目的 基于网络药理学及分子对接技术,探究白花蛇舌草和半枝莲药治疗卵巢癌的作用机制。并对药对活性成分槲皮素进行体外细胞实验,验证其对卵巢癌的作用。方法 从中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems P...目的 基于网络药理学及分子对接技术,探究白花蛇舌草和半枝莲药治疗卵巢癌的作用机制。并对药对活性成分槲皮素进行体外细胞实验,验证其对卵巢癌的作用。方法 从中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology,TCMSP)数据库筛选白花蛇舌草和半枝莲的活性成分并找出对应的靶点;在GeneCards数据库中检索出卵巢癌相关靶点;用jvenn在线作图工具得到药对和疾病相同的靶点交集;将交集靶点导入STRING平台,构建蛋白质-蛋白质相互作用(protein-protein interaction network,PPI)关系,用Cytoscape做出白花蛇舌草和半枝莲药对治疗卵巢癌的主要靶点图,用Metascape数据库对主要靶点进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。用分子对接对结果进行验证。并对白花蛇舌草-半枝莲活性成分槲皮素进行CCK-8细胞增殖实验和流式细胞术检测细胞凋亡实验。结果 与卵巢癌相关的白花蛇舌草-半枝莲药对成分-靶点网络中包含30种成分、109个靶点。其相关性位于前3位的候选化合物分子为槲皮素、木犀草素、β-谷甾醇。这些成分通过AKT1、BCL2L1、CASP3、CASP7等信号蛋白来抑制卵巢癌细胞的生长和转移,涉及信号通路有癌症的途径、乙型肝炎、脂质和动脉粥样硬化、AGE-RAGE信号通路在糖尿病并发症中的应用、PI3K-AKT信号通路等。分子对接结果显示核心成分与核心靶点均有较好的结合能力。不同浓度槲皮素可明显抑制卵巢癌细胞增殖,且浓度越高细胞抑制率越高,细胞凋亡率也随浓度增高,数据结果差异有统计学意义(P<0.01)。结论 从网络药理学和分子对接技术得出白花蛇舌草和半枝莲药对可通过多成分、多靶点、多通路治疗卵巢癌的作用机制。槲皮素能有效抑制卵巢癌细胞并促进其凋亡。展开更多
Ocean boundaries present a significant effect on the vibroacoustic characteristics and sound propagation of an elastic structure in practice.In this study,an efficient finite element/wave superposition method(FE/WSM)f...Ocean boundaries present a significant effect on the vibroacoustic characteristics and sound propagation of an elastic structure in practice.In this study,an efficient finite element/wave superposition method(FE/WSM)for predicting the three-dimen-sional acoustic radiation from an arbitrary-shaped radiator in Pekeris waveguides with a lossy seabed is proposed.The method is based on the FE method(FEM),WSM,and sound propagation models.First,a near-field vibroacoustic model is established by the FEM to obtain vibration information on a radiator surface.Then,the WSM based on the Helmholtz boundary integral is used to pre-dict the far-field acoustic radiation and propagation.Furthermore,the rigorous image source method and complex normal mode are employed to obtain the near-and far-field Green’s function(GF),respectively.The former,which is based on the spherical wave decomposition,is adopted to accurately solve the near-field source strength,and the far-field acoustic radiation is calculated by the latter and perturbation theory.The simulations of both models are compared to theoretical wavenumber integration solutions.Finally,numerical experiments on elastic spherical and cylindrical shells in Pekeris waveguides are presented to validate the accuracy and efficiency of the proposed method.The results show that the FE/WSM is adaptable to complex radiators and ocean-acoustic envi-ronments,and are easy to implement and computationally efficient in calculating the structural vibration,acoustic radiation,and sound propagation of arbitrarily shaped radiators in practical ocean environments.展开更多
文摘目的 基于网络药理学及分子对接技术,探究白花蛇舌草和半枝莲药治疗卵巢癌的作用机制。并对药对活性成分槲皮素进行体外细胞实验,验证其对卵巢癌的作用。方法 从中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology,TCMSP)数据库筛选白花蛇舌草和半枝莲的活性成分并找出对应的靶点;在GeneCards数据库中检索出卵巢癌相关靶点;用jvenn在线作图工具得到药对和疾病相同的靶点交集;将交集靶点导入STRING平台,构建蛋白质-蛋白质相互作用(protein-protein interaction network,PPI)关系,用Cytoscape做出白花蛇舌草和半枝莲药对治疗卵巢癌的主要靶点图,用Metascape数据库对主要靶点进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。用分子对接对结果进行验证。并对白花蛇舌草-半枝莲活性成分槲皮素进行CCK-8细胞增殖实验和流式细胞术检测细胞凋亡实验。结果 与卵巢癌相关的白花蛇舌草-半枝莲药对成分-靶点网络中包含30种成分、109个靶点。其相关性位于前3位的候选化合物分子为槲皮素、木犀草素、β-谷甾醇。这些成分通过AKT1、BCL2L1、CASP3、CASP7等信号蛋白来抑制卵巢癌细胞的生长和转移,涉及信号通路有癌症的途径、乙型肝炎、脂质和动脉粥样硬化、AGE-RAGE信号通路在糖尿病并发症中的应用、PI3K-AKT信号通路等。分子对接结果显示核心成分与核心靶点均有较好的结合能力。不同浓度槲皮素可明显抑制卵巢癌细胞增殖,且浓度越高细胞抑制率越高,细胞凋亡率也随浓度增高,数据结果差异有统计学意义(P<0.01)。结论 从网络药理学和分子对接技术得出白花蛇舌草和半枝莲药对可通过多成分、多靶点、多通路治疗卵巢癌的作用机制。槲皮素能有效抑制卵巢癌细胞并促进其凋亡。
基金financially supported by the National Key Research and Development Plan of China (No. 2016YFC1401203)the National Natural Science Foundation of China (Nos. 42006168 and 11404079)
文摘Ocean boundaries present a significant effect on the vibroacoustic characteristics and sound propagation of an elastic structure in practice.In this study,an efficient finite element/wave superposition method(FE/WSM)for predicting the three-dimen-sional acoustic radiation from an arbitrary-shaped radiator in Pekeris waveguides with a lossy seabed is proposed.The method is based on the FE method(FEM),WSM,and sound propagation models.First,a near-field vibroacoustic model is established by the FEM to obtain vibration information on a radiator surface.Then,the WSM based on the Helmholtz boundary integral is used to pre-dict the far-field acoustic radiation and propagation.Furthermore,the rigorous image source method and complex normal mode are employed to obtain the near-and far-field Green’s function(GF),respectively.The former,which is based on the spherical wave decomposition,is adopted to accurately solve the near-field source strength,and the far-field acoustic radiation is calculated by the latter and perturbation theory.The simulations of both models are compared to theoretical wavenumber integration solutions.Finally,numerical experiments on elastic spherical and cylindrical shells in Pekeris waveguides are presented to validate the accuracy and efficiency of the proposed method.The results show that the FE/WSM is adaptable to complex radiators and ocean-acoustic envi-ronments,and are easy to implement and computationally efficient in calculating the structural vibration,acoustic radiation,and sound propagation of arbitrarily shaped radiators in practical ocean environments.
