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Objective::Bioinformatic analysis was used to compare the gene expression profile between asthma patients and healthy people, and the gene characteristics of asthma were preliminarily identified and the potential mechanism and drugs were revealed. Method::The GSE74986 gene expression profile was downloaded from the gene expression omnibus (GEO) and the differentially expressed genes (DEGs) were analyzed by GEO2R. Then the gene heat map of DEGs was made by Morpheus, and their gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis were performed by DAVID 6.8. Moreover, the protein-protein interaction (PPI) network and hub genes were constructed by String 10.5. Finally, the significant modules were analyzed by MCODE in Cytoscape 3.6.1, small molecule drugs related to asthma were screened through Coremine Medical. Result::A total of 510 DEGs were screened, including 29 up-regulated genes and 481 down-regulated genes. DEGs were mainly involved in these biological processes and pathways, including chromatin silencing, transcriptional regulation of RNA polymerase Ⅱ promoter, protein transport, messenger RNA (mRNA) processing, RNA splicing, ubiquitin-mediated proteolysis, protein processing in the endoplasmic reticulum, RNA transport, and myeloid differentiation factor (MyD)-dependent Toll-like receptor signaling pathway, platelet activation, nucleotide binding oligomerization domain (NOD)-like receptor signaling pathway and so on. A total of 9 hub genes were obtained, including T-complex protein 1 subunit theta (CCT8), T-complex protein 1 subunit alpha (TCP1), 26S protease regulatory subunit S10B (PSMC6), heat shock protein 90 alpha (HSP90A)A1, cell cycle protein C (CCNC), HSP90AB1, 26S proteasome non-ATPase regulatory subunit 6 (PSMD6), ubiquitin-specific protease 14 (USP14) and eukaryotic translation initiation factor 4E (EIF4E). Two important modules were obtained. The genes in two modules mainly involved these biological process, such as splice, ubiquitin-mediated proteolysis, protein modification, RNA modification and so on. Some potential molecular drugs for the treatment of asthma, such as anisomycin and genistein, have been developed. Conclusion::DEGs and hub genes can contribute to understanding the molecular mechanism of asthma and providing potential therapeutic targets and drugs for the diagnosis and treatment of asthma.
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Objective:To analyze the effective active ingredients of Belamcandae Rhizoma and Ephedrae Herba couplet medicines(BREH)in the treatment of bronchial asthma based on network pharmacology, in order to predict their potential targets and explore the mechanism. Method:Active ingredients and predict their targets were collected from traditional Chinese medicine system pharmacology(TCMSP) database. Drugs-components-targets network and Proteins interations network were built by STRING database and Cytoscape software. ClusterProfiler and ClueGO was used to enrich the biological function and metabolic pathway of core targets. Finally, candidate targets were mapped onto the pictures of correlative pathways. Result:The 38 effectively active ingredients were screened out, including luteolin, stigmasterol, diosmetin, naringenin, quercetin, iristectorigenin A, isorhamnetin. There were 214 candidate targets relating to bronchial asthma, and 55 core ones were selected to be mainly studied, including RAC-alpha serine/threonine-protein kinase (Akt1), tumor necrosis factor (TNF), mitogen-activated protein kinase 1 (MAPK1), vascular endothelial growth factor A (VEGFA), interleukin-10 (IL-10), NF-kappa-B inhibitor alpha (NFKBIA), and a number of relevant gene ontology(GO) functions and Kyoto Encyclopedin of Genes and Genomes(KEGG) pathways were enriched. Conclusion:BREH may regulate the Th1, Th2 and Th17 cell differentiations, Asthma, IL-17, phosphatidylinositol-3-kinases(PI3K)/Akt, MAPK, NF-κB, VEGF signaling pathways, so as to interfere the process of cell metabolism, and inhibit gene expression of proinflammatory factor in the treatment of bronchial asthma.
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Objective: To explore the potential mechanism of Shema Zhichuan liquid in treatment of asthma by network pharmacology. Method: Bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine (TCM), systematic pharmacological database and analysis platform of TCM were employed to find the components in Shema Zhichuan liquid and their targets, and asthma-related genes were obtained from the comparative toxicogenomics database (CTD). The data set of Shema Zhichuan liquid-gene and asthma-gene were imported into the Draw Venn Diagram for intersection analysis. The obtained data set of Shema Zhichuan liquid-asthma-gene was imported into String 11.0 for protein-protein interaction (PPI) analysis, and was visualized by Cytoscape 3.6.1, and further important modules were analyzed with MCODE. DAVID 6.8 was used to analyze pathway enrichment and biological process of Shema Zhichuan liquid-asthma-gene. Result: A total of 399 components and 2 099 potential targets were obtained from Shema Zhichuan liquid, 98 asthma-related targets were retrieved, 45 common genes and 16 hub genes were screened, including transforming growth factor-β1(TGF-β1), heme oxygenase-1 (HMOX1), interleukin-4 (IL-4), etc. Enrichment analysis showed that the common biological processes of Shema Zhichuan liquid and asthma were related to inflammation, contraction and remodeling of airway, cell proliferation and apoptosis, etc. The common biological pathways mainly included tumor necrosis factor (TNF) signaling pathway, receptor with high affinity for immunoglobulin E (Fc epsilon RI) signaling pathway, nuclear transcription factor-kappa B (NF-κB) signaling pathway, nucleotide binding oligomerization domain (NOD)-like receptor signaling pathway and so on. Conclusion: Shema Zhichuan liquid serves as a multi-target, multi-pathway treatment for asthma, which can provide a reference for the further research and clinical application of this preparation.
