Varicella-zoster virus(VZV) is a neurotropic alphaherpesvirus that causes chickenpox and shingles. ORF7 is an important virulence determinant of VZV in both human skin and nerve tissues,however, its specific function ...Varicella-zoster virus(VZV) is a neurotropic alphaherpesvirus that causes chickenpox and shingles. ORF7 is an important virulence determinant of VZV in both human skin and nerve tissues,however, its specific function and involved molecular mechanism in VZV pathogenesis remain largely elusive. Previous yeast two-hybrid studies on intraviral protein-protein interaction network in herpesviruses have revealed that VZV ORF7 may interact with ORF53, which is a virtually unstudied but essential viral protein. The aim of this study is to identify and characterize VZV ORF53, and to investigate its relationship with ORF7. For this purpose, we prepared monoclonal antibodies against ORF53 and, for the first time, characterized it as a ~40 k Da viral protein predominantly localizing to the trans-Golgi network of the infected host cell. Next, we further confirmed the interaction between ORF7 and ORF53 by co-immunoprecipitation and co-localization studies in both plasmid-transfected and VZV-infected cells. Moreover, interestingly, we found that ORF53 lost its trans-Golgi network localization and became dispersed in the cytoplasm of host cells infected with an ORF7-deleted recombinant VZV, and thus ORF7 seems to play a role in normal subcellular localization of ORF53. Collectively, these results suggested that ORF7 and ORF53 may function as a complex during infection, which may be implicated in VZV pathogenesis.展开更多
In the course of the cryoplant modernization, a control network will be set up in order to facilitate the control, the supervision, the centralized data acquisition and the alarm handling of the cryogenic system for H...In the course of the cryoplant modernization, a control network will be set up in order to facilitate the control, the supervision, the centralized data acquisition and the alarm handling of the cryogenic system for HT-7U tokamak. The paper introduces the preliminary design of control network based on the Controller Link Network for HT-7U tokamak cryogenic system. The multi-layer structure mentioned in the paper is the mainstream of automatic control. The control philosophy, the structure of the network and the components for control are also presented.展开更多
Subjective: This study aimed to investigate the therapeutic mechanisms of 7-hydroxyflavone (7-HF) in treating myocardial ischemia/reperfusion injury (MI/RI) via network pharmacology, molecular docking, target validati...Subjective: This study aimed to investigate the therapeutic mechanisms of 7-hydroxyflavone (7-HF) in treating myocardial ischemia/reperfusion injury (MI/RI) via network pharmacology, molecular docking, target validation, and experiments at the animal level. Methods: Firstly, the genes of 7-HF were acquired from PharmMapper, TCMSP, and SwissTargetPrediction. At the same time, MI/RI-related genes were obtained from OMIM, GeneCards, and TTD online platforms. Subsequently, string platform and Cytoscape 3.9.2 were used to construct protein-protein interaction network diagrams and 7-HF-targets-signaling pathways-MI/RI network. Then, the Metascape platform was used to conduct functional enrichment analyses. Next, AutoDock Vina and Pymol were used to perform molecular docking. The hub targets were validated in the GSE66360. Lastly, SOD, MDA, transmission electron microscope, quantitative real-time PCR, and western blot were used to validate in MI/RI rats. Results: 139 genes of 7-HF, 4832 genes of MI/RI were obtained. The 47 interact genes between 7-HF and MI/RI targets for MI/RI were likely to act through multiple pathways. And NQO1 was a critical target in the above process. In an animal experiment, 7-HF could relieve the injured interfibrillar mitochondria and myocardial fibers, decrease the expression of MDA and SOD, and increase the expression of Nrf2, NQO1 and HO-1 in the mRNA and protein level in the MI/RI rats. Conclusion: This study preliminarily demonstrated that 7-HF could provide cardioprotection by inhibiting the oxidative stress and up-regulating Nrf2/NQO1/HO-1 signaling pathway based on network pharmacology, molecular docking, target validation, and animal experiments.展开更多
