OBJECTIVE To explore mecha⁃nisms of imperatorin on regulating P-glycoprotein(P-gp)in blood-brain barrier(BBB)based on net⁃work pharmacology combined with in vitro experi⁃ment.METHODS Drug targets were predicted using ...OBJECTIVE To explore mecha⁃nisms of imperatorin on regulating P-glycoprotein(P-gp)in blood-brain barrier(BBB)based on net⁃work pharmacology combined with in vitro experi⁃ment.METHODS Drug targets were predicted using the Pharmapper and Swiss targets data⁃bases;disease targets were obtained through the Genecards database;intersections between drugs and disease targets were screened by Cytoscape software;the obtained core targets were used to construct protein-protein interaction(PPI)network,gene ontology(GO)functions,and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.The effects of imperatorin(20,50,100μmol·L^(-1))on P-gp activity were monitored in hCMEC/D3 in vitro BBB model,and the effects of imperatorin on the expression of target proteins were verified using Western blot method.RESULTS 55 drug targets and 3102 disease targets were obtained from the network pharmacology screening,and 37 core targets were obtained after the combination.Enrichment analysis showed that core targets were closely related to chemical synaptic trans⁃mission regulation,neurotransmitter receptor activity,protein kinase regulation activity,G proteincoupled receptor signaling pathway,neural active ligand receptor interaction pathway,PI3K-Akt sig⁃naling pathway,VEGF signaling pathway,etc..In vitro experimental validation suggested that all tested concentration groups of imperatorin signifi⁃cantly reduced the activity and expression of P-gp,which were achieved by significantly downregu⁃lating the phosphorylation levels of PI3K and Akt,and repressing the expression of VEGFR2 pro⁃tein.CONCLUSION Network pharmacology was used to predict the core targets and signaling pathways of imperatorin on regulating P-gp in BBB and relevant validation was conducted through in vitro experiments,providing a refer⁃ence basis for further exploration of the mecha⁃nisms of imperatorin on regulating P-gp in BBB.展开更多
针对目前CFD(Computational Fluid Dynamics)软件数据可视化分析所需计算量大且操作不灵活的问题,面向CFD数据可视化分析需求,实现了一个CFD数据可视化分析服务原型软件。在该原型软件中,研究了自适应客户端的服务自适应QoS(Quality of ...针对目前CFD(Computational Fluid Dynamics)软件数据可视化分析所需计算量大且操作不灵活的问题,面向CFD数据可视化分析需求,实现了一个CFD数据可视化分析服务原型软件。在该原型软件中,研究了自适应客户端的服务自适应QoS(Quality of Service)优化技术,降低不同客户端计算环境对服务质量的影响;研究设计了基于消息中间件的服务集成接口,提高了服务使用的灵活性。面向云计算环境的CFD数据可视化分析服务发挥了云端服务器的性能优势,应用了“云+端”的开发新模式,具备灵活性和可扩展性。展开更多
基金Natural Science Foundation of Hebei Province(H2022206456)Natural Sci⁃ence Foundation of Hebei Province(H2021206449)+1 种基金Undergraduate Innovative Experiment Program of Hebei Medical University(USIP2022173)Undergraduate Innovative Experiment Program of Hebei Medical University(USIP2023107)。
文摘OBJECTIVE To explore mecha⁃nisms of imperatorin on regulating P-glycoprotein(P-gp)in blood-brain barrier(BBB)based on net⁃work pharmacology combined with in vitro experi⁃ment.METHODS Drug targets were predicted using the Pharmapper and Swiss targets data⁃bases;disease targets were obtained through the Genecards database;intersections between drugs and disease targets were screened by Cytoscape software;the obtained core targets were used to construct protein-protein interaction(PPI)network,gene ontology(GO)functions,and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.The effects of imperatorin(20,50,100μmol·L^(-1))on P-gp activity were monitored in hCMEC/D3 in vitro BBB model,and the effects of imperatorin on the expression of target proteins were verified using Western blot method.RESULTS 55 drug targets and 3102 disease targets were obtained from the network pharmacology screening,and 37 core targets were obtained after the combination.Enrichment analysis showed that core targets were closely related to chemical synaptic trans⁃mission regulation,neurotransmitter receptor activity,protein kinase regulation activity,G proteincoupled receptor signaling pathway,neural active ligand receptor interaction pathway,PI3K-Akt sig⁃naling pathway,VEGF signaling pathway,etc..In vitro experimental validation suggested that all tested concentration groups of imperatorin signifi⁃cantly reduced the activity and expression of P-gp,which were achieved by significantly downregu⁃lating the phosphorylation levels of PI3K and Akt,and repressing the expression of VEGFR2 pro⁃tein.CONCLUSION Network pharmacology was used to predict the core targets and signaling pathways of imperatorin on regulating P-gp in BBB and relevant validation was conducted through in vitro experiments,providing a refer⁃ence basis for further exploration of the mecha⁃nisms of imperatorin on regulating P-gp in BBB.
文摘针对目前CFD(Computational Fluid Dynamics)软件数据可视化分析所需计算量大且操作不灵活的问题,面向CFD数据可视化分析需求,实现了一个CFD数据可视化分析服务原型软件。在该原型软件中,研究了自适应客户端的服务自适应QoS(Quality of Service)优化技术,降低不同客户端计算环境对服务质量的影响;研究设计了基于消息中间件的服务集成接口,提高了服务使用的灵活性。面向云计算环境的CFD数据可视化分析服务发挥了云端服务器的性能优势,应用了“云+端”的开发新模式,具备灵活性和可扩展性。