code for proteins and is an important factor in regulating gene expression at the post-transcriptional level. Studies have shown that ncRNA plays an important regulatory role in methamphetamine-induced addiction and neurotoxicity, but the specific mechanism is unclear. This article reviews the current research progress of ncRNA in regulating METH-induced addiction and neurotoxicity, in order to provide a reference for ncRNA as a forensic identification index and potential drug intervention target for METH abusers.
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Advances in the mechanism of action of cyclic RNA in Parkinson's disease
liujuan, Li Yanjie, Qin hewei, Ma luyao, Zhao nannan, Xu zhenhua
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Parkinson's disease (PD) is a neurodegenerative disease characterized by the degenerative death of dopaminergic neurons in the substantia nigra, exhibiting a range of motor and non-motor symptoms that have a serious impact on the quality of life of patients. Circular RNA (circRNA, CircRNA) is a covalent closed-loop noncoding RNA that plays an important role in the progression of PD disease. This article reviews the involvement of circRNA in oxidative stress, regulation of transcriptional levels, neuroinflammation, autophagy, and α-synuclein.
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Analysis of application characteristics of acute liver injury animal model based on data mining
huyilong, zhangshuangli, qiuguangnan, fengyifan, miaomingsan, miaojinxin
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Objective To investigate the modeling elements of various types of animal models for acute liver injury, and to provide references and suggestions for the establishment and evaluation of animal models for ALI. Methods The animal experimental literature of acute liver injury from 2002 to 2022 was searched in the databases of China Knowledge Network, WanFang, Chongqing Vip, Chinese Medical Journal Full Text Data, PubMed, etc. The animal species, positive control drugs, modeling methods, modeling drugs and drug administration of the animal models of acute liver injury involved in the literature were summarized and summarized. The results were analyzed using Excel, SPSS Modeler18.0 and Cytoscape3.8.2. Results A total of 896 papers were included in the database. The most used animal models for acute liver injury were male KM mice; the modeling methods were mainly chemical liver injury, alcoholic liver injury, drug-related liver injury and immune liver injury, and the corresponding main modeling methods were : ① intraperitoneal injection of 10.0 mL 0.1% CCl4 vegetable oil, 24 h before the experiment; ② gavage of 12.0 mL 50.0%-56.0% ethanol, 16 h before the experiment; ③intraperitoneal injection of APAP 300 mg/kg, 24 h before the experiment; ④ tail vein injection of Con A 20 mg/kg, 8 h before the experiment. The evaluation of the model was based on liver pathological indexes as the gold index, combined with biochemical indexes Serum ALT, AST, liver tissue homogenate SOD, MDA content and activity were used as direct indicators. Conclusions Since the causes of acute liver injury vary in clinical practice, the preparation of animal models of acute liver injury should be based on the specific study content and characteristics of the study, and the corresponding modeling methods should be selected.
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The mechanism of Yantiao fang regulating Rho/ROCK signaling pathway on apoptosis of intestinal epithelial cells in mice with acute gastrointestinal injury caused by sepsis
Chen Qian, Wang D, Zhang DY, Jia SL, Wang LH, Cao YJ, Li YH
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Objective To investigate the effect of Yantiao Formula on apoptosis of intestinal epithelial cells in mice with acute gastrointestinal injury caused by sepsis by regulating Rho/ROCK signaling pathway. Methods 70 BALB/c mice were randomly divided into blank group (10 mice), sham operation group (10 mice) and model group (50 mice).Mice in blank group were fed normally without treatment.Sham operation group mice only open free cecum without perforation ligation;A mouse model of acute gastrointestinal injury caused by sepsis was established by cecal ligation and perforation (CLP). The mice were randomly divided into model group, Yantiao formula low-dose, medium-dose and high-dose groups, and ROCK inhibitor group.Hematoxylin-eosin (HE) staining was used to observe the histopathological changes of mice ileum.Serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were determined by ELISA.The expression of PCNA and Ki-67 in mouse ileal cells was detected by immunohistochemistry.The expressions of Caspase 3 and Bax were detected by western blotting.The expression of ROCK mRNA and MLC mRNA in the Rho/ROCK pathway of mouse ileum were detected by RT-qPCR. Results The intestinal mucosa of the ileum tissue of mice with acute gastrointestinal injury caused by sepsis was atrophied obviously, villi were disordered, rupture and shedding were observed, epithelial cells were necrotic and shedding, inflammatory cell infiltration was obvious, and Chiu's pathological score was increased.Compared with blank group and sham group, the serum levels of pro-inflammatory mediators (IL-1β, IL-6, TNF-α) and mRNA levels of Caspase 3, Bax, ROCK and MLC in peripheral blood of mice in model group were increased, while the levels of anti-inflammatory mediators (IL-10) and expressions of PCNA and Ki-67 in ileum were decreased.Compared with model group, the histopathological changes of ileum in all Yantiao fang groups were improved to varying degrees with the increase of dose: the pathological score of Chiu's was decreased, the levels of IL-1β, IL-6 and TNF-α in serum were decreased, and the levels of IL-10 were increased.In addition, the expressions of PCNA and Ki-67 were increased, while the expressions of Caspase 3, Bax, ROCK mRNA and MLC mRNA were decreased. Conclusion Yantiao fang can inhibit the apoptosis of intestinal epithelial cells in mice with acute gastrointestinal injury caused by sepsis by regulating Rho/ROCK signaling pathway, so as to reduce the inflammatory reaction of intestinal tissue and ultimately prevent the damage of intestinal mucosal tissue.
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Research status and trend of animal models of depression: a bibliometric analysis based on CiteSpace
YANG JIAHUI, LIN MENG, LUO XIAOQUAN, LUO TAO, GONG MEIFU
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【Abstract】Objective With the help of literature metrology, the scientific literature in the field of animal models of depression was analyzed, so as to better understand the development trends and hot spots in this field.Methods We obtained publications on depression and animal models from 2013 to 2022 from the Web of Science core set (WOSCC) database. Citespace 6.1R 1(64-bit) Basic was used to analyze the annual publications, countries, institutions, authors and keywords related to this field.Results A total of 1000 articles were included in this study. From 2013 to 2022, the number of papers published gradually increased and stabilized. In terms of the number of articles, the United States has the most published articles (256) and the most Polish Academy of Sciences (50) . Wegener Gregers is considered the most influential author in the field, with 23 published articles. When analyzing keywords, “Animal Model” was the most frequent, followed by“Major depression”. Conclusions This study highlights the important research trends and hot spots in the field of animal models of depression. The US, China and Japan are leading the way in terms of publication, indicating their significant contribution to the development of animal models of depression. However, international cooperation is limited and there is more cooperation within institutions and groups. The field focuses on signaling pathways and therapeutic approaches to determine the pathogenesis of depression and better treatments. The study provides a visual analysis of trends in depression research to help researchers keep abreast of the latest developments.
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Effect of gender difference on the model of rheumatoid arthritis induced by bovine type II collagen
Sun Wenting, Wan Yingying, Yang Jiaxi, Wang Wenqian, Wang Haonan, Ye Wanting, Kou Qiuai
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Objective To construct female and male bovine collagen-induced arthritis (CIA) models and compare the effects of gender differences on the joint and extra-articular manifestations of CIA models. Methods The CIA model was induced by injection of bovine type II collagen and Freund's complete adjuvant into female and male SD rats. The general condition, arthritis index, foot swelling, serum inflammatory factors and plasminogen activator inhibitor levels, spleen index, knee and ankle joint pathology, right rear paw bone destruction, and pulmonary interstitial lesions of rats in each group were evaluated. Results The arthritis index of female CIA rats was significantly higher than that of male CIA rats on the 21st day after initial immunization (P<0.05), but there was no significant difference in the degree of foot swelling between the two groups at any time point of observation (P>0.05); Serum tumor necrosis factor α, interleukin1β and spleen index of female CIA rats were significantly higher than those of male CIA rats (P<0.001; P<0.001; P<0.05), there was no significant difference in plasminogen activator inhibitor levels (P>0.05); The scores of inflammatory cell infiltration and synovial hyperplasia in the knee and ankle pathology of female CIA rats were significantly higher than those of male CIA rats (P<0.05), and the cartilage damage of knee joint and the bone damage of right rear paw of female CIA rats were significantly higher than that of male rats (P<0.05); Both male and female CIA rats showed pulmonary interstitial inflammatory cell infiltration and mild fibrosis, but the pulmonary interstitial lesions in females were more severe than those in males. Conclusion Both female and male CIA models constructed with SD rats can have both arthritis and pulmonary interstitial lesions, but the lesion degree of female CIA rats is more serious. When using CIA models for RA related research, attention should be paid to the impact of gender differences.
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Effects and mechanism of NCTD on proliferation and apoptosis of human leukemia cells by targeting PPP5C
zhangxin, cuibingjie, yuguoxing, wangfei, zhaoliang, gaona, dujing
Abstract:
Objective To study the effects and mechanism of norcantharidin (NCTD) on proliferation and apoptosis of human leukemia NB4 and K562 cells by targeting phosphoprotein phosphatase 5 catalytic (PPP5C). Methods NB4 and K562 cells were cultured in vitro, and the pcDNA3.1 and PPP5C-pcDNA3.1 plasmids were electroporated into NB4 and K562 cells. NB4 and K562 stable cell lines were screened with geneticin (G418). The protein and mRNA expression levels of PPP5C were identified by Western blot and qRT-PCR. The proliferation ability, migration ability and apoptosis rate of NB4、K562 cells were determined by CCK-8 assay, transwell assay and the Live DeadTM animal cell viability/toxicity detection kit. NB4 and K562 cells were divided into control group and different doses of NCTD group, and cultured in 1640 medium containing 0, 8, 16, 32 μg/ml NCTD. The Live DeadTM animal cell viability/toxicity detection kit detected the number of dead and live cells and cell morphology was recorded by microscope. Western blot was used to detect the protein expression levels of caspase 3, Cleaved caspase 3, JNK, p-JNK, p38, p-p38 and α-tubulin in cells of each group. Results? the proliferation ability of cells, the migration ability and apoptosis rate of NB4、K562 cells are enhanced after overexpression of PPP5C in human leukemia NB4 and K562 cells; Compared with the control group, each concentration group of NCTD promoted apoptosis in a dose-dependent manner; PPP5C overexpression antagonizes the killing effect of NCTD on leukemia cells. Conclusions NCTD can promote the apoptosis of NB4 and K562 cells and inhibit the proliferation of cells by inhibiting PPP5C.
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Research on the Mechanism of LSC Immune Escape with Intervention by TCM
ZHANG Meiling, 章, CuiYaru, ChengShupeng, LingZhiming
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Leukaemia is a critical disease with a high incidence in clinic at present, with an extremely high fatality rate. Among them, immune escape from leukaemia stemcells(LSC) is the main factor for recurrence and progression after leukaemia-induced remission. The clinical diagnosis and treatment of TCM has distinct advantages of syndrome differentiation and treatment. Based on the purpose of diagnosis and treatment, the treatment of leukaemia by TCM emphasises the "harmony of yin and yang" to estore human function, which is conducive to improving the body's autoimmunity and conforms to the mechanism of intervention for tumour cell immunity escape. This article discusses the echanism and research progress of TCM intervention in Lsc immune escape from literature research and TCM theory.
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Effects of polysaccharide content and anti-inflammatory, hemostatic and antioxidant activity before and after preparation of Mosla chinensis-jiangxiangru
Maqiuting, Xulei, Zhuyuchen, Xumengting, Zhangwenkai, Liuzhiyong
Abstract:
Abstract：Objective:Exploring the changes in polysaccharides in Jiangxiangyu before and after giner juice, and evaluation of polysaccharide anti -inflammatory and antioxidant antioxidant activity before and after the processing. Methods: The content of polysaccharides beforeand after processing was determined by phenol-sulfuric acid method（Elsholtzia chinensis polysaccharide-JXRPs, Ginger Elsholtzia chinensis polysaccharide-JZJXRPs); The body internal uses the swelling model of rats and the body fat polysaccharide (LPS) to induce mousemacrophages RAW264.7 inflammation model.The best administration concentration is selected by using cell proliferation (MTT) method, Elisa method measures the expression of IL-6, IL-12, NO, IL-4, and IL-10 in the cells;Observe the bleeding time of mice to evaluate its hemostatic effect by observing the tail -cutting method; finally, use the ability to remove DPPH and ABTS to evaluate its in vitro antioxidant activity.Results: The contents of JXRPs and JZJXRPs were 13% and 22%,As a result of the swelling of rats, after 4h in injection, compared with the model group, JXRPs ppear significant difference in dosage doses of 200 mg/kg (P <0.05), and JZJXRPs When the dose is 100 mg/kg, you can significantly reduce the swelling of rats (P <0.05);The in vitro anti-inflammatory results show that the polysaccharides before and after the processing can significantly inhibit cell secretion of IL-6, IL-12 and NO (P <0.01), promote cell secretion of IL-4 and IL-10 (P <0.01), and the processing of the processing The post -effects are stronger.The results of the mouse break the hemostatic experiment show that: compared with the control group, the JXRPs group can speed up the hemostatic effect but there is no significant difference, and there is asignificant difference in the dosage of the JZJXRPs (P <0.05) in the medium dose (P <0.05), and the High doses have accelerated trend but there is no significant difference; The results of antioxidant activity in vitro showed that JXRPs and JZJXRPs had different degrees of scavenging ability for DPPH and ABTS, with IC50 values of JXRPs of 0.2215 mg/ml and 0.2110 mg/ml of JZXRPs, respectively, and IC50 values of 0.1651 mg/ml and 0.1884 mg/ml of JZJXRPs, respectively.Conclusion:After the Jiangxiangyu is produced by ginger juice, it can promote the dissolution of polysaccharides and increase the polysaccharide content. JZJXRPS anti -inflammatory hemostasis and antioxidant capacity are stronger than JXRPS, which can lay the foundation for the follow -up research and clinical application of JXRPS.
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Research progress of SHP-2 in tumor-associated macrophages
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Abstract: Tumor-associated macrophages (TAMs) are the dominant cell group in the tumor microenvironment (TME) and are the most important regulatory cells of immune system suppression and tumor cell proliferation in Tmes. Src homologous 2 protein tyrosine phosphatase 2 (SHP-2) is a non-receptor protein tyrosine phosphatase that plays an important role in signaling from the cell surface to the nucleus and is a key intracellular regulatory factor mediating cell proliferation and differentiation, involved in a variety of growth factor and cytokine signaling pathways. Recent studies have shown that SHP-2 is a key enzyme that determines the function of tumor-associated macrophages, but because of its variable function, it plays different or even opposite roles in different solid tumor microenvironments. Based on this, this paper reviews the function of SHP-2 in TAMs and the role of ShP-2 in related solid tumors, providing a solid scientific basis for tumor immunity and targeted therapy.
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Antitumor mechanism of Ardisia Crenata
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Ardisia Crenata Radix is a traditional Chinese medicine, which belongs to Myrsinaceae, and its main components are coumarins, saponins, flavonoids and volatile oil. Bergenin, ardisicrenoside A, ardisicrenoside B,ardisiacripin A,ardisiacripin B and embelin are active anticancer compounds with the in-depth study of the anti-tumor effect of Ardisia Crenata Radix. They show high potential in oral cancer, nasopharyngeal carcinoma, liver cancer, colon cancer, bladder cancer, cervical cancer and leukemia mainly through inducing tumor cell apoptosis, increasing tumor cytotoxicity, inhibiting cell proliferation, inhibiting tumor cell metastasis and migration, and inducing cell regulatory enzyme cascade reaction. However, the preclinical experimental data of cinnabar root anti-tumor mechanism are lack of high-quality, multi-sample and multi-repeated randomized controlled trials, and the clinical research data are lack of tumor prognosis, pharmacodynamics and pharmacokinetic data. Accurate research experiments and clinical trials should be designed to further explore the pharmacological effects of mining cinnabar root.
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Research progress in immunoregulation mechanism of exosomes on bacterial infection
Abstract:
Exosomes are small endosomal derived extracellular vesicles with lipid bilayer structure, which contain substances such as protein, lipids, DNA, RNA, miRNA and lncRNA. Exosomes participate in pathogen recognition, antigen presentation, autophagy regulation, immune activation and immunosuppression in bacterial infection. Studies have shown that miRNA, lncRNA and protein in exosomes play important roles in regulating antibacterial reaction of organism. We reviewed the immunomodulatory effects of exosomes on several intracellular and extracellular bacterial infections to provide evidence for studying the interaction between exosomes and bacterial infections.
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Application and challenges for NHP laboratory animals in neuroscience
HuLingfeng, FanShengtao, LiuJie
Abstract:
【Abstract】: Currently, non-human primates (NHPs) are becoming increasingly important in laboratory animals, especially in the field of neuroscience, where many significant breakthroughs have been made, including research on brain development, neurodegenerative diseases and psychiatric disorders, but as their breeding and use grows, biosafety and animal ethics issues should be taken into account. This review summarizes the application and challenges of NHP laboratory animal in the neuroscience field from the aspects of NHP overview, feeding and operation, biosafety, and animal ethics.
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Research progress on evaluation of type 2 diabetic peripheral neuropathy animal model
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Diabetic peripheral neuropathy is a common diabetic complication. At the moment, our understanding of its pathogenesis is incomplete, and there are no effective treatment options. In-depth research requires the use of animal experiments. The criteria for modeling success and the evaluation method for peripheral nerve function recovery are critical for carrying out animal experiments on type 2 diabetic peripheral neuropathy, but there is a lack of sorting out and analyzing the evaluation methods for type 2 diabetic peripheral neuropathy models. As a result, the author reviewed recent data, summarized and analyzed the evaluation methods of animal models of type 2 diabetic peripheral neuropathy from small and large nerve fibers, and proposed future development directions in order to provide a reference for related research.
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A review and promising future directions of machine learning in laboratory animal facility management
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As the intelligence level gradual improving in domestic laboratory animal facilities，a large amount of valuable data has been accumulated. The data has not been fully exploited due to lacking of analytical means. In the context of Big data, Machine learning algorithms have achieved remarkable results in biomedical, building science and other fields, and also provide a reference for their application in laboratory animal facility management. In this paper, the contents, methods and models of machine learning methods applied to various systems of laboratory animal facilities at home and abroad are reviewed and prospected.
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Optimization of the preparation method of lung tissue cryosections for multiplex immunofluorescence staining
Ye Qianchen, Xu Dan, Wen Fuqiang, Chen Jun, WANG TAO
Abstract:
Objective Optimizing the preparation method of mouse lung cryosections to improve the quality of lung cryosections helps to enhance the specificity of immunofluorescence staining and obtain more accurate and reliable experimental results. Methods C57BL/6 mice were used to make cryosections by the traditional post-freezing fixation method, the pre-freezing fixation method, and a modified perfusion pre-freezing fixation method, respectively. A laser scanning confocal fluorescence microscope was used to observe lung tissue immunofluorescence staining. The whole areas of mouse lung slices were scanned by fluorescence microscope, and then the numbers of intact airways per unit area of lung tissue were calculated. Results For the lung cryosections made by the traditional post-freezing fixation method, the alveoli structure was damaged, and the airway wall was seriously broken with non-specific staining. The lung cryosections made by the pre-freezing fixation method showed relatively intact alveolar and airway structures but collapsed alveoli and several destroyed airways. The structure and morphology of the alveoli and airways were intact and clear in the lung cryosections prepared by the modified perfusion pre-freezing fixation method. In addition, the locations of target genes were accurate with multiple immunofluorescence staining. The number of intact airways (diameter ≥100 μm) per unit area in the lung cryosections from the modified perfusion pre-freezing fixation method was higher than from the pre-freezing fixation method (0.66±0.15 /mm2 vs. 0.33±0.14 /mm2, P<0.05), and was also significantly higher than that from the traditional post-freezing fixation method (0.66±0.15 /mm2 vs. 0.02±0.04 /mm2, P<0.01). Conclusions The modified perfusion pre-freezing fixation method is beneficial to maintain mouse lung tissue's morphological integrity and obtain high-quality multiplex immunofluorescence staining results.
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To explore the effects of different types of drinking water on the growth and fecal flora of mice
Abstract:
【Abstract】 Objective to explore the effects of different types of drinking water on growth and fecal flora of mice. Methods SPF NIH mice were selected and divided into 5 groups with 32 males and females in each group. they were fed with pure water (control group), acidified water, alkalized water, weak acid water and solid water, respectively. diet and body weight were monitored continuously for 20 days. after the experiment, animal feces samples were collected, and the V3-V4 region was amplified with bacterial16S rDNA universal primers. Illumina Miseq high-throughput sequencing platform was used for high-throughput sequencing, and microbial community, alpha diversity and beta diversity were analyzed by bioinformatics method. Results in terms of body weight, the water of weak acid in female mice was higher than that in the control group at different pH values, while the other groups were lower than that in the control group(P﹥0.05). in male mice, the body weight of acidified water group was higher than that of control group, while that of other groups was lower than that of control group, but there was no statistical difference between groups(P﹥0.05). the body weight of female and male mice with solid water was lower than that of control group(P < 0.05). in terms of food intake and water intake, the water intake and water intake of female mice in the alkalized water group were lower than that of other groups, and the water intake of female and male mice in the solid water group was lower than that of other groups. through OTU cluster analysis, the dilution curve showed that the data volume of this sequencing was reasonable. the fecal flora of NIH mice was divided into five phyla, among which bacteroidetes and firmicutes were the main phyla. at the genus level, pseudopurpuromonas, lactobacillus and mycobacterium were the main genera. there were differences in fecal flora abundance and diversity among the five drinking water types. alpha analysis showed that the acidified water group had the highest flora abundance and diversity, while the solid water group had the lowest flora diversity. beta analysis showed that the fecal flora of the solid water group and the control group were the most similar, followed by alkalized water group, acidified water group and weak acid water group, respectively. Conclusions through the exploration of different types of drinking water, it is revealed that the solid form of drinking water has a great effect on the body weight, feed intake, water intake and fecal flora of mice, and the abundance and diversity of fecal flora of mice are affected by different pH values of drinking water, especially acidified water has a greater effect on the fecal flora of mice.