Background:The compound Luteolin-7-rutinoside(L7R)is a flavone derivative of luteolin,predominantly identified in plant species belonging to the families Asteraceae.Conversely,Myristic acid is characterized by its str...Background:The compound Luteolin-7-rutinoside(L7R)is a flavone derivative of luteolin,predominantly identified in plant species belonging to the families Asteraceae.Conversely,Myristic acid is characterized by its structure as a 14-carbon,unsaturated fatty acid.In this investigation,we endeavor to elucidate the putative mechanisms underlying the therapeutic effects of Myristic Acid and Luteolin 7-rutinoside in the context of oral cancer treatment,employing network pharmacology coupled with molecular docking methodologies.Methods:The protein targets of Myristic Acid and Luteolin 7-rutinoside were identified through a search on the Swiss Target Database.Subsequently,a compound-target network was constructed using Cytoscape 3.9.1.Targets associated with OC were retrieved from the OMIM and GeneCards databases.The overlap between compound targets and OC-related targets was determined,and the resulting shared targets were subjected to protein-protein interaction(PPI)network analysis using the STRING database.Additionally,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were conducted on the identified targets.Molecular docking were performed to investigate the interactions between the core target and the active compound.Results:The component target network comprises 103 nodes and 102 edges.Among the proteins in the protein-protein interaction(PPI)network,those with higher degrees are TNF,PPARG,and TP53.Analysis through Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways indicates that the treatment of OC with Myristic Acid and Luteolin 7-rutinoside primarily involves the regulation of miRNA transcription and inflammatory response.The identified signaling pathways include Pathways in cancer,PPAR signaling pathway,EGFR signaling pathway,and TNF signaling pathway.Molecular docking studies reveal that Luteolin 7-rutinoside and Myristic acid exhibit higher affinity towards TNF,PPARG,TP53,and EGFR.Conclusion:This study reveals the potential molecular mechanism of Myristic Acid and Luteolin 7-rutinoside in the treatment of oral cancer,and provides a reference for subsequent basic research.展开更多
Objective:To investigate the potential targets and mechanisms of Draconis Sanguis(DS),a valuable traditional Chinese medicine derived from the resin of the palm tree Daemonorops draco Bl(D.Sanguis,Xue Jie),in the trea...Objective:To investigate the potential targets and mechanisms of Draconis Sanguis(DS),a valuable traditional Chinese medicine derived from the resin of the palm tree Daemonorops draco Bl(D.Sanguis,Xue Jie),in the treatment of myocardial infarction(MI).Methods:We explored the potential mechanisms of DS in the treatment of MI using network pharmacology,bioinformatic techniques,and transcriptomic analysis,followed by validation through in vivo and in vitro experiments.Results:Network pharmacology and bioinformatic analyses identified five genes(Fpr1,Glul,Mme,Mmp9,and Pla2g7)as potential targets for MI treatment.Moreover,DS significantly ameliorated cardiac function,inflammatory responses,and MI-induced myocardial fibrosis in vivo.Transcriptomic and bioinformatic analyses identified Pla2g7 as the most critical target in the DS treatment of MI.Molecular docking revealed that the key active ingredient in DS has a strong affinity for this gene.Furthermore,DS reduced the expression of Pla2g7(P=.0009),NLRP3(P=.003),interleukin-18(P<.001),and interleukin-1b(P=.004)mRNAs in vivo.Conclusions:The results indicate that DS can downregulate the expression of Pla2g7 and reduce the inflammatory response.This demonstrates the potential therapeutic target of DS and the mechanism underlying its cardioprotective effects.展开更多
The aromatic Baeckea frutescens leaves(BFL)known as“Gang-Song-Cha”is a popular drink(Tea)in South China.To explore the healthcare value,a systematic and in-depth study on BFL alleviating rheumatoid arthritis(RA)was ...The aromatic Baeckea frutescens leaves(BFL)known as“Gang-Song-Cha”is a popular drink(Tea)in South China.To explore the healthcare value,a systematic and in-depth study on BFL alleviating rheumatoid arthritis(RA)was carried out by integrating network pharmacology,molecular docking,and experimental verification.The efficacy was first evaluated,and the BFL extract could ameliorate RA by inhibiting articular swelling,lowering immune organ index,improving the ankle pathologies,and