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The randomized controlled trials( RCTs) about modified Sanzi Yangqin Decoction in the treatment of patients with exacerbation of chronic obstructive pulmonary disease( AECOPD) were collected from 7 databases( PubMed,CNKI,etc.) till December25,2018 from their inception. All the studies searched were strictly evaluated and independently screened by two researchers according to the inclusion and exclusion criteria,and the methodological quality of included studies was evaluated. In order to systematically review the efficacy and safety of modified Sanzi Yangqin Decoction for treating AECOPD,the Meta-analysis and trial sequential analysis were conducted by using Stata/SE 14. 0 and TSA 0. 9. 5. 10 Beta,respectively. A total of 22 RCTs involving 2 012 patients were included. The results of Meta-analysis suggested that: as compared with the control group,the clinical symptoms in AECOPD patients were improved( RR = 1. 19,95%CI[1. 15,1. 24],P = 0); the pulmonary functions including forced expiratory volume in one second( FEV_1)( SMD= 0. 96,95%CI[0. 39,1. 52],P= 0. 001),the percentage of forced expiratory volume in one second( FEV_1%)( SMD =0. 80,95%CI[0. 20,1. 41],P = 0. 009),forced vital capacity( FVC)( SMD = 0. 69,95% CI[0. 06,1. 31],P = 0. 032),first seconds breathing volume percentage of forced vital capacity( FEV_1/FVC) were improved( SMD = 0. 81,95%CI[0. 64,0. 97],P = 0);the arterial oxygen partial pressure( PaO_2) was improved( SMD= 0. 87,95%CI[0. 41,1. 32],P= 0); the arterial partial pressure of carbon dioxide( PaCO_2) was decreased( SMD =-0. 91,95%CI[-1. 33,-0. 49],P = 0) in the trial group. In addition,the incidence of adverse reactions in the experimental group was low,and there were no serious adverse events. The trial sequential analysis( TSA) showed that the studies included in the improvement of clinical efficacy had passed the conventional and TSA threshold at the same time,further confirming the efficacy of trial group. This research showed that,conventional Western medicine treatment,combined with modified Sanzi Yangqin Decoction in treating acute exacerbation patients with chronic obstructive pulmonary disease could improve the clinical efficiency and pulmonary functions,improve the PaO_2,decrease the PaCO_2,with a high safety. However,the quality of existing research is low,requiring more high quality clinical trials for further validation.
Subject(s)
Humans , Drugs, Chinese Herbal , Therapeutic Uses , Forced Expiratory Volume , Lung , Pulmonary Disease, Chronic Obstructive , Drug Therapy , Randomized Controlled Trials as TopicABSTRACT
<p><b>OBJECTIVE</b>To investigate the allo-NK cell-mediated killing effect enhanced by decitabine on leukemia stem cells(LSC) and the underlying mechanisms.</p><p><b>METHODS</b>LSC were separated from KG1a cells by using immunomagnetic beads. Allo-NK cells were isolated and purified from PBMC of healthy donors. Cytotoxicity of allo-NK cells against LSC were measured by LDH releasing assay. The apoptosis induced by allo-NK cells in LSC and the expressions of NKG2D ligands including MICA/B and ULBP1-3 on LSC were detected by flow cytometry.</p><p><b>RESULTS</b>The killing rate of allo-NK cells to LSC treated with 10 µmol/L decitabine for 24 hours was significant higher than that to LSC without treatment(60.52%±3.52% vs 22.08%±2.07%, 73.93%±2.33% vs 28. 99%±3.13%, 83.08%±1.32% vs 36.44%±2.40%, respectively)at the effector-target ratios of 5:1, 10:1, 20:1 (P<0.05). At the effector-target ratio of 10:1, decitabine significantly enhanced the apoptosis of LSC induced by allo-NK cells (7.84%±0.34% vs 3.33%±0.64%)(P<0.05). The expressions of NKG2D ligands(MICA/B,ULBP1,ULBP2,ULBP3) on LSC treated with decitabine 10 µmol/L for 24 hours were significantly increased (P<0.05).</p><p><b>CONCLUSION</b>Decitabine may enhance the allo-NK cell-mediated killing effects on LSC by up-regulation of the expressions of NKG2D ligands on LSC.</p>