AIM To investigate whether common variants in the oxidative pathway genes influence inflammatory bowel disease(IBD)risk among Moroccan patients.METHODS The distribution of(TAAA)n_rs12720460 and(CCTTT)n_rs3833912 NOS2 ...AIM To investigate whether common variants in the oxidative pathway genes influence inflammatory bowel disease(IBD)risk among Moroccan patients.METHODS The distribution of(TAAA)n_rs12720460 and(CCTTT)n_rs3833912 NOS2 A microsatellite repeats,HIF-1 A_rs11549467 and NFKB1-94 ins/delA TTG_rs28362491 was analyzed in 507 subjects grouped in 199 IBD and 308 healthy controls.Genotyping was performed withpolymerase chain reaction-fluorescent method and the TaqMan~?allelic discrimination technology.RESULTS The allele and genotype frequencies of HIF1 A_rs11549467,NFKB1_rs28362491 and NOS2 A_(TAAA)n did not differ significantly between patients and controls.Analysis of NOS2 A_(CCTTT)n markers evidenced differences between patients and healthy controls.A preferential presence of the(CCTTT)8(P=0.02;OR=1.71,95%CI:1.07-2.74),(CCTTT)14(P=0.02;OR=1.71,95%CI:1.06-2.76)alleles in IBD,(CCTTT)8(P=0.008;OR=1.95,95%CI:1.17-3.23)in CD and(CCTTT)7(P=0.009;OR=7.61,95%CI:1.25-46.08),(CCTTT)11(P=0.05;OR=0.51,95%CI:0.25-1.01),(CCTTT)14(P=0.02;OR=2.05,95%CI:1.07-3.94),(CCTTT)15(P=0.01;OR=2.25,95%CI:1.16-4.35)repeats in UC patients indicated its possible association with higher disease risk which need to be confirmed in a larger sample size.CONCLUSION Our results suggest that the NOS2 A_(CCTTT)n gene variations may influence IBD susceptibility in the Moroccan population.展开更多
目的采用网络药理学与分子对接技术探讨生脉注射液的活性成分和治疗新型冠状病毒肺炎(COVID-19)的潜在作用机制。方法利用TCMSP及BATMAN-TCM数据库筛选生脉注射液的活性化合物,通过TCMSP及Targetnet在线数据库预测作用靶点,通过Cytoscap...目的采用网络药理学与分子对接技术探讨生脉注射液的活性成分和治疗新型冠状病毒肺炎(COVID-19)的潜在作用机制。方法利用TCMSP及BATMAN-TCM数据库筛选生脉注射液的活性化合物,通过TCMSP及Targetnet在线数据库预测作用靶点,通过Cytoscape3.7.1构建活性成分-作用靶点网络图;在GeneCards及OMIM数据库中以"coronavirus pneumonia"为关键词搜索冠状病毒肺炎相关疾病靶点,与生脉注射液化合物靶点进行交集筛选出共同靶点作为研究靶点,将共同靶点导入STRING数据库获取数据后在Cytoscape 3.7.1软件中构建蛋白质-蛋白质相互作用网络图;利用R语言进行GO(gene ontology)功能、KEGG(Kyoto encyclopedia of genes and genomes)通路富集分析,预测其作用机制,并构建"成分-靶点-通路"网络图;通过DiscoveryStudio 2.5软件对关键靶点进行分子对接分析。结果生脉注射液筛选得到22个活性化合物,分别为邻苯二甲酸二辛酯、β-谷甾醇、当归酰基戈米辛O、戈米辛A、戈米辛R、五味子丙素、内南五味子酯乙、长南酸、南五味子内酯、香蒲木脂素B、新杜松烷酸A、新杜松烷酸B、新杜松烷酸C、新南五味子木脂宁、五味子内酯A、五味子内酯E、五味子酸、尿苷、薯蓣皂苷元、鸟嘌呤核苷、N-反式阿魏酰酪胺、豆甾醇。相应作用靶点224个,与COVID-19的共同靶点16个,分别为CASP3、CASP8、PTGS2、BCL2、BAX、PRKCA、PTGS1、PIK3CG、F10、NOS3、DPP4、NOS2、TLR9、ACE、ICAM1、PRKCE,关键靶点涉及CASP3、PTGS2、NOS2、NOS3、ICAM1。GO功能富集分析得到生物过程(BP)条目771个,细胞组成(CC)条目11个,分子功能(MF)条目79个。KEGG通路富集分析筛选得到67条(P<0.05)信号通路,主要涉及糖尿病并发症AGE-RAGE信号通路、凋亡通路、P53信号通路、小细胞肺癌通路等。分子对接结果显示与关键靶点对接较好的成分有五味子内酯E、豆甾醇、N-反式阿魏酰酪胺。结论生脉注射液中的活性化合物五味子内酯E、豆甾醇、N-反式阿魏酰酪胺等能作用于CASP3、PTGS2、NOS2、NOS3等靶点调节多条信号通路发挥抗炎、免疫调节、抗休克、增加血氧饱和度等作用,从而可能发挥对COVID-19的治疗作用。展开更多