regulating serum levels of tumor necrosis factorα(TNF-α),interleukin(IL)-6,and IL-10 in CIA rats.Then the anti-RA mechanism of BFL was investigated by leveraging the high-content and active component 5-hydroxy-7-methoxy-2-isopropylchromone(Chro),and the potential signaling pathway and related target proteins for Chro acting on RA were analyzed by Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment and docking simulation.Finally,the experimental validations were conducted on rheumatoid arthritis fibroblast-like synoviocytes(RAFLS),and compound Chro could inhibit cell invasion and migration,block cell cycle at G2/M phase and induce apoptosis,and reduce the secretion of inflammatory cytokines by suppressing the PI3K-Akt pathway.These results provided pharmacological basis for the folk usage of“Gang-Song-Cha”for intervening RA.展开更多
BACKGROUND Metastasis is the main reason leading to death in colorectal cancer(CRC)and about 25%of CRC patients developed metastasis when first diagnosed.Thus,unveiling biomarkers of CRC metastasis is of great signifi...BACKGROUND Metastasis is the main reason leading to death in colorectal cancer(CRC)and about 25%of CRC patients developed metastasis when first diagnosed.Thus,unveiling biomarkers of CRC metastasis is of great significance.AIM To reveal biomarkers of CRC metastasis.METHODS Weighted gene co-expression network analysis was conducted to identify metastatic biomarkers in CRC through a systematic analysis of the GSE29621 dataset.Comprehensive validation was performed subsequently using publicly available datasets from The Cancer Genome Atlas and Gene Expression Omnibus and supplemented with experimental verification in CRC cell lines.Moreover,the identified hub gene charged multivesicular body protein 7(CHMP7)was further subjected to clinical correlation analysis via Kaplan-Meier survival curves and Gene Set Enrichment Analysis to assess its prognostic significance and potential mechanistic involvement in CRC progression.RESULTS CHMP7 was identified as a key metastatic biomarker of CRC which displayed lower expression in CRC tissues,especially in CRC patients with metastasis and CRC cell lines with high metastasis potential.The expression of CHMP7 was significantly correlated with normal,metastatic tumor,pathologic stage,and lymphatic invasion(P<0.05).CRC patients with higher expression of CHMP7 exhibited better overall survival.Besides,Gene Set Enrichment Analysis results showed that CHMP7 might be involved in metastatic related pathways.CONCLUSION Our results indicate that CHMP7 might be a prognostic biomarker correlated with CRC metastasis.展开更多
基金supported by the National Natural Science Foundation of China (No. 81601762)the National Science and Technology Major Project of Infectious Diseases (No. 2017ZX10304402)+1 种基金the National Science and Technology Major Projects for Major New Drugs Innovation and Development (No. 2017ZX09101005-005-003)the Scientific Research Foundation of State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics (No. 2016ZY005)
文摘Varicella-zoster virus(VZV) is a neurotropic alphaherpesvirus that causes chickenpox and shingles. ORF7 is an important virulence determinant of VZV in both human skin and nerve tissues,however, its specific function and involved molecular mechanism in VZV pathogenesis remain largely elusive. Previous yeast two-hybrid studies on intraviral protein-protein interaction network in herpesviruses have revealed that VZV ORF7 may interact with ORF53, which is a virtually unstudied but essential viral protein. The aim of this study is to identify and characterize VZV ORF53, and to investigate its relationship with ORF7. For this purpose, we prepared monoclonal antibodies against ORF53 and, for the first time, characterized it as a ~40 k Da viral protein predominantly localizing to the trans-Golgi network of the infected host cell. Next, we further confirmed the interaction between ORF7 and ORF53 by co-immunoprecipitation and co-localization studies in both plasmid-transfected and VZV-infected cells. Moreover, interestingly, we found that ORF53 lost its trans-Golgi network localization and became dispersed in the cytoplasm of host cells infected with an ORF7-deleted recombinant VZV, and thus ORF7 seems to play a role in normal subcellular localization of ORF53. Collectively, these results suggested that ORF7 and ORF53 may function as a complex during infection, which may be implicated in VZV pathogenesis.
