Leucine-rich repeat kinase 1 （LRRK1） plays a critical role in regulating cytoskeletal organization, osteoclast activity, and bone resorption with little effect on bone formation parameters. Deficiency of Lrrkl in mi...Leucine-rich repeat kinase 1 （LRRK1） plays a critical role in regulating cytoskeletal organization, osteoclast activity, and bone resorption with little effect on bone formation parameters. Deficiency of Lrrkl in mice causes a severe osteopetrosis in the metaphysis of the long bones and vertebrae bones, which makes LRRK1 an attractive alternative drug target for the treatment of osteoporosis and other high-turnover bone diseases. This review recent advances on the functions of the Lrrkl-related family members, Lrrkl deficiency-induced skeletal phenotypes, LRRK1 structure-function, potential biological substrates and interacting proteins, and the mechanisms of LRRK1 action in osteoclasts.展开更多
Meisoindigo, an indirubin derivative, is a new type of cancer chemotherapeutic agent. It exhibited higher activity against rodent tumors than indirubin itself. Experiments have shown the improved absorption of meisoin...Meisoindigo, an indirubin derivative, is a new type of cancer chemotherapeutic agent. It exhibited higher activity against rodent tumors than indirubin itself. Experiments have shown the improved absorption of meisoindigo, compared to indirubin to be one of the major reasons for the enhancement of antitumor activity. Studies on the mechanism of meisoindigo action indicate that it strongly inhibits DNA biosynthesis in tumor cells. Strong inhibition of the drug on assembly of microtubule protein was also obtained. By means of FCM technique the effects of meisoindigo on mouse leukemia L1210 cell cycle were examined. Experimental results showed that under the action of meisoindigo the S phase cells accumulated and the traverse of the cells in G2 + M phase to G1 phase may also be blocked to some extent.展开更多
Objective:Use network pharmacology to explore the anti-COVID-19 mechanism of Huashi Baidu Recipe,supplemented by molecular docking verification.Methods:Thorugh databases such as TCMSP,GeneCard,String,and software such...Objective:Use network pharmacology to explore the anti-COVID-19 mechanism of Huashi Baidu Recipe,supplemented by molecular docking verification.Methods:Thorugh databases such as TCMSP,GeneCard,String,and software such as Cytoscape,AutoDockVina,network relationships was established,and the binding ability of active ingredients and targets is calculated through molecular docking,and biological function enrichment analysis was conducted.Result:The ingredients in Huashi Baidu Recipe that had strong affinity with SARS-CoV-23CL hydrolase(3CLpro)and angiotensin converting enzyme 2(ACE2)receptors include Quercetin,Baicalein,Astragaloside IV,Wogonin and other ingredients;25 active ingredients which obtained by screening had strong affinity with targets such as IL6,IL1B,NOS2 and CCL2.The biological function enrichment analysis mainly focused on Th17,Th1 and Th2 cell differentiation,NF-κB,MAPK,TNF,IL-17signaling pathway,etc.Conclusion:The active ingredients of Huashi Baidu Recipe may inhibit the infection and replication of SARS-CoV-2 virus,regulate RAS system’balance,inhibit excessive immune inflammatory response,and prevent inflammatory storm from appearing to fight COVID-19.展开更多
基金supported by National Institutes of Health grant AR066831-01ASBMR GAP grant to Weirong R Xingsupported by a senior research career scientist award from the Department of Veteran’s Affairs
文摘Leucine-rich repeat kinase 1 （LRRK1） plays a critical role in regulating cytoskeletal organization, osteoclast activity, and bone resorption with little effect on bone formation parameters. Deficiency of Lrrkl in mice causes a severe osteopetrosis in the metaphysis of the long bones and vertebrae bones, which makes LRRK1 an attractive alternative drug target for the treatment of osteoporosis and other high-turnover bone diseases. This review recent advances on the functions of the Lrrkl-related family members, Lrrkl deficiency-induced skeletal phenotypes, LRRK1 structure-function, potential biological substrates and interacting proteins, and the mechanisms of LRRK1 action in osteoclasts.
文摘Meisoindigo, an indirubin derivative, is a new type of cancer chemotherapeutic agent. It exhibited higher activity against rodent tumors than indirubin itself. Experiments have shown the improved absorption of meisoindigo, compared to indirubin to be one of the major reasons for the enhancement of antitumor activity. Studies on the mechanism of meisoindigo action indicate that it strongly inhibits DNA biosynthesis in tumor cells. Strong inhibition of the drug on assembly of microtubule protein was also obtained. By means of FCM technique the effects of meisoindigo on mouse leukemia L1210 cell cycle were examined. Experimental results showed that under the action of meisoindigo the S phase cells accumulated and the traverse of the cells in G2 + M phase to G1 phase may also be blocked to some extent.
基金National Natural Science Foundation of China(No.81273662,81473592)。
文摘Objective:Use network pharmacology to explore the anti-COVID-19 mechanism of Huashi Baidu Recipe,supplemented by molecular docking verification.Methods:Thorugh databases such as TCMSP,GeneCard,String,and software such as Cytoscape,AutoDockVina,network relationships was established,and the binding ability of active ingredients and targets is calculated through molecular docking,and biological function enrichment analysis was conducted.Result:The ingredients in Huashi Baidu Recipe that had strong affinity with SARS-CoV-23CL hydrolase(3CLpro)and angiotensin converting enzyme 2(ACE2)receptors include Quercetin,Baicalein,Astragaloside IV,Wogonin and other ingredients;25 active ingredients which obtained by screening had strong affinity with targets such as IL6,IL1B,NOS2 and CCL2.The biological function enrichment analysis mainly focused on Th17,Th1 and Th2 cell differentiation,NF-κB,MAPK,TNF,IL-17signaling pathway,etc.Conclusion:The active ingredients of Huashi Baidu Recipe may inhibit the infection and replication of SARS-CoV-2 virus,regulate RAS system’balance,inhibit excessive immune inflammatory response,and prevent inflammatory storm from appearing to fight COVID-19.
