Objective The aim of the study was to screen key proteins involved in the treatment of human gastric cancer subcutaneous xenografts in nude mice by the traditional Chinese medicine formula Weichang’an and to explore ...Objective The aim of the study was to screen key proteins involved in the treatment of human gastric cancer subcutaneous xenografts in nude mice by the traditional Chinese medicine formula Weichang’an and to explore its mechanism of action in treating gastric cancer.Methods Sixteen 7-to 8-week-old female BALB/C nude mice were used to establish a human gastric cancer subcutaneous xenograft model by bilateral axillary injection of MKN45 cells.Mice with successfully established tumors were randomly divided into the Weichang’an group and the model group,with eight mice in each group.Mice in the Weichang’an group were orally administered 0.5mL of Weichang’an decoction,while mice in the model group were given 0.5 mL of normal saline by gavage once a day for 21 consecutive days.On day 28,the animals were sacrificed by cervical dislocation,and tumors were excised to measure tumor weight and assess the tumor suppression rate.Tandem mass tags(TMT)quantitative proteomics was used to analyze the tumor samples,identify differentially expressed proteins,and perform Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Results Compared with the model group,the tumor weight in the Weichang’an group was significantly reduced(p<0.001),and the tumor suppression rate was 41.40%,indicating that Weichang’an can inhibit the growth of human gastric cancer subcutaneous xenografts in nude mice.TMT quantitative proteomics identified a total of 2,856 proteins,with 13 proteins showing downregulated expression and 25 proteins showing upregulated expression in the Weichang’an group.GO enrichment analysis revealed that differentially expressed proteins were mainly enriched in cellular components such as the cell membrane,extracellular matrix,and envelope,and participated in biological processes like negative regulation of cell adhesion hematopoiesis,and skeletal system development,with functions in cell adhesion molecule binding and molecular sensor activity.The KEGG pathway enrichment analysis identified the autophagy-lysosome pathway.Conclusion Weichang’an may exert its therapeutic effect on gastric cancer by regulating the expression of various proteins and modulating the autophagy-lysosome pathway.展开更多
ObjectiveThe aim of the study is to explore the molecular mechanism of Yadanzi(Brucea javanica)in the treatment of glioblastoma(GBM)by using the methods of bioinformatics and network pharmacology.Methods The Tradition...ObjectiveThe aim of the study is to explore the molecular mechanism of Yadanzi(Brucea javanica)in the treatment of glioblastoma(GBM)by using the methods of bioinformatics and network pharmacology.Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and literature retrieval method were applied to obtain the active ingredients of Yadanzi(Brucea javanica),and to predict the relevant targets of the active ingredients.The GBM-related targets were retrieved and screened through the Gene Expression Profling Interactive Analysis(GEPIA)database,and mapped to each other with the targets of the components of Yadanzi(Brucea javanica)to obtain the intersection targets.The GBM differentially expressed gene targets were imported into the String database to obtain the protein interaction relationship,the Cytoscape software was used to draw the protein interaction network,the Cytobba and MCODE plug-ins were used to screen the core genes and important protein interaction modules,and the GEPIA database was applied to make survival analysis of the core genes.The network map of“active ingredients-targets”was constructed through the Cytoscape 3.6.1 software.Gene Ontology(GO)biological function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis for GBM differentially expressed genes were performed through the DAVID database.ResultsThrough TCMSP and literature retrieval,23 potential active ingredients and 129 related targets were obtained from Yadanzi(Brucea javanica).In the GEPIA database,247 GBM differentially expressed genes were screened,including 113 upregulated genes and 134 downregulated genes.After mapping with the targets related to the active ingredients of Yadanzi(Brucea javanica),six intersection targets were obtained,that is,the potential action targets of Yadanzi(Brucea javanica)in treating GBM,including MMP2,HMOX1,BIRC5,EGFR,CCNB2,and TOP2A.Cytoscape software was applied to build an“active ingredient-action target”network.Two active ingredients and five action targets of β-sitosterol(BS)and luteolin were found,and the targets were mainly concentrated in BS.It was found by KEGG pathway enrichment analysis that GBM differentially expressed genes were mainly involved in signaling pathways related to Staphylococcus aureus infection,phagosome formation,tuberculosis and systemic lupus erythematosus and other infectious and autoimmune diseases.It was found by GO enrichment analysis that the GBM differentially expressed genes mainly involved such