Objective:To investigate whether angiotensinⅡtype 1 receptor(AGTR1 A1166C)gene polymorphism was associated with the effectiveness of valsartan monotherapy in Chinese patients with essential hypertension.Methods:This ...Objective:To investigate whether angiotensinⅡtype 1 receptor(AGTR1 A1166C)gene polymorphism was associated with the effectiveness of valsartan monotherapy in Chinese patients with essential hypertension.Methods:This retrospective analysis included 198 patients(≥18 years of age)who received valsartan monotherapy(80 mg/day)for newly developed essential hypertension at the authors’center between January 1,2020 and December 31,2023.Genotyping for AGTR1 A1166C gene polymorphism was done by polymerase chain reaction(PCR)-melting curve analysis of genomic DNA from peripheral blood samples.A dominant genetic model for AGTR1 A1166C(AA genotype versus AC+CC genotype)was used.Multivariate regression analysis of baseline variables and AGTR1 polymorphism was conducted to identify predictors of target blood pressure attainment(<140/90 mmHg)at the 4-week follow-up.Results:The median age of the 198 patients was(53.7±13.5)years,and 58%were men.Genotyping assays showed that 164 patients had the AA genotype,and 34 patients were of the AC/CC genotype,including 30 with the AC genotype and 4 with the CC genotype.Allele distribution was consistent with Hardy Weinberg equilibrium.109 Patients(55.1%)attained the blood pressure target.Multivariate analysis showed that smoking(versus no smoking,HR 0.314,95%CI 0.159-0.619,P=0.001)and AGTR1 A1166C AA genotype(versus AC/CC,HR 2.927,95%CI 1.296-6.611,P=0.023)were significant and independent predictors of target attainment.25 Patients(73.5%)with AGTR1 A1166C AC/CC genotype attained the target versus 51.2%(51/164)of patients with AGTR1 A1166C AA genotype(P=0.017).Patients with AGTR1 A1166C AC/CC genotype had a significantly greater reduction in systolic blood pressure[(33.1±10.8)mmHg versus(29.2±11.7)mmHg in AA carriers;(P=0.029)].Conclusions:Hypertensive patients carrying one or two C alleles of the AGTR1 A1166C gene were more responsive to valsartan treatment.展开更多
Hypertriglyceridemia （HTG） is an important metabolic disease and strongly associated with the development of hypertension, atherosclerosis,coronary artery disease, and type 2 diabetes mellitus（T2DM）. HTG risk is a...Hypertriglyceridemia （HTG） is an important metabolic disease and strongly associated with the development of hypertension, atherosclerosis,coronary artery disease, and type 2 diabetes mellitus（T2DM）. HTG risk is affected by various factors and might occur owing to the complex synergistic interaction between the genetic background and environmental factors;.展开更多
利用噬菌体衣壳蛋白MS2和带有序列特异性茎环结构(含有MS2蛋白结合位点)的RNA之间的高度亲和力,对外源性人血管紧张素1型受体(angiotensin II receptor type 1,AGTR1)mRNA 3′端非翻译区(3′untranslated region,3′UTR)片段进行红色荧...利用噬菌体衣壳蛋白MS2和带有序列特异性茎环结构(含有MS2蛋白结合位点)的RNA之间的高度亲和力,对外源性人血管紧张素1型受体(angiotensin II receptor type 1,AGTR1)mRNA 3′端非翻译区(3′untranslated region,3′UTR)片段进行红色荧光标记,进而在活细胞(HeLa)内研究该mRNA片段的应激生物学行为。通过在pSG5空载体质粒上先后插入两个双链DNA目的片段AGTR1-3′UTR和24×MS2,构建重组质粒pSG5/AGTR1-3′UTR/24×MS2,并将该质粒与重组质粒pERFP/MS2和pEGFP/C1-G3BP共转染入Hela细胞。荧光显微成像结果显示,AGTR1-3′UTR-24×MS2 mRNA片段能够携带具有入核信号的MS2-RFP融合蛋白离开胞核进入胞浆,而且在亚砷酸盐刺激下,红色荧光标记的AGTR1-3′UTR-24×MS2 mRNA片段可在胞浆中形成与应激蛋白G3BP-GFP共定位的颗粒。该结果表明,针对AGTR1-3′UTR片段的MS2-RFP荧光标记系统构建成功,该荧光标记系统能有效避免假阳性的荧光信号。在细胞受到氧化应激时,AGTR1-3′UTR会被招募至胞浆中的应激颗粒结构中,启示了AGTR1-3′UTR区域对于调控AGTR1 mRNA在细胞内的应激定位具有重要作用。展开更多