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The therapeutic effect of licorice zinc on chloasma mice was explored based on nrF-2 /HO-1 pathway
Du Xiaoshuang, Liu Ping, Deng Ying, Yang Hongqiu, Du Yu
Abstract:
[Abstract] Objective To investigate the therapeutic effect of licorice zinc on melasma. Methods Melasma was induced by 100 mJ/cm2 UVB irradiation combined with 15 mg/kg progesterone injection. Tranexamic acid (0.065 g/kg) and low (0.65 g/kg)/medium (1.3 g/kg)/high (2.6 g/kg) zinc licorice were treated for 14 days. Skin was taken for HE and Masson-Fontana staining; and SOD, MDA, GSP-Px, TNF-α, IL-1β and IL-6 contents; plasma protein Nrf-2, nuclear protein Nrf-2, and HO-1 expression levels were measured. Results High dose of zinc licorice significantly reduced melanocyte formation, collagen cell necrosis and inflammatory infiltration, significantly up-regulated the expression of GSP-Px and SOD, decreased the expression of MDA, IL-6, IL-1β and TNF-α, up-regulated the expression of nuclear proteins Nrf-2 and HO-1, and down-regulated the expression of plasma protein Nrf-2. Conclusion Zinc licorice activates Nrf-2/HO-1 pathway to initiate high expression of HO-1, SOD and GSP-Px against oxidative stress, thereby reducing melanogenesis.
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Study on the mechanism of oral microflora involved in areca nut extract induced oral ulcer in rats
pengdongdong, chenxiangchi, tangzining, liuxuewu, yuanxiangzhong, limeng, liqiao, zhangzeheng
Abstract:
Objective The model of oral ulcer in rats was constructed by areca nuts extract, and the structural changes and diversity characteristics of oral flora were observed, so as to explore the pathogenesis of oral flora involved in oral ulcer in rats induced by areca nuts extract, providing theoretical support for clinical prevention and treatment of oral ulcer. Methods Thirty SD rats were randomly divided into normal group, model group, drug treatment group, 10 rats/group. The rat oral mucosa was injected with 10g/mL areca nuts extract subcutaneously to replicate the rat oral ulcer model. Ulceration area, ulceration score, and levels of TNF-α, IL-2, and IL-8 in local tissues were observed, and HE staining was performed on oral mucosal tissues to observe the morphological changes of oral mucosal tissues. High-throughput sequencing method was used to analyze the structure distribution of oral microbial flora and microbial community diversity. Results Compared with normal group, the ulcer area of rats in model group was significantly increased (P<0.01), the ulcer score was significantly increased (P<0.01), the levels of IL-2, IL-8 and TNF-α in oral mucosal tissue were significantly increased (P<0.01), and the shannon index of oral saliva of rats was significantly increased (P<0.05).simpson index was significantly decreased (P<0.01), Strep-tococcus and Veillonella were significantly decreased (P<0.05,0.01), oral mucosal epithelial cell proliferation or focal necrosis, mucosal lamina propria edema and hemorrhage were observed in model group. It was accompanied by abundant infiltration of neutrophils and monocytes. Compared with model group, the ulcer area and ulcer score of model group were significantly decreased (P<0.05), the levels of IL-2, IL-8 and TNF-α in oral mucosal tissue were significantly decreased (P<0.05,0.01), and the shannon index of oral saliva of rats was significantly decreased (P<0.05). Simpson index was significantly increased (P<0.01), Strep-tococcus was significantly increased (P<0.001), Staphylococcus was significantly decreased (P<0.01), and the pathological degree of oral mucosa was significantly improved. Conclusion Areca nuts extract can successfully reproduce the rat model of oral ulcer, and it is speculated that the development of oral ulcer disease induced by areca nuts extract may be related to the imbalance of oral flora and local tissue inflammatory mediators.
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Effects of 5-Aza-CdR on hippocampal neurogenesis in mice via the Notch1 pathway
wangbaojie, suliqing, yanlei, zhangzhiyong, 王志广, baosuya, shaoguo
Abstract:
【 Abstract】 Objective To investigate the effect of 5-Aza-CdR on Notch1 pathway and neural regeneration, and to explore the effects of 5-Aza-CdR on learning memory ability in mice by exploring active avoidance behavioral experiments on mice. Methods Sixty 6- to 8-week-old ICR male SPF-grade mice were divided into two groups, and 5-Aza-CdR was administered to one group of mice via lateral ventricular injection (i.c.v.), while the other group was injected with BSA as a control group. 5-Aza-CdR was administered to mice by lateral ventricular injection (i.c.v). mRNA and protein expression levels of Notch1 and HES1 were detected by real-time PCR and Western blot 24 hours after injection; 5-bromo-2'-deoxyuridine (BrdU)-positive cells were observed by laser confocal microscopy and Notch1 expression in hippocampal DG by laser confocal microscopy; Notch1 methylation changes were detected by MS-PCR; and learning and memory behaviours of mice were assessed by measuring passive avoidance tests and shuttle avoidance assays. RESULTS Injection of 5-Aza-CdR increased hippocampal Notch1 pathway activity and promoted neuronal regeneration in the DG region, decreased methylation levels in the Notch1 promoter region, and enhanced the ability of mice to perform active avoidance behaviour. Conclusion The effect of 5-Aza-CdR on active avoidance behavior may be related to the influence of hippocampal neural regeneration through the Notch1 pathway.
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Effects of emodin on autophagy and cycle arrest in fibroblast-like synoviocytes in rheumatoid arthritis
Tao Bonan, WANG Yonglan, HONG Lan, YUAN Lin
Abstract:
Objective: Based on the cGAS/STING signaling pathway to investigate the potential effect of emodin (EMD) on autophagy of human rheumatoid arthritis fibroblast synovial cells (MH7A). Methods: CCK-8 method was used to detect the results of MH7A cell proliferation, and the concentration of drug was screened according to cell survival rate. Then, autophagy inhibitor 3-MA was added to further verify the effect of emodin on autophagy. Autophagy of MH7A cells was detected by MDC method. The protein expression levels of cGAS, STING, p-STING, LC3-I, LC3-II, p62 and Beclin-1 were detected by Western blot. Results: MDC staining indicated that emodin could enhance autophagy of MH7A cells. Western Blot results indicated that emodin could decrease the expressions of autophagy related proteins cGAS, STING, p-STING and P62, and increase the expressions of LC3-II and Beclin-1 in MH7A cells. After addition of autophagy inhibitor 3-MA, the expression of P62 protein in MH7A cells increased, while the expression of LC3-II and Beclin-1 protein decreased. Conclusion: Emodin may accelerate autophagy and inhibit MH7A cell proliferation by down-regulating cGAS/STING signaling pathway.
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Progression of the Relationship between Pyrozosis and Atherosclerosis
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Pyroptosis is a programmed mode of death, and activated aspartase-1 (caspase-1) can induce the occurrence of pyroptosis, promoting the release of inflammatory factors. In recent years, studies have found that pyroptosis may be closely related to the occurrence, development and outcome of atherosclerosis. This article reviews the relevant studies of endothelial cells pyroptosis, vascular smooth muscle cells pyroptosis and macrophages pyroptosis in the development of atherosclerosis, aiming to provide new ideas for the pathogenesis and diagnosis and treatment of atherosclerosis.
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Gli2 regulates the activation of Hedgehog pathway on proliferation, metastasis and epithelial mesenchymal transformation of Tca8113 cells
Liu Maolin, Wang Xiaotang, Song Xiaona, Ma Yunfei, Chang Xiaoqi, Song Guohua
Abstract:
Objective: To investigate the effects of Gli2 on the proliferation, growth, migration and invasion of oral cancer cells (Tca8113) at the cellular level, and to clarify the molecular mechanism of Gli2 regulation on the migration and invasion of oral cancer cells. Methods: siRNA was used to inhibit Gli2 expression in Tca8113 cells. The effects of Gli2 on the proliferation, growth, migration and invasion of Tca8113 cells were examined by CCK-8, plate cloning and transwell chamber assay. Further, qRT-PCR and Western blot were used to explore the mechanism of Gli2 regulation of malignant proliferation and metastasis of Tca8113 cells. Results: The mRNA and protein expression of Gli2 in oral cancer cells (Tca8113) were increased. Interference with Gli2 expression inhibited the proliferation, growth, migration and invasion of Tca8113 cells. Further studies showed that interfering with Gli2 expression inhibited mRNA and protein expression of key factors in Hedgehog (Hh) pathway. In addition, interference with Gli2 expression can significantly affect mRNA and protein expression of key factors in Epithelial mesenchymal transformation (EMT) pathway. Conclusion: Gli2 is abnormally activated during oral cancer, and interference with Gli2 expression significantly inhibits the proliferation, growth, migration and invasion of oral cancer cells. Gli2 influences the migration and invasion of oral cancer cells by regulating Hh pathway and EMT pathway. This study provides a new way to elucidate the pathogenesis of oral cancer and a new perspective for clinical treatment of oral cancer.
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A model study of blood in urine (bladder cancer) under scorching humid fever under MNU-induced SD rats
changtuo, wangjie, linan, wangtianqi
Abstract:
Objective: To investigate the modeling process and mold formation rate of N-methyl-N-nitrosourea (MNU)-induced lower jiao dampness-heat syndrome uremia bladder cancer (BC) model. Methods: Batch samples were collected by bladder perfusion (MNU) and H&E staining and pathological observation of pathological tissues were carried out at a total of 6 time points before, during and after molding, so as to understand the formation and development of carcinoma in situ of the bladder. Results: The experimental process was smooth, and no obvious urinary tract bleeding in rats occurred during the operation. By this modeling technique, considerable bladder tumors can be obtained after the eighth week, and there are obvious epithelial hyperplasia, damage and large-scale tumor formation in the bladder of rats in the model group. Conclusion: MNU can induce SD rat bladder cancer model with obvious model formation and low mortality, and the experimental data can provide a certain reference for the establishment, improvement and application of bladder cancer model.
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Protective effects of HIF-1α pathway in cold storage of isolated organs
wangzhiyang, zhengsiyang, zhuliang
Abstract:
Organ transplantation is the main treatment for organ failure. The functional protection of donor organs during ex vivo transportation is the key to the success of organ transplantation. How to protect the functions of donor organs during in vitro transportation is one of the key issues in the field of organ transplantation research. In a hypoxic environment, the transcriptional activity of a series of genes in cells is activated. These genes are mainly involved in angiogenesis, iron metabolism, glucose metabolism, and cell proliferation/survival. In aerobic organisms, hypoxia-inducible factor-1α (HIF-1α) is involved in the regulation of the expression of various genes to maintain the homeostasis of tissues and cells under hypoxic conditions, thereby adapting to the hypoxia. Many studies have shown that the HIF-1α pathway plays an important role in protecting isolated organs from cold ischemia injury during cold storage. HIF-1α has been a hot spot in the research on the protective mechanism of cold ischemia injury of isolated organs. The intervention of the HIF-1α-related signal pathway is expected to become a new strategy for maintaining organ function during cold storage of isolated organs.
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Advances in animal models of diet-induced nonalcoholic fatty liver disease
Wang Jialin, Wang Chongyang, Li Yang, Chen Xianwei, Yuan Zhongnan, Zou Chaoxia, Zou Chendan
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The establishment of scientific and effective animal models is a key step to complete disease research. Diet induction is a common method to establish animal models of nonalcoholic fatty liver disease (NAFLD). The common animal models of diet-induced NAFLD mainly include high-fat and high-sugar diet-induced model, high-fat and high-cholesterol diet-induced model, and choline-deficient diet-induced model. Due to the different nutrients ingested by different modeling methods, the pathological characteristics such as fatty deformation, inflammation and fibrosis of the liver are different. In addition, different animal models vary in disease progression, disease severity, and applicable studies. This article analyzes and compares the common animal models of NAFLD induced by different diets in modeling methods, modeling time, pathological characteristics, applicable research, and related advantages and disadvantages, so as to provide reference for NAFLD researchers to select animal models.
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Isolation and extraction of Kupffer cells and hepatic stellate cells in mouse liver
mawenmeng, wuhao, yanyutong, sunxun, zhengqianqian
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【】Objective It is to explore the extraction and purification methods of Kupffer cells and hepatic stellate cells from mouse liver, and provide reference and suggestions for the separation and extraction methodology of primary non parenchymal cells from mouse liver.Methods Based on in vivo collagenase perfusion digestion, different reagents and methods such as Percoll and OptiPrep were used to extract C57BL/6 mice Kupffer cells and hepatic stellate cells and evaluate the purity through flow cytometry and immunofluorescence methods. Results The two-layer Percoll method for extracting Kupffer cells and the two-layer OptiPrep method for extracting hepatic stellate cells are feasible,and the purity can reach more than 90%.The cell yield was 1~2×107/liver, the cell survival rate was more than 90%.After 48 hours of primary cell culture, the number of Kupffer cells F4/80-positive cells and hepatic stellate cells α-SMA-positive cells reached more than 75%. Conclusions The separation and extraction method of Kupffer cells and hepatic stellate cells from mouse liver is perfect, reliable, cost-effective and reproducible.
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Application Research Progress of Single-cell RNA-sequencing Technology in Neurodegenerative Diseases
Abstract:
Neurodegenerative diseases (NDs) are the mental diseases closely related to the central nervous system, characterized by morphological abnormalities and slowly progressive loss of function in specific neuron groups. The main diseases include Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Multiple sclerosis (MS) and Huntington's disease (HD). However, the directly therapies for NDs are not founded. In recent years, single-cell RNA-sequencing (scRNA-seq) technology has been widely used in various neurodegenerative diseases. It has been found that the pathogenesis of NDs are involved in conditions of immune cells and biological processes such as mitochondrial function, angiogenesis, inflammation and synaptic transmission. The antilepsis of induced pluripotent stem cells (iPSC) is a potential treatment for NDs. Ultimately, the application of scRNA-seq technology in various NDs was reviewed in this paper ,and provided reference for the future prevention and treatment of NDs.
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Research progress on modeling methods and evaluation indexes of kidney injury in zebrafish
lanailin, Huangchunhua, Xiaming, Limaojuan, Wangsiqi, Loudidong
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Renal function is to filter blood , regulate fluid and electrolyte balance, which is crucial for health of the body, moreover, the kidney is susceptible to toxicity of various compounds in and out of the body, resulting in renal function damage, hence the prevention and treatment of renal function injury caused by various factors is also a hot research topic. Zebrafish is an ideal animal model as it is closely related to humans in terms of morphology, physiology and function of kidney and its response to compounds. In this paper, we will review the methods and evaluation indexes of zebrafish kidney injury modeling.
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Microvascular morphometric analysis of cerebral cortical functional areas in C57BL/6 mice of different months of age
Abstract:
Abstract: Objective To observe and analyze the different functional areas of cerebral cortex in C57BL/6 mice of different months. Methods Improved alkaline phosphatase staining was used to reveal the microvascular morphology of the cerebral cortex of C57BL/6 mice, including motor cortex (primary motor cortex, secondary motor cortex), sensory cortex (primary somatosensory cortex, secondary somatosensory cortex), visual cortex (primary visual cortex, secondary visual cortex), auditory cortex (primary auditory cortex, secondary auditory cortex), olfactory cortex (extrorhinal cortex, entorhinal cortex). Images were captured by OLMPUS BX51 microscope combined with Image-Pro Plus 5.1 software. The microvascular length density (Lv), microvascular surface area density (Sv) and microvascular volume density (Vv) were analyzed by Image-Pro Plus 5.1 software. Results The levels of alkaline phosphatase in microvessels of different functional areas of cerebral cortex increased with age and reached the peak in adults. There were four patterns for pia vessels to enter the cortex including T shape, Y shape, large arc, small arc. The Lv, Sv and Vv in different functional areas of the same aged mice showed a downtrend trend in the motor cortex, sensory cortex, visual cortex, auditory cortex and olfactory cortex. Moreover, the microvascular density of Lv, Sv and Vv in the motor cortex and sensory cortex was statistically significant compared with those in the olfactory cortex (P<0.05). The vascular densities of different functional areas in the aged mice were lower than those in the adult ones, but there was no statistical significance (P>0.05). Conclusion The improved alkaline phosphatase staining may clearly reveal the microvascular architecture in cerebral cortex of C57BL/6 mice and it provides morphological reference for the research of cerebrovascular diseases and the preparation of animal models.
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Research progress of traditional Chinese medicine for stroke based on epigenetic regulation
Abstract:
Epigenetics is a branch of molecular biology, and is a research hotspot in the post-gene era in the field of life sciences. The application of epigenetic modification research methods is the frontier field of the pathogenesis of ischemic stroke, and it is the interpretation of traditional Chinese medicine in the treatment of ischemia. Targets of stroke and effective approaches to their mechanisms of action. At present, the etiology and pathogenesis of ischemic stroke has not been fully clarified, and modern medical treatment is still insufficient. The treatment of ischemic stroke with traditional Chinese medicine has unique advantages and broad prospects. The latest research has found that traditional Chinese medicine can participate in the regulation of abnormal epigenetic modification in the treatment of stroke. This article mainly starts from the epigenetic basis of traditional Chinese medicine theory of stroke and the application of DNA methylation, non-coding RNA and histone modification in stroke treatment and traditional Chinese medicine research, and explains the appearance of traditional Chinese medicine in the treatment of stroke. The role of heredity in order to provide new ideas and scientific basis for traditional Chinese medicine treatment of the disease
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Geniposide promotes skin ulcer wound healing in diabetic rats through PI3K/Akt pathway
Abstract:
Objective To investigate the protective effect of geniposide on diabetic skin ulcer and its mechanism. Methods Rats were divided into normal group, model group and geniposide subgroup (Gen-L: 200 mg/kg; Gen-H: 500 mg/kg). The diabetic rats were given normal saline or geniposide by intragastric administration (n = 6). Treatment was administered once a day, and the wound healing and inflammation of each group were recorded every day. After 7 days of treatment for diabetic skin ulcers, the wound area, tissue sections, TUNEL staining and Western blot were used to quantitatively analyze the changes of wound healing, apoptosis and related regulatory protein expression. Results Compared with the model group, geniposide (200 mg/kg and 500 mg/kg) orally could significantly promote the wound healing and increase the contraction of the injured area in diabetic rats. In the study of skin wound apoptosis in diabetic rats, TUNEL staining positive cells in geniposide subgroup were significantly reduced (P<0.05). Geniposide can significantly inhibit skin inflammation and promote wound repair, which may be related to the promotion of PI3K and Akt phosphorylation. Conclusion Geniposide can promote skin wound repair in diabetic rats by inhibiting inflammatory response and apoptosis.
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Effect of Dingkun Pill on PI3K/AKT/mTOR signal pathway in rats with endometriosis
Abstract:
[Abstract] Objective: To explore the effect of Dingkun Pill on PI3K/Akt/mTOR signaling pathway in rats with endometriosis (EMs). Methods: The EMs rat model was constructed by heterotopic transplantation of endometrial tissue and randomly divided into five groups: model group (M group), Dingkun Pill low (1.13g/kg) dose group (DKP-L group), Dingkun Pill medium (2.26g/kg) dose group (DKP-M group), Dingkun Pill high (4.52g/ kg) dose group (DKP-H group), gestrinone (60mg/kg) group (GES group), with 12 rats in each group. Another 12 normal SD rats were opened the abdomen without transplantation ectopic endometrial tissue, and set as sham operation group (sham group). The rats were killed after intervention with drugs, the volume of ectopic endometrium and the weight of ectopic lesions of rats in each group were measured, the microvessel density (CD31 positive rate) and the expression of VEGF and MMP-9 in rat ectopic endometrial tissue were detected by immunohistochemical staining; the rat serum VEGF, MMP-9, iNOS and TNF-α levels were detected by enzyme-linked immunosorbent assay (ELISA); the expression of PI3K/Akt/mTOR pathway related proteins in rat ectopic endometrial tissue was detected by western blotting. Results: Compared with the sham group, the microvessel density, VEGF and MMP-9 expression, serum VEGF, MMP-9, iNOS and TNF-α levels, p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR in the ectopic endometrial tissue were significantly increased in the M group (P<0.05); compared with the M group, the ectopic endometrial volume, the weight of the ectopic lesion, the microvessel density of the ectopic endometrial tissue, VEGF and MMP-9 expression, the serum VEGF, MMP-9, iNOS and TNF- α levels, p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR in ectopic endometrial tissue were all decreased in the drug intervention group, and DKP-L, DKP-M and DKP-H groups were dose-dependent (P<0.05); compared with the DKP-H group and the GES group, there was no significant difference in the indicators of rats (P>0.05). Conclusion: Dingkun Dan can reduce inflammation and inhibit ectopic endometrial growth in EMs rats, which may be achieved by blocking PI3K/Akt/mTOR signal pathway.
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Experimental Study on Mongolian Drugs Hatagaqi-7 Promoting Ulcer Wound Healing of diabetes Rats via HIF-1α
DongChenghai, Cheliger, ChaoRiya, manzhu, Bao Yonglin, GongLimin
Abstract:
Objective: To study the effect of mongolian drugs Hatagaqi-7 promoting ulcer wound healing of diabetes rats via hypoxia inducible factor-1α(HIF-1α). Methods: Adult male SD rats were randomly divided into control group, diabetes group, mongolian drug group and cytokine group. Besides the control group, the other three groups were treated with intraperitoneal injection of streptozotocin to establish the diabetes model. The ulcer wounds were prepared in the back of the four groups. One week later, the mongolian drug group was treated with hattagelge-7, and the cytokine group was treated with recombinant bovine basic fibroblast growth factor for two consecutive weeks. Then fasting blood glucose (FBG), wound area, wound pathology, the expression level of advanced glycation end products (AGEs), receptor of AGE (RAGE), HIF-1α, vascular endothelial growth factor (VEGF) and the levels of interleukin-1β(IL-1β), interferon-γ(IFN-γ), malondialdehyde (MDA) and total antioxidant capacity (T-AOC) were detected. Results: The FBG of diabetes group, mongolian drug group and cytokine group were higher than those of the the control group(P<0.05), and there was no significant difference among the three groups (P>0.05). Compared with the control group, the area of ulcer wound, the scope of unrepaired tissue under microscope, the expression level of AGEs, RAGE and the levels of IL-1β, IFN-γ, MDA in the wound tissue of the diabetes group increased, the level of T-AOC and expression levels of HIF-1α, VEGF of the diabetes group decreased (P<0.05). Compared with the diabetes group, the area of ulcer wound, the scope of unrepaired tissue under microscope, the expression level of AGEs, RAGE and the levels of IL-1β, IFN-γ, MDA in the wound tissue of the mongolian drug group and cytokine group decreased, the level of T-AOC and expression levels of HIF-1α, VEGF of the mongolian drug group and cytokine group increased (P<0.05) and the indexes of mongolian drug group were better than those of cytokine group. Conclusion: Mongolian drugs Hatagaqi-7 promotes ulcer wound healing of diabetes rats, and the inhibiton of AGEs and RAGE expression and the activaton of HIF-1 α is a possible molecular mechanism.