biological processes(BP)as the processing and presentation of exogenous antigenic peptides and polysaccharide antigens through MHC Il molecules,y-interferon-mediated signaling pathways,extracellular matrix composition,and chemical synapses transmission;it involved cellular components such as cell junctions,axon terminal buttons,extracellular space,vesicle membranes for endocytosis,and MHC Il protein complexes;molecular functions such as calcium-mediated ionic protein binding,MHC Il molecular receptor activity,immunoglobulin binding,and phospholipase inhibitor activity were also involved.Survival analysis was conducted by GEPIA on the top 37 core targets in degree value,and a total of five genes related to GBM prognosis were obtained.Among them,FN1 and MMP2 were highly expressed while GABRD(v-aminobutyric acid A receptor delta subunit),RBFOX1,and SLC6A7 were expressed at a low level in cancer patients.Conclusion The pathogenesis of GBM is closely related to the human immune system,and BS and luteolin may be the main material basis of Yadanzi(Brucea javanica)for the treatment of GBM and the improvement of prognosis.The molecular mechanism may be related to the physical barrier formed by destroying the tumor cell stromal 68 Treatment of Glioblastoma Based on Bioinformatics and Network Pharmacology Zhao,Si.molecules and its involvement in tumor immune response.展开更多
Informative proteins are the proteins that play critical functional roles inside cells.They are the fundamental knowledge of translating bioinformatics into clinical practices.Many methods of identifying informative b...Informative proteins are the proteins that play critical functional roles inside cells.They are the fundamental knowledge of translating bioinformatics into clinical practices.Many methods of identifying informative biomarkers have been developed which are heuristic and arbitrary,without considering the dynamics characteristics of biological processes.In this paper,we present a generative model of identifying the informative proteins by systematically analyzing the topological variety of dynamic protein-protein interaction networks(PPINs).In this model,the common representation of multiple PPINs is learned using a deep feature generation model,based on which the original PPINs are rebuilt and the reconstruction errors are analyzed to locate the informative proteins.Experiments were implemented on data of yeast cell cycles and different prostate cancer stages.We analyze the effectiveness of reconstruction by comparing different methods,and the ranking results of informative proteins were also compared with the results from the baseline methods.Our method is able to reveal the critical members in the dynamic progresses which can be further studied to testify the possibilities for biomarker research.展开更多
基金funded by the Special Research Project of Traditional Chinese Medicine in Henan Province(2022ZY2031).
文摘Objective The aim of the study was to screen key proteins involved in the treatment of human gastric cancer subcutaneous xenografts in nude mice by the traditional Chinese medicine formula Weichang’an and to explore its mechanism of action in treating gastric cancer.Methods Sixteen 7-to 8-week-old female BALB/C nude mice were used to establish a human gastric cancer subcutaneous xenograft model by bilateral axillary injection of MKN45 cells.Mice with successfully established tumors were randomly divided into the Weichang’an group and the model group,with eight mice in each group.Mice in the Weichang’an group were orally administered 0.5mL of Weichang’an decoction,while mice in the model group were given 0.5 mL of normal saline by gavage once a day for 21 consecutive days.On day 28,the animals were sacrificed by cervical dislocation,and tumors were excised to measure tumor weight and assess the tumor suppression rate.Tandem mass tags(TMT)quantitative proteomics was used to analyze the tumor samples,identify differentially expressed proteins,and perform Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Results Compared with the model group,the tumor weight in the Weichang’an group was significantly reduced(p<0.001),and the tumor suppression rate was 41.40%,indicating that Weichang’an can inhibit the growth of human gastric cancer subcutaneous xenografts in nude mice.TMT quantitative proteomics identified a total of 2,856 proteins,with 13 proteins showing downregulated expression and 25 proteins showing upregulated expression in the Weichang’an group.GO enrichment analysis revealed that differentially expressed proteins were mainly enriched in cellular components such as the cell membrane,extracellular matrix,and envelope,and participated in biological processes like negative regulation of cell adhesion hematopoiesis,and skeletal system development,with functions in cell adhesion molecule binding and molecular sensor activity.The KEGG pathway enrichment analysis identified the autophagy-lysosome pathway.Conclusion Weichang’an may exert its therapeutic effect on gastric cancer by regulating the expression of various proteins and modulating the autophagy-lysosome pathway.