目的利用生物信息学、网络药理学、分子对接、动力学模拟方法探讨冬虫夏草治疗非小细胞肺癌的关键靶点及其分子机制。方法利用TCMSP数据库检索冬虫夏草的活性成分和靶点,并利用GEO数据库获取与非小细胞肺癌相关的数据集,使用R语言软件...目的利用生物信息学、网络药理学、分子对接、动力学模拟方法探讨冬虫夏草治疗非小细胞肺癌的关键靶点及其分子机制。方法利用TCMSP数据库检索冬虫夏草的活性成分和靶点,并利用GEO数据库获取与非小细胞肺癌相关的数据集,使用R语言软件进行差异分析,获取差异表达基因(DEGs)。通过WGCNA分析确定与肿瘤发生密切相关的基因模块,并取交集获取非小细胞肺癌的枢纽基因,将这些枢纽基因与药物靶点进行映射,利用Cytoscape软件构建“活性成分-疾病枢纽靶点”网络图。使用String数据库和Cytoscape构建靶标蛋白相互作用(PPI)网络,筛选出关键靶点。利用Enrihr在线工具进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。利用CB-Dock2平台和Discovery Studio 2021Client软件对关键成分和靶点进行分子对接验证和可视化。最后利用Gromacs v2022.03软件对分子对接所得的复合物进行100 ns分子动力学模拟分析。结果共筛选得到冬虫夏草活性成分10个,自身靶点276个和作用于非小细胞肺癌的靶点9个,通过对虫草甾醇和花生四烯酸2个核心成分富集分析提示,主要涉及氧化物酶体增殖物激活受体(PPAR)信号通路、神经活性配体与受体的相互作用、脂肪细胞的脂肪分解调节、腺苷酸活化蛋白激酶(AMPK)信号通路、叉头框转录因子(FoxO)信号通路等。分子对接结果显示,虫草甾醇和花生四烯酸与过氧化物酶体增殖物激活受体γ(PPARG)、1型血管紧张素Ⅱ受体(AGTR1)和内皮PAS结构域蛋白1(EPAS1)这3个核心靶点具有良好的结合能力,动力学模拟进一步验证虫草甾醇与PPARG、AGTR1复合物结合稳定。结论冬虫夏草可能通过调控巨噬细胞极化、神经活性配体与受体、脂质代谢、氧化应激、免疫调节等过程,多种协同作用发挥抗非小细胞肺癌作用。展开更多
基金Science and Technology Key Project of Xuzhou Municipal Health Commission,Jiangsu Province,China(XWKYHT20210531)Pengcheng Yingcai-Medical Young Reserve Talent Programme(XWRCHT20220013).
文摘Objective:To investigate whether angiotensinⅡtype 1 receptor(AGTR1 A1166C)gene polymorphism was associated with the effectiveness of valsartan monotherapy in Chinese patients with essential hypertension.Methods:This retrospective analysis included 198 patients(≥18 years of age)who received valsartan monotherapy(80 mg/day)for newly developed essential hypertension at the authors’center between January 1,2020 and December 31,2023.Genotyping for AGTR1 A1166C gene polymorphism was done by polymerase chain reaction(PCR)-melting curve analysis of genomic DNA from peripheral blood samples.A dominant genetic model for AGTR1 A1166C(AA genotype versus AC+CC genotype)was used.Multivariate regression analysis of baseline variables and AGTR1 polymorphism was conducted to identify predictors of target blood pressure attainment(<140/90 mmHg)at the 4-week follow-up.Results:The median age of the 198 patients was(53.7±13.5)years,and 58%were men.Genotyping assays showed that 164 patients had the AA genotype,and 34 patients were of the AC/CC genotype,including 30 with the AC genotype and 4 with the CC genotype.Allele distribution was consistent with Hardy Weinberg equilibrium.109 Patients(55.1%)attained the blood pressure target.Multivariate analysis showed that smoking(versus no smoking,HR 0.314,95%CI 0.159-0.619,P=0.001)and AGTR1 A1166C AA genotype(versus AC/CC,HR 2.927,95%CI 1.296-6.611,P=0.023)were significant and independent predictors of target attainment.25 Patients(73.5%)with AGTR1 A1166C AC/CC genotype attained the target versus 51.2%(51/164)of patients with AGTR1 A1166C AA genotype(P=0.017).Patients with AGTR1 A1166C AC/CC genotype had a significantly greater reduction in systolic blood pressure[(33.1±10.8)mmHg versus(29.2±11.7)mmHg in AA carriers;(P=0.029)].Conclusions:Hypertensive patients carrying one or two C alleles of the AGTR1 A1166C gene were more responsive to valsartan treatment.
