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Objective:To investigate the effects of cannabidiol(CBD)on the NOD-like receptor protein 3(NLRP3)inflammasome in the brains of rats with multiple cerebral concussions(MCC).Methods:Rats were subjec-ted to the MCC model and divided into Sham,MCC,vehicle(MCC+TW),CBD-L(10 mg/kg),and CBD-H(40 mg/kg)groups.Immunofluorescence double staining was used to observe changes in NLRP3 and microglial cells in the brain,and Western Blot was performed to detect the expression changes of the NLRP3 inflammasome.Results:A sig-nificant increase in lectin-positive microglial cells of the cortex with enlarged cell bodies and elevated immunofluores-cence intensity of NLRP3 in the activated microglial cells was revealed by immunofluorescence double staining following MCC(P＜0.05).The immunofluorescence intensity of NLRP3 in the activated microglial cells was downregulated by the administration of CBD,with a more pronounced effect observed in the CBD-H group compared to the CBD-L group(P＜0.05).The expression of NLRP3,caspase-1,and apoptosis-associated speck-like protein(ASC)in the cortex,hippocampus,and basal ganglia of rats following MCC was significantly increased,as shown by Western Blot analysis(P＜0.05),and cortical areas are more elevated.The expression of these proteins in different brain regions was reduced by CBD-10 and CBD-40 intervention(P＜0.05).Conclusion:Cannabidiol can reduce the inflammatory response of multiple cerebral concussions rats through NLRP3 inflammasome and protect nerve tissue.
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Objective:To explore the potential molecular mechanism of Erigeron breviscapus in the prevention and treatment of ischemic stroke through network pharmaco-molecular docking.Methods:The Chinese Herbal Medicine Systematic Pharmacology Platform(TCMSP)database provided active ingredients and potential targets of Erigeron breviscapus.Ischemic stroke-related targets were searched through the Online Mendelian Inheritance in Man(OMIM)database,the bioinformatics and chemoinformatics(DrugBank)database and human gene comprehensive database(GeneCards).The targets criteria were de-weighted by the Protein Data Bank(Uniprot)and imported into the Venny online platform to obtain the intersecting targets of both.The intersecting targets were visualized by STRING database and Cytoscape 3.7.1 software for protein-protein interaction(PPI),followed by the enrichment analysis of intersection targets for gene ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway.AutoDock Vina1.5.6 software was used to verify the molecular docking of key active ingredients and core targets and realize the vi-sualization of docking results.Results:Eleven active ingredients and 176 targets were obtained.There were 690 targets ischemic stroke-related targets and 69 intersection targets.Through PPI network,10 core genes were screened according to the degree value,including tumor necrosis factor(TNF),interleukin-6(IL-6),serine/threonine protein kinase 1(AKT1),interleukin-1β(IL-1β)and vascular endothelial growth factor A(VEGFA).KEGG enrichment included the advanced glycation end products-receptor(AGE-RAGE)signaling pathway,interleukin-17(IL-17)signaling pathway,tumor necrosis factor(TNF)signaling pathway,etc.The top 3 active ingredients and the top 5 target proteins were selected according to the degree value,and the molecular docking results demonstrated a considerable binding ability.Conclusion:Erigeron breviscapus in the treatment of ischemic stroke may work through multiple active ingredients,such as quercetin,kakaferol,and luteolin,which act on TNF,IL-6,AKT1,IL-1β,and VEGFA,and through a varie-ty of signaling pathways such as IL-17,TNF,etc.showing the characteristics of multi-components,multi-targets,and multi-pathways.
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Objective This study was aimed to investigate the expression of monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF) mRNA in rats with acute methanol poisoning. Methods Animal models of acute methanol poisoning in rats were duplicated using a plexiglas chamber exposed to a mixture of N2O/O2. Right atrium venous blood of rats were taken at each time point (2 h, 12 h, 24 h,3 d,1 w), and gas chromatography was used to determine the methanol concentration of the rat blood (n=5) . Then got brain tissue to extract total RNA and reverse transcription (n=3) . SYBRGreen real-time PCR was used to monitor the expression of MCP-1 and VEGF mRNA. Results (1) Results of methanol concentration determination:The blood methanol concentration of the low-dose group was significantly increased in comparison with that of the saline control group at 2 h and 12 h time points ( < 0.05) . In the high-dose group, the blood methanol concentration was increased significantly compared with the low-dose group as well as the saline group at 2 h, 12 h and 24 h time points ( < 0.05); (2) The expression of MCP-1 mRNA: The expression level of MCP-1 were significantly enhanced along with the time lapse after acute poisoning,and became most severely at 24 h. The expression levels of MCP-1 have significant differences in groups,of which high-dose group was higher than low-dose group at 2 h, 3 d and 1 w ( <0.05);(3) The expression of VEGF mRNA:The expression level of VEGF was significantly enhanced along with the time lapse after acute poisoning,and became most severely at 24 h. The expression levels of MCP-1 have significant differences in groups,of which high-dose group was higher than low-dose group at 2 h and 12 h ( <0.05) . Conclusion The expression levels of MCP-1 and VEGF mRNA were significantly enhanced, and the degree of poisoning was apparently related with the dose administered. MCP-1 and VEGF might play the important roles in the pathogenesis and progression of brain injured.
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AIM: To study the effects of Ginkgo biloba extract (GbE) on cerebral ischemia-reperfusion injury. METHODS: Cerebral ischemia-reperfusion injury was produced by 10 min or 20 min occlusion of bilateral carotid arteries followed by 5 d or 1 d reperfusion in gerbils. Ninety-five gerbils were divided into 4 groups: sham-operation, ischemia-reperfusion, GbE 50 mg*kg-1 and GbE 100 mg*kg-1 groups. Drugs were given intragastrically 2 d prior to ischemia and during reperfusion. The effects of GbE on the contents of calcium, sodium, water in cortex, and lipid peroxide(LPO) in brain hemispheres, as well as the density of neuron in hippocampal CA1 sector were observed. RESULTS: GbE could reduce the increase of calcium, sodium, water content in a manner of dose-depedance. The dosage of GbE 100 mg*kg-1 could decrease the content of LPO and the mortality, increase the density of neuron in hippocampal CA1 sector. CONCLUSION: GbE has protective effects on cerebral ischemia reperfusion injury.
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AIM: To observe tumor-seeking specificity of [ 125 I]-(A14)-insulin in human hepatoma bearing nude mice METHODS: The in vivo tissue distribution and inhibition studies of [ 125 I]-(A14)-insulin in human hepatoma bearing nude mice were performed RESULTS: In the tissue distribution study, a significant accumulation of [ 125 I]-(A14)-insulin was observed in the tumor site of nude mice The tumor/blood and tumor/muscle radioactive ratio gradually increased with lengthening time following injection of [ 125 I]-(A14)-insulin The inhibition ratio in the tumor tissue of nude mice in the inhibition study was 35 0% CONCLUSION: There is a specific uptake of [ 125 I]-(A14)-insulin through receptor-mediated process in the hepatoma tissue of nude mice [
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Objective To investigate the toxicity of alpha terthienyl to the larvae of Aedes albopictus , its influencing factors and effect on the larva deve lopment. Methods Under experimental ultraviolet A (UVA),the number of dead,pupal or eclosive mosquito larvae was determined on the condition of different doses of alpha terthienyl and different disposal time in the dark;the number of dead larvae was also determined under sunlight on the condition of different doses of alpha terthienyl and different disposal time to water. Results The LC 50 of alpha terthienyl to Aedes albopictus larvae was 2.37 ?g/L under UVA. The best effect was shown when the larvae were incubated with alpha terthienyl 3 h in dark. Alpha terthienyl could significantly inhibit the larva deve lopment and the emergence of the pupae. Under strong sunlight, the larvae were quickly killed by high concentration alpha terthienyl. The 24 hours effect of alpha terthienyl was better when it was applied at 5 AM than that of at 10 AM and 1PM. Conclusion Alpha terthienyl is an effective, practicable larvicide which prohibits the growth and development of the larvae of Aedes albopictus .
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AIM: To investigate the changes of regional cerebral blood flow(rCBF) in AIDS patients without acquired immunodeficiency syndrome dementia complex(ADC). METHODS: 99m Tc-ECD brain SPECT imaging was performed in 4 AIDS patients without ADC and 16 sex and age-matched normal controls. The rCBF percentage compared to the cerebellum were calculated using a semi-quantitative processing software.RESULTS: The rCBF in the right and left frontal, temporal, porietal lobe, basal ganglia and thalamus, cyrus rectus and pons were decreased significantly in AIDS patients without ADC than those of the control subjects ( P
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Objective To explore possible mechanisms of hepatic fibrosis by investigating the ultrastructural dynamic changes of liver tissue, especially several kinds of cells related to hepatic fibrosis.. Methods. Murine schistosomal hepatic fibrosis model was established by infecting mice with Schistosoma japonicum cercariae. Routine transmission electron microscopy was used to observe the liver tissue. H.E. staining was used for examining the pathological changes. . Results . H.E. staining showed that the model was established successfully. Ultrastructural observation showed that at the 6th week after infection, the necrosis of hepatocytes around the acute granulomas occurred; the number of sinusoidal endothelial fenestrae and vitamin A droplets in fat-storing cells decreased; large phagosomes and rough endoplasmic reticulum could be seen in the cytoplasm of Kupffer′s cells. At the 8th week, steatosis was found in some hepatocytes, some microvilli emerged on a few inter-hepatocytic surfaces and the inter-hepatocytic spaces were enlarged. Large collagen fibrillar bundles filled in the perisinusoidal spaces, and capillarization of hepatic sinusoids was observed. Secretory vesicles filled with collagen fibrils appeared in the cytoplasm of fat-storing cells with large amount of collagenous fiber bundles surround the cells. Rough endoplasmic reticulum increased in Kupffer′s cells. At the 10th week, fat-storing cells were activated and transformed into myofibroblasts. At the 12th week, the number of myofibroblasts decreased but that of fibroblasts and fiber cells increased. . Conclusion . Activation of fat-storing cells and transformation from fat-storing cells into myofibroblasts are the critical link in the development of hepatic fibrogenesis following schistosome infection. Kupffer′s cells, necrotic hepatocytes and sinusoidal endothelial cells may relate to the activation of fat-storing cells. Capillarization of hepatic sinusoids possibly accelerates the development of hepatic fibrosis.
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AIM: To observe the immunoregulation of all ogeneic cornea on the human peripheral blood T lymphocytes in vitro. METHODS: After Co-culture of human peripheral blood lymphocytes and allogeneic cornea in vitro, T lymphocytes were labeled by monoclonal ant ibody, and analyzed by fluorescent activated cell sorter (FACS). RESULTS: CD25 expression on T lymphocytes in control was 25.2%, after stimulated by the allogeneic cornea or PDB, CD25 expression on T lymphocy tes was 56.8% and 80.9%, respectively. After stimulated by the allogeneic corn ea, CD25 expression on CD 4+ or CD 8+ T lymphocytes were 67.3% and 52.3% , respectively. CONCLUSION: Allageneic cornea stimulates CD25 expression on huma n peripheral blood T lymphocytes, and the CD25 expression on CD 4+ T lymphocy tes is more prominent than CD 8+ T lymphocytes.