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Effect of Osteoking on lowering blood sugar and improving intestinal flora in db/db mice
dengshaoyou, zhaoyulan, wangpeijin, lirong, zhaohongbin, jiaojianlin, zhenghong
Abstract:
Objective:To investigate the effects of Osteoking on hyperglycemia and regulating gut microbiota in db/db mice. Methods:The wild mice were used as the cntrol group and db/db mice were randomly into model group and Osteoking group. After intragastric administration for 12 weeks, Fasting blood glucose, serum glycosylated hemoglobin and insulin levels were measured , the changes of intestinal microflora were determined and functional pathways related to intestinal microflora in mice were predicted by 16S rDNA sequencing technology. Results:Compared with model group, Osteoking decreased fasting blood glucose (P < 0.01), serum glycosylated hemoglobin (P < 0.01), insulin resistance index (P < 0.01), and increased insulin content (P < 0.01) in db/db mice. Osteoking increased the abundance of beneficial bacteria of intestinal microflora, while decreased the abundance of harmful bacteria; the abundance of Marvinbryantia was increased. Osteoking alleviated the decrease of metabolism of D-arginine and D-ornithine, sphingolipid and galactose metabolism( P < 0.05), while inhibited lysine degradation, sulfur relay system and propanoate metabolism( P < 0.05). Conclusion:Osteoking has the effects of hypoglycemic properties and improving the intestinal microflora imbalance in db/db mice.
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Research progress on the role of autophagy in the pathogenesis of systemic sclerosis
lixin, sun xiaolin, wang yongfu
Abstract:
【Abstract】 Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular lesions and skin fibrosis, which can cause structural and functional damage to multiple organs. The pathogenesis of SSc is complex, which may be related to genetic, environmental factors and abnormal immune mechanisms. Autophagy is an evolutionarily conservative process of self degradation in the body, which can participate in the pathogenesis of body immunity and autoimmune diseases through a variety of pathways. This article mainly reviews the research progress on the role of autophagy in the angiopathy and fibrosis of SSc through regulating immune cells and mediating signal pathways.
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The role and mechanism of miRNAs in alcoholic liver injury in rats
Abstract:
Objective To investigate the role and mechanism of miRNAs in alcoholic liver injury in rats. Methods Randomly divided 30 male SD rats into model group and control group. The model group was gavaged with 56% liquor and the control group with distilled water for 8 weeks. The liver tissue was dissected. The miRNAs in the liver tissue were detected, analyzed and the target genes of differential miRNAs were predicted by rat miRNA chip. Gene Ontology (GO) and KEGG Pathway enrichment analysis were used to understand the function of differential miRNA target genes. Differential miRNA-mRNA-Pathway regulatory network was constructed using Cytoscape to further screen regulatory key miRNAs versus key pathways, qRT-PCR was performed on selected miRNAs for expression quantity validation analysis. Results: A total of 12 differentially expressed miRNAs (P < 0.05, fold change ≥ 2) were screened out, including 2 upregulated and 10 downregulated miRNAs by comparative analysis of microarray data between the model and control groups. GO classification annotation of differential miRNA target genes showed that there were close associations between differential miRNAs and biological functions such as antioxidant activity, metabolic process, biological regulation, cell killing, signal transduction, and enzyme regulatory activity. Differential miRNA target genes KEGG pathway analysis revealed that AMPK signaling pathway, PI3K Akt signaling pathway, Hippo signaling pathway, Wnt signaling pathway, cancer, autophagy, insulin resistance, Ras signaling pathway and other signaling pathways may play important regulatory roles in alcoholic liver injury lesions. The hub miRNAs and pathways screened by constructing the differential miRNA-mRNA-pathway regulatory network were mir-145-5p, mir-107-3p, mir-297, Hippo signaling pathway, cancer, PI3K Akt signaling pathway, AMPK signaling pathway, etc. The results of qRT-PCR showed that picking validation gene expression trend and gene chip results were consistent. Conclusion: In this study, we established a miRNA profile in alcoholic liver injury in rats, which suggests that mir-145-5p, mir-107-3p and mir-297 may play an important role in the process of liver alcoholic pathology.
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Osteopontin (OPN) activates the PI3K/AKT pathway via upregulating LGALS3BP in promotion of hepatoma cell migration
denglinlin, anriwen, zhaofangxin, linting, liucuihua, hongmei, wujianqiang, zhangxuan
Abstract:
Abstract: Objective To investigate the effect and mechanism of osteopontin (OPN) on hepatoma cell migration through galectin 3 binding protein (LGALS3BP). Methods Human hepatoma cell lines SMMC-7721, SMMC-P (stably transfected with empty eukaryotic expression vectors) and SMMC-OPN (stably transfected with OPN gene) were cultured. The mRNA expression levels of OPN and LGALS3BP were detected by qRT-PCR. Western blot assay was used to analyze the relative expressions of OPN and LGALS3BP. The protein expression level of PI3K/AKT pathway, including p-PI3K, PI3K, p-AKT and AKT were detected by western blot. Wound healing assay was performed to explore the cell migration ability. After transfection with LGALS3BP-targeting small interfering RNA (si-LGALS3BP) and negative control small RNA (si-NC) into SMMC-OPN cells respectively, cell migration ability and the relative expression of PI3K/AKT pathway related proteins were detected. Results Compared with SMMC-7721 and SMMC-P, the migration ability of SMMC-OPN cells was significantly reinforced, and the expression of LGALS3BP was obviously up-regulated at both mRNA and protein. Meanwhile, the relative expression quantity of p-PI3K/PI3K and p-AKT/AKT proteins were significantly increased. Wound healing assay showed that the si-LGALS3BP could obviously suppress the migration ability of SMMC-OPN cells. Furthermore, the relative expression of p-AKT/AKT and p-PI3K/PI3K proteins in SMMC-OPN cells were significantly decreased after transfection with si-LGALS3BP. Conclusion OPN could activate PI3K/AKT pathway through up-regulating LGALS3BP expression in promoting hepatoma cells migration.
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Establishment method and effect evaluation of two common pressure uler rat models
liuyi, lixiaolei, liangxinpei, wangna, mashan, zhangxinping, jiarufu, zhangsu, lixian
Abstract:
Objective : By comparing two different methods of establishing rat models of pressure uler, to explore a more suitable method for preparing animal models of pressure uler. Methods : 18 male SD rats were randomly divided into control group ( n = 6 ), model group A ( n = 6 ) and model group B ( n = 6 ). Control group : iodophor treatment was performed after hair removal at the simulated modeling site. Model A group : longitudinal compression was performed by simple deep tissue foreign body implantation ; model group B : transverse compression was performed by magnet compression method. The whole process time and each stage time of pressure uler model in each group were recorded. The general condition of rats was observed, and the molding rate, mortality rate and infection rate were compared. Results : The naked eye observed that the model A group and the model B group gradually appeared redness and swelling, ulceration, bleeding, exudation and necrosis. Comparison of the whole time of pressure uler in model group A and model group B : the difference between the two groups was statistically significant ( P0.05 ) ; the difference between the two groups was statistically significant ( P < 0.05 ). The difference between the two groups was statistically significant ( P < 0.05 ). There was significant difference between the two groups in stage IV ( P < 0.05 ). The mental and motor scores of the rats in the control group were significantly different from those in the model group A and the model group B ( P < 0.05 ). The general state of rats in model group A and model group B was significantly different, and the coat color was dim and the activity decreased. The model rate of rats in model A and model B was 100 %. The mortality and infection rate of model A group were higher than those of model B group, which were 33.34 % and 16.70 % respectively. Conclusion : Both methods can successfully prepare a four-stage model of pressure uler. The two methods have both commonalities and their own characteristics. The magnet compression method takes a short time, the rats are generally in good condition, and the mortality and infection rate are low. It is suitable for short-term intervention research ; the simple deep tissue foreign body implantation method takes a long time, requires rats to have a certain tolerance, has a high infection rate and a high mortality rate, and can be used in long-term observation of pressure uler rats.
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Research progress in the regulation of glutamate in traditional Chinese medicine in the treatment of depression
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Glutamate is a major excitatory neurotransmitter in the central nervous system and a potential neurotoxin. During the development of depression, there is an increase in glutamate concentration in the hippocampus, and when glutamate accumulates, it will cause serious damage to neurons and brain tissue, aggravating the depressive state. Therefore, glutamate accumulation may be an important mechanism for depression. Astrocytes, glutamate transporters and glutamate receptors play important regulatory roles in the concentration of glutamate. This article reviews the mechanism of action of traditional Chinese medicine therapy on the treatment of depression by regulating astrocytes, glutamate transporters, and glutamate receptors, and provides new ideas for exploring the treatment of depression by traditional Chinese medicine.
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To explore cognitive differences among dogs with different sociability
song meng yu, guo yi jun, zhao xue rong, bai jing, zhou zi juan, wang jing yu
Abstract:
Objective:Exploring whether there are differences in the cognitive abilities of socially different Labradors. Methods:The Dog Mentality Assessment (DMA) test created by the Swedish Working Dog Association was modified to use 12 behavioral variables from five subtests of the DMA test: Social contact, Play I, Distance-play, Ghosts and Play II to assess the sociability of the dogs. According to the scoring criteria,49 Labradors provided by The China Guide Dog Training Centre In Da Lian was scored on the social behavioral variables, which were classified into high (n=15) and low (n=34) sociability groups using cluster analysis. A new system for testing canine cognitive ability was developed based on Bray et al.'s Dog Cognitive Development Battery (DCDB), which tests different domains of cognitive ability such as social cue use, unsolvable task, inhibitory control, cognitive flexibility, working memory and multi-step problem solving task, and the dogs' behavioral performance and duration of the test were recorded. Statistical analysis was performed to determine whether there were differences in the cognitive abilities of socially diverse dogs. Results:Dogs in the high and low social subgroups differed significantly on behavioral variables in the unsolvable task, the inhibitory control test and the multi-step problem solving task. In the unsolvable task, dogs in the high social grouping average looked at people time for significantly longer than dogs in the low social grouping (P=0.008) and average looked at people for significantly less latency time than dogs in the low social grouping (P=0.0001). In the inhibitory control, dogs in the high social group chose correctly significantly more than dogs in the low social group (P=0.034) and chose for significantly less time than dogs in the low social group (P=0.039). In the multi-step problem solving task, dogs in the high social group successful completion number of stakes significantly higher than dogs in the low social group (P=0.044); the percentage of operation pale time was significantly lower than dogs in the low social group (P=0.05); the average latency time to solve bone task was significantly higher than dogs in the low social group (P=0.037); and the percentage of operation bone time was significantly lower than dogs in the low social group ( P=0.038). On tests involving manipulable apparatus, dogs in the high social group spent more time looking at people than dogs in the low social group and less time manipulating the apparatus than dogs in the low subgroup, but there were no statistically significant differences (P>0.05). Conclusions:High sociability labradors showed greater cognitive ability,they were more able to suppress impulses during the test, were more able to complete multi-step problem solving task and were more inclined to change strategies to seek new cues from people rather than obsessing over manipulating the apparatus when they were unable to solve a problem.
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Construction of a prognostic risk marker of colon adenocarcinoma based on weighted gene co-expression network and its clinical significance
Abstract:
Objective Due to the poor prognosis of colon adenocarcinoma (COAD) patients, it is necessary to screen prognosis-related genes in COAD and establish a new prognostic risk assessment model. Methods COAD-related data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were used as the training set and the validation set, respectively. Weighted gene co-expression network analysis (WGCNA)， Cox regression model and Least Absolute Selection and Shrinkage Operator (LASSO) regression analysis were used to screen prognosis-related genes of COAD and construct a prognostic model. Receiver Operating Characteristic (ROC) curve was combined with survival curve to verify the accuracy of the model, and a nomogram was established. The patients were divided into two groups according to the median value of risk score. The immune cell proportion score (IPS) was used to evaluate the immunotherapy response of the two groups. Results A total of 15 feature genes were screened. The area under the ROC curve (AUC) in the predictive model of COAD patients was >0.6, and the survival rate of high-risk group was significantly lower than that of low-risk group (P<0.05, suggesting good distinguishing ability for high- and low-risk COAD patients. Patients in the low-risk group had a higher IPS (P=0.026), indicating a better response to immunotherapy. Conclusions The model developed for COAD in this study has a good ability to predict the survival of people at high and low risk of COAD.
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Quality Evaluation for Animal Studies on Acupuncture for Glaucoma
lijiaxian, lianglina, 李亚敏, xukai, huangziyang, lixiaoyu, jinyu, zhouwei
Abstract:
Objective To evaluate the quality of animal studies on acupuncture for glaucoma by the SYRCLE’s risk of bias tool, ARRIVE 2.0 guidelines and GSPC checklist. Methods Databases of CNKI, VIP, Wanfang, Sinomed, PubMed, Web of Science, Embase, and Cochrane Library were conducted to find animal research articles on acupuncture for glaucoma. Risk of bias was assessed for included studies using the SYRCLE’s tool, and the reporting quality was evaluated using the ARRIVE 2.0 guidelines and GSPC checklist, statistical analysis was performed by Excel and SPSS software. Results Thirty articles met the inclusion/exclusion criteria and were included in the final analysis. 6 of the 10 items of the SYRCLE’s tool had a low-risk rate of <50%, and the non-low-risk items focused on selectivity bias, implementation bias, and measurement bias. 12 of the 22 essential sub-items of the ARRIVE 2.0 guidelines had a low-risk rate of <50%; 9 of the 16 recommended sub-items had a low-risk rate of <50%; 12 of the 19 subentries of the GSPC list had a low-risk rate of <50%, and randomization, blinding, thical statement, housing and husbandry, animal care and monitoring, protocol registration were non-low-risk items in the ARRIVE 2.0 guidelines and GSPC list. Conclusion The quality of methodology and experimental reportings in animal studies on acupuncture for glaucoma are generally low, and the descriptions of several items are not yet complete, which affects the readers' judgment on whether the animal studies can be further translated into clinical studies. It is advised to further promote the SYRCLE’s tool and reporting guidelines for animal experiments, to enhance the design, performance, and reporting of animal experiments, ensure the reproducibility of experiments and results, and provide reliable evidence for the translation of results to the clinic.
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miR-181a-5p overexpression in the small intestine in a mouse model of subcutaneous transplantation of oral cancer
Abstract:
[Abstarct] Objective By detecting changes in metabolites and metabolic pathways in the small intestine of mice with subcutaneous transplantation of oral cancer, the effects of overexpression of miR-181a-5p on metabolites and metabolites in the small intestine of mice with subcutaneous transplantation of oral cancer were analyzed. Methodes Three groups existed in the experiment: the Control group, the Negative control group, and the Over expression of miR-181a-5p group in the experimental group. To construct a subcutaneous transplantation tumor mouse model of oral cancer, different groups of treated cell suspensions were subcutaneously injected into the right point and upper location of the groin of M-NSG severely immunodeficient female mice. The pathogenic changes in each group were identified while additionally following the changes in the mice's body weight and small intestinal tissues using HE staining. By using tandem Orbitrap mass spectrometry and ultra-high performance liquid chromatography-tandem time-of-flight mass spectrometry, the metabolites in the small intestine of mice in the NC group, OE group, and Control group have been detected. By pre-analyzing the original data and quality rating sample data, XCMS was able to assess which metabolites were different between the Control group and NC group and between NC group and OE group. To establish the unique metabolic pathways, KEGG enrichment analysis was used. Results A total of 170 distinct metabolites were found in the small intestinal tissues of the Control and NC groups. Choline metabolism, alanine, aspartate, and glutamate metabolism, GABA synaptic metabolism, glycerophospholipid metabolism, cAMP signaling route, cancer center carbon metabolism, and niacin and niacin amine metabolic pathways are important signaling pathways for metabolite enrichment. In the NC group, 16 distinct metabolites with VIP values larger than 2 were found in the small intestine of mice compared to the OE group that overexpressed miR-181a-5p. Glycerin phosphoylcholine, palmitic acid, 3-hydroxybutyryl carnitine, -hydroxybutyric acid, etc. are example of the metabolites which significantly vary. The primary raised metabolism path is the one for choline. Conclusions Mice's small intestine suffered slight changes as a result of subcutaneous transplantation of oral cancer, with the greatest effect in the metabolites critical in energy metabolism. The choline metabolic path was the pathway that selected absolutely metabolites in the small intestine of mice with the subcutaneous grafts of oral cancer.
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The effect of cobalt dichloride regulating inflammatory response and insulin resistance in 3T3-L1 adipocytes based on HIF-1α/ autophagy pathway
yuexinxin, Fu Yang, Li Yi Rang, Yin xiao yan, Yu Fei, Fu quan wei
Abstract:
Objective: To investigate the effect of hypoxia inducer cobalt chloride (CoCl2) on autophagy in 3T3-L1 adipocytes. Methods: 3T3-L1 adipocytes were cultured and induced to become mature adipocytes. CoCl2 was used as an inducer of hypoxia in vitro. Mature adipocytes were divided into control group, CoCl2 intervention group with different concentrations and different time. According to the above results, 150μmol/L cobalt chloride was selected to intervene adipocytes for 0h,12h,24h and 48h, respectively. Then the cells were collected for related tests. MTT assay was used to detect cell survival in each group. The expressions of HIF-1α, autophagy-related protein LC3Ⅱ, Beclin 1 and glucose transporter Glut-1 were analyzed by Western blot. The level of autophagy activity was detected by immunofluorescence.The levels of TNF-α and IL-6 in the supernatants of adipocytes were measured by ELISA. Results: The survival rate of adipocytes was decreased after treatment with 150μmol/L CoCl2 for 24 hours. The expression levels of HIF-1α, LC3-Ⅱ, Beclin 1 and Glut-1 proteins were significantly increased in 24h. Autophagy activity level was significantly increased in 24h. The secretion levels of inflammatory cytokines TNF-α and IL-6 were not significantly increased in 24h. Conclusion: Autophagy can be moderately activated by 150μmol/L CoCl2 intervention in adipocytes for 24 hours. The activation of autophagy can be activated in a HIF-1α-dependent manner, which plays a role in protecting adipocytes from inflammatory damage and improving insulin resistance.
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Progress in microglia-astrocyte interactions and their mediated neuroinflammation in Alzheimer's disease
HU Xin, WANG Qian, ZHANG Chen-xi, ZHENG Hui-hui, LI Peng-yang, ZHAO Hong-ye, DENG Feng-chun
Abstract:
Alzheimer's disease (AD) is an aggressive neurodegenerative disease whose pathogenesis is hitherto unknown. Neuroinflammation is a chronic inflammatory response in the central nervous system (CNS) activated by microglia and astrocytes that is difficult to subside autonomously and is associated with multiple inflammatory factors and the blood-brain barrier (BBB). Recent studies have shown that neuroinflammation has become the third major pathological feature in AD after β-amyloid (Aβ) deposition and neurogenic fiber tangles (NFTs). In this paper, we summarize and analyze microglia and astrocytes and their interaction, and organize and discuss the role of microglia-astrocyte interaction in neuroinflammation and AD. In order to provide a reference for the involvement of microglia and astrocytes in the pathological alterations of neuroinflammation in AD.
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Research progress of miRNA in neuroprotection of ischemic stroke
Abstract:
Ischemic stroke is a cerebrovascular disease with high disability and mortality, and can be life-threatening in severe cases, which has a heavy social and economic burden worldwide. The etiology and pathological process of ischemic stroke are mediated by a variety of molecular processes, and some of these molecular mechanisms are dynamically regulated after transcription. Increasing evidence has shown that Micro-ribonucleic-acid (miRNA), as an important mediator of post-transcriptional gene silencing, plays a crucial role in gene expression and the pathological process of ischemic stroke. In this review, we present the neuroprotective effects of mirnas in different mechanisms of ischemic stroke. Since the promotion or inhibition of miRNA expression through specific drug and non-drug therapy may be beneficial to the recovery of ischemic stroke, the clinical diagnosis and treatment of miRNA in ischemic stroke are also discussed in detail in this paper, aiming to provide a certain reference for clinical and basic research in this field.
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Research progress on the effect of miRNAs on liver metastasis of digestive system tumors
Abstract:
Liver is the most common organ that tumors spread to, and expression of miRNA is very important in the process of liver metastasis. In this study, research progress of related miRNAs in regulating liver metastases from digestive system malignant tumors was collated and analyzed. Through searching related literature, this paper provides an introduction to the role of miRNAs in liver metastasis of colorectal cancer, gastric cancer, pancreatic cancer and gallbladder cancer, which helps with the diagnosis, treatment and research of tumor liver metastasis.
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Establishment of chronic alcoholic brain injury model in mice
Abstract:
【Abstract】 Objective To establish an effective and reliable chronic alcoholic brain injury model in mice. Methods C57BL/6J mice were randomly assigned into the control group and the model group. Mice in the model group were given free access to 5% (v/v) alcohol in drinking water, and were intragastrically administered with 28% (v/v) alcohol. The gavage dosage increased gradually over the first two weeks (from 0 to 6 g/kg body weight), and remained at 6 g/kg body weight for the subsequent four weeks. Mice in the control group were provided with normal water and given same amount of saline via gavage. At the end of the experiment, the cognitive function and motor ability of mice were evaluated through behavioral tests. The morphological changes of brain tissue of mice were examined by histopathological staining. Results Compared to the control group, mice in the model group showed cognitive impairments and motor dysfunction in the behavioral tests. The pathological examination of the brain tissue from the model group mice showed morphological damage and cell necrosis in the hippocampus. Conclusions The mouse model of chronic alcoholic brain injury was successfully and effectively established in this study, providing a valuable tool for investigating the underlying mechanisms and potential therapeutic interventions for chronic alcoholic encephalopathy.
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Molecular mechanism and prognosis of patients with HBV infection with DLBCL
Abstract:
In recent years, hepatitis B virus (HBV) infection patients with diffuse large B cell lymphoma (DLBCL) have shown an upward trend, and its etiology is complex and treatment is difficult, so it has received extensive attention from scholars at home and abroad. Based on the review and analysis of the research of domestic and foreign scholars, this paper further discusses the mechanism of the occurrence and development of DLBCL caused by HBV infection and the clinical prognosis of related patients, and finally finds that at the genomic and transcriptome levels, HBV may mainly induce the changes of BCL6, FOXO1, ZFP36L1 and other genes, and activate various regulatory genes through HBV's X protein, thereby inducing clonal proliferation of lymphocytes and eventually forming lymphoma. For the clinical prognosis assessment, the clinical prognosis assessment mainly analyzes and compares the patient's age of onset, sex, organ involvement, international prognostic index (IPI), lactate dehydrogenase (LDH) level, proliferation index (Ki-67), bcl-2, bcl-6, inflammatory index and other factors, aiming to put forward a theoretical basis for the clinical diagnosis and treatment of DLBCL and basic research.
