Objective:To study the key target genes and signaling pathways in the treatment of Allergic Rhinitis(AR)with Radix Aconiti Lateralis Preparata(aka Fuzi).Methods:The TCMPS and PubChem databases were used to screen the ...Objective:To study the key target genes and signaling pathways in the treatment of Allergic Rhinitis(AR)with Radix Aconiti Lateralis Preparata(aka Fuzi).Methods:The TCMPS and PubChem databases were used to screen the active ingredients and target genes of Fuzi using oral bioavailability and drug similarity as screening conditions,and the GeneCards database was used to screen the target genes of AR.The online tool Venny2.1 was used to screen the target genes of Fuzi for the treatment of Allergic Rhinitis;the STRING database was used to obtain the protein-protein interaction(PPI)network of drug-disease targets,and the key target genes were identified by the MCC algorithm.The potential biological processes and signaling pathways were identified by GO enrichment and KEGG enrichment analysis.Finally,animal experiments were conducted to demonstrate the therapeutic effect ofFuzi on Allergic Rhinitis.Results:The TCMSP,PubChem and GeneCards databases were used to screen the 21 active compound components of Fuzi and 68 potential therapeutic target genes of Fuzi for Allergic Rhinitis.PPI network analysis identified the top ten key target genes,namely:PTGS2,TNF,IL6,AKT1,ALB,STAT3,CCL2,CXCL8,VEGFA and JUN,GO functional and KEGG pathway enrichment analysis showed that the significantly enriched functions and pathways of Fuzi on Allergic Rhinitis were closely related to Allergic Rhinitis.Finally,animal experiments were conducted to verify that Fuzi is effective in the treatment of Allergic rhinitis.Conclusion:Increased expression of IL-6 and TNF-αin nasal mucosal tissues of patients with Allergic Rhinitis was positively correlated with indicators related to the disease activity of AllergicRhinitis.Fuzi ameliorated the inflammatory changes in mice with Allergic Rhinitis by inhibiting the activation of Toll-like signaling pathway in the nasal mucosa and decreasing the expression activity of IL-6 and TNF-α.展开更多
Obiective:To investigate the prognostic value of ORMDL2 in human glioma and its relationship with immune invasion.Methods:The clinical survival data from TCGA-LGG&GBM,CGGA and GEO were used to evaluate the clinica...Obiective:To investigate the prognostic value of ORMDL2 in human glioma and its relationship with immune invasion.Methods:The clinical survival data from TCGA-LGG&GBM,CGGA and GEO were used to evaluate the clinical prognostic value of ORMDL2.The cut off value of ORMDL2 was detected with pROC package to draw ROC curve to prove its value in differential diagnosis of glioma.The first 300 genes with the most significant positive correlation with ORMDL2 were selected to establish PPI network through STRING database and conduct GO and pathway analysis.The relationship between the expression of ORMDL2 mRNA and immune cell infiltration was investigated by using ssGSEA and TIMER2.0 databases.Results:The expression of ORMDL2 mRNA in glioma was significantly higher than that in adjacent normal tissues,and the difference was most significant in high-grade glioma.The expression of ORMDL2 was increased in human glioma,which was related to the clinicopathological characteristics and poor prognosis of glioma patients.In addition,the increased expression of ORMDL2 was associated with a series of immune infiltrating cells,including macrophages.Conclusion:ORMDL2 plays an important role in glioma immune cell infiltration and is a biomarker of prognosis of glioma patients.展开更多
Objective:To explore the potential active ingredients and targets of Astragalus,and also to predict the targets and mechanisms of Astragalus in the treatment of diabetic cardiomyopathy.Based on the predicted results,t...Objective:To explore the potential active ingredients and targets of Astragalus,and also to predict the targets and mechanisms of Astragalus in the treatment of diabetic cardiomyopathy.Based on the predicted results,the key signaling pathways were validated in a diabetic cardiomyopathy model mouse.Methods:Compounds and targets in Astragalus were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The protein names to corresponding"Gene Symbol ID"was convert by STRING database.We obtained targets of diabetic cardiomyopathy data from DisGeNET datasets.The protein-protein