目的:通过网络药理学结合分子对接技术探讨三化复遂汤治疗急性脑梗死(Acute Cerebral Infarction,ACI)的作用机制。方法:借助中药系统药理学数据库和分析平台(TCMSP)和本草组鉴(Herb)两大数据库筛选出三化复遂汤的活性成分,结合STRING...目的:通过网络药理学结合分子对接技术探讨三化复遂汤治疗急性脑梗死(Acute Cerebral Infarction,ACI)的作用机制。方法:借助中药系统药理学数据库和分析平台(TCMSP)和本草组鉴(Herb)两大数据库筛选出三化复遂汤的活性成分,结合STRING数据库、Uniprot数据库及Swiss Target Prediction平台预测活性成分相关靶点。采用Gene Cards、DRUGBANK及OMIM数据库检索ACI相关疾病靶点,在Venny 2.1数据库中获取复方与疾病交集靶点,通过Cytoscape 3.7.1构建“复方-活性成分-疾病-靶点”网络图,在STRING平台获取药物与疾病靶点蛋白质-蛋白质相互作用(PPI)网络图,并获取PPI网络图的关键靶点,在David数据库中行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析,最后从复方-疾病网络图中选取高度值的化合物,在Pub Chem、PDB数据库中获取相关蛋白分子文件,于Auto Dock Tools 1.5.6软件上处理,最终在Py MOL软件行可视化分析。结果:三化复遂汤关键活性成分有槲皮素、木犀草素、山柰酚、汉黄芩素等,治疗关键靶点为信号转导及转录激活蛋白(Signal Transducer and Activator of Transcription,STAT)3、丝氨酸/苏氨酸蛋白激酶(Akt Serine/Threonine Kinase,AKT)1、热休克蛋白90α家族A类成员1(Heat Shock Protein 90 Alpha Family Class A Member 1,HSP90AA1)、白细胞介素(Interleukin,IL)-6、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)1等,KEGG气泡图显示关键靶点主要富集于磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinase,PI3K)-蛋白激酶B(Akt)和晚期糖基化终末产物(Advanced Glycation End-Product,AGE)与其受体(Receptor for Advanced Glycation End Products,RAGE)等信号通路上,分子对接示AKT1中的7nh5与木犀草素结合能最高。结论:三化复遂汤中槲皮素、木犀草素、山柰酚和汉黄芩素等通过PI3K-Akt和AGE-RAGE等信号通路,主要在STAT3、AKT1、HSP90AA1、IL-6、TNF、MAPK1等靶点上干预ACI,从而改善缺血灶局部神经炎症反应,延缓细胞凋亡,减轻氧化应激反应。通过分子对接验证后发现,AKT1是三化复遂汤治疗ACI过程中的关键靶点。展开更多
Based on a partial postcranial skeleton collected from the Lower Cretaceous Napai Formation of Guangxi, China, we erect a new sauropod taxon, Fusuisaurus zhaoi gen. et sp. nov. The holotype specimen consists of the le...Based on a partial postcranial skeleton collected from the Lower Cretaceous Napai Formation of Guangxi, China, we erect a new sauropod taxon, Fusuisaurus zhaoi gen. et sp. nov. The holotype specimen consists of the left ilium, left pubis, anterior caudals, most of the dorsal ribs and distal end of the left femur. Fusuisaurus zhaoi is diagnosed by a unique combination of character states among the known sauropods. It displays several synapomorphies of Titanosauriformes but lacks many derived features seen in other titanosauriforms, suggesting that the new taxon represents the basalmost known titanosauriform and providing new evidence that Titanosauriformes originated from Asia. A size comparison suggests that Fusuisaurus zhaoi is among the largest Early Cretaceous sauropods, providing an important addition to the Early Cretaceous Chinese sauropod diversity.展开更多
文摘目的:通过网络药理学结合分子对接技术探讨三化复遂汤治疗急性脑梗死(Acute Cerebral Infarction,ACI)的作用机制。方法:借助中药系统药理学数据库和分析平台(TCMSP)和本草组鉴(Herb)两大数据库筛选出三化复遂汤的活性成分,结合STRING数据库、Uniprot数据库及Swiss Target Prediction平台预测活性成分相关靶点。采用Gene Cards、DRUGBANK及OMIM数据库检索ACI相关疾病靶点,在Venny 2.1数据库中获取复方与疾病交集靶点,通过Cytoscape 3.7.1构建“复方-活性成分-疾病-靶点”网络图,在STRING平台获取药物与疾病靶点蛋白质-蛋白质相互作用(PPI)网络图,并获取PPI网络图的关键靶点,在David数据库中行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析,最后从复方-疾病网络图中选取高度值的化合物,在Pub Chem、PDB数据库中获取相关蛋白分子文件,于Auto Dock Tools 1.5.6软件上处理,最终在Py MOL软件行可视化分析。结果:三化复遂汤关键活性成分有槲皮素、木犀草素、山柰酚、汉黄芩素等,治疗关键靶点为信号转导及转录激活蛋白(Signal Transducer and Activator of Transcription,STAT)3、丝氨酸/苏氨酸蛋白激酶(Akt Serine/Threonine Kinase,AKT)1、热休克蛋白90α家族A类成员1(Heat Shock Protein 90 Alpha Family Class A Member 1,HSP90AA1)、白细胞介素(Interleukin,IL)-6、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)1等,KEGG气泡图显示关键靶点主要富集于磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinase,PI3K)-蛋白激酶B(Akt)和晚期糖基化终末产物(Advanced Glycation End-Product,AGE)与其受体(Receptor for Advanced Glycation End Products,RAGE)等信号通路上,分子对接示AKT1中的7nh5与木犀草素结合能最高。结论:三化复遂汤中槲皮素、木犀草素、山柰酚和汉黄芩素等通过PI3K-Akt和AGE-RAGE等信号通路,主要在STAT3、AKT1、HSP90AA1、IL-6、TNF、MAPK1等靶点上干预ACI,从而改善缺血灶局部神经炎症反应,延缓细胞凋亡,减轻氧化应激反应。通过分子对接验证后发现,AKT1是三化复遂汤治疗ACI过程中的关键靶点。
基金National Nature Science Foundation of China(39960015)National Science Fund for Distinguished Young Scholars(30125006)+1 种基金Project of "Ten,Hundred and Thousand Outstanding Scholars" of Guangxi Provincial GovernmentState Forestry Administration
文摘Based on a partial postcranial skeleton collected from the Lower Cretaceous Napai Formation of Guangxi, China, we erect a new sauropod taxon, Fusuisaurus zhaoi gen. et sp. nov. The holotype specimen consists of the left ilium, left pubis, anterior caudals, most of the dorsal ribs and distal end of the left femur. Fusuisaurus zhaoi is diagnosed by a unique combination of character states among the known sauropods. It displays several synapomorphies of Titanosauriformes but lacks many derived features seen in other titanosauriforms, suggesting that the new taxon represents the basalmost known titanosauriform and providing new evidence that Titanosauriformes originated from Asia. A size comparison suggests that Fusuisaurus zhaoi is among the largest Early Cretaceous sauropods, providing an important addition to the Early Cretaceous Chinese sauropod diversity.