文摘AIM To investigate whether common variants in the oxidative pathway genes influence inflammatory bowel disease(IBD)risk among Moroccan patients.METHODS The distribution of(TAAA)n_rs12720460 and(CCTTT)n_rs3833912 NOS2 A microsatellite repeats,HIF-1 A_rs11549467 and NFKB1-94 ins/delA TTG_rs28362491 was analyzed in 507 subjects grouped in 199 IBD and 308 healthy controls.Genotyping was performed withpolymerase chain reaction-fluorescent method and the TaqMan~?allelic discrimination technology.RESULTS The allele and genotype frequencies of HIF1 A_rs11549467,NFKB1_rs28362491 and NOS2 A_(TAAA)n did not differ significantly between patients and controls.Analysis of NOS2 A_(CCTTT)n markers evidenced differences between patients and healthy controls.A preferential presence of the(CCTTT)8(P=0.02;OR=1.71,95%CI:1.07-2.74),(CCTTT)14(P=0.02;OR=1.71,95%CI:1.06-2.76)alleles in IBD,(CCTTT)8(P=0.008;OR=1.95,95%CI:1.17-3.23)in CD and(CCTTT)7(P=0.009;OR=7.61,95%CI:1.25-46.08),(CCTTT)11(P=0.05;OR=0.51,95%CI:0.25-1.01),(CCTTT)14(P=0.02;OR=2.05,95%CI:1.07-3.94),(CCTTT)15(P=0.01;OR=2.25,95%CI:1.16-4.35)repeats in UC patients indicated its possible association with higher disease risk which need to be confirmed in a larger sample size.CONCLUSION Our results suggest that the NOS2 A_(CCTTT)n gene variations may influence IBD susceptibility in the Moroccan population.
文摘目的采用网络药理学与分子对接技术探讨生脉注射液的活性成分和治疗新型冠状病毒肺炎(COVID-19)的潜在作用机制。方法利用TCMSP及BATMAN-TCM数据库筛选生脉注射液的活性化合物,通过TCMSP及Targetnet在线数据库预测作用靶点,通过Cytoscape3.7.1构建活性成分-作用靶点网络图;在GeneCards及OMIM数据库中以"coronavirus pneumonia"为关键词搜索冠状病毒肺炎相关疾病靶点,与生脉注射液化合物靶点进行交集筛选出共同靶点作为研究靶点,将共同靶点导入STRING数据库获取数据后在Cytoscape 3.7.1软件中构建蛋白质-蛋白质相互作用网络图;利用R语言进行GO(gene ontology)功能、KEGG(Kyoto encyclopedia of genes and genomes)通路富集分析,预测其作用机制,并构建"成分-靶点-通路"网络图;通过DiscoveryStudio 2.5软件对关键靶点进行分子对接分析。结果生脉注射液筛选得到22个活性化合物,分别为邻苯二甲酸二辛酯、β-谷甾醇、当归酰基戈米辛O、戈米辛A、戈米辛R、五味子丙素、内南五味子酯乙、长南酸、南五味子内酯、香蒲木脂素B、新杜松烷酸A、新杜松烷酸B、新杜松烷酸C、新南五味子木脂宁、五味子内酯A、五味子内酯E、五味子酸、尿苷、薯蓣皂苷元、鸟嘌呤核苷、N-反式阿魏酰酪胺、豆甾醇。相应作用靶点224个,与COVID-19的共同靶点16个,分别为CASP3、CASP8、PTGS2、BCL2、BAX、PRKCA、PTGS1、PIK3CG、F10、NOS3、DPP4、NOS2、TLR9、ACE、ICAM1、PRKCE,关键靶点涉及CASP3、PTGS2、NOS2、NOS3、ICAM1。GO功能富集分析得到生物过程(BP)条目771个,细胞组成(CC)条目11个,分子功能(MF)条目79个。KEGG通路富集分析筛选得到67条(P<0.05)信号通路,主要涉及糖尿病并发症AGE-RAGE信号通路、凋亡通路、P53信号通路、小细胞肺癌通路等。分子对接结果显示与关键靶点对接较好的成分有五味子内酯E、豆甾醇、N-反式阿魏酰酪胺。结论生脉注射液中的活性化合物五味子内酯E、豆甾醇、N-反式阿魏酰酪胺等能作用于CASP3、PTGS2、NOS2、NOS3等靶点调节多条信号通路发挥抗炎、免疫调节、抗休克、增加血氧饱和度等作用,从而可能发挥对COVID-19的治疗作用。