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Study on the mechanism of lncRNA SNHG16 regulating the resistance of hepatoma cells to sorafenib by miR-570
Abstract:
Objective: To explore the mechanism of long non-coding RNA SNHG16 (Long non-coding RNA small nucleolar RNA host gene16, lncRNA SNHG16) to anti-liver cancer cell resistance by regulating minimal RNA-570 (miR-570). Methods: The expression of lncRNA SNHG16 and miR-570 of HepG 2 and HepG 2-R cells in human normal liver and hepatoma cells was measured by real-time fluorescence RT-PCR, cell proliferation, apoptosis and invasion were measured by MTT assay, FACS and Transwell test, and cell expression changes of CyclinD1, P21MMP-9 and MMP-2 were determined by Western Blot assay. Results: Compared with normal hepatocytes, lncRNA SNHG16 expression was increased and miR-570 expression was decreased in hepatoma cells (P<0.05). Compared with HepG2-P group, LncRNA SNHG16 and IC50 values were increased in HepG2-R group, and the inhibition rates of miR-570 and HepG2-R cells were decreased at Sorafenib concentrations of 1, 2, 4, 8, 16μmol/L (P<0.05). HepG2-R pcDNA SNHG16 as overexpression group, lncRNA SNHG16 expression was significantly increased (P<0.05), and compared with HepG2-R pcDNA group, In HepG2-R pcDNA SNHG16 group, the number of migrated cells, the expressions of CyclinD1, P21, MMP-9 and MMP-2 were decreased, while the expression of inhibition rate, apoptosis rate and P21 were increased (P<0.05). Compared with HepG2-R anti-miR-NC group, miR-570 level in HepG2-R anti-miR-570 group was decreased (P<0.05), and compared with HepG2-R anti-miR-NC group, HepG2-R anti-miR-570 group decreased the levels of CyclinD1, MMP-9 and MMP-2, and increased the levels of inhibition rate, apoptosis rate and P21 (P<0.05). Dual luciferase reporting experiment showed that compared with miR-NC group, miR-570 reduced the luciferase activity of WT-SNHG16 (P<0.05), but had little effect on the luciferase activity of T-SnHG16 (P>0.05). Overexpression of lncRNA SNHG16 decreased the expression of miR-570 in HepG2-R cells (P<0.05). Compared with HepG2-R pcDNA SNHG16 miR-NC group, In HepG2-R pcDNA SNHG16 miR-570 group, the number of migrated cells, the levels of CyclinD1, MMP-9 and MMP-2 were increased, while the levels of inhibition rate, apoptosis rate and P21 were decreased (P<0.05). Conclusion: By regulating the drug resistance of HepG2-R hepatoma cells, the mechanism is related to the regulation of miR-570 by lncRNA SNHG16, and it can be used as a new target for drug-resistant HCC cell therapy.
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Study on the Mechanism of Hyperuricemia combined with Nonalcoholic Fatty Liver based on PI3K/Akt/NF-kB
Abstract:
Abstract: Objective: To study the pathogenesis of hyperuricemia combined with nonalcoholic fatty liver disease (HUA-NAFLD) based on PI3K/Akt/NF-kB signaling pathway. Methods: 64 SD rats were randomly divided into blank group, HUA group, NAFLD group, and HUA-NAFLD group, 16 rats in each group. The samples were collected at the end of the 8th and 12th week, respectively. The serum biochemical indexes of the rats were detected; The pathological changes and lipid deposition in liver tissue were observed by hematoxylin-eosin staining (HE) and Oil Red O staining; the expression levels of PI3K/Akt/NF-kB signaling pathway-related proteins in liver tissue were detected by Western blot. Results: Compared with the other three groups, the liver index of the rats in the HUA-NAFLD group was significantly increased (P<0.05). Compared with the blank group, the levels of UA and LDL in the HUA group were increased, the levels of HDL in the NAFLD group were decreased, the levels of UA, CHOL, TG and LDL in the HUA-NAFLD group were increased, and the levels of HDL were decreased (P＜0.05); Compared with the HUA-NAFLD group, the levels of CHOL, TG and LDL were decreased in the HUA group, and the levels of UA, TG and LDL in the NAFLD group were decreased (P＜0.05). The results of HE and oil red O staining showed that compared with the other three groups, rat liver cells in the HUA-NAFLD group had a large number of fat vacuoles, blurred liver cord structure and more severe lesions. The WB results showed that compared with the blank group, the phosphorylation levels of AKT and p65 in the NAFLD group were significantly increased, and the phosphorylation levels of AKT, PI3K, p65 and IKKβ in the HUA-NAFLD group were significantly increased, and compared with the HUA-NAFLD group, the phosphorylation levels of AKT and p65 in the HUA-NAFLD group decreased significantly(P<0.05). The phosphorylation level of IKKβ decreased significantly in the HUA group, and compared with the HUA group, the phosphorylation level of p65 in the NAFLD group increased significantly (P<0.05). Conclusion: Compared with the single disease group, the HUA-NAFLD group has more abnormal biochemical indexes and more severe liver lesions. The PI3K/Akt/NF-KB signaling pathway may play an important role in the pathogenesis of HUA, NAFLD and HUA-NAFLD.
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Study on Allicin improves human peritoneal mesenchymal cell-mesenchymal transformation induced by high glucose through the JAK2/STAT3 signaling pathway
Gan Linwang, Li Qiancheng, Gao Lichao, Liu Qi, Li Ying, Wang Yujie, Ou Santao
Abstract:
Objective To investigate the mechanism of allicin in improving human peritoneal mesenchymal cell-mesenchymal transformation induced by high glucose. Methods human peritoneal mesothelial cells (HPMCs) were cultured and divided into two groups. Group 1: ①Control group; ②8.5 mM D-glucose induced group (8.5 mM DG group); ③17 mM D-glucose induced group (17 mM DG group); ④34 mM D-glucose induced group (34 mM DG group); ⑤68 mM D-glucose induced group (68 mM DG group). Except the control group, the other groups were induced with D-glucose of 8.5 mM, 17 mM, 34 mM and 68 mM, respectively, for 48 h. Group 2: ① control group; ②34 mM D-glucose induced group (HG group); ③34 mM D-glucose + low dose allicin induction group (AL-L group); ④34 mM D-glucose + medium dose allicin induction group (AL-M group); ⑤34 mm-glucose + high-dose allicin induction group (AL-H group); ⑥34 mM D-glucose + JAK2 inhibitor induction group (JAK2 group). HG group was induced with 34 mM D-glucose for 48 h, AL-L group, AL-M group and AL-H group were pretreated with 34 mM D-glucose for 6h, and then induced with 10 ng/mL, 20 ng/mL and 40 ng/mL allicin for 48 h, respectively. JAK2 group was pretreated with 1 μmol/L AG490 for 6 h and induced with 34 mM D-glucose for 48 h. The contents of IL-6, TNF-α and IL-1β in HPMCs supernatant were determined by Elisa. CCK-8 was used to detect cell proliferation and morphology. The expressions of JAK2, p-JAK2, STAT3, p-STAT3, N-cadherin, E-cadherin, Vimentin, α-SMA, MCP-1, p65 and p-p65 proteins were detected by Western blot. Results Compared with the control group, the relative survival rate of HPMCs in the high glucose induced group was significantly reduced (P<0.01), and cell morphology was abnormal, the expressions of α-SMA, N-cadherin and Vimentin that promote epithele-mesenchymal transdifferentiation were significantly up-regulated, and the expression of E-cadherin, which inhibits EMT, was significantly down-regulated. JAK2/STAT3 signaling pathway was activated, leading to the occurrence of EMT (P<0.01). Allicin can significantly promote the proliferation of HPMCs induced by high glucose, restore abnormal cell morphology, regulate the level of EMT-related proteins, and improve the epithelial-mesenchymal transdifferentiation of HPMCs. Compared with the high glucose induction group, the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α of HPMCs in allicin treatment group were significantly decreased, and the expressions of pro-inflammatory proteins p-p50 and MCP1 were significantly down-regulated, indicating that allicin could improve the inflammation caused by EMT. Conclution Allicin can improve EMT and inflammation induced by high glucose by inhibiting JAK2/STAT3 signaling pathway to regulate the levels of markers of EMT, inflammatory signaling proteins and inflammatory factors.
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Influence of hyperoside on autophagy in rats with nephrotic syndrome by regulating AMPK/mTOR/ULK1 signaling pathway
kongloujiao, wangxin, liujing, guoxiaoyang, xuemingwei
Abstract:
Objective To investigate the influences of hypericin (Hyp) on renal autophagy and AMPK/mTOR/ULK1 pathway in nephrotic syndrome (NS) rats. Methods Thirty-two 6-week-old SD rats were grouped into normal group (N group), NS group, Hyp group (60 mg/kg Hyp), Hyp AMPK inhibitor group (Hyp CC group) (60 mg/kg Hyp group) 0.2 mg/kg CC), 8 per group. After administration, an automatic analyzer was applied to detect the levels of 24-h urine total protein (UTP), blood urea nitrogen (BUN), serum creatinine (Scr) and albumin (ALB); HE staining and TEM observation were applied to observe renal pathological morphology and ultrastructure; Western blot was applied to detect the expression of autophagy, podocyte and AMPK/mTOR/ULK1 pathway proteins in kidney; immunofluorescence staining was applied to visualize the localization of autophagosomes and podocytes. Results Compared with the N group, the glomerular volume of the NS group increased, the renal tubules atrophied or partially disappeared, and the basement membrane thickened; UTP, BUN, Scr, basement membrane thickness, foot process width and the ratio of p-AMPK/AMPK were obviously increased (P<0.05), the protein levels of ALB, LC3-II/I, Beclin-1, Atg5, Atg7, NPHS2, the relative fluorescence intensity of NPHS2 and Beclin-1, and the ratios of p-AMPK/AMPK and p-ULK1/ULK1 were obviously decreased (P<0.05). Compared with NS group, Hyp treatment was able to improve glomerular morphology, decrease UTP, BUN, Scr, basement membrane thickness, foot process width and ratio of p-AMPK/AMPK (P<0.05), increase protein levels of ALB, LC3-II/I, Beclin-1, Atg5, Atg7, NPHS2, the relative fluorescence intensity of NPHS2 and Beclin-1 and the ratios of p-AMPK/AMPK and p-ULK1/ULK1 (P<0.05). AMPK inhibitor group CC could attenuate the autophagy-promoting and kidney-protecting effects of Hyp. Conclusion Hyp may enhance the autophagy activity of renal cells and attenuate renal pathology such as podocyte injury in NS rats by activating the AMPK/mTOR/ULK1 pathway.
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Study of core symptom impact on baicalein in an animal model of attention deficit hyperactivity disorder SHR rat
zhang yongting, Zhou Rongyi, Ma Bingxiang, Wu Chenlei, Xie Xinyue, Ding Xueying
Abstract:
Objective To explore the efficacy and potential mechanism of baicalin in regulating the core clinical symptoms of ADHD through the Morris water maze test and The open field test. Methods Thirty SHR rats were randomly divided into model group, methylphenidate hydrochloride(MPH) group, baicalin group, baicalin + tetrabenazine group and MPH + tetrabenazine group, with 6 rats in each group. Another 6 WKY rats were used as normal control group. The rats in the MPH group (1.5 mg/kg) and the baicalin group(150 mg/kg) were given the corresponding drugs (1 mL/100 g) by gavage, and those in the normal control group and the model group were given an equal volume of normal saline by gavage . In addition to the corresponding drug gavage,the rats in the MPH+tetrabenazine group and the baicalin+tetrabenazine group were given intraperitoneal injection of tetrabenazine(3 mg/kg) according to body weight (0.5 ml/100 g).The course of treatment was 4 weeks for all groups. Open field and Morris water maze experiments were carried out at the specified time, and the experimental results were recorded and analyzed Results In the open field experiment, the total distance and average speed in the MPH group and baicalin group were significantly lower than those in the model group (P < 0.05), and there was no significant difference between the two groups (P > 0.05);In the open field experiment, the total distance and average speed in the baicalin + bubenazine group were significantly lower than those in the model group (P < 0.05), and obviously higher than those in the baicalin group. In the water maze test, the latency of baicalin + bubenazine group was significantly shorter than that in the model group (P < 0.05), and significantly longer than that in the baicalin group (P < 0.05). The percentage of movement distance and stay time in the target quadrant in the baicalin + bubenazine group were obviously higher than those in the model group. It was significantly lower than that in baicalin group (P < 0.05).Conclusion Baicalin can control the core symptoms of hyperactivity, impulse and inattention in SHR rats, and its curative effect may be related to the regulation of dopamine vesicle transport.
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Study on the mechanism of ethyl acetate extract of Liujunzi Decoction on the energy metabolism of EC9706 cells in CAFs conditioned medium
Chen Xing, Lou Xiangyu, Shang Yiwan, Zhou Zhexu, Liu Yang, Liu Yaru, Hu Xiaobo, Chen Yulong
Abstract:
Objective: To explore the molecular mechanism of ethyl acetate extract of Liujunzi Decoction(EAELD) on energy metabolism of esophageal cancer EC9706 cells in conditioned medium of cancer-associated fibroblasts (CAFs). Methods: Methyl thiazol tetrazolium (MTT) assay was used to detect the effect of EAELD on the proliferation activity of EC9706. The effects of EAELD on lactate and glucose in the supernatant of EC9706 cells in CAFs conditioned medium were detected by colorimetry. seahorse system energy metabolism analysis system was used to detect the effect of EAELD on energy metabolism of EC9706 cells in CAFs conditioned medium. Real-time fluorescent quantitative PCR (q-PCR) and western blotting were used to detect the mRNA and protein expression of energy metabolism-related molecules.. Results: Compared with DMEM, except for the 10μg/mL group,EAELD had a significant inhibitory effect on the proliferation of EC9706 cells (P < 0.05). The inhibitory concentration (IC30) of 25μg/mL and half inhibitory concentration (IC50) of 40μg/mL were selected as the low and high dose groups for subsequent experiments. Among EC9706 cells cultured by CAFM, both low-dose and high-dose EAELD groups could significantly reduce Non-mitochondrial oxygen consumption, Basal respiration value, Maximum respiration value, Oxygen consumption of ATP synthesis, Spare respiration capacity, Basal glycolysis, Compensative glycolysis and glycolysis potential (P <0.01). Decreased the lactate content of EC9706 cells (P <0.01), down-regulated the mRNA expression of GLUT1 (P <0.05, P <0.01), down-regulated the protein expression of p-PKM2, HK2, PKM2 and MCT1 (P <0.01); The high-dose EAELD group could down-regulate the Mitochondrial oxygen consumption and basal use The glycolytic ratio of EC9706 cells (P <0.05), reduce glucose uptake of EC9706 cells (P <0.05), down-regulate the protein expression of p-PKM2 and GLUT1 (P <0.01, P <0.05); The low dose group of EAELD could down-regulate the mRNA expression of MCT1 (P <0.05). Conclusions:EAELD can interfere with the energy metabolism of EC9706 cells in CAFs conditioned medium, and its mechanism may be related to the regulation of HK2, PKM2, GLUT1, MCT1 and MCT4 mRNA and protein expression.
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Application characteristics of animal model of osteosarcoma based on data mining
yushuaike, luomaoli, wanglianrui, zhoutianbao, baili, miaomingsan
Abstract:
Objective To summarize the key points of animal modeling of osteosarcoma, and to provide reference and suggestions for improving the modeling methods and evaluation indexes.Methods The database was established by searching the relevant literature on the animal model of osteosarcoma in CNKI, Wanfang database and PubMed. The species of experimental animals, gender, modeling methods, types of cancer cell lines and detection indicators were summarized, and the database was established for statistical analysis. Results A total of 284 literatures were included. Statistical analysis found that BALB / c-nu / nu nude mice were preferred in osteosarcoma model animals(227 cases，75.17%), followed by SD rats (20 cases, 6.62%). Subcutaneous cell fluid transplantation in the back (66 cases, 21.85%), subcutaneous cell fluid transplantation in the axils (55 cases, 18.21%) or in situ cell fluid transplantation (51 cases, 16.89%) were used as modeling methods. Human MG-63 cells (100 cases, 33.11%) and mouse UMR-106 cells (39 cases, 12.91%) were selected as the cancer cell lines.The most detected indexes were tumor tissue apparent index (238 cases, 83.80%), tumor tissue HE staining (129 cases, 45.42%), Animal apparent indicator (94 cases, 33.10%)，tumor tissue immunohistochemistry (89 cases, 31.34%), etc. Conclusions At present, osteosarcoma BALB / c-nu / nu nude mice aged 4 to 6 weeks are used as experimental animals, and human MG-63 cell heterotopic transplantation (back and axillary transplantation) is used to establish the animal model, and the detection indexes of osteosarcoma are comprehensively evaluated by animal apparent index, tumor apparent index and tumor histopathology. It is suggested to select serum biochemical index, apparent index of tumor tissue as well, HE staining of tumor tissue and immunohistochemistry of tumor tissue to evaluate the model. However, there is still a lack of animal model preparation and evaluation criteria with high clinical consistency. In this paper, the advantages and disadvantages are summarized through literature mining and data analysis, in order to provide reference for the establishment of a good OS model and better application to OS mechanism research and new drug development.
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Effects of moderate intensity and high intensity intermittent exercise on myocardial mitochondria autophagy in mice with nonalcoholic fatty liver disease
he miao, li jia hang, liu xin, yang wei, wu liang wen, fan jing jing
Abstract:
Objective To investigate the effects of moderate aerobic exercise and high intensity intermittent exercise on myocardial mitochondria autophagy in mice with non-alcoholic fatty liver disease and its possible mechanism. Methods Forty 3-week-old male C57BL/6J mice were randomly divided into normal feeding group (Chow group, n=10) and high fat feeding group (HFD group, n=30). At week 18, those whose body weight in HFD group exceeded 20%~30% (including 20%) of the ordinary diet group were judged as obese mice (n=26). Two mice were randomly selected for liver oil red O staining to confirm the successful establishment of NAFLD mouse model. Sixteen NAFLD mice were randomly selected and divided into moderate intensity aerobic exercise group (MICT group) and high intensity intermittent aerobic exercise group (HIIT group), with 8 mice in each group. The two groups were given exercise training for 8 weeks, respectively, and the samples were weighed after intervention. Masson staining was used to observe myocardial fibrosis. The ultrastructure of myocardial cells was observed by transmission electron microscopy. Mitochondrial autophagy and mitochondrial biogenesis were detected by Western Blot. Results ⑴ Compared with Chow group, body weight and heart index in HFD group were significantly increased and decreased. Compared with HFD group, the body weight of MICT and HIIT group increased significantly, and the heart index of MICT group increased. (2) Masson results showed that compared with Chow group, the content of collagen fibers in myocardium in HFD group was significantly increased, and the myocardial fibers were disorganized and broken under electron microscope. The morphology of myocardium was disorganized, mitochondria were swollen, crists were broken and blurred, and lipid droplets were included. Compared with HFD group, the myocardial collagen fiber content in MICT and HIIT groups was significantly reduced, the myocardial fiber arrangement was slightly recovered under transmission electron microscopy, the Z-line was clearly visible, the degree of mitochondrial degeneration was slightly improved, and the lipid droplets were also slightly reduced. Among them, the improvement effect of MICT group on the cardiac tissue structure was better than that of HIIT group. (3) Western Blot results showed that compared with Chow group, the expression levels of PINK1 and Beclin1 in myocardial tissue of HFD group had no significant changes, while the expressions of Parkin, LAMP1 and PGC-1α were significantly decreased (p<0.01). p62 protein expression and LC3-II/LC3-I ratio were significantly increased (p<0.05, p<0.01); Compared with HFD group, the expression levels of PINK1 and Beclin1 in MICT and HIIT groups were not significantly changed, while the expression of PGC-1α was up-regulated, and the expressions of Parkin and LAMP1 in MICT group were significantly increased (p<0.05). p62 protein expression and LC3-II/LC3-I ratio were significantly decreased (p<0.05, p<0.01), Parkin and LAMP1 expression levels were up-regulated, LC3-II/LC3-I ratio and p62 protein expression were significantly decreased in HIIT group (p<0.05, p<0.01). Conclusion Different forms of aerobic exercise can effectively ameliorate myocardial structural and functional injury in NAFLD mice, which may be through stimulating the autophagy flux of mitochondria in cardiomyocytes, activating autophagy and restoring the normal autophagy function of cells, so as to ameliorate myocardial cell damage, and moderate continuous aerobic exercise has better improvement effect.
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Exploring the Management Innovation Mechanism of Emergency Science and Technology Research Projects in the Medical Field
CHEN Yujun, SU Meiyangyi, WANG Qingxuan, GAO Ran
Abstract:
Objective The emergency technology research project highlights the two key aspects of "emergency" and "research", which are how to effectively achieve the goal results.Organizations that undertake such projects need to develop reasonable project management mechanisms to ensure the successful implementation of emergency technology research projects.This article aims to investigate the current problems in the management of emergency technology research projects in the medical field through research, analyze possible improvement measures, and improve the efficiency and quality of scientific research management.Methods This article combines the author's practical experience, investigates the current status of scientific research management in relevant units, and conducts questionnaire surveys on the management aspects that are most concerned by scientific management and researchers.Based on the problems reflected in the survey, experts are organized to discuss and demonstrate.Results Through the research, it is found that: 1. At present, there are few management norms for emergency technology research projects;2. The most concerned issue for scientific researchers is administrative approval and project funding;3. The most concerned issue for scientific management personnel is how to meet the management requirements of higher-level units and the needs of scientific researchers under the premise of legal compliance.Conclusion Emergency technology research projects have their own unique characteristics compared to conventional technology projects. Management optimization can be carried out in terms of project approval, fund use, resource allocation, and safety. This study provides innovative solutions for the management of emergency technology research projects, and provides useful experience and reference for various scientific research units in managing such projects.