文摘ObjectiveThe aim of the study is to explore the molecular mechanism of Yadanzi(Brucea javanica)in the treatment of glioblastoma(GBM)by using the methods of bioinformatics and network pharmacology.Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and literature retrieval method were applied to obtain the active ingredients of Yadanzi(Brucea javanica),and to predict the relevant targets of the active ingredients.The GBM-related targets were retrieved and screened through the Gene Expression Profling Interactive Analysis(GEPIA)database,and mapped to each other with the targets of the components of Yadanzi(Brucea javanica)to obtain the intersection targets.The GBM differentially expressed gene targets were imported into the String database to obtain the protein interaction relationship,the Cytoscape software was used to draw the protein interaction network,the Cytobba and MCODE plug-ins were used to screen the core genes and important protein interaction modules,and the GEPIA database was applied to make survival analysis of the core genes.The network map of“active ingredients-targets”was constructed through the Cytoscape 3.6.1 software.Gene Ontology(GO)biological function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis for GBM differentially expressed genes were performed through the DAVID database.ResultsThrough TCMSP and literature retrieval,23 potential active ingredients and 129 related targets were obtained from Yadanzi(Brucea javanica).In the GEPIA database,247 GBM differentially expressed genes were screened,including 113 upregulated genes and 134 downregulated genes.After mapping with the targets related to the active ingredients of Yadanzi(Brucea javanica),six intersection targets were obtained,that is,the potential action targets of Yadanzi(Brucea javanica)in treating GBM,including MMP2,HMOX1,BIRC5,EGFR,CCNB2,and TOP2A.Cytoscape software was applied to build an“active ingredient-action target”network.Two active ingredients and five action targets of β-sitosterol(BS)and luteolin were found,and the targets were mainly concentrated in BS.It was found by KEGG pathway enrichment analysis that GBM differentially expressed genes were mainly involved in signaling pathways related to Staphylococcus aureus infection,phagosome formation,tuberculosis and systemic lupus erythematosus and other infectious and autoimmune diseases.It was found by GO enrichment analysis that the GBM differentially expressed genes mainly involved such biological processes(BP)as the processing and presentation of exogenous antigenic peptides and polysaccharide antigens through MHC Il molecules,y-interferon-mediated signaling pathways,extracellular matrix composition,and chemical synapses transmission;it involved cellular components such as cell junctions,axon terminal buttons,extracellular space,vesicle membranes for endocytosis,and MHC Il protein complexes;molecular functions such as calcium-mediated ionic protein binding,MHC Il molecular receptor activity,immunoglobulin binding,and phospholipase inhibitor activity were also involved.Survival analysis was conducted by GEPIA on the top 37 core targets in degree value,and a total of five genes related to GBM prognosis were obtained.Among them,FN1 and MMP2 were highly expressed while GABRD(v-aminobutyric acid A receptor delta subunit),RBFOX1,and SLC6A7 were expressed at a low level in cancer patients.Conclusion The pathogenesis of GBM is closely related to the human immune system,and BS and luteolin may be the main material basis of Yadanzi(Brucea javanica)for the treatment of GBM and the improvement of prognosis.The molecular mechanism may be related to the physical barrier formed by destroying the tumor cell stromal 68 Treatment of Glioblastoma Based on Bioinformatics and Network Pharmacology Zhao,Si.molecules and its involvement in tumor immune response.
基金supported by National Natural Science Foundation of China(30970780)Ph.D.Programs Foundation of Ministry of Education of China(20091103110005)+4 种基金the Project for the Innovation Team of Beijing,National Natural Science Foundation of China(81370038)the Beijing Natural Science Foundation(7142012)the Science and Technology Project of Beijing Municipal Education Commission(km201410005003)the Rixin Fund of Beijing University of Technology(2013-RX-L04)the Basic Research Fund of Beijing University of Technology
文摘Informative proteins are the proteins that play critical functional roles inside cells.They are the fundamental knowledge of translating bioinformatics into clinical practices.Many methods of identifying informative biomarkers have been developed which are heuristic and arbitrary,without considering the dynamics characteristics of biological processes.In this paper,we present a generative model of identifying the informative proteins by systematically analyzing the topological variety of dynamic protein-protein interaction networks(PPINs).In this model,the common representation of multiple PPINs is learned using a deep feature generation model,based on which the original PPINs are rebuilt and the reconstruction errors are analyzed to locate the informative proteins.Experiments were implemented on data of yeast cell cycles and different prostate cancer stages.We analyze the effectiveness of reconstruction by comparing different methods,and the ranking results of informative proteins were also compared with the results from the baseline methods.Our method is able to reveal the critical members in the dynamic progresses which can be further studied to testify the possibilities for biomarker research.