基金partially supported by grants from the National Nature Science Foundation of China[81502869]Suzhou Key technologies of prevention and control of major diseases and infectious diseases[Gwzx201506,Gwzx201605,Gwzx201706]
文摘Hypertriglyceridemia （HTG） is an important metabolic disease and strongly associated with the development of hypertension, atherosclerosis,coronary artery disease, and type 2 diabetes mellitus（T2DM）. HTG risk is affected by various factors and might occur owing to the complex synergistic interaction between the genetic background and environmental factors;.
文摘利用噬菌体衣壳蛋白MS2和带有序列特异性茎环结构(含有MS2蛋白结合位点)的RNA之间的高度亲和力,对外源性人血管紧张素1型受体(angiotensin II receptor type 1,AGTR1)mRNA 3′端非翻译区(3′untranslated region,3′UTR)片段进行红色荧光标记,进而在活细胞(HeLa)内研究该mRNA片段的应激生物学行为。通过在pSG5空载体质粒上先后插入两个双链DNA目的片段AGTR1-3′UTR和24×MS2,构建重组质粒pSG5/AGTR1-3′UTR/24×MS2,并将该质粒与重组质粒pERFP/MS2和pEGFP/C1-G3BP共转染入Hela细胞。荧光显微成像结果显示,AGTR1-3′UTR-24×MS2 mRNA片段能够携带具有入核信号的MS2-RFP融合蛋白离开胞核进入胞浆,而且在亚砷酸盐刺激下,红色荧光标记的AGTR1-3′UTR-24×MS2 mRNA片段可在胞浆中形成与应激蛋白G3BP-GFP共定位的颗粒。该结果表明,针对AGTR1-3′UTR片段的MS2-RFP荧光标记系统构建成功,该荧光标记系统能有效避免假阳性的荧光信号。在细胞受到氧化应激时,AGTR1-3′UTR会被招募至胞浆中的应激颗粒结构中,启示了AGTR1-3′UTR区域对于调控AGTR1 mRNA在细胞内的应激定位具有重要作用。
文摘目的利用生物信息学、网络药理学、分子对接、动力学模拟方法探讨冬虫夏草治疗非小细胞肺癌的关键靶点及其分子机制。方法利用TCMSP数据库检索冬虫夏草的活性成分和靶点,并利用GEO数据库获取与非小细胞肺癌相关的数据集,使用R语言软件进行差异分析,获取差异表达基因(DEGs)。通过WGCNA分析确定与肿瘤发生密切相关的基因模块,并取交集获取非小细胞肺癌的枢纽基因,将这些枢纽基因与药物靶点进行映射,利用Cytoscape软件构建“活性成分-疾病枢纽靶点”网络图。使用String数据库和Cytoscape构建靶标蛋白相互作用(PPI)网络,筛选出关键靶点。利用Enrihr在线工具进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。利用CB-Dock2平台和Discovery Studio 2021Client软件对关键成分和靶点进行分子对接验证和可视化。最后利用Gromacs v2022.03软件对分子对接所得的复合物进行100 ns分子动力学模拟分析。结果共筛选得到冬虫夏草活性成分10个,自身靶点276个和作用于非小细胞肺癌的靶点9个,通过对虫草甾醇和花生四烯酸2个核心成分富集分析提示,主要涉及氧化物酶体增殖物激活受体(PPAR)信号通路、神经活性配体与受体的相互作用、脂肪细胞的脂肪分解调节、腺苷酸活化蛋白激酶(AMPK)信号通路、叉头框转录因子(FoxO)信号通路等。分子对接结果显示,虫草甾醇和花生四烯酸与过氧化物酶体增殖物激活受体γ(PPARG)、1型血管紧张素Ⅱ受体(AGTR1)和内皮PAS结构域蛋白1(EPAS1)这3个核心靶点具有良好的结合能力,动力学模拟进一步验证虫草甾醇与PPARG、AGTR1复合物结合稳定。结论冬虫夏草可能通过调控巨噬细胞极化、神经活性配体与受体、脂质代谢、氧化应激、免疫调节等过程,多种协同作用发挥抗非小细胞肺癌作用。