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Effects of compound active tea of Lithocarpus litseifolius on uric acid and renal function in mice with hyperuricemia nephropathy
陈, zengyanan, DUXIAOLANG, MUZEJING, liaochengdong, zhangchanghua, caolan
Abstract:
Abstract：Objective To explore the effect of compound active tea of Lithocarpus litseifolius on uric acid and kidney function on mice with hyperuricemia nephropathy , and to provide experimental basis for the development of hyperuricemia nephropathy drugs and functional food. Methods The mouse model of hyperuricemia nephropathy was established by potassium oxyoxide with adenine. Mice were randomly divided into normal group, model group, benbromarone positive drug group (10 mg?kg-1?d-1), and Compound active tea of Lithocarpus litseifolius high,middle, low-dose groups (10g?kg-1?d-1,3.33g?kg-1?d-1,1.11g?kg-1?d-1).1h after the last dose, urine protein (UP) was measured by CBB method,urea nitrogen (UUN) was measured by the urease method;Blood was collected for uric acid (UA) by enzyme ratio method and urea nitrogen (BUN) by urease method;the serum content of interleukin cells 6 (IL-6) and tumor necrosis factor(TNF-α) was measured byeuzymelinked immunosorbent assay;uate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) in mouse kidneys were measured by quantitative fluorescence analysis.Kidney tissues were harvested and histopathological changes were observed by HE staining.Results Compared with the normal group,the UP, UUN, UA, BUN, IL,URAT1 and ULUT9 of model group mice were significant increased (P<0.01),TNF-α was increased (P<0.05),the renal tissue structure was normal.Compared with the model group,the UP,UUN,UA,BUN of benbromarone positive drug group were significant decreased(P<0.01),IL-6 and TNF-α were decreased(P<0.05),URAT1 was increased(P<0.05),little glomerular atrophy and deformation in the kidney,kidney tubular dilatation was occasionally seen,and no inflammatory cell infiltration.Compared with the model group,the UP,UUN,UA,BUN,IL-6 and URAT1 of high-dose group of compound active tea of Lithocarpus litseifolius were significant decreased(P<0.01),TNF-α and GLUT9 levels were decreased(P <0.05);the UP, UA, UUN content , the levels of IL-6, URAT 1and GLUT9 of middle-dose group of compound active tea of Lithocarpus litseifolius were significant decreased(P<0.01),BUN together with reduced levels of TNF-α(P <0.05);the UP,UUN,UA,IL-6 and URAT1 of low-dose group of compound active tea of Lithocarpus litseifoliuswere significant decreased(P<0.01),BUN content and reduction of TNF-α and GLUT9 levels (P<0.05),the kidney condition of the mice in compound active tea of Lithocarpus litseifolius group was improved.Conclusion: the compound active tea of Lithocarpus litseifolius can reduce uric acid in mice with hyperuricemia nephropathy, and it has a certain protective effect on the kidney,the mechanism may be related to the inhibition of uric acid reabsorption, and the specific mechanism should be further investigated.
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HDAC6 inhibitors improve diabetic nephropathy by protecting glomerular endothelial cell mitochondria
Abstract:
objective: To investigate the protective effect and mechanism of histone deacetylase 6 (HDAC6) specific small molecule inhibitor Tubastatin A on renal injury in diabetic nephropathy (DN) mice. Methods: C57BL/6 mice were randomly divided into 3 groups: control group, DN group and Tubastatin A group. Mice in the DN group and Tubastatin A group were intraperitoneally injected with燬TZ?80爉g/kg) daily for 3 days after the removal of one kidney. Tubastatin A group received Tubastatin A treatment every 3 days for 8 weeks. RNA sequencing analysis of differentially expressed genes in kidney tissue of DN group and Tubastatin A group. Mitochondrial damage was assessed by transmission electron microscopy, and ROS levels in kidney tissue were estimated by DHE staining. Mouse glomerular endothelial cells (mGEC) were exposed to high glucose medium (HG) or 40 mM mannitol (control) with or without Tubastatin A treatment. Western blot analysis was used to analyze the expression of HDAC6, kidney injury markers KIM1 and EMT markers, and flow cytometry was used to detect mitochondrial ROS and apoptosis in cells. Results: HDAC6 expression was up-regulated in DN mouse kidney tissue and mGEC cells exposed to HG, consistent with increased levels of KIM1. Histological analysis showed significant morphological changes in DN mice, including glomerular hypertrophy, mesangial matrix accumulation, glomerular basement membrane thickening, tubular basement membrane thickening and the presence of glomerular, intertubular fibrosis; Tubastatin A treatment alleviated these changes. Compared with control DMSO, Tubastatin A significantly decreased the expression of KIM1, HDAC6, α-SMA, N-cadherin, vimentin (P<0.05) and up-regulated the expression of E-cadherin (P<0.05) in mGEC cells under HG treatment. RNA-sequencing revealed the enrichment of genes related to ECM-receptor interaction and tricarboxylic acid (TCA) cycle in the kidney tissue of Tubastatin A mice compared with DN mice. Transmission electron microscopy showed that the proportion of damaged mitochondria in glomerular endothelial cells in Tubastatin A group was significantly lower than that in DN group (P<0.01). DHE staining showed that the level of ROS in the kidney tissue of Tubastatin A group was lower than that of DN group (P<0.01). In mGEC cells, Tubastatin A treatment down-regulated HG-induced mitochondrial ROS levels in mGEC cells (P<0.01), and reduced apoptosis (P<0.05). Conclusion: Tubastatin A ameliorates HG-induced glomerular endothelial cell injury and DN progression, and its mechanism is related to the protection of mitochondrial homeostasis and inhibition of EMT.
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Effects of human amniotic epithelial cells transplantation on the improvement of endometrium and MMP-8, VEGF in rat model of uterine scar
Abstract:
Objective: To investigate the effect of human amniotic epithelial cells (hAECs) transplantation on endometrium improvement and matrix metalloproteinase-8 (MMP-8) and vascular endothelial growth factor (VEGF) in a rat model of uterine scar. Methods: The uterine scar model of rats was established and randomly divided into model group and transplantation group, with 18 rats in each group. The other 18 rats were selected as sham operation group. The rats in the transplantation group were injected with hAECs in the scar of the uterus, and the rats in the model group and the sham operation group were only given the same amount of PBS. After 4 weeks, the uterine tissues of 8 rats in each group were collected and HE staining was used to observe the histomorphological changes, and the endometrial thickness and the number of glands were measured. Masson staining was used to observe endometrial fibrosis. Endometrial growth and receptivity were evaluated by immunohistochemical staining for cytokeratin and integrin β3, respectively. The mRNA expression levels of MMP-8 and VEGFA in endometrial tissues were detected by RT-qPCR. Western blotting was used to detect the protein expression levels of MMP-8 and VEGFA. After 8 weeks, the remaining 10 rats in each group were selected for gestational ability determination. Results: Compared with the sham-operation group, the endometrial thickness, the number of glands, the IOD value of keratin and integrin β3, the mRNA and protein relative expression levels of MMP-8 and VEGFA, the pregnancy rate and the number of uterine embryos in the model group and the transplantation group were significantly decreased (P<0.05). Compared with the model group, the endometrial thickness, the number of glands, the IOD value of keratin and integrin β3, the mRNA and protein relative expression levels of MMP-8 and VEGFA, the pregnancy rate and the number of uterine embryos were significantly increased in the transplantation group (P<0.05). In addition, hAECs transplantation could improve the pathological morphology of endometrial tissue in rats with uterine scar. Reduce the degree of endometrial fibrosis. Conclusion: hAECs transplantation could improve endometrial injury, reduce scar formation, improve endometrial receptivity, and enhance pregnancy function in model rats, which may be related to the promotion of MMP-8 and VEGFA expression.
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Effect of inhibition of the mitochondrial inner membrane protein OMA1 on apoptosis in a Rot-induced Parkinson's disease cell model
shijin, Lihaining, Luyue, Xuting
Abstract:
Objective To investigate the effect of inhibition the mitochondrial inner membrane protein OMA1 on rotenone-induced apoptosis in Parkinson's disease (PD) cell model. Methods SH-SY5Y cells were cultured in vitro, treated with Rot (final concentrations of 0.05, 0.1, 0.2, 0.3, 0.4 μmol/L) for 24 h, and the best Rot (0.2 μmol/L) was selected for subsequent experiments. The experiment was divided into control group (cells without special treatment), PD model group (0.2 μmol/L Rot treated cells for 24 h), Negative control group (negative control sequence of OMA1 siRNA transfected on the basis of normal control group), OMA1 siRNA group (0.2 μmol/L Rot treated cells for 24 h and transfected with OMA1 siRNA). CCK-8 was used to detect cell survival rate, inverted phase contrast microscope was used to observe cell morphology in each group, Western blot was used to detect changes in the expression of OMA1 and apoptosis-related proteins Caspase-3, Bax, and Bcl-2, and TUNEL apoptosis kit was used to detect cell apoptosis. Results Compared with the control group, the survival rate of SH-SY5Y cells decreased in a concentration-dependent manner with increasing Rot concentration (P<0.05). Compared with the control group, the expression of OMA1 and apoptotic protein Caspase-3 expression were increased and Bax/Bcl-2 values were increased in the PD model group (P<0.01). Compared with the PD model group, the cells in the OMA1 siRNA group, the OMA1 siRNA group gradually restored morphological changes, decreased apoptotic protein Caspase-3 expression and Bax/Bcl-2 values, and TUNEL apoptosis staining suggested reduced apoptosis (P<0.01). Conclusions Inhibition of the mitochondrial inner membrane protein OMA1 ameliorates apoptosis induced by the Rot-induced PD cell model, which in turn may have a protective effect on neurons.
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The effect of CeO2NPs on organ structures and redox indicators in male mice
Abstract:
Objective To investigate the effects of CeO2NPs sub-acute exposure on body weight, organ structures and redox indicators in male mice. Methods 35 male ICR mice were randomly divided into five groups with seven mice in each group. Normal control group and CeO2NPs (100, 500, 1000, 5000 ug/kg) test groups were set up. Mice were injected CeO2NPs intraperitoneally every other day for 28 days. Results Compared with the control group, there was no significant difference in weight gain (P>0.05) , but there was significant difference in liver coefficient, epididymal coefficient and sperm survival rate (P<0.01). In the 5000 ug/kg group, CeO2NPs were deposited in the liver and spleen, and granuloma was found. The activities of SOD and GSH-Px in serum of 100 ug/kg group were increased, while the content of MDA was decreased, which showed the antioxidant effect of CeO2NPs. With the increase of dose, the oxidative stress induced by CeO2NPs was enhanced. Conclusion The low dose of CeO2NPs is safe and has antioxidant effect. With the increase of dose, the toxicity of CeO2NPs to the body also increases gradually.
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Research progress on gut microbiota and obesity-related metabolic diseases
Su Hei Yan Pa Er Ha Ti, ZHANG Jiaojiao, MA Zhuang, WANG Junren, LI Yanhong
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Obesity centered metabolic diseases such as diabetes, hypertension, and cancer are increasing at an alarming rate worldwide and have become global public health concerns. The treatment of obesity and related metabolic diseases has gradually become a research hotspot. Currently, an increasing number of studies have proved that gut microbiota can regulate energy balance and glycolipid metabolism, and regulate the occurrence and development of obesity and related metabolic diseases. It is very likely that the gut microbiota is a potential new target for the treatment and prevention of metabolic diseases. In this paper, we summarize the progress of gut microbiota in the development and progression of obesity associated metabolic diseases and analyze the role of gut microbiota in metabolic diseases.
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Research progress of exosomal microRNA in early screening and treatment of Alzheimer's disease
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Exosomes, as small molecule extracellular vesicles secreted by a variety of cells, play an important role in the pathological process of Alzheimer's disease by transporting a variety of bioactive substances such as microRNA. Studies have shown that the expression of exosomal microRNA changes in the early stages of AD patients, and exogenous injection of mesenchymal stem cell-derived exosomal microRNA can improve the learning and memory ability of AD animal models. This paper reviews the research progross of exosomes in early screening and treatment of Alzheimer's disease.
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Research progress of disease-syndrome combination models of chronic obstructive pulmonary disease
Abstract:
Chronic obstructive pulmonary disease (COPD) is a common respiratory disease with high morbidity and mortality, which has become an important health problem in today's society. Traditionray Chinese Medicine has accumulated rich historical experience in the treatment of COPD and has unique clinical advantages. In order to further explore the therapeutic effect of traditional Chinese medicine on this disease, the preparation of COPD animal model combining disease and syndrome is the key premise of studying the occurrence and development of the disease. The combined models of disease and syndrome summarized in this paper include five types: the animal model of lung qi deficiency, the animal model of lung and spleen deficiency, the animal model of phlegm-heat stagnation of lung, the animal model of phlegm-stasis obstructing lung, and the animal model of cold drink. Now the common disease and syndrome in recent years combined with the method of class modeling are simply described and combed, in order to provide new ideas for researchers, and promote the research process of traditional Chinese medicine treatment of this disease.
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Research Progresses on the Effects of the Plateau on Mitochondrial Function and Energy Metabolism
LIBOSHEN, ZHANGYUXUAN, FANRONGHUI, LIMAOXING
Abstract:
The plateau is a unique environment with low pressure, low oxygen and high cold. The plateau environment will reduce the metabolism of energy substances and mitochondrial work, thus affecting the plateau operation. In recent years, mitochondrial damage has attracted wide attention. As the energy factory of cells, mitochondria are closely linked to the movement of the body. We focused our attention on mitochondrial damage at high altitude, and summarized the effects of high altitude on the metabolism of basic energy substances and the changes of key enzyme activities and mitochondrial structure and function in mitochondrial biochemical energy supply response. It was found that protein, carbohydrate and lipid metabolism was negatively affected at high altitude, resulting in fatigue, hyperlipidemia and body repair. The activities of enzymes related to pyruvate metabolism, tricarboxylic acid cycle, β-oxidation and oxidative phosphorylation are inhibited, and the morphology and number of mitochondria are changed, which will lead to impaired mitochondrial function and affect exercise energy supply. In the future, the exploration of the mechanism of plateau cell injury will vigorously promote the research of plateau injury prevention and treatment drugs.
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A review of animal models of vascular dementia
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Abstract: Vascular Dementia (VD) is caused by cerebrovascular diseases, either hemorrhage or ischemic damage in the brain, with ischemia being the most common. In recent years, much more efforts have been made to study the etiology, pathogenesis and prevention of VD. The establishment of appropriate animal models for studying the mechanism of VD and exploring efficacy of VD treatment has become one of key issues in the research field. On the basis of the conventional methods such as the bilateral occlusion of the common carotid arteries (2VO) and the four-vessel occlusion, the researchers had modified these methods to improve the stability with better reflection of the clinical manifestations of VD. This paper mainly summaries these modified methods, and discuss possible cellular and molecular mechanisms and their advantages and disadvantages.
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Keratin 17 knockout aggravates wound healing in diabetic mice
Abstract:
Objective To explore the effects of keratin 17 (Krt17) knockout on wound healing in diabetic mice. Methods To establish the diabetic models, 60% high-fat diet was fed and streptozotocin was administered intraperitoneally at 40mg/kg once per day for 5 consecutive days in wild-type (WT) and Krt17 knockout (Krt17-/-) mice at six weeks of age. The mice were anesthetized with isoflurane, the back was shaved, and a 6 mm circular skin lesion was made in vivo at one week after successful modeling. Western blotting and immunofluorescence staining were used to detect the expression and localization of KRT17 and histopathological examination was analyzed in wound healing on the 8th day. Photos were taken at 0, 2, 4, 6 and 8 days after wound manufacturing, and wound healing rate was calculated. Results KRT17 was mainly expressed in mouse hair follicles in physiological conditions. When the skin was injured, the expression of KRT17 in keratinocytes in the proximal wound was significantly increased. However, the expression of KRT17 in wounds of diabetic mice was significantly down-regulated compared with that of control mice. The wound healing rate of Krt17-/- mice was significantly reduced and the local inflammatory reaction was more persistent compared with WT mice. Conclusions Krt17 knockout aggravates wound healing in diabetic mice. Krt17 may be an important modifier gene of diabetic wound healing.
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Effects of baicalin on proliferation and apoptosis of laryngeal cancer cells via miR-125b-5p/IRF4 axis
WANGJIAN, SUNYONGDONG, ZHOUXINGWEI, LIULEI, TONGXINGKE, CHENLONG, HEXIAN
Abstract:
Objective: To explore the mechanism of baicalein inhibiting the proliferation and migration of laryngeal cancer cells. Methods: Hep-2 cells were used as the research object. The cell proliferation activity of each group was detected by MTT method, cell migration was detected by scratch assay, cell apoptosis was detected by flow cytometry, western blot was used to detect the expression levels of Beclin-1, LC3II/I, p62 and HDAC1 in laryngeal cancer cells in each group, RT-PCR detection of the expression levels of miR-449a in each group of cells. The targeted binding sites of miR-449a and HDAC1 were analyzed by bioinformatics software and identified by dual luciferase reporter gene experiments. The number of autophagosomes was observed by projection microscopy. Results: Baicalein significantly inhibited the proliferation and migration of laryngeal cancer cells, and significantly induced apoptosis. Baicalein increased the protein expression levels of intracellular autophagy-related genes Beclin1 and LC3II, but decreased the protein expression levels of p62 and LC3I. Baicalein significantly increased the expression level of miR-449a in laryngeal cancer cells and decreased the protein expression of HDAC1. There is a binding effect between HDAC1 and miR-449a. Baicalein combined with miR-449a mimic to treat laryngeal cancer cells can more significantly inhibit cell proliferation and HDAC1 protein expression, as well as more effectively up-regulate the relative expression of miR-449a and induce autophagy. Conclusion: Baicalein can mediate autophagy and inhibit the proliferation and migration of laryngeal cancer cells via the miR449a/HDAC1 axis.
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Effects of low-dose BPA and DEHP on the expression of AKR1C3 in prostate of adult rats
Huangdongyan, Wushuangshuang, Shaocongcong, Suxin, Yangrongfu, Wangkaiyue, Zhouping, Wujianhui
Abstract:
Objective To investigate the effects of of low dose of bisphenol A (BPA) and di (2-ethyl) hexyl phthalate (DEHP) on Aldo-keto reductase 1C3 (AKR1C3) in adult SD rats. Method 56 adult male SD rats were randomly divided into 7groups (8 rats in each group) and they were given BPA (10.0µg/kg,30.0µg/kg,90µg/kg, i.g.), DEHP (30.0µg/kg ,90.0µg/kg ,270 µg/kg, i.g.) and vehicle respectively once a day for 4 weeks. The animals were sacrificed on the day subsequent to last treatment and the blood was collected, the prostate tissues were dissected and categorized into different lobes. The levels of AKR1C3 in serum and prostate were detected by enzyme-linked immunosorbent assay (ELISA), and the expression of AKR1C3 in each lobe of prostate was analyzed by immunohistochemistry. Result After the administration of BPA, the expression of AKR1C3 in 90µg/kg and 270µg/kg group increased, and there was significant difference in the high-dose group (P<0.05); The level and protein expression of AKR1C3 in dorsal prostate increased, and there was significant difference in 10µg/kg group (P<0.01, P<0.001). After administration of DEHP, the level of serum AKR1C3 in 270µg/kg group was significantly higher than that in the control group (P<0.001), the level of AKR1C3 in the ventral prostate was significantly higher than that in the control group (P<0.05, P<0.01), and the expression of AKR1C3 protein increased, there was significant difference in 270µg/kg group (P<0.05); The level of AKR1C3 in 90µg/kg and 270µg/kg dose group of dorsal prostate was higher than that in the control group, and there was significant difference in 30µg/kg group (P<0.05). The expression of AKR1C3 protein in each group increased, and there was significant difference in 30µg/kg and 90µg/kg dose group (P<0.001, P<0.05). Conclusion Low-dose BPA and DEHP can promote the expression of AKR1C3 in the prostate of adult SD rats, but the sensitivity of ventral and dorsal lobes of prostate to BPA and DEHP is different.
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Bone marrow mesenchymal stem cells isolated from rats by bone marrow and slice adherent culture in vitro and PKH26 labeling
Abstract:
Objective To establish an efficient method for isolation and culture of rat bone marrow mesenchymal stem cells (BMSCs), and apply PKH26 to label them in vitro to explore the effect of PKH26 labeling on the biological characteristics of BMSCs, as well as the in vitro tracing. Methods The bone of both hind limbs of 5d suckling rats were separated, the surrounding muscle and fascia were removed, and cut into small pieces for culture. BMSCs were purified by fluid exchange and passage, and the third generation cell surface antigen was determined by flow cytometry. Under the same culture conditions, the third generation BMSCs were labeled with PKH26. Cell morphology and proliferation status were observed under fluorescence microscope in the labeled group and the unlabeled group, and the adipogenic induction characteristics and identification of the labeled group and the unlabeled group were compared. Results The bone marrow slice method was used to separate the hind limb bones of suckling mice. The BMSCs were slender spindle shaped and uniform in shape. A large number of BMSCs could be rapidly obtained in a short time; The results of flow cytometry showed that the expression of CD29 was (91.18 ± 1.29)%, the expression of CD90 was (91.18 ± 1.29)%, and the expression of CD45 was (1.74 ± 0.36)%; PHK26 labeling had no significant effect on the morphology and proliferation of BMSCs cells (P>0.05), and had no effect on the induction of osteogenesis and adipogenesis. Conclusions A large number of high-purity BMSCs can be rapidly cultured by the method of 5-day rat bone marrow slices, which can be used as seed cells for bone tissue engineering; PKH26 can label rat BMSCs in vitro.
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Regulation of ADAM10 gene osteogenic differentiation of bone marrow mesenchymal stem cells and tibial fracture union through Notch1 pathway
TangXiaoxu, Liu wanting, Douyinxia, Li Fuqin, Wang Nan
Abstract:
Objective To study the regulation of a disintegrin and metalloproteinase 10 (ADAM10) gene on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and tibial fracture union. Methods BMSCs of SD rats were cultured, BMSCs stably transfected with negative control (NC) shRNA or ADAM10 shRNA pGFP-V-RS vector were established, the osteogenesis was induced for 14 days. During the induction process, DMSO or 10 μmol/L Notch1 agonist valproic acid (VPA) were added. absorbance at 405nm of alizarin red staining, ALP activity and the expression levels of ADAM10, OCN, Runx2, CoL-I, NICD and Hes1 were detected. The tibial fracture model of SD rats was established and NC shRNA or ADAM10 shRNA pCMV5.0 vector was injected locally. The fracture healing and gene expression were observed for 4 weeks later. Results The expression level of ADAM10 in BMSCs in sh-ADAM10 group was lower than that in sh-NC group. After osteogenesis induction, the absorbance value of alizarin red staining at 405nm, ALP activity and the expression levels of OCN, Runx2, CoL-I, NICD and Hes1 of sh-ADAM10 group were higher than those in sh-NC group (P<0.05). the absorbance value of alizarin red staining at 405nm, ALP activity and the expression levels of OCN, Runx2, CoL-I of sh-ADAM10 VPA group after osteogenesis induction were lower than those in sh-ADAM DMSO group (P < 0.05). The fracture healing of tibial fracture rats in sh-ADAM10 group was better than that in sh-NC group, and the expression levels of OCN, Runx2, CoL-I, NICD and Hes1 were higher than those in sh-NC group (P<0.05). Conclusion Knockdown of ADAM10 can promote the osteogenic differentiation of BMSCs and the healing of tibial fractures by inhibiting Notch1 pathway.
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The improvement effect and mechanism of modified Chaihu Guizhi Decoction on osteoporosis rats by regulating Wnt/β-catenin signaling pathway
Abstract:
Objective: To investigate the improvement effect of modified Chaihu Guizhi Decoction (CGD) on osteoporosis rats by regulating the Wnt/β-catenin signaling pathway. Methods: SD rats were separated into CK group, Model group, low-dose CGD group (CGD-L group, 5 g/kg), high-dose CGD group (CGD-H group, 20 g/kg), and estradiol valerate group (EV group, 9 mg/kg), DKK-1 (Wnt/β-catenin pathway inhibitor) group (100 mg/kg), and CGD-H DKK-1 group (20 g/kg 100 mg/kg), 12 per group. Except for the CK group, the rats in other groups were given 70 mg/kg retinoic acid to build the OP rat model, and the rats in the CK group were given the same amount of normal saline. From the 4th week of modeling, the corresponding drug intervention was given for 4 weeks. ELISA was applied to detect the levels of collagen type I C-terminal peptide (CTX-Ⅰ) and osteocalcin (BGP) in serum of rats; the changes of bone volume fraction, bone trabecular thickness, bone mineral density and bone trabecular number were observed; HE staining was applied to detect the pathological changes of rat femur; Alkaline phosphatase (ALP) calcium-cobalt staining was applied to detect osteoblast activity in rat femur; the activity of osteoclasts in rat femur tissue was detected by tartrate-resistant acid phosphatase (TRAP) staining; Western blot was applied to detect Wnt and β-catenin proteins in femoral tissue of rats in each group. Results: Compared with the CK group, the femoral tissue of the Model group had severe pathological damage, CTX-I level and osteoclast activity increased, BGP level, bone volume fraction, bone trabecular thickness, bone mineral density, bone trabecular number, osteoblast activity, Wnt, β-catenin protein expression decreased (P<0.05); compared with the Model group, the pathological damage of the femur in the CGD-L group, the CGD-H group and the EV group was alleviated, CTX-I level and osteoclast activity decreased, BGP level, bone volume fraction, trabecular thickness, bone mineral density, bone trabecular number, osteoblast activity, Wnt, β-catenin protein expression increased, the trends of the corresponding indicators in the DKK-1 group were opposite to the above (P<0.05); compared with the CGD-H group, the femoral tissue of the CGD-H DKK-1 group was severely damaged, CTX-I level and osteoclast activity increased, BGP level, bone volume fraction, bone trabecular thickness, bone mineral density, bone trabecular number, osteoblast activity, Wnt, β-catenin protein expression decreased (P<0.05). Conclusion: CGD may improve OP of rats by activating the Wnt/β-Catenin pathway.
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Acupoint catgut embedding affects the level of inflammation in rheumatoid arthritis through PD-1/OX40 signaling pathway
Chen Li-chuan, Duan bo, Yu Zhao, Ma Zhi-yi, Meng Qian-wen
Abstract:
Objective: This experiment studied the effect and mechanism of acupoint catgut embedding on rheumatoid arthritis by regulating PD-1 / OX40 signal pathway. Methods: 25 female SD rats were induced with complete Freund's adjuvant to establish rheumatoid arthritis model rats, and then treated with acupoint catgut embedding and drug therapy. The rats were divided into 5 groups: control group, model group, leflunomide group, acupoint catgut embedding group and acupoint catgut embedding leflunomide group. The degree of inflammation was judged by evaluating the arthritis index; The contents of serum IL-6 and IL-8 were detected by ELISA; He staining was used to observe synovitis cell infiltration, smooth abdominal tissue, fibrous tissue, macrophage proliferation and angiogenesis; The contents of PD-1 / OX40 and CD4 cd28-pd-1lowox40 T cell subsets were detected by flow cytometry. Results: except the control group, there were erythema and moderate swelling from ankle to metatarsal or metacarpal joint in each group. After 14 days, there was no significant change in the score of the model group, but the inflammatory factor scores of leflunomide group, acupoint catgut embedding group and acupoint catgut embedding leflunomide group began to decline, and the acupoint catgut embedding leflunomide group decreased the fastest. The contents of IL-6 and IL-8 in serum of model group increased significantly (P < 0.01), and the contents of IL-6 and IL-8 in serum of rats in flutamide group, acupoint catgut embedding group and acupoint catgut embedding leflunomide group decreased significantly (P < 0.01). The synovial tissue of the model group was damaged, with a large number of inflammatory cell infiltration, vascular dilatation and fibroblast proliferation. After leflunomide and acupoint catgut embedding treatment, the inflammatory cell infiltration in the synovial tissue of the model group was significantly reduced and the vascular proliferation was inhibited, and the effect was the most obvious when Leflunomide and acupoint catgut embedding worked together. In the model group, the content of pd-1lowox40 decreased significantly (P < 0.01), the content of CD4 cd28-pd-1lowox40 T cells increased significantly (P < 0.01), and the content of pd-1lowox40 in acupoint catgut embedding group and leflunomide acupoint catgut embedding group increased significantly (P < 0.01) The content of CD4 cd28-pd-1lowox40 T cells in acupoint catgut embedding group and acupoint catgut embedding leflunomide group decreased significantly (P < 0.01). Conclusion: acupoint catgut embedding can improve the symptoms of rheumatoid arthritis, and has the effect of combined treatment with leflunomide. Its mechanism may be related to PD-1 / OX40 signal pathway.
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Left to right shunt slows cardiac remodeling in rats with pulmonary hypertension
Abstract:
【Abstract】Objective: The prognosis of patients with left-to-right shunt congenital heart disease associated pulmonary hypertension is significantly better than that of idiopathic pulmonary hypertension, but the specific mechanism is unclear. The purpose of this project is to make a rat model of idiopathic pulmonary hypertension and congenital heart disease with pulmonary hypertension, and compare the similarities and differences between the two models in pulmonary vascular remodeling and cardiac remodeling. Methods: Male SD rats were divided into three groups: control group (n=8), monocrotaline (MCT) group (50mg/kg) to simulate idiopathic pulmonary hypertension (n=8); Cervical arteriovenous shunt surgery monocrotaline (MCT) group (50mg/kg) simulated left to right shunt congenital heart disease with pulmonary hypertension (n=8). Three weeks after the establishment of the model, echocardiography, left and right cardiac catheter pressure measurement and lung histopathological staining were performed to compare the cardiac and pulmonary phenotypes of the rats. Results: Compared with the control group, there was no significant difference between the MCT group and the operation MCT group in the right ventricular hypertrophy, right ventricular dysfunction, mean pulmonary artery pressure, pulmonary vascular remodeling and other indicators 3 weeks after operation. But in many indexes related to left heart, the rats in the operation MCT group were significantly better than those in the simple MCT group. Compared with the control group, the left ventricular lumen diameter (LVID; d) and left ventricular ejection fraction (EF%) in the operation MCT group did not decrease in the diastolic period; The maximum rate of increase of right ventricular internal pressure (MAX dp/dt) and the maximum rate of decrease of left ventricular internal pressure (MIN dp/dt) in the operation MCT group were lower than those in the simple MCT group. Conclusion: Left to right shunt surgery can not change MCT-induced pulmonary hypertension and right heart remodeling, but can produce left heart compensation, which may be beneficial to the prognosis of patients. The animal model of this project establishes the basis for studying the different pathological mechanisms of idiopathic pulmonary hypertension and pulmonary hypertension associated with congenital heart disease.
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Monkeypox virus infection and the animal model of Monkeypox
Abstract:
Monkeypox is an infectious disease caused by Monkeypox virus （MPXV） infection. The host of MPXV remains unclear, and rodents and nonhuman primates consider the potential hosts. Monkeypox is rapidly spreading globally. However, the animal models for Monkeypox have not developed in the last decades in China. MPXV is a pathogen that seriously threat to human health. Its transmission among the population has presented new characteristics. Therefore, this article describes the discovery of MPXV and the early epidemic, different types of infection and co-infection. In addition, the experimental infection and animal models for Monkeypox in rodents and nonhuman primates were expounded in this paper.
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The expression of IGHG1 in acute myeloid leukemia THP-1 cell and the influences on cell proliferation, apoptosis and invasion by regulating TGF-β/Smad pathway
Abstract:
Objective To investigate the expression of immunoglobulin γ-1 heavy chain constant region (IGHG1) in acute myeloid leukemia (AML) THP-1 cell and its influences on cell proliferation, apoptosis and invasion by regulating the transforming growth factor β (TGF-β)/Smad pathway. Methods The bone marrow specimens of 9 children with AML, the bone marrow specimens of 8 children with fracture,human bone marrow stromal cells HS-5 and human AML cells THP-1, HL60 were used as research objects,Western Blot was used to detect IGHG1 protein expression; THP-1 cells were divided into: blank group (cells without any treatment), si-NC group, si-IGHG1-1 group, si-IGHG1-2 group, si-IGHG1-3 group, TGF-β group,si-IGHG1-1 TGF-β group,si-IGHG1-1 TGF-β LY364947 group, CCK-8 method was used to detect cell proliferation; apoptosis was detected by flow cytometry; Transwell experiment was used to detect cell invasion ; Western blot was used to detect the protein expression of IGHG1, TGF-β, p-Smad2, and p-Smad3 in each group of cells. Results Compared with the bone marrow of children with fracture, the expression level of IGHG1 protein [(0.24?.03) vs (0.87?.12] in the bone marrow of children with AML was significantly higher (P<0.05); compared with HS-5 cell, the expression level of IGHG1 protein in human AML cells THP-1, HL60 was significantly increased [(0.89?.14)(0.75?.08) vs (0.21?.02)] (P<0.05); compared with the blank group , the OD450 value (24, 48, 72h) of THP-1 cells, the number of invaded cells, and the protein expression of TGF-β, p-Smad2, and p-Smad3 were significantly reduced in the si-IGHG1-1 group, and the apoptosis rate was increased (P<0.05), while the corresponding indexes in TGF-β group were opposite (P<0.05); the TGF-β reversed the effects of silencing IGHG1 on the proliferation, apoptosis and invasion of THP-1 cells; compared with si-IGHG1-1 TGF-β group, TGF-β, p-Smad2, p-Smad3 protein, OD450 values (24, 48, 72 h) and invasion number of cells decreased significantly in si-IGHG1-1 TGF-β LY364947 group, and the cell apoptosis rate was increased (P<0.05). Conclusions IGHG1 is highly expressed in AML cells. Silencing IGHG1 can inhibit the proliferation and invasion of AML cells, and promote the apoptosis of AML cells. This mechanism may be related to the inhibition of TGF-β/Smad pathway.
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The relationship between atmospheric pollutants and some adverse pregnancy outcomes
jinjian, Chang Hui, Huang Hehuan, Peng Rui, Zhang Xiaoan
Abstract:
With the rapid development of China's economy and the continuous acceleration of urbanization, the problem of air pollution is becoming increasingly prominent, which has a great impact on human health. In recent years, a large number of research work has emerged both domestically and internationally, and research results have shown a certain correlation between exposure to atmospheric pollutants during pregnancy and adverse pregnancy outcomes. The impact of air pollution on the health and embryonic development of pregnant women has received more attention. This article mainly provides a brief review on the impact of atmospheric pollutants on some adverse pregnancy outcomes and their possible biological mechanisms.
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Research Progress on Model Organism Zebrafish in Neurodegenerative Diseases
Huang Kongli, Su Shijie, Wang Yuting, LIU ZHUANGZHUANG, CAO DANDAN, WANG PEI, CHEN GUANLIN, Wang Qi
Abstract:
Neurodegenerative disease （NDD）is a chronic and progressive neurological disease characterized by the loss of a large number of specific neurons. It mainly includes Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). Although the lesions and etiologies of different types of neurodegenerative diseases are different, delayed neurodegenerative lesions and cell loss in specific brain areas are their common characteristics. For this reason, it is collectively referred to as neurodegenerative diseases. In recent years, zebrafish have attracted increasing attention from society as a new type of model organism. Although there are some differences between zebrafish and human central nervous systems, zebrafish neural conduction systems, neuronal and glial cell types, and disease-related gene homology are very similar to those of humans. Zebrafish has been widely used in the study of neurodegenerative diseases, and some achievements have been made in this field to improve our understanding of these diseases, but because of the complexity, multi-factors and multi-gene regulation of neurodegenerative diseases, the etiology and pathogenesis of zebrafish are not clear, so the treatment of this kind of disease has always been a difficult problem. By consulting relevant literature from home and abroad in recent years, this study reviews recent advances in neurodegenerative diseases using zebrafish as a model organism.
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Progress in irisin and its upstream and downstream antidepressants
Sangjiala, Lishanshan, Cuixin, Renqingqing, Houruiling, Panxingfang, Wangshenjun, Zhao
Abstract:
Depression is the main cause of disability, and the adverse effects on people are difficult to eliminate. Despite the increasing number of antidepressants, depression is still not adequately treated clinically, and new mechanisms still need to be explored. As the beneficial effects of irisin on the nervous system are gradually elucidated, studies have found that irisin has an antidepressant effect, and irisin may become a new target for the treatment of depression. This study aims to explore the mechanism of irisin and its upstream and downstream antidepressants, by reviewing the existing studies to explain the link between depression and irisin, propose the potential mechanism of SIRT1 / PGC-1α mediating FNDC5/Irisin to regulate BDNF and promote neurogenesis to improve depression, and provide a new idea for the study of irisin and its upstream and downstream antidepressants.
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Advances of CREB in the regulation of memory through synaptic plasticity and its relation with Alzheimer’s disease
Luo Zhuohui, pang shuo, Zhang lianfeng
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Alzheimer’s disease is an irreversible heterogeneous neurodegenerative disease. AD patients are featured with memory loss and impaired synaptic plasticity. With a view to cAMP responsive element-binding protein which is intimately associated with synaptic plasticity. this assay summarized progress on the structure, signal pathway, downstream genes and relative memory regulation. The involvement of CREB in AD development would serve as references for AD researches based on synaptic plasticity improvement.
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Research progress on the regulation of lymphangiogenesis and its role in myocardial infarction
Abstract:
Lymphatic system plays an important role in regulating interstitial fluid homeostasis, lipid metabolism and immune function. After myocardial infarction, enhanced lymphangiogenesis accelerates the clearance of infiltrating immune cells, reduces the production of pro-inflammatory cytokines, reduces edema, inflammation, and fibrosis, and promotes the recovery of damaged heart function. Vascular endothelial growth factor-C (VEGF-C) and its receptor VEGFR-3 are components of the lymphangiogenesis pathway and play a critical role in maintaining tissue fluid balance and myocardial function after cardiac injury. Lymphatic vessels are closely related to the immune system. Different immune cell groups can stimulate or inhibit lymphatic remodeling. Macrophages are congenital immune cells widely distributed in organs and tissues, and play an important role in various physiological and pathological processes such as organ development, host defense, acute and chronic inflammation, tissue homeostasis and remodeling. More mechanisms of lymphangiogenesis need to be identified to provide effective targets for clinical stimulation of lymphangiogenesis to treat heart disease. This paper reviews the basic pathological changes of the heart and lymphatic vessels after myocardial infarction, the regulatory factors of lymphangiogenesis, and the influence of macrophages on lymphangiogenesis.
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Effects of LncRNA FGD5-AS1 targeting and regulating miR-129-5p on the proliferation, apoptosis, migration and invasion of oral squamous cell carcinoma cells
Abstract:
Objective To investigate the effects of long non-coding RNA (LncRNA) FGD5-AS1 on the proliferation, apoptosis, migration and invasion of oral squamous cell carcinoma (OSCC) cells through targeted regulation of miR-129-5p. Methods The expression of FGD5-AS1 in OSCC was analyzed by online database. The tumor tissues, normal tissues, and the human oral mucosal cells (HOK) and OSCC cells (SCC-9, HSC-4, SCC-25, CAL-27) cultured in vitro from 30 OSCC patients collected in our hospital were used as research subjects, qRT-PCR method was performed to detect the expression of FGD5-AS1 and miR-129-5p. The CAL-27 cell line with the highest FGD5-AS1 expression was randomly separated into Control group (normal culture, no transfection), si-NC group (transfected with si-NC), si-FGD5-AS1 group (transfected with si-FGD5-AS1), si-FGD5-AS1 NC inhibitor group (co-transfected with si-FGD5-AS1 and NC inhibitor) and si-FGD5-AS1 miR-129-5p inhibitor group (co-transfected with si-FGD5-AS1 and miR -129-5p inhibitor), CCK-8 method and clone formation assay were used to detect the proliferation ability of CAL-27 cells; the apoptosis level of CAL-27 cells was detected by flow cytometry; the migration ability of CAL-27 cells was detected by wound-healing assay; Transwell chamber was used to detect the invasion ability of CAL-27 cells; and dual luciferase reporter experiment verified the targeting relationship between FGD5-AS1 and miR-129-5p; the expression of high mobility group protein B1(HMGB1) was detected by Western blot. In vivo xenograft tumor model was constructed and divided into sh-NC group, sh-FGD5-AS1 group, miR-129-5p inhibitor group, and sh-FGD5-AS1 miR-129-5p inhibitor group. Tumor volume and tumor were detected. QRT-pcr was used to detect the expression of FGD5-AS1 and miR-129-5p in transplanted tumor tissues. The expression of HMGB1 and Ki67 was detected by immunohistochemistry. Results Database analysis showed that the expression level of FGD5-AS1 in OSCC tumor tissues was 4 times higher than that in normal tissues, and FGD5-AS1 expression was associated with poor grade in OSCC patients. Compared with normal tissues or human oral mucosal cells, the expression of FGD5-AS1 in tumor tissues and OSCC cell lines was significantly increased, and the expression of miR-129-5p was significantly decreased (P<0.05), the CAL-27 cells with the highest expression level of FGD5-AS1 were selected for transfection experiments. Compared with the Control group and the si-NC group, the apoptosis rate of the si-FGD5-AS1 group was significantly increased, and the OD value (48 h, 72 h, 96 h), scratch healing rate and the number of invaded cells were significantly reduced (P<0.05). MiR-129-5p was the target gene of FGD5-AS1. Inhibiting the expression of miR-129-5p was able to reverse the effects of interference FGD5-AS1 on the proliferation, apoptosis, migration and invasion of OSCC cells, thereby restoring the cancer-promoting effect of FGD5-AS1. After FGD5-AS1 was disrupted, HMGB1 expression was down-regulated by significantly enhancing miR-129-5p expression (P<0.05). In vivo experiments showed that FGD5-AS1 silencing significantly inhibited the growth and expression of HMGB1 and Ki67 (P<0.05), inhibition of miR-129-5p was the opposite; Inhibition of miR-129-5p reversed the inhibition of FGD5-AS1 on tumor growth and expression of HMGB1 and Ki67 (P<0.05). Conclusions FGD5-AS1 is up-regulated in OSCC cells. Interfering with FGD5-AS1 can inhibit proliferation, migration and invasion of OSCC cells and promote apoptosis by targeting miR-129-5p / HMGB1 axis.
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Behavioral assessment in the parkinson’s model of nonhuman primates
Abstract:
Parkinson's disease is a neurodegenerative disease, can cause a series of patients with symptoms of movement and the movement, behind the pathogenesis is unclear, to explore the mechanism behind these phenotypic requires an appropriate animal model of rodents in the movement and the movement is very difficult to accurately simulate the patient symptoms, causes related to preclinical studies have limitations, in translational medicine. Non-human primate animal models can make up the gap between rodents and humans, thus the non-human primate PD model of movement and the movement symptoms, is very important to research on mechanism and therapy, this review summarizes the different behavior in quantitative way, and compared the advantages and disadvantages between different methods, for studying the PD monkey model provides a behavioral testing for help.
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Advances in the construction of animal models of severe asthma
Wei Dandan, Wang Liting, Long Jie, Chen Yanjiao, Wang Yu, Yang Yongqing, Xu Yudong
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Severe asthma (SA), which requires high doses of glucocorticoids in combination with other medications to maintain symptom control or is uncontrollable even with these treatments, is currently a challenge in the clinical management of asthma. The establishment of a stable and reproducible experimental animal model that highly mimics the pathophysiological and clinical characteristics of patients with severe asthma is a key fundamental link in deepening the study on the pathogenesis of severe asthma, identifying potential therapeutic targets and developing targeted drugs. This paper reviews the experimental studies related to the construction of animal models of severe asthma in the past 10 years, and summarizes the recent progress in the establishment and evaluation of animal models of severe asthma from three aspects: animal selection, animal model construction protocols, and model pathological phenotypes. To summarize and analyze the latest progress in the construction of SA animal models, and provide a reference for SA basic research based on animal models.
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Research progress in experimental models of pulmonary arterial hypertension
xiejincheng, Chenjianying, Dengshaodong, Xiao mengyuan
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Pulmonary hypertension is a chronic progressive disease that, if not treated promptly, can ultimately lead to right heart failure and even death In order to explore the pathogenesis of pulmonary arterial hypertension and find more effective treatment methods, it is necessary to establish a suitable experimental model. In this paper, Pubmed, CNKI and other databases were used to search relevant literature, and the preparation methods and research progress of various experimental models of pulmonary arterial hypertension in recent years were summarized. The preparation methods of the models were classified to show the pathological characteristics of the disease more directly. On this basis, the present situation and existing problems of the in vitro and in vivo model of pulmonary arterial hypertension were discussed, in order to provide reference for the pathogenesis and clinical research of pulmonary arterial hypertension.
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Research progress of experimental premenstrual dysphoria model in rodents
Abstract:
Premenstrual dysphoric disorder (PMDD) is a subtype of Premenstrual syndrome with high prevalence in women during their reproductive life. It includes physical symptoms such as breast tenderness, headache as well as serious emotional symptoms such as anxiety, depression and irritability. These symptoms are menstrual specific, they appear before menstruation and disappear within a week after it ends. PMDD threatens the health of female patients all over the world, In The Diagnostic and Statistical Manual of Mental Disorder(Fifth edition ed,DSM-5）, PMDD is identified as one of the five types of depression. At present, studies on the pathological mechanism of PMDD mainly focus on hormone and receptor expression, which is the theoretical basis of the animal model establishment, as well. Animal model that can model after clinical symptoms of human beings is a very important to connect basic research to clinical research, which is also crucial to explore the pathogenesis and develop appropriate drugs. Although many kinds of animal models of PMDD have been used in experimental studies, there are still many limitations, which resulting in a barrier to further investigation of PMDD. Therefore, this review arranged the known pathogenesis research of PMDD and discuss the existing animal models of PMDD, aims to provide reference for PMDD related mechanism research and drug development.