interaction network(PPI network)was established using STRING database.Cytoscape 3.6.0 was used to construct a disease-drug-target gene network map and to screen the 10 closest target genes by Cytohuba plug-in.The overlapping genes were then subjected to gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)-based enrichment analysis.Finally,the key molecules of the MAPK signaling pathway were validated by in vitro experiments.Animal experiments were performed using 21 Kunming mice randomly divided into normal group,model group,and Chinese herbal medicine Astragalus group,with seven mice in each group.The myocardium of mice in each group was stained with HE to compare the pathological morphological changes,and Western Blot was also used to compare the key molecules of MAPK signaling pathway,ERK1 and p-p38.Results:Astragalus contained 20 active ingredients with 188 corresponding targets,220 targets related to diabetic cardiomyopathy and 37 targets acting in conjunction with Astragalus.The common targets were imported into the STRING database to obtain a PPI network graph of overlapping genes,with 37 nodes and 391 edges.The PPI network map was imported into Cytoscape 3.6.0 software,and the most significant top 10 hub genes were obtained using the MCC algorithm in the cytoHubba plugin,namely AKT1,TP53,CASP3,MMP9,EGF,IL-10,CXCL8,IL-1β,VEGFA,PPARG.GO functional enrichment analysis yielded 40 entries for biological process(BP),23 entries for cellular component(CC),22 entries for molecular function(MF)and 94 entries for KEGG pathway enrichment screening,mainly involving PI3K-AKT,MAPK,HIF-1,FOXO,TNP pathway and other inflammation or apoptosis regulatory pathways.Animal experiments showed that Astragalus can improve the inflammatory state of myocardial tissue in mice with diabetic cardiomyopathy,and the expression of ERK1 and p-p38 protein in myocardial tissue of mice in the model group was higher than that in the normal group(P<0.05,P<0.01),and after the intervention with Astragalus,the expression of ERK1 and p-p38 protein was significantly lower than that in the model group,and the difference was statistically significant(P<0.05,P<0.01).Conclusion:Astragalus has multi-target,multi-component and multi-pathway action characteristics in the treatment of diabetic cardiomyopathy,which can exert anti-inflammatory and anti-oxidative stress effects by regulating protein expression of MAPK signaling pathway ERK1,p-p38.展开更多
基金Natural Science Foundation of Hainan Province(No.820RC627)。
文摘Objective:To study the key target genes and signaling pathways in the treatment of Allergic Rhinitis(AR)with Radix Aconiti Lateralis Preparata(aka Fuzi).Methods:The TCMPS and PubChem databases were used to screen the active ingredients and target genes of Fuzi using oral bioavailability and drug similarity as screening conditions,and the GeneCards database was used to screen the target genes of AR.The online tool Venny2.1 was used to screen the target genes of Fuzi for the treatment of Allergic Rhinitis;the STRING database was used to obtain the protein-protein interaction(PPI)network of drug-disease targets,and the key target genes were identified by the MCC algorithm.The potential biological processes and signaling pathways were identified by GO enrichment and KEGG enrichment analysis.Finally,animal experiments were conducted to demonstrate the therapeutic effect ofFuzi on Allergic Rhinitis.Results:The TCMSP,PubChem and GeneCards databases were used to screen the 21 active compound components of Fuzi and 68 potential therapeutic target genes of Fuzi for Allergic Rhinitis.PPI network analysis identified the top ten key target genes,namely:PTGS2,TNF,IL6,AKT1,ALB,STAT3,CCL2,CXCL8,VEGFA and JUN,GO functional and KEGG pathway enrichment analysis showed that the significantly enriched functions and pathways of Fuzi on Allergic Rhinitis were closely related to Allergic Rhinitis.Finally,animal experiments were conducted to verify that Fuzi is effective in the treatment of Allergic rhinitis.Conclusion:Increased expression of IL-6 and TNF-αin nasal mucosal tissues of patients with Allergic Rhinitis was positively correlated with indicators related to the disease activity of AllergicRhinitis.Fuzi ameliorated the inflammatory changes in mice with Allergic Rhinitis by inhibiting the activation of Toll-like signaling pathway in the nasal mucosa and decreasing the expression activity of IL-6 and TNF-α.
