构建柴胡活性成分-作用靶点网络和蛋白相互作用网络,对靶点涉及的功能和通路进行分析,探讨柴胡抗抑郁的作用机制。通过TCMSP数据库、文献挖掘和本实验室已有研究获取柴胡主要活性成分,利用DRAR-CPI服务器、Gene Cards和OMIM数据库预测...构建柴胡活性成分-作用靶点网络和蛋白相互作用网络,对靶点涉及的功能和通路进行分析,探讨柴胡抗抑郁的作用机制。通过TCMSP数据库、文献挖掘和本实验室已有研究获取柴胡主要活性成分,利用DRAR-CPI服务器、Gene Cards和OMIM数据库预测和筛选柴胡活性成分抗抑郁的作用靶点。采用Cytoscape软件构建活性成分-作用靶点网络,采用String数据库和Cytoscape软件绘制蛋白相互作用网络,通过Systems Dock Web Site对成分与靶点进行分子对接验证。采用DAVID数据库对靶点进行GO及KEGG通路分析,通过Dis Ge NET数据库对靶点所属的类型进行归属。筛选得到柴胡15个活性成分,涉及50个作用靶点。网络分析结果表明,柴胡主要涉及细胞过程、代谢过程、对应激的应答等生物过程,通过调节PI3K-AKT、MAPK、Rap1、Ras、Fox O和neurotrophin等信号通路来发挥抗抑郁作用。本研究体现了柴胡多成分-多靶点-多途径的作用特点,为进一步开展柴胡抗抑郁作用机制的研究提供了新思路和新方法。展开更多
The interactions between C8H17(OC2H4)nSO4Na (C8E.S; n=0, 1, 3) andC8H17NC6H5Br(C8Py), C8EnS and CmH2m+2NC5H5Br (CmPy; m=10, 12, 14, 16), t-C8H17C6H4(OC2H4)9.8SO4Na (C8φE9.8S) and cmPy in micelles have been studied by...The interactions between C8H17(OC2H4)nSO4Na (C8E.S; n=0, 1, 3) andC8H17NC6H5Br(C8Py), C8EnS and CmH2m+2NC5H5Br (CmPy; m=10, 12, 14, 16), t-C8H17C6H4(OC2H4)9.8SO4Na (C8φE9.8S) and cmPy in micelles have been studied bysuxface tension method. The partial ternary "phase diagram" of C8EnS-C8Py-H2O andC8EnS-C12Py-H2O systems have been obtained. The results show that with the increaseof n, the interaction between C8EnS and C8Py decreases and the stability of aqueous so-lution of C8EnS-C8Py increases. With the increase of m, the interaction between C8E3Sand CmPy increases and the stability of aqueous solution of C8E3S-CmPy decreases. Theinteraction between C8φE9.8S and CmPy is strong while the aqueous so1ution of C8φE9.8S-C.Py is still very stable.展开更多
The rapid accumulation of mutations in the SARS-CoV-2 Omicron variant that enabled its outbreak raises questions as to whether its proximal origin occurred in humans or another mammalian host. Here, we identified 45 p...The rapid accumulation of mutations in the SARS-CoV-2 Omicron variant that enabled its outbreak raises questions as to whether its proximal origin occurred in humans or another mammalian host. Here, we identified 45 point mutations that Omicron acquired since divergence from the B.1.1 lineage. We found that the Omicron spike protein sequence was subjected to stronger positive selection than that of any reported SARS-CoV-2 variants known to evolve persistently in human hosts, suggesting a possibility of hostjumping. The molecular spectrum of mutations(i.e., the relative frequency of the 12 types of base substitutions) acquired by the progenitor of Omicron was significantly different from the spectrum for viruses that evolved in human patients but resembled the spectra associated with virus evolution in a mouse cellular environment. Furthermore, mutations in the Omicron spike protein significantly overlapped with SARS-CoV-2 mutations known to promote adaptation to mouse hosts, particularly through enhanced spike protein binding affinity for the mouse cell entry receptor. Collectively, our results suggest that the progenitor of Omicron jumped from humans to mice, rapidly accumulated mutations conducive to infecting that host,then jumped back into humans, indicating an inter-species evolutionary trajectory for the Omicron outbreak.展开更多
文摘构建柴胡活性成分-作用靶点网络和蛋白相互作用网络,对靶点涉及的功能和通路进行分析,探讨柴胡抗抑郁的作用机制。通过TCMSP数据库、文献挖掘和本实验室已有研究获取柴胡主要活性成分,利用DRAR-CPI服务器、Gene Cards和OMIM数据库预测和筛选柴胡活性成分抗抑郁的作用靶点。采用Cytoscape软件构建活性成分-作用靶点网络,采用String数据库和Cytoscape软件绘制蛋白相互作用网络,通过Systems Dock Web Site对成分与靶点进行分子对接验证。采用DAVID数据库对靶点进行GO及KEGG通路分析,通过Dis Ge NET数据库对靶点所属的类型进行归属。筛选得到柴胡15个活性成分,涉及50个作用靶点。网络分析结果表明,柴胡主要涉及细胞过程、代谢过程、对应激的应答等生物过程,通过调节PI3K-AKT、MAPK、Rap1、Ras、Fox O和neurotrophin等信号通路来发挥抗抑郁作用。本研究体现了柴胡多成分-多靶点-多途径的作用特点,为进一步开展柴胡抗抑郁作用机制的研究提供了新思路和新方法。
文摘The interactions between C8H17(OC2H4)nSO4Na (C8E.S; n=0, 1, 3) andC8H17NC6H5Br(C8Py), C8EnS and CmH2m+2NC5H5Br (CmPy; m=10, 12, 14, 16), t-C8H17C6H4(OC2H4)9.8SO4Na (C8φE9.8S) and cmPy in micelles have been studied bysuxface tension method. The partial ternary "phase diagram" of C8EnS-C8Py-H2O andC8EnS-C12Py-H2O systems have been obtained. The results show that with the increaseof n, the interaction between C8EnS and C8Py decreases and the stability of aqueous so-lution of C8EnS-C8Py increases. With the increase of m, the interaction between C8E3Sand CmPy increases and the stability of aqueous solution of C8E3S-CmPy decreases. Theinteraction between C8φE9.8S and CmPy is strong while the aqueous so1ution of C8φE9.8S-C.Py is still very stable.
基金supported by grants from the National Natural Science Foundation of China(31922014)。
文摘The rapid accumulation of mutations in the SARS-CoV-2 Omicron variant that enabled its outbreak raises questions as to whether its proximal origin occurred in humans or another mammalian host. Here, we identified 45 point mutations that Omicron acquired since divergence from the B.1.1 lineage. We found that the Omicron spike protein sequence was subjected to stronger positive selection than that of any reported SARS-CoV-2 variants known to evolve persistently in human hosts, suggesting a possibility of hostjumping. The molecular spectrum of mutations(i.e., the relative frequency of the 12 types of base substitutions) acquired by the progenitor of Omicron was significantly different from the spectrum for viruses that evolved in human patients but resembled the spectra associated with virus evolution in a mouse cellular environment. Furthermore, mutations in the Omicron spike protein significantly overlapped with SARS-CoV-2 mutations known to promote adaptation to mouse hosts, particularly through enhanced spike protein binding affinity for the mouse cell entry receptor. Collectively, our results suggest that the progenitor of Omicron jumped from humans to mice, rapidly accumulated mutations conducive to infecting that host,then jumped back into humans, indicating an inter-species evolutionary trajectory for the Omicron outbreak.