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Analysis of animal models of keratitis based on the characteristics of clinical conditions of traditional Chinese and Western medicine
Abstract:
Abstract: Keratitis is a common ophthalmic disease with a high rate of blindness. This paper reviews a large number of relevant literature of animal models of keratitis, summarizes and analyzes the mechanism of existing animal models of keratitis, and evaluates the clinical anastomosis degree of traditional Chinese and Western medicine in combination with the established clinical diagnostic standards of traditional Chinese and Western medicine, analyzes its advantages and disadvantages, and puts forward some suggestions. It is found that most of the existing models are based on Western medical theories, and lack the diagnostic standards of traditional Chinese medicine. The model is mostly modeled by a single factor, which cannot well simulate the real lesion process of the disease; The diagnosis of the model lacks apparent indicators; It is recommended that animals be modeled by combining disease evidence. It is very important to prepare animal models of keratitis with high clinical compatibility and establish perfect evaluation standards, which can help us better understand the occurrence and development of keratitis in modern medical experiments, and effectively prevent and treat it.
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Study on the uptake and transport properties of euscaphic acid in Caco-2 cell model based on UPLC-TQ-MS
wangning, xieli, ding wenhuan, tian li
Abstract:
ABSTRACT: Objective Caco-2 cell model was established to explore euscaphic acid uptake and transport mechanism in this study. Methods Ultra-high performance liquid chromatography-triple quadrupole-mass spectrometry(UPLC-TQ-MS) was employed to determine the content of euscaphic acid. The effects of different time and temperature on its uptake were investigated. Based on the results of the uptake studies, the effects of different concentrations, P-gp inhibitors, chelating agents and pH values on its bidirectional transport were explored. Results The uptake of euscaphic acid was (8.38 ?0.87) μg穖g-1 for 180 min on the Caco-2 cell model at 37 癈. The apparent permeability coefficient (Papp values) of euscaphic acid for low, medium and high concentrations were(61.41 ?.92)?0-4、(146.90?4.91)?0-4 and (167.18?.72)?0-4 cm穝-1 respectively, which were positively correlated with the concentrations. P-gp inhibitors and chelating agents had no effect on its Papp values. Weakly acidic environment (pH6.00) significantly increased its Papp value, and the efflux rate (ER) ranged from 0.8–1.4. Conclusion The above results indicate that euscaphic acid has good transmembrane permeability in Caco-2 cell model, and the uptake mode is mainly passive diffusion. It is not a substrate of P-gp and there is no cellular bypass transport. This research may provide an experimental basis for the in vivo intestinal absorption of medicines containing euscaphic acid.
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Mechanism of taxifolin regulating endoplasmic reticulum stress PERK-ATF4 pathway to reduce myocardial hypertrophy in hypertensive rats
yujinyu, hanjing, zhangying, yuwen
Abstract:
【Abstract】 Objective To investigate the impact and molecular mechanism of taxifolin (TAX) on myocardial hypertrophy in spontaneously hypertensive rats (SHR). Methods Twenty-four SHRs were separated into SHR control group (SHR group), TAX group (20 mg/kg), and TAX PERK activator CCT020312 (CCT) group (20 mg/kg TAX 2 mg/kg CCT), 8 per group; another 8 normal blood pressure Wistar-Kyoto (WKY) rats were regarded as the normal control group (WKY group), and all were given corresponding drugs for 8 weeks of continuous intervention. During the experiment, the changes in blood pressure of the rats were observed, and after the intervention, the thickness of the diastolic ventricular septum (IVSd), the thickness of the systolic ventricular septum (IVSs), and the left ventricular ejection fraction (LVEF) were detected by echocardiography to determine the degree of myocardial hypertrophy and cardiac function, then the cardiac index and left ventricular index were calculated, hematoxylin-eosin (HE) staining, wheat germ agglutinin (WGA) staining and Masson staining were performed to evaluate the pathological changes of myocardial tissue, real-time quantitative PCR (qRT-PCR) was performed to detect the expressions of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), type I collagen α1 chain (COL1A1) and type III collagen α1 chain (COL3A1) mRNA in myocardial tissues, Western blot was performed to detect the expressions of protein kinase R-like endoplasmic reticulum kinase (PERK)-activator of transcription 4 (ATF4) pathway-related proteins in cardiac muscle. Results After the intervention, compared with the WKY group, the systolic blood pressure (SBP), diastolic blood pressure (DBP), IVSd, IVSs, cardiac index, left ventricular index, myocardial cell cross-sectional area, collagen volume fraction (CVF), myocardial tissue ANP, BNP, COL1A1 and COL3A1 mRNA expressions, glucose-regulated protein 78 (GRP78), ATF4, C/EBP homologous protein (CHOP) protein levels and p-PERK/PERK ratio in the SHR group increased (all P<0.05), LVEF decreased (P<0.05); compared with SHR group, the SBP, DBP, IVSd, IVSs, cardiac index, left ventricular index, myocardial cell cross-sectional area, CVF, myocardial tissue ANP, BNP, COL1A1 and COL3A1 mRNA expressions, GRP78, ATF4, CHOP protein levels and p-PERK/PERK ratio in TAX group decreased (all P<0.05), LVEF increased (P<0.05); CCT020312 partially reversed the protective effects of TAX on cardiac function and cardiac hypertrophy. Conclusion TAX can improve hypertensive myocardial hypertrophy by inhibiting endoplasmic reticulum stress (ERS), and its mechanism may be related to inhibiting PERK-ATF4 pathway.
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Study on tissue distribution difference of ligustrazine-Salvia miltiorrhiza before and after compatibility in acute myocardial ischemia model rats
lirong, goujian, liuting, gongzipeng, luyuan, liuchunhua, hunagyong, sunjia
Abstract:
Objective To investigate the difference in tissue distribution of ligustrazine hydrochloride and Salvia miltiorrhiza (Danshen) in Acute myocardial ischemia (AMI) rats. Methods AMI model was induced by subcutaneous injection of isoproterenol hydrochloride. UPLC-MS/MS method was used to determine the content differences of ligustrazine and danshensu in heart, liver, spleen, lung, kidney and brain tissues after single intravenous injection of Danshen injection (DGI), Ligustrazine injection (CGI) and Shenxiong glucose injection (SGI) at different time points. Results After intravenous injection, ligustrazine and danshensu were widely distributed in tissues of AMI rats and reached their peak rapidly. Before and after compatibility, the content of ligustrazine was the highest in brain tissue and the lowest in liver tissue. The content of danshensu in kidney tissue was the highest, and in brain tissue was the lowest, indicating that ligustrazine could penetrate the blood-brain barrier more easily than danshensu, and the main accumulation tissues were different. The AUC of ligustrazine and danshensu in the heart of the target organ was significantly increased (P < 0.001). Conclusion It is speculated that the combination of ligustrazine and salvia miltiorrhiza may enhance the therapeutic effect by increasing the distribution of main pharmacodynamic components in the heart, so that SGI can play a better role.
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The role of PI3K/Akt/mTOR signaling pathway in the pathogenesis of TRALI rats
liushuangchun, Zhang Xijiang, Chen Zaihuan, Wang Luqian, Lin Hairong
Abstract:
Objective: To study the effect of PI3K/Akt/mTOR signaling pathway on the pathogenesis of TRALI. Methods: Animal model was established by the method of trauma-blood loss-massive transfusion, and the pulmonary histopathological changes were detected by HE staining to determine whether the rats had pulmonary edema. The protein and mRNA expression levels of TNF-α, IL-6 and IL-1β in peripheral blood or lung tissues in TRALI rat models were detected by ELISA and qRT-PCR. The expression levels of PI3K/Akt/mTOR signaling pathway related proteins and apoptosis-related proteins Bax, Bcl-2 and Caspase3 were detected by western blotting. Results: Alveolar tissue structure was seriously damaged, the alveolar wall was thickened, there was pink edema fluid in the alveolar cavity, inflammatory cells infiltrated, edema was obvious in TRALI model rat. The expression levels of inflammatory cytokines TNF-α, IL-6 and IL-1β were significantly increased in peripheral blood and lung tissues (P<0.05); PI3K/Akt/mTOR signaling pathway was activated, the expression of p-mTOR/mTOR was significantly increased, and the expression of apoptotic protein Bax and Caspase 3 was inhibited, and the expression of anti-apoptotic protein Bcl-2 was increased (P<0.05). Conclusion: As a potential drug target, mTOR is an important means for clinical prevention and control of the occurrence and development of TRALI by defining the exact time target of its protective and damaging effects and selecting the optimal time of medication due to its complicated mechanism.
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Alterations of Gut Microbiota - Short Chain Fatty Acid Axis in IBS-D Rats and the Effect of Sodium Butyrate
zhan kai, Wu haomeng, zheng huan, qin shumin, Huang shaogang, yang yuanming
Abstract:
Objective To explore the alterations of gut microbiota - short chain fatty acid metabolic axis in IBS-D rat model, and to explore the effect of sodium butyrate on this axis. Methods Seventeen Wistar rats were randomly divided into three groups. The IBS-D rat model was induced by 4% acetic acid enema combined with restraint stress. During the modeling period, sodium butyrate was injected intraperitoneally. The fecal flora of rats was detected by 16sRNA technology, and the fecal short chain fatty acid content of rats was detected by liquid chromatography mass spectrometry (LC-MS). Results Compared with the normal group, the weight of the model group was decreased, AWR score and fecal water content have a significant increase, the relative abundance of intestinal probiotics was decreased，while that of g-Blautia was elevated, the fecal acetic acid content was increased significantly, and the contents of butyric acid and valeric acid was decreased significantly in the model group. After drug intervention, compared with the model group, the weight of rats in the sodium butyrate group was increased, the AWR score and fecal water content was decreased significantly, the relative abundance of g-Blautia was decreased significantly, and the fecal butyric acid and valeric acid content was obviously increased. Conclusions Sodium butyrate can alleviate diarrhea and colon visceral hypersensitivity in IBS-D rats by improving the imbalance of gut microbiota - short chain fatty acid metabolic axis.
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Advances in Ferroptosis-Based Therapy for Aging and Aging-Related Diseases
Zhou yongchang, Tao Siman, Chen Shengqiang, Pu Xiuying
Abstract:
Ferroptosis is a novel form of programmed cellular necrosis proposed in recent years, which is found in various diseases and seriously impacts on human health. Numerous studies have shown that inhibition or promotion of ferroptosis can improve many aging and aging-related diseases, and Traditional Chinese medicine plays an important role in this regard. This paper reviews the effects and mechanisms of Ferroptosis on aging and aging-related diseases, and compares the research progress of TCM in the treatment of ferroptosis-mediated aging and aging-related diseases in recent years, aiming to provide more options for the treatment and prevention of aging and aging-related diseases.
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Research progress in the pathogenesis of inflammatory bowel disease
Houxiaoting, Menghuan, Xuejiachen, Zhanghuamin, Wangkesi, Wangxude
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Inflammatory bowel disease (IBD) is a global idiopathic disease, involving the ileum, rectum and colon. IBD begins to appear early in clinical symptoms, including abdominal discomfort, diarrhea, hematochezia, fever, fatigue and weight loss. The diagnosis of IBD is based on the comprehensive evaluation of relevant clinical manifestations, endoscopic examination results and histopathological characteristics of pathological tissue specimens. Biological agents, oral corticosteroids, salicylic acid and surgery are the main conventional treatments for IBD. In recent years, considerable progress has been made in elucidating the pathogenesis of IBD. In clinical practice, it is considered that the complex interaction between genetic susceptibility, environmental factors and intestinal mucosal barrier leads to abnormal oxidative stress, autophagy and mucosal immune response. This paper briefly summarizes and expounds the research progress of genetic and environmental factors, intestinal mucosal barrier function, oxidative stress, autophagy dysfunction and adaptive immune response, so as to provide basis for further research and development of treatment methods and improvement of clinical treatment effect.
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Effect of Bushen Jianpi Kaixin formula on autophagy and apoptosis in AD rats
li ying, Wang Ying, Kong Mingwang
Abstract:
Objective To investigate the effects of Bushen Jianpi Kaixin Formula (BSJPKXF) on the learning and memory ability of Alzheimer s disease (AD) model rats and the related autophagy and apoptosis in cortex of AD model rats, and exploring the underlying mechanism of BSJPKXS. Method The 60 eligible rats were randomly divided into six groups (n = 10): control group, AD group, Bushen group (BS, 3.6g/kg·d), Jianpi group (JP, 4.05g/kg·d), Kaixin group (KX, 2.34g/kg·d) and Bushen Jianpi Kaixin group (BSJPKX, 9.99g/kg·d). AD mouse model was established by intraperitoneal injection of D-gal. The rats in BS group, JP group, KX group and BSJPKX group were gavaged with corresponding drugs once a day. The rats in control group and AD group were treated with equal amount of normal saline one time per day. After four weeks, the learning and memory ability was tested by Morris water maze. The open-field test was used for detecting the cognitive function in rats. The expression of LC3-I, LC3-II and Beclin in cerebral cortical tissues were detected by western bolt. The expression of Bax and Bcl-2 in cerebral cortical tissues were detected by immunohistochemistry. The related mRNA level of Beclin 1, P62, Bax and Bcl-2 in cerebral cortical tissues were detected by RT-PCR. Result Compared with the control group, D-gal significantly decreased the spatial learning and memory ability of rats in the AD group (P < 0.01), decreased the expression of Beclin, LC3-I/LC3-II, Bcl-2 and Bcl-2/Bax, increased the mRNA level of P62 and the expression of Bax (P < 0.01). After treatment, related to the AD model group, Bushen Jianpi Kaixin formula improved the spatial learning memory ability of rats in the BSJPKX group (P < 0.01), increased the expression of Beclin, LC3-I/LC3-II, Bcl-2 and Bcl-2/Bax, decreased the mRNA level of P62 and the expression of Bax (P < 0.01). Conclusion Bushen Jianpi Kaixin formula can improve cognitive impairment in AD rats. The mechanism is presumedly related to the reduction of neural autophagy and apoptosis.
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The evaluation of experimental animal studies on acupuncture for hypertension based on the SYRCLE’s tool and the ARRIVE guidelines
Tang wenjing, ZHANG Yue, LI Yuxi, ZHONG Dongling, JIN Rongjiang, ZHANG Lili, LI Juan
Abstract:
Objective To evaluate the risk of bias and reporting quality of animal experimental studies on acupuncture for hypertension, and analyze the deficiencies in experimental design, implementation and reporting, so as to decrease the risk of bias of researches and improve the reporting quality of animal studies. Methods Databases including China national knowledge infrastructure（CNKI）, Wanfang database（WANFANG）, Chinese science and technology periodical database（VIP）, Chinese biomedical literature database（CBM）, Web of Science, PubMed, Embase, and The Cochrane Library were searched from inception to October 8, 2022. Two researchers independently screened experimental studies related to acupuncture interventions in hypertensive animals according to eligibility criteria. The SYRCLE’s tool and the ARRIVE guidelines 2.0 were used to evaluate the risk of bias and reporting quality of the included literature. Excel 2019 was used to extract data and descriptive analysis was conducted according to the results. Results A total of 79 animal experiments on acupuncture for hypertension were included, among which 16 and 21 were published in Chinese core journals and science citation index（SCI）journals respectively. The result of SYRCLE’s tool showed that 5 of the 10 items were evaluated as well, while the rest were unclear risk or high risk of bias. Of the 79 included articles, the risk of bias of 19 articles were low, while the remaining studies had some risk of bias. The results of the ARRIVE guidelines 2.0 indicated that 19 of the 38 sub-items were well reported, while the rest were poorly reported.The reporting quality of 51 articles were good and the remaining studies were inadequately reported. Conclusions At present, the risk of bias of acupuncture intervention in hypertensive animal experiments is high and the reporting quality is generally low. The inadequate description of some important entries had impact on the reproducibility of the experiments and the translation of the results.The SYRCLE’s tool and ARRIVE guidelines 2.0 are recommended to be used as reference during experimental design and reporting, thus improving the standardization and reporting quality of acupuncture for hypertensive animals.
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Autophagy: the key mechanism of exercise in improving neurodegenerative diseases
Chen Xianghe, Qiu Xiao, Liu Chi, Shen Ziming, Zhou Xiangxiang
Abstract:
Autophagy regulation of neurological diseases is the focus of current research in the field of neuroscience. Autophagy disorder leads to protein expression, deposition and dysfunction such as Aβ、Tau、α-syn and causes neurodegenerative diseases such as AD, PD and HD. Exercise is an important means to improve neurodegenerative diseases, which is closely related to the up-regulated expression of LC3, Beclin-1, Lamp1 and other autophagic factors after the activation of AdipoR1/AMPK/TFEB, AMPK/mTOR and other pathways. Higher autophagy level can remove the deposition of Aβ、Tau、α-syn and other proteins in the brain and can improve the neurodegeneration, synaptic structure and function disorder caused by neurodegenerative diseases. This study reviewed and analyzed the mechanism of autophagy in the improvement of neurodegenerative diseases by exercise, which will provide a solid theoretical basis and new research ideas for the improvement of neurodegenerative diseases by exercise.
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Research advances of trophoblast cells in threatened abortion complicated with intrauterine hemorrhage
HuoYan, Zhu Jun nan, Fu Ya qi, Chen Ping, Xu Guang li
Abstract:
Threatened abortion complicated with intrauterine hemorrhage is a common disease during pregnancy.Its pathogenesis is related to the imbalance of maternal-fetal interface microenvironment and the obstruction of uterine spiral artery remodeling. Trophoblast cells are the outermost layer of the maternal-fetal interface microenvironment .Its proliferation, migration and invasion are closely related to normal pregnancy.It plays an irreplaceable role in immune tolerance and regulation, uterine spiral artery remodeling, and maintenance of maternal-fetal interface microenvironment.In recent years, trophoblast cells have become the main line of research in autoimmune diseases and other fields.Studies have found that it plays an important role in the diagnosis and treatment of threatened abortion complicated with intrauterine hemorrhage.This article reviews the research progress of trophoblast in the treatment of threatened abortion complicated with intrauterine hemorrhage.
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The mechanism of chemotherapy-induced thrombocytopenia in hematological malignant tumors
liliang, kong chun fang, jin cheng hao
Abstract:
Chemotherapy is the main cornerstone of hematological tumor therapy. However, foot therapy and high-dose chemotherapy drugs often cause bone marrow hematopoiesis inhibition, among which thrombocytopenia is more common, which can increase the risk of bleeding, delay follow-up treatment, increase treatment costs, and even endanger life. In recent years, more and more studies have found that anti-tumor drugs can mediate thrombocytopenia through cell aging, apoptosis, autophagy and ferroptosis. Therefore, this article reviews the mechanism of chemotherapy-induced thrombocytopenia in hematological malignant tumors in recent years.
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ZHANG Gedi, LIU Gengxin, LUO Fuli, YAN Ziyou
2023,33(7):17-25, DOI: 10. 3969 / j.issn.1671-7856. 2023. 07. 003
Abstract:
Objective To predict the mechanism of Shenshuai Prescription (SSR) in chronic kidney disease(CKD)-related myocardial injury using network pharmacology and molecular docking method. Methods We used the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and Herb herbal medicine identification database (http:/ / herb. ac. cn/ ), and the SwissTargetPrediction database to screen target information of active ingredients. We then used the UniProt database to screen for human targets and standard gene names. A drug active ingredient target network diagram was constructed using Cytoscape 3. 7. 2 software, and the GeneCards database was used to collect disease-related targets. The “ Shenshuai Recipe” against CKD myocardial injury gene target database was established using Venny 2. 1, and the STRING database was used to build the main component target interaction network and screen key targets. Cytoscape 3. 7. 2 software was imported for topology analysis and a protein-protein interaction network diagram was constructed. Finally, the DAVID platform was used for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and Gene Ontology (GO) biological function annotation. Results After screening, there were 252 active compounds in SSR and 649 common targets of SSR and CKD myocardial injury, among which AKT Serine/ Threonine Kinase 1 (AKT1), Tumor Necrosis Factor (TNF), Mitogen-Activated Protein Kinase 3 (MAPK3), and Vascular Endothelial Growth Factor A (VEGFA) may be important targets of SSR in treating CKD myocardial injury. GO analysis identified 1485 Biological process items, 176 Cell component items, and 386 Molecular function items, of which plasma membrane, cytosol, and cytoplasm had the largest number of enriched genes, and 313, 304, 276 genes were distributed respectively. KEGG analysis indicated that HIF-1α, Lipid and atherosclerosis, AGE-RAGE signaling path in diagnostic complexes, phosphoinositide 3-kinase (PI3K)-AKT, and insulin resistance pathways might be involved in the mechanisms of SSR in treating CKD myocardial injury. Conclusions SSR might play a role in cardiorenal protection by participating in multiple mechanisms, including improving insulin resistance, improving lipid metabolism, antiatherosclerosis, and regulating the expression of inflammatory factors and vascular endothelial growth factor, with the PI3K/Akt and mitogen-activated protein kinase pathways being potentially important signal regulation pathways.
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WANG Xing, CHEN Ziqi, LI Lin, LIAO Jinhua, WANG Xiaolin, LIU Jiangyuan, LIAO Donghua
2022,32(7):27-33,57, DOI: 10. 3969 / j.issn.1671-7856. 2022. 07. 004
Abstract:
Objective To observe the therapeutic effect of Zhenwu decoction on myocardial pathomorphology and cardiomyocyte apoptosis in rats with heart failure induced by coronary artery ligation, and to explore its effect on apoptosis- related proteins and the PI3K-AKT signaling pathway. Methods At 4 weeks after the operation, surviving rats were randomly divided into six groups with seven rats in each group as follows. (1) Sham operation group: normal saline was administered intragastrically for 28 days at 4 weeks after the operation. (2) model group: normal saline was administered intragastrically for 28 days after 4 weeks. (3) positive control group: 5 mg / kg losartan potassium was administered for 28 days after 4 weeks. ( 4) Zhenwu decoction low dose group: after 4 weeks, 6 g / kg Zhenwu decoction crude drug was administered for 28 days. ( 5 ) Zhenwu decoction middle dose group: 12 g / kg Zhenwu decoction crude drug was administered intragastrically for 28 days after 4 weeks. (6) Zhenwu decoction high dose group: 18 g / kg Zhenwu decoction crude drug was administered intragastrically for 28 days after 4 weeks. Changes in the electrocardiogram, color ultrasound, cardiomyocyte apoptosis, myocardial morphology, PI3K, AKT1 and p-AKT1 protein levels in myocardial tissue, immunohistochemical changes of Bax, Bcl-2, caspase 3, 8, 9 and BNP in the abdominal aorta were observed before and after modeling. Results ( 1) The ST segment of the heart failure model was elevated after coronary artery ligation, indicating that model establishment was successful. (2)The left ventricular mass index and BNP level of heart failure rats were increased significantly, and LVEF and LVFS were decreased significantly, whereas the left the ventricular mass index, BNP level, LVEF and LVFS were improved in the other groups. ( 3) Myocardial fibers in the model group were disordered and broken accompanied by cardiomyocyte swelling, hypertrophy. and inflammatory cell infiltration, which were relieved to various degrees in the other groups. Apoptosis in the model group was significant, which was alleviated after by Zhenwu decoction and positive control group drugs. (4)Compared with the model group, Bcl-2 was increased, and Bax and Caspase 3, 8, 9 were decreased in each treatment group. There was no significant difference in protein expression between Zhenwu decoction middle dose and sham operation groups. (5)Compared with the sham operation group, PI3K, p-AKT1 and AKT1 expression in the model group was increased, and Zhenwu decoction suppressed protein expression of PI3K, p- AKT1 and AKT1. Conclusions Zhenwu decoction reduces cardiomyocyte apoptosis and myocardial pathological changes in HF rats by regulating the PI3K-AKT pathway, enhancing myocardial contractility, and delaying the progression of heart failure.