基金Finance Science and Technology Project of Hainan Province(ZDYF2022SHFZ088),Hainan Medical University Postgraduate Innovative Research Project Category B(HYYS2021B16)。
文摘Obiective:To investigate the prognostic value of ORMDL2 in human glioma and its relationship with immune invasion.Methods:The clinical survival data from TCGA-LGG&GBM,CGGA and GEO were used to evaluate the clinical prognostic value of ORMDL2.The cut off value of ORMDL2 was detected with pROC package to draw ROC curve to prove its value in differential diagnosis of glioma.The first 300 genes with the most significant positive correlation with ORMDL2 were selected to establish PPI network through STRING database and conduct GO and pathway analysis.The relationship between the expression of ORMDL2 mRNA and immune cell infiltration was investigated by using ssGSEA and TIMER2.0 databases.Results:The expression of ORMDL2 mRNA in glioma was significantly higher than that in adjacent normal tissues,and the difference was most significant in high-grade glioma.The expression of ORMDL2 was increased in human glioma,which was related to the clinicopathological characteristics and poor prognosis of glioma patients.In addition,the increased expression of ORMDL2 was associated with a series of immune infiltrating cells,including macrophages.Conclusion:ORMDL2 plays an important role in glioma immune cell infiltration and is a biomarker of prognosis of glioma patients.
基金Hainan Provincial Natural Science Foundation Innovation Research Team Project(No.2019CXTD407)Hainan Medical College Youth Cultivation Fund Project(No.HYPY201912)The Youth Cultivation Fund of the First Affiliated Hospital of Hainan Medical College(No.HYYFYPY202006)。
文摘Objective:To explore the potential active ingredients and targets of Astragalus,and also to predict the targets and mechanisms of Astragalus in the treatment of diabetic cardiomyopathy.Based on the predicted results,the key signaling pathways were validated in a diabetic cardiomyopathy model mouse.Methods:Compounds and targets in Astragalus were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The protein names to corresponding"Gene Symbol ID"was convert by STRING database.We obtained targets of diabetic cardiomyopathy data from DisGeNET datasets.The protein-protein interaction network(PPI network)was established using STRING database.Cytoscape 3.6.0 was used to construct a disease-drug-target gene network map and to screen the 10 closest target genes by Cytohuba plug-in.The overlapping genes were then subjected to gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)-based enrichment analysis.Finally,the key molecules of the MAPK signaling pathway were validated by in vitro experiments.Animal experiments were performed using 21 Kunming mice randomly divided into normal group,model group,and Chinese herbal medicine Astragalus group,with seven mice in each group.The myocardium of mice in each group was stained with HE to compare the pathological morphological changes,and Western Blot was also used to compare the key molecules of MAPK signaling pathway,ERK1 and p-p38.Results:Astragalus contained 20 active ingredients with 188 corresponding targets,220 targets related to diabetic cardiomyopathy and 37 targets acting in conjunction with Astragalus.The common targets were imported into the STRING database to obtain a PPI network graph of overlapping genes,with 37 nodes and 391 edges.The PPI network map was imported into Cytoscape 3.6.0 software,and the most significant top 10 hub genes were obtained using the MCC algorithm in the cytoHubba plugin,namely AKT1,TP53,CASP3,MMP9,EGF,IL-10,CXCL8,IL-1β,VEGFA,PPARG.GO functional enrichment analysis yielded 40 entries for biological process(BP),23 entries for cellular component(CC),22 entries for molecular function(MF)and 94 entries for KEGG pathway enrichment screening,mainly involving PI3K-AKT,MAPK,HIF-1,FOXO,TNP pathway and other inflammation or apoptosis regulatory pathways.Animal experiments showed that Astragalus can improve the inflammatory state of myocardial tissue in mice with diabetic cardiomyopathy,and the expression of ERK1 and p-p38 protein in myocardial tissue of mice in the model group was higher than that in the normal group(P<0.05,P<0.01),and after the intervention with Astragalus,the expression of ERK1 and p-p38 protein was significantly lower than that in the model group,and the difference was statistically significant(P<0.05,P<0.01).Conclusion:Astragalus has multi-target,multi-component and multi-pathway action characteristics in the treatment of diabetic cardiomyopathy,which can exert anti-inflammatory and anti-oxidative stress effects by regulating protein expression of MAPK signaling pathway ERK1,p-p38.