基金National 863-803 Project of China(No.2002AA834020)
文摘In the course of the cryoplant modernization, a control network will be set up in order to facilitate the control, the supervision, the centralized data acquisition and the alarm handling of the cryogenic system for HT-7U tokamak. The paper introduces the preliminary design of control network based on the Controller Link Network for HT-7U tokamak cryogenic system. The multi-layer structure mentioned in the paper is the mainstream of automatic control. The control philosophy, the structure of the network and the components for control are also presented.
文摘Subjective: This study aimed to investigate the therapeutic mechanisms of 7-hydroxyflavone (7-HF) in treating myocardial ischemia/reperfusion injury (MI/RI) via network pharmacology, molecular docking, target validation, and experiments at the animal level. Methods: Firstly, the genes of 7-HF were acquired from PharmMapper, TCMSP, and SwissTargetPrediction. At the same time, MI/RI-related genes were obtained from OMIM, GeneCards, and TTD online platforms. Subsequently, string platform and Cytoscape 3.9.2 were used to construct protein-protein interaction network diagrams and 7-HF-targets-signaling pathways-MI/RI network. Then, the Metascape platform was used to conduct functional enrichment analyses. Next, AutoDock Vina and Pymol were used to perform molecular docking. The hub targets were validated in the GSE66360. Lastly, SOD, MDA, transmission electron microscope, quantitative real-time PCR, and western blot were used to validate in MI/RI rats. Results: 139 genes of 7-HF, 4832 genes of MI/RI were obtained. The 47 interact genes between 7-HF and MI/RI targets for MI/RI were likely to act through multiple pathways. And NQO1 was a critical target in the above process. In an animal experiment, 7-HF could relieve the injured interfibrillar mitochondria and myocardial fibers, decrease the expression of MDA and SOD, and increase the expression of Nrf2, NQO1 and HO-1 in the mRNA and protein level in the MI/RI rats. Conclusion: This study preliminarily demonstrated that 7-HF could provide cardioprotection by inhibiting the oxidative stress and up-regulating Nrf2/NQO1/HO-1 signaling pathway based on network pharmacology, molecular docking, target validation, and animal experiments.
文摘Background:The compound Luteolin-7-rutinoside(L7R)is a flavone derivative of luteolin,predominantly identified in plant species belonging to the families Asteraceae.Conversely,Myristic acid is characterized by its structure as a 14-carbon,unsaturated fatty acid.In this investigation,we endeavor to elucidate the putative mechanisms underlying the therapeutic effects of Myristic Acid and Luteolin 7-rutinoside in the context of oral cancer treatment,employing network pharmacology coupled with molecular docking methodologies.Methods:The protein targets of Myristic Acid and Luteolin 7-rutinoside were identified through a search on the Swiss Target Database.Subsequently,a compound-target network was constructed using Cytoscape 3.9.1.Targets associated with OC were retrieved from the OMIM and GeneCards databases.The overlap between compound targets and OC-related targets was determined,and the resulting shared targets were subjected to protein-protein interaction(PPI)network analysis using the STRING database.Additionally,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were conducted on the identified targets.Molecular docking were performed to investigate the interactions between the core target and the active compound.Results:The component target network comprises 103 nodes and 102 edges.Among the proteins in the protein-protein interaction(PPI)network,those with higher degrees are TNF,PPARG,and TP53.Analysis through Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways indicates that the treatment of OC with Myristic Acid and Luteolin 7-rutinoside primarily involves the regulation of miRNA transcription and inflammatory response.The identified signaling pathways include Pathways in cancer,PPAR signaling pathway,EGFR signaling pathway,and TNF signaling pathway.Molecular docking studies reveal that Luteolin 7-rutinoside and Myristic acid exhibit higher affinity towards TNF,PPARG,TP53,and EGFR.Conclusion:This study reveals the potential molecular mechanism of Myristic Acid and Luteolin 7-rutinoside in the treatment of oral cancer,and provides a reference for subsequent basic research.
基金the National Natural Science Foundation of China(82222075).
文摘Objective:To investigate the potential targets and mechanisms of Draconis Sanguis(DS),a valuable traditional Chinese medicine derived from the resin of the palm tree Daemonorops draco Bl(D.Sanguis,Xue Jie),in the treatment of myocardial infarction(MI).Methods:We explored the potential mechanisms of DS in the treatment of MI