目的:运用网络药理学的研究方法联合分子对接探讨玉液汤治疗糖尿病肾病的机制。方法:通过高通量基因表达数据库(gene expression omnibus,GEO)获取糖尿病肾病转录组基因表达情况,提取与自噬相关的基因。利用中药系统药理学数据库与分析...目的:运用网络药理学的研究方法联合分子对接探讨玉液汤治疗糖尿病肾病的机制。方法:通过高通量基因表达数据库(gene expression omnibus,GEO)获取糖尿病肾病转录组基因表达情况,提取与自噬相关的基因。利用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)工具筛选得出玉液汤的活性成分及相关靶点,将药物预测靶点与疾病靶点进行映射得到与自噬相关的玉液治疗糖尿病肾病的靶点。利用String(search tool for the retrival of interacting genes/proteins)数据库结合Cytoscape 3.7.2软件构建玉液汤治疗糖尿病肾病的“药物-有效活性成分-靶点”网络和蛋白质相互作用网络,使用Metascape对玉液汤治疗糖尿病肾病的作用靶点进行基因本体论(Gene Ontology,GO)生物学过程分析和京都基因和基因组数据库KEGG(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析,最后运用Pymol等软件对玉液汤的核心活性成分与核心靶点蛋白进行分子对接验证。结果:(1)筛选得到符合条件的糖尿病肾病与自噬相关基因100个,玉液汤的潜在作用靶点共1428个。将获得的糖尿病肾病与自噬相关的基因与玉液汤潜在作用靶点进行映射,获得22个治疗靶点。GO生物学过程富集分析与KEGG通路富集分析发现玉液汤治疗糖尿病肾病与自噬相关的通路可能包括mTOR信号通路、磷脂酶D信号通路、胰岛素抵抗、EGFR酪氨酸激酶抑制剂抵抗、细胞凋亡、PI3K/Akt信号通路、NF-κB信号通路等。(2)蛋白互作网络表明VEGFA、ERBB2、GASP3、MAPK8、MYC、CDKN1A、EGFR、BCL2L1可能是玉液汤治疗糖尿病肾病的关键作用靶点。分子对接实现4个核心活性成分与8个核心靶点蛋白结合。结论:玉液汤通过多成分、多靶点、多通路作用治疗糖尿病肾病,为玉液汤治疗糖尿病肾病的在自噬相关方面的药理作用研究和临床应用提供新的理论依据。展开更多
Klinefelter＇s syndrome （KS） is the most common sex chromosome disease in men. Classical features of the syndrome include a eunuchoidal body habitus, small testes and hypergonadotrophic hypogonadism. There has been ...Klinefelter＇s syndrome （KS） is the most common sex chromosome disease in men. Classical features of the syndrome include a eunuchoidal body habitus, small testes and hypergonadotrophic hypogonadism. There has been an increased risk of diabetes mellitus and autoimmune disease for KS patients. This paper reports a case of KS in association with type 1 diabetes mellitus. The patient was a 21-year-old man, who has been confirmed by absolute insulin deficiency and positive IA-2 autoantibody. The hyperinsulinemic euglycemic clamp test indicated his insulin sensitivity in normal range, and his blood glucose was controlled well by the insulin therapy.展开更多
文摘目的:运用网络药理学的研究方法联合分子对接探讨玉液汤治疗糖尿病肾病的机制。方法:通过高通量基因表达数据库(gene expression omnibus,GEO)获取糖尿病肾病转录组基因表达情况,提取与自噬相关的基因。利用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)工具筛选得出玉液汤的活性成分及相关靶点,将药物预测靶点与疾病靶点进行映射得到与自噬相关的玉液治疗糖尿病肾病的靶点。利用String(search tool for the retrival of interacting genes/proteins)数据库结合Cytoscape 3.7.2软件构建玉液汤治疗糖尿病肾病的“药物-有效活性成分-靶点”网络和蛋白质相互作用网络,使用Metascape对玉液汤治疗糖尿病肾病的作用靶点进行基因本体论(Gene Ontology,GO)生物学过程分析和京都基因和基因组数据库KEGG(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析,最后运用Pymol等软件对玉液汤的核心活性成分与核心靶点蛋白进行分子对接验证。结果:(1)筛选得到符合条件的糖尿病肾病与自噬相关基因100个,玉液汤的潜在作用靶点共1428个。将获得的糖尿病肾病与自噬相关的基因与玉液汤潜在作用靶点进行映射,获得22个治疗靶点。GO生物学过程富集分析与KEGG通路富集分析发现玉液汤治疗糖尿病肾病与自噬相关的通路可能包括mTOR信号通路、磷脂酶D信号通路、胰岛素抵抗、EGFR酪氨酸激酶抑制剂抵抗、细胞凋亡、PI3K/Akt信号通路、NF-κB信号通路等。(2)蛋白互作网络表明VEGFA、ERBB2、GASP3、MAPK8、MYC、CDKN1A、EGFR、BCL2L1可能是玉液汤治疗糖尿病肾病的关键作用靶点。分子对接实现4个核心活性成分与8个核心靶点蛋白结合。结论:玉液汤通过多成分、多靶点、多通路作用治疗糖尿病肾病,为玉液汤治疗糖尿病肾病的在自噬相关方面的药理作用研究和临床应用提供新的理论依据。
文摘Klinefelter＇s syndrome （KS） is the most common sex chromosome disease in men. Classical features of the syndrome include a eunuchoidal body habitus, small testes and hypergonadotrophic hypogonadism. There has been an increased risk of diabetes mellitus and autoimmune disease for KS patients. This paper reports a case of KS in association with type 1 diabetes mellitus. The patient was a 21-year-old man, who has been confirmed by absolute insulin deficiency and positive IA-2 autoantibody. The hyperinsulinemic euglycemic clamp test indicated his insulin sensitivity in normal range, and his blood glucose was controlled well by the insulin therapy.