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WANG Xue-qiao, RAO Yu-teng, WU Wei-peng, CHENG Peng, LI Wei, JIANG Dai-xun, CHEN Wu
2014,24(6):22-26, DOI: 10.3969.j.issn.1671.7856.2014.006.005
Abstract:
Objective To establish a canine model of intervertebral disc extrusion by surgery and observe the histological and microcirculatory changes of the spinal cord, in order to accumulate data for studies on the pathology and mechanism of treatment for intervertebral disc extrusion. Methods Normal healthy adult dogs were divided randomly into two groups: normal control group and model group. To simulate the intervertebral disc extrusion caused by spinal cord compression, 6Fr double lumen catheter with ballon was inserted into the spinal cord T12-T13 and filled with about 5 mL Iohexol after the exposure of spinal cord L1 by hemilaminectomy. The spinal cord blood flow (SCBF) at the L1 level before and after compression was measured by laser-Doppler flowmetry. Morphological changes of the compressed spinal cord at 14 days after compression was examined by histopathology.Results The (Texas spinal cord injury score) (TSCIS) scores of the motor function of bilateral hind limbs were highly significantly decreased (P<0.01). The blood flow of spinal cord at the L1 level was significantly decreased (P<0.05) after compression than that before. Compared with the normal control group, the model group showed abnormal vacuolization in the white matter and the number of normal neurons in the ventral horn of gray matter was significantly lower(P<0.01). Conclusions Our findings demonstrate that canine models of intervertebral disc extrusion can be successfully established by balloon catheter compression, showing local impairment of microcirculation and histological changes in the spinal cord. This canine model may provide a useful model for evaluation of therapeutic effects of acupuncture and for mechanism studies.
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2021,31(8):48-54, DOI: 10. 3969 / j.issn.1671-7856. 2021. 08. 007
Abstract:
Objective To explore the effects of salidroside ( SAL) on nuclear transcription factor-E2 related factor 2 / Kelch-like epichlorohydrin-related protein 1 ( Nrf2 / Keap1) signaling pathway and wound healing in rats with diabetic foot ulcer (DFU). Methods Diabetes was induced in rats by feeding of a high-fat and high-glucose diet and intraperitoneal injecting of streptozotocin (STZ), and the back of the foot was shaved and cut to the fascia to create an ulcer wound with an area of approximately 3 mm×7 mm to establish DFU rat model. The rats were randomly allocated to a DFU model group; Sal-L (0. 1 g(kg·d)), Sal-M (0. 2 g / (kg·d)), Sal-H (0. 3 g( kg·d)) groups, metformin group (MET, 0. 65 g / (kg·d)), and set normal blood glucose wound rats as the control group (NC group), and all were gavaged daily for 2 weeks. The body mass and concentration of fasting-blood glucose (FBG) of all the rats were measured on the 7th and 14th days of treatment; the expression of CD34 was assessed by immunohistochemistry; the microvascular density (MVD) of the wounds was calculated; the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) concentrations were measured biochemically, and the expression of Nrf2 and Keap1 proteins in the wound tissue was measured by Western blot. Results Prior to the start of treatment, there was no significant difference in the body masse between the groups, while the FBG of the DFU, Sal-L, Sal-M, Sal-H, and MET groups was higher than that of the NC group (P<0. 05). On the 7th and 14th day of treatment, the body mass, FBG, MDA content, and Keap1 protein expression in the DFU, Sal-L, Sal-M, Sal- H, and MET groups were higher than those in the NC group (P<0. 05); and the wound healing rate, CD34 positive cells, MVD, SOD activity, and Nrf2 protein expression were significantly lower (P<0. 05). The body mass, FBG, MDA content, and Keap1 protein expression in the Sal-L, Sal-M, Sal-H, and MET groups were lower than those in the DFU group (P< 0. 05); and the wound healing rate, CD34 positive cells, MVD, SOD activity, and Nrf2 protein expression were significantly higher (P<0. 05). However, there were no significant differences between the Sal-L and MET groups (P> 0. 05). Conclusions Sal may increase the antioxidant capacity and promote wound healing in rats with DFU via the Nrf2 / Keap1 signaling pathway.
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2017,27(5):19-22, DOI: 10.3969.j.issn.1671-7856.2017.05.007
Abstract:
In this paper, the present situation and development trend of the laboratory animal industry in China are expounded comprehensively and objectively. Through comparative analysis, relative to Europe and the United States one hundred years of accumulated huge resources and strong financial support, the overall laboratory animal industry in China is far behind. The whole nation system should make great efforts to realize leaping development and to catch up. Laboratory animal resources are still the foundation and weak link of the development of laboratory animal industry. This study can provide a scientific basis for the competent authorities at all levels to develop fast and efficient laboratory animal industry development strategy, and also provide reference for the development of the laboratory animal industry itself.
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CHEN Ting, LI Feng-di, DENG Wei, QIN Chuan
2014,24(1):72-73, DOI: 10.3969.j.issn.1671.7856.2014.001.017
Abstract:
Objective To compare mouse inner canthus veniplex injection and tail intravenous injection.Methods 4～6 weeks BALB/c mice were injected with normal saline respectively, the time and the difficulty were compared. Results mouse inner canthus veniplex injection is easier than tail intravenous injection.Conclusion mouse inner canthus veniplex injection is an easier and more successful method for mouse intravenous injection.
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LI Yan-hong, LIU Ying, QIN Chuan
2012(6):65-71, DOI: 10.3969/j.issn.1671.7856.2012.06.015
Abstract:
There are some correlations between the variation of thymus,T、B cells of adaptive immune system, neutrophil, macrophage, NK/NKT cells, Dendritic cells etc of natural immune system and immunosenescence. Immunosenescence mainly associated with the varies of adaptive immune system, therefor, this article will introduce the inordinately varies of the number, surface molecules, cytokines and signal transduction as well as the dysfunction of T and B cell with age.
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ZHAO Xing-mei, WANG Yan, CHEN Hua-de
2014,24(2):38-41, DOI: 10.3969.j.issn.1671.7856.2014.002.009
Abstract:
Objective To study the effects of Shenqi-fuzheng injection (SQ) in different doses injected into Zusanli acupoint in treating heart-qi deficiency syndrome and explore its dose-to-effet relationship.Methods The rat model of heart-qi deficiency syndrome was established by forced burden swimming and gavage of large doses of propranlolum. Seven groups of rats were set up with 8 rats in each group: the blank control group, the model group and 5 treatment groups which received a Chinese medicine Shenqi-fuzheng injection (SQ) in different doses (0.05 mL, 0.10 mL, 0.15 mL, 0.20 mL and 0.25 mL per rat, respectively) at ST36 acupoints. The treatment was administered for consecutive 10 days. The general conditions and symptoms of the rats were observed and recorded. The serum concentrations of atrial natriuretic peptide (ANP) and cyclic adenosine monophosphate (cAMP) were assayed by ELISA. The activity of serum superoxide dismutase (SOD) was detected by colorimetry. The pathological changes of myocardial tissue were observed using HE staining. Results Compared with the blank control group, the model group showed obvious heart failure symptoms such as fatigue, purple tongue, short and rapid breath, the concentration of ANP was increased while cAMP decreased, and SOD activity was declined (P<0.001 for all). The pathology of myocardial tissue showed inflammatory cell infiltration and seriously swollen cardiomyocytes in disordered arrangement. Compared with the model group, all treatment groups showed that symptoms were relieved, ANP concentration was decreased, and cAMP concentration and SOD activity were increased. Among them, the changes of indicators in the SQ-0.05 mL group were mildest (P<0.05) while strongest in the SQ-0.20 mL group (P<0.001). The pathological changes of myocardial tissue in the SQ-0.20 mL group were mildest and close to normal. Conclusions ST36 acupoint injection with the Chinese medicine Shenqi-fuzheng injection is an effective therapy for heart-qi deficiency syndrome in rats. The treatment effects are positively correlated with the doses of drug in the range of from 0.05 mL to 0.20 mL per rat.
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ZHAO Yong, WU Jing, MAO Feng-feng, ZHAO Shan-min, ZHANG Cai-qin, BAI Bing, SHI Chang-hong
2012(7):17-20, DOI: 10.3969.j.issn.1671.7856.2012.007.005
Abstract:
ObjectiveDiscussion the common problem of tumor-burdened in node-mice,In order to improve the success rate of tumor burden. MethodThrough analysis the influence of various factors of tumor-burden in node-mice, seek the solution of problem in tumor burdended. ResultSummarized the various factors in the tumor burden, and put forward reasonable suggestions.ConclusionNode-mice tumor burden is the base of the oncology, drug and biological products of safety evaluation and effectiveness screening. This paper is to provide reasonable suggestions for the preparation of good nude mice tumor model.
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2013,23(11):0-0, DOI:
Abstract:
[Abstract] Objective To study the effects of D-galactose on the expression of P-ERK 1/2 in hippocampus of mice and on learning and memory ability Methods Twenty Kunming mice, half male and half female, were divided into two groups. To establish aging model of mice, D-galactose was injected daily in the subcutaneous for 35 days in the dosage of 125 mg / kg. The control group was given saline. In the modeling period, the general condition of mice was observed. Step-down and morris water maze were carried out to test the learning and memory ability at the last one week. After the experiment, the animals were sacrificed to extract hippocampal tissue. The expression of P-ERK1 / 2 in hippocampal of mice was detected by western blot. Results Step-down test showed that compared with the control group, the latency in the model group decrease significantly (P <0.01) and the number of electric shock in the model group increase significantly (P <0.01). Morris water maze showed that the latency of escape in the model group were longer than the control group (P <0.01). Western blotting results showed that the expression of P-ERK1 / 2 significantly decreased in the model group and the effect is more pronounced in male mice. Conclusion D-galactose may impair learning and memory ability by inhibiting the expression of P-ERK1 / 2 in hippocampal of mice and the effect is more pronounced in male mice.
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WANG Jun-feng, SHI Mei-lian, WU Yan-qiu, GUO Jian-guang, FU Jie, SUN Zong-guo, GAO Jing-hua, XU Ping
2012(3):17-22, DOI: 10.3969/j.issn.1671.7856.2012.03.004
Abstract:
ObjectiveTo determine the growth rate, organ index, blood Physiological and biochemical Parameters of germ-free KM mice during different growing Period, baby germ-free KM mice were obtained by hysterectomy form SPF KM mice and reared by hand feeding under aseptic condition. Methods(1) Weight and body size of the mice were measured at different days(from 0 to 112days; n=60; 30♀,30♂) to create a growth curve (2) The weight of the live mice and major organ size after dissection were measured at different days selected randomly (day = 8,6,112; n = 60 30♀,30♂) to determine the growth of these mice. (3) The blood Physiological and biochemical Parameters were measured by collected blood samples from the infraorbital vessels. Results(1) The weight of germ-free KM mice increased with the growing days, and the growth rate reached maximum within 1-2weeks Post-weaning. Significant difference was found between males and females(P＜0.05) after 4th week. (2) All the major organs (heart, liver, spleen, lung and brain) increased with the ages except the thyme gland, and the growth of cecum size was obvious. (3) Difference of blood Physiological and biochemical Parameters was found between males and females at the same age, and the difference types increased with the growth of mice age. ConclusionThe results of growth rate and blood physiological and biochemical parameters could provide reference for the evaluation of germ-free KM mice colony.
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ZHAO Jing-shu, WANG Rong, ZHANG Jing-yan, WU Yan-chuan, JI Zhi-juan
2012(2):66-69, DOI: 10.3969/j.issn.1671.7856.2012.02.015
Abstract:
ObjectiveTo establish an in vitro model of caloric restriction (CR) with human neuroblastoma cell line SH-SY5Y cells and observe the effects of different energy supplies on the growth of SH-SY5Y cells. MethodsHuman neuroblastoma cell line SH-SY5Y cells were cultured in different media with glucose at different concentrations:low glucose group (2 g/L), normal glucose group (3.15 g/L) and high glucose group (4.5 g/L). MTT metabolic rate, cell growth curve and LDH leakage rate were measured to observe the cell growth status of different groups. ResultsCompared with the normal control group, the cells of the high glucose group had shorter cytoplasmic processes and shrank cell bodies, showed a little bit lower MTT metabolic rate, higher LDH leakage rate and poorer growth status, while the cultured cells of the low glucose group had more extensive processes, greatly lower MTT metabolic rate and lower LDH leakage rate, and the cells grew slower but showed good morphology. ConclusionsCulture at high glucose concentration is injurious to cells and induces a higher metabolic rate, so the cells are inclined to be senescent and to die. Culture at low glucose concentration in an allowable range of caloric restriction is protective to the cells, unharmful to the cells, and favorable for cell growth and prolongs the cell survival.
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2013,23(11):0-0, DOI:
Abstract:
Objective To analyze the difference of growth and organ coefficient between mutant mice and normal mice using inbred BALB/c curly mutant mouse model．Methods 21d，42d and 63d three different age groups of BALB/c mutant curly and normal BALB/c mice of 20 each，half male and half female，were selected to measure body weight，head length，body length，tail length and to compare the head body ratio，tail body ratio and organ coefficient．Results F4 generation BALB/c mutant curly has completely homozygous mice．Head body ratio，tail body ratio of mutant curly mice aged 21d and 42d were lower than those of normal mice (P< 0.05)，body weight，head body ratio，tail body ratio of mutant curly mice aged 63d were lower than those of normal mice (P< 0.05)．Heart，spleen，ovarian，uterine coefficient of 21d mutant mice were greater than those of normal mice (P< 0.05，P＜0.01)；heart and thymus coefficient of 42d mutation curly mice were lower than those of normal mice，brain and testis coefficient were higher than those of normal mice (P< 0.05，P< 0.01)；heart and uterus coefficient of 63d mutant curly mice lower than those of normal mice，brain coefficient was higher than those of normal mice (P<0.05，P< 0.01)．Conclusion There are differences in appearance and organ coefficient of BALB/c mutant curly and normal mice，these different mutations have very important significance for the study of BALB/c mutant curly mice growth，cardiovascular system，immune system and reproductive system．
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LIU Qin, WANG Li-ping, CHEN Fang, ZHANG Yi
2015,25(7):69-73, DOI: 10.3969.j.issn.1671.7856. 2015.007.015
Abstract:
Adipose-derived stem cells(ASCs) as potential seeded cells have been widely used in tissue engineering. Thus to obtain enough, high activity, high purity adipose-derived stem cells is the particular important premise of the application in tissue engineering. In this paper, the isolation and purification methods of ASCs were reviewed and the merit and demerit of different methods were compared in order to provide theoretical basis for safe and high-effective isolation and purification of ASCs.
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WEI Rong-fei, LI Meng-yuan, XU Da-mo, GAO Ran
2017,27(6):33-36,45, DOI: 10.3969.j.issn.1671-7856.2017.06.007
Abstract:
Objective To establish a C57BL/6 mouse model of intestinal infection induced by S. Typhimurium. Methods In order to improve the infectious sensitivity of S. Typhimurium, C57BL/6 mice were intragastrically given 5% (w/v) NaHCO3. Then mice were challenged with S. Typhimurium. The health condition, survival and body weight of mice were observed from day 0 to day 7 after the bacterial infection. The pathological changes were also examined. Results the mice challenged with S. Typhimurium showed decreased body weight and typical clinical signs, including in appetence, piloerection and low survival rate. Macroscopic dissection revealed that intestinal hyperemia and swelling were founded in the mice challenged with S. Typhimurium. Histopathology showed intestinal epithelial and mucosal damages. Conclusions We have successfully established a C57BL/6 mouse model of S. Typhimurium infection. This model may be of crucial significance for studying the biological functions of associated immunological molecules or cytokines in the process of inflammatory bowel disease induced by S. Typhimurium.
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ZHANG Zhicheng, YUAN Yuan, WANG Xuan, SONG Qingkai, DAI Jiejie
2018,28(5):21-27, DOI: 10.3969/j. issn. 1671 -7856. 2018. 05. 005
Abstract:
Parkinson’s disease (PD) is a progressive neurodegenerative disorder, with an etiology that is now considered to be due to interaction between genetic and environmental factors. Typical PD features include loss of dopaminergic neurons in the nigrostriatal region, with typical motor traits of PD associated with dopamine deficiency. Animal models have contributed to determining PD etiology and pathogenesis, as well as testing new therapeutic schedules and novel drug research. Rodents, tree shrews, primates, and other animal models of PD have been established by different method . These models each have their own advantages and limitations, showing different clinical features and pathological mechanisms to those in humans. Therefore, the appropriate model for scientific research must be carefully considered. This article reviews the main neurotoxic and transgenic models of PD.
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LOU Qi, SHI Qiao-juan, GUO Hong-gang, LI Wei, LU Ling-qun, ZHOU Wen-wei, SA Xiao-ying
2012(3):5-11, DOI: 10.3969/j.issn.1671.7856.2012.03.002
Abstract:
ObjectiveTo investigate the pathogenesis of nonalcoholic fatty liver disease(NAFLD), provide a reference for the evaluation of fatty liver therapeutic effect, the liver function, lipid metabolism,insulin resistance and liver apoptosis of NAFLD rats established by high cholesterol feeding were continuously monitored from 4~16 weeks. Methods 40 NAFLD rats established by high cholesterol feeding were randomly divided into the 4,8,2,6 weeks model group and a group of normal rats were set up for control, the serum GLU、CHO、TG、HDL、LDL、GPT、GOT and insulin were tested, the liver apoptosis and pathological changes were observed, then analyzed the effect of the liver function, lipid metabolism,insulin resistance and apoptosis on the pathological changes in non-alcoholic fatty liver rats. ResultsAfter 4 weeks of high cholesterol feeding, the rats had got the liver injury, disorder of lipid metabolism, insulin resistance. Liver cell apoptosis were increased obviously, and pathological changes were characterized by cell steatosis and inflammatory, the lesions became more serious with time went on. ConclusionsRats established by high cholesterol feeding could get the nonalcoholic fatty liver disease and the lesions became more serious with time over during 4~16 weeks. Lipid metabolism disorder and insulin resistance were the important cause of liver cell steatosis and inflammatory. The model we established is suitable for the evaluation of fatty liver therapeutic effect.
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PENG Zhuo-ying, CONG Zhe, LI Xiang, XUE Jing, WEI Qiang
2017,27(9):1-6, DOI: 10.3969.j.issn.1671-7856.2017.09.001
Abstract:
Objective To stimulate a human monocytic cell line THP-1 cells to differentiate into M1, M2 macrophages and dendritic (DC) cells by optimization of different methods, and lay the foundation for the study of M1, M2 and DC cell models in vitro. Methods THP-1 cells were stimulated by PMA and GM-CSF/M-CSF, respectively. Then, they were induced to differentiate into M1, M2 macrophages and DC cells by adding different cytokines, such as LPS, IL-6 and IFN-γ for M1 macrophages, IL-4, IL-13 and IL-6 for M2 macrophages, and IL-4 for DCs. Subsequently, the morphology of cells was observed and the expression of cell surface (CD) molecules was detected by flow cytometry. Results After stimulation with the two methods, the trends of CD molecules expression were basically the same. The expression of CD80 and CD86 on the THP-1-M1 cells were increased significantly, and CD163 and CD209 were highly expressed on the THP-1-M2 cells. For THP-1-DC cells, the expression of CD14 was significantly decreased, while the expression of CD80, CD86 and CD11c increased. M1, M2 macrophages and DC cells were adherent after stimulation with PMA. However, DC cells were partially adherent after GM-CSF/M-CSF treatment. M1 and M2 macrophages were also growing in suspension. Conclusions Both methods used in this study can successfully induce THP-1 cells to differentiate into different subtypes, but there are some differences in the morphology of the induced cells. Appropriate stimulation method can be selected according to the experimental requirements.
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JI Xiao-fang, YU Hui-qing, YUE Liang-liang, XU Xu-jun, CHEN Jian-quan, CHENG Guo-xiang, LIU Zong-ping
2017,27(8):75-79, DOI: 10.3969.j.issn.1671-7856.2017.08.015
Abstract:
Objective In order to study the biological characteristics of macrophages and provide the materials to study the survival mechanism of intracellular parasites, we conducted this study to establish a high-purity alveolar macrophage isolation and culture method. Methods Goat lungs were lavaged with normal saline in sterile environment several times, and cells were collected and then goat alveolar macrophages were purified by density gradient centrifugation using peripheral blood mononuclear cells (PBMC) solution. The isolated goat alveolar macrophages were cultured in cell culture medium containing 10% fetal bovine serum and cell morphology was observed under an inverted microscope every day,and the phagocytic activity of the cells was detected by chicken red blood cell phagocytosis test. Flow cytometry was used to detect CD14, a characteristic monocyte-macrophage surface marker. Results The adherent cells were characterized by typical macrophage morphology, pseudopodia and protrusions, showing round and irregular shape, rich cytoplasm, and large cell body. Of the cultured macrophages, 54.5% could phagocytize chicken erythrocytes and showed good phagocytic activity. After one month of in vitro culture, 93.7% of the cells were able to express CD14 antigen, which had a macrophage-specific immunophenotype. Conclusions The alveolar macrophages obtained in this study have high purity and good bioactivity, thus provide a cell model for studying the immune mechanism of intracellular parasites.
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LI Rifei, YUAN Na, YE Dongyang, LI Riyong, LI Yaohan, ZUO Runan, SHI Xi, CHEN Qiang, LI Yinqian
2018,28(2):113-118, DOI: 10.3969. j. issn. 1671 -7856. 2018. 02. 020
Abstract:
Breast cancer is the most common spontaneous malignancy in women, causing a serious threat to women’s health. Experimental animal models have been important research tools in bringing insights into the related mechanisms of breast cancer, as well as in delivering improved therapies for the disease. To reveal the pathogenesis of various breast cancers and facilitate the development of new drugs, ideal animal models of breast cancer should share some common tumor molecular characteristics and biological behavior with that of human breast cancer. In this review, five types of experimental animal breast cancer models were included, which may provide a basis for research on diagnosis and treatment of human breast cancer.
