Recent fast advance in biomedical research at the“omic”levels has led to an explosion of big data for the understanding the molecular makeup of diseases,which have revealed the intimate unmatched relationships betwe...Recent fast advance in biomedical research at the“omic”levels has led to an explosion of big data for the understanding the molecular makeup of diseases,which have revealed the intimate unmatched relationships between the genomic variabilities and the current organ-or system-based definition and classification of disease in Western medi⁃cine.The major challenges in the effort to establish and develop precision medicine are how diseases should be defined and classified in an integrated systemic or omic scale and also on an individualized basis.The phenomics approach to the understanding of diseases will allow the transition from focused phenotype/genotype studies to a systemic largescale phenome and genome,proteome,metabolome approach and the identification of a systemically integrated setof biomarkers for diagnosis and prognosis of disease phenome(or Zhenghou).Phenome-wide associated study(PheWAS)may soon lead the field of medical research and provide insightful and novel clues for redefinition of the disease phenome and its clinical classifications and personalized treatment and ultimately precision medicine.Pharma⁃cophenomics is to characterize the phenomes of drug response and also to identify the corresponding therapeutic targets at the level of systems biology.As a complement of pharmacogenomics/proteomics/metabolomics,pharmacoph⁃enomics offers a suite of new technologies and platforms for the transition from focused phenotype-genotype study to a systematic phenome-genome approach and refine drug research with systematically-defined drug response and thera⁃peutic targets.Therefore,pharmacophenomics will provide a new paradigm for the study of drug response including effects and toxicities at the level of systems biology and will identify the corresponding therapeutic targets and principles for combination treatment and prevention of disease using Fangji or Fufang that takes into account individual variability in genes,environment,and lifestyle for each person.展开更多
Objective:To examine the therapeutic effect of Fangji Fuling Decoction(FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments.Methods:A sepsis mouse model was constructe...Objective:To examine the therapeutic effect of Fangji Fuling Decoction(FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments.Methods:A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide(LPS).RAW264.7 cells were stimulated by 250 ng/m L LPS to establish an in vitro cell model.Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis.Through ectopic expression and depletion experiments,the effect of FFD on multiple organ damage in septic mice,as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A(MAPK14/FOXO3A) signaling pathway,was analyzed.Results:FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro(P<0.05).Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis.As confirmed by in vitro cell experiments,FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation(P<0.05).Furthermore,FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice(P<0.05).Conclusion:FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.展开更多
Objective: With the development of the society, the number of people who catch the nephrotic syndrome(NS) is going up roughly. As we all know, traditional Chinese medicine(TCM), especially Fangji Huangqi Decoction(FHD...Objective: With the development of the society, the number of people who catch the nephrotic syndrome(NS) is going up roughly. As we all know, traditional Chinese medicine(TCM), especially Fangji Huangqi Decoction(FHD), has a long history with good curative effects on NS. However, the mechanism of FHD treating NS has not been clearly elucidated.Methods: In this study, TCMSP platform was employed to screen active compounds of each herb of Fangji Huangqi Decoction combined with literatures. Furthermore, PharmMapper and SEA were used to predict and screen the active targets of FHD, and the HOME-NCBI-GENE, GeneCards and OMIM database were used to screen the active targets of NS. The GO and KEGG pathways involved in the targets were analyzed by Clue GO. Finally, contribution index was used to screen the active ingredients of FHD in the treatment of NS.Results: After drug-likeness(DL) and bioavailability(OB) filtering, 43 compounds were selected from FHD,interacting with 85 NS-related targets. Systematic analysis of the constructed networks revealed that it was mainly involved in PI3 K-Akt signaling pathway, MAPK signaling pathway, T cell receptor signaling pathway and TNF signaling pathway. The contribution index of every active ingredient also indicated five compounds, including astragaloside IV, quercetin, glycyrrhizic acid, glycyrrhizin and fangchinoline.Conclusions: These results have successfully predicted the pharmacodynamic material basis and the mechanism efficiency of FHD in the treatment of NS.展开更多
文摘Recent fast advance in biomedical research at the“omic”levels has led to an explosion of big data for the understanding the molecular makeup of diseases,which have revealed the intimate unmatched relationships between the genomic variabilities and the current organ-or system-based definition and classification of disease in Western medi⁃cine.The major challenges in the effort to establish and develop precision medicine are how diseases should be defined and classified in an integrated systemic or omic scale and also on an individualized basis.The phenomics approach to the understanding of diseases will allow the transition from focused phenotype/genotype studies to a systemic largescale phenome and genome,proteome,metabolome approach and the identification of a systemically integrated setof biomarkers for diagnosis and prognosis of disease phenome(or Zhenghou).Phenome-wide associated study(PheWAS)may soon lead the field of medical research and provide insightful and novel clues for redefinition of the disease phenome and its clinical classifications and personalized treatment and ultimately precision medicine.Pharma⁃cophenomics is to characterize the phenomes of drug response and also to identify the corresponding therapeutic targets at the level of systems biology.As a complement of pharmacogenomics/proteomics/metabolomics,pharmacoph⁃enomics offers a suite of new technologies and platforms for the transition from focused phenotype-genotype study to a systematic phenome-genome approach and refine drug research with systematically-defined drug response and thera⁃peutic targets.Therefore,pharmacophenomics will provide a new paradigm for the study of drug response including effects and toxicities at the level of systems biology and will identify the corresponding therapeutic targets and principles for combination treatment and prevention of disease using Fangji or Fufang that takes into account individual variability in genes,environment,and lifestyle for each person.
文摘Objective:To examine the therapeutic effect of Fangji Fuling Decoction(FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments.Methods:A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide(LPS).RAW264.7 cells were stimulated by 250 ng/m L LPS to establish an in vitro cell model.Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis.Through ectopic expression and depletion experiments,the effect of FFD on multiple organ damage in septic mice,as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A(MAPK14/FOXO3A) signaling pathway,was analyzed.Results:FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro(P<0.05).Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis.As confirmed by in vitro cell experiments,FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation(P<0.05).Furthermore,FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice(P<0.05).Conclusion:FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.
基金financially supported by the National Natural Science Foundation of China (No. 31570346 and No. 31770362)Research Project Supported by Shanxi Scholarship Council of China (2017-017)+1 种基金Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province (201605D111004)Science and Technology Innovation Team of Shanxi Province (201605D131045-18)
文摘Objective: With the development of the society, the number of people who catch the nephrotic syndrome(NS) is going up roughly. As we all know, traditional Chinese medicine(TCM), especially Fangji Huangqi Decoction(FHD), has a long history with good curative effects on NS. However, the mechanism of FHD treating NS has not been clearly elucidated.Methods: In this study, TCMSP platform was employed to screen active compounds of each herb of Fangji Huangqi Decoction combined with literatures. Furthermore, PharmMapper and SEA were used to predict and screen the active targets of FHD, and the HOME-NCBI-GENE, GeneCards and OMIM database were used to screen the active targets of NS. The GO and KEGG pathways involved in the targets were analyzed by Clue GO. Finally, contribution index was used to screen the active ingredients of FHD in the treatment of NS.Results: After drug-likeness(DL) and bioavailability(OB) filtering, 43 compounds were selected from FHD,interacting with 85 NS-related targets. Systematic analysis of the constructed networks revealed that it was mainly involved in PI3 K-Akt signaling pathway, MAPK signaling pathway, T cell receptor signaling pathway and TNF signaling pathway. The contribution index of every active ingredient also indicated five compounds, including astragaloside IV, quercetin, glycyrrhizic acid, glycyrrhizin and fangchinoline.Conclusions: These results have successfully predicted the pharmacodynamic material basis and the mechanism efficiency of FHD in the treatment of NS.
