ABSTRACT
Objective:Computer network pharmacology technology was used to screen the main active ingredients of Tripterygium hypoglaucum radix-Leonurus japonicus herba for the treatment of rheumatoid arthritis(RA), predict the targets of the active ingredients, establish a pharmaceutical ingredient-active ingredient-target network, and further explore the potential mechanism of Tripterygium hypoglaucum radix-Leonurus japonicus herba for the treatment of RA. Method:RA disease targets were collected through DisGeNET, TTD, and Drugbank databases, the potential active components of Tripterygium hypoglaucum radix and Leonurus japonicus herba and their corresponding targets were obtained from the Chinese Medicine System Pharmacology Analysis Platform (TCMSP); common targets for drugs and diseases were screened by using the ImageGP platform; a common target interaction (PPI) network model was constructed by using the String database, a "drug-active ingredient-key target" network was constructed by using Cytoscape software, a protein interaction network was constructed by using the String database, gene function (GO) analysis and pathway enrichment analysis based on the Kyoto Gene and Genomic Encyclopedia (KEGG) were performed by using the ClueGO plug-in. Result:Through screening, 9 active pharmaceutical ingredients were obtained, involving a total of 235 targets, and 7 active ingredients were related to the disease targets. 24 common targets for Tripterygium hypoglaucum radix Leonurus japonicus herba-disease were obtained. The common targets were mainly enriched in 278 biological processes and 141 signaling pathways to play a role in the treatment of RA. Conclusion:The therapeutic effect of Tripterygium hypoglaucum radix Leonurus japonicus herba on RA reflects the characteristics of multi-component-multi-target-multi-channel of traditional Chinese medicine, and provides a scientific basis for explaining its mechanism and clinical application of RA.
ABSTRACT
Objective:To study the mechanism of Wulingsan (WLS) in the treatment of rheumatoid arthritis (RA) by network pharmacology. Method:The active components of WLS were screened on traditional Chinese medicine systems pharmacology(TCMSP) platform, and the targets were predicted in DragBank database. The "component-target" network was constructed by Cytoscape 3.2.1 software. Disease targets were searched in TTD, DrugBank and DisGenet databases. The Venn diagram was built to extract the target of WLS in the treatment of RA, and the gene oesthetics(GO) function annotation and Kyoto Encyclopedin of Genes and Genomes(KEGG) signal pathway enrichment analysis were performed by cluego plugin. The TCM-component-target-pathway network of WLS was constructed, and the network feature analysis was made by Network Analyzer. Result:Totally 52 components and 297 potential targets in WLS and 1 845 targets relating to RA were excavated, and 49 common targets of WLS-RA were obtained. The common targets were mainly enriched in 322 biological processes and 31 signaling pathways. Conclusion:WLS may regulate targets, such as prostaglandin epoxide synthase 2 (PTGS2), transforming growth factor-β1 (TGF-β1), cysteine aspartate protein-3 (Caspase-3), transcription factor p65 (RELA), progesterone receptor (PGR), and adjust cancer-related pathways, tumor necrosis factor(TNF) signaling pathways, interleukin-17(IL-17) signaling pathways, nuclear factor-κB(NF-κB) signaling pathways, Th17 cell differentiation, so as to inhibit the inflammatory response, regulate immune function and adjust apoptosis to treat rheumatoid arthritis.
ABSTRACT
The severe local thermal trauma activates a number of systemic inflammatory mediators, such as TNF-α, NF-κB, resulting in a disruption of gut barrier. The gastrointestinal tight junction (TJ) is highly regulated by membrane-associated proteins including zonula occludens protein-1 (ZO-1) and occludin, which can be modulated by inflammatory cytokines. As splenectomy has been shown to reduce secretion of cytokines, we hypothesized that (1) severe scald injury up-regulates TNF-α and NF-κB, meanwhile down-regulates expression of ZO-1 and occludin, leading to the increased intestinal permeability, and (2) splenectomy can prevent the burn-induced decrease in ZO-1 and occludin expression, resulting in improved intestinal barrier. Wistar rats undergoing a 30% total body surface area (TBSA) thermal trauma were randomized to receive an accessorial splenectomy meanwhile or not. Intestinal injury was assessed by histological morphological analysis, and serum endotoxin levels, TNF-α, NF-κB, ZO-1 and occludin levels were detected by Western blotting in the terminal ileum mucosal tissue. 30% TBSA burn caused a significant increase in serum endotoxin levels, but NF-κB, and TNF-α, and the average intestinal villus height and mucosal thickness were decreased significantly. Burn injury could also markedly decrease the levels of ZO-1 and occludin in terminal ileum mucosal tissue (all P<0.01). Splenectomy at 7th day after burn significantly reversed the burn-induced breakdown of ZO-1 and occludin (all P<0.01). The results of this study suggest that severe thermal injury damages the intestinal mucosal barrier. Splenectomy may provide a therapeutic benefit in restoring burn-induced intestinal barrier by decreasing the release of inflammatory cytokines and recovering TJ proteins.
Subject(s)
Animals , Female , Male , Rats , Blotting, Western , Endotoxins , Blood , Hot Temperature , Intestinal Mucosa , NF-kappa B , Blood , Occludin , Metabolism , Rats, Wistar , Splenectomy , Tumor Necrosis Factor-alpha , Blood , Zonula Occludens-1 Protein , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To understand the immunological status of Japanese encephalitis (JE) antibodies amongst migrant workers and to provide epidemiological basis for public health strategies on JE prevention and control in Shenzhen.</p><p><b>METHODS</b>A multi-stage random sampling method was used, and 1003 migrant workers aged 18 to 60 from 44 factories were investigated and their serum specimens were collected. The enzyme-linked immunosorbent assay (ELISA) was used to detect JE antibodies qualitatively.</p><p><b>RESULTS</b>The gross IgG seroprevalence rate for JE was 20.2% (203/1003). Sex-specified seroprevalence was 21.2% (103/485) for male and 19.3% (100/518) for female, respectively (χ(2) = 579, P > 0.05). Age-specific seropositive rates were 22.6% (12/53) for those below 20 years old, 18.7% (120/642) for those between 20-years old, 26.0% (58/223) for those between 30-years old and 15.3% (13/85) for those on or above 40 years old (χ(2) = 7.96, P > 0.05). Proportions for self-reported positive immunization, non-immunization and unclear immunization history were 22.1% (30/136), 22.1% (51/231) and 19.2% (122/636), respectively (χ(2) = 501, P > 0.05). Seroprevalence by region of origins showed that workers from Guangdong province was the highest (30.5%, 50/164), followed by workers from Guangxi (29.7%, 22/74) whilst workers from Shan(3)xi (5.4%, 2/37) had the lowest rate. Seroprevalence rate for managers (29.0%, 31/107) was higher than that of technicians (7.1%, 1/14) (χ(2) = 21.78, P < 0.05). Serological positive rate of workers with university or above educational background was the highest (32.7%, 16/49), followed by that for individuals with college degree (10.3%, 10/97) (χ(2) = 13.02, P < 0.05).</p><p><b>CONCLUSION</b>No associations are detected between JE seroprevalence and age, or sex, or self-reported immunization histories amongst migrant labor workers in Shenzhen. However, correlations between JE serological positive rate and region of origins, occupation and educational attainment are found to be significant. The gross seroprevalence of JE antibodies suggests that the level of JE antibodies amongst Shenzhen migrant workers is low and the population immunity barrier has yet to be established. It is necessary to strengthen prevention and control strategies of JE among labor workers of Shenzhen.</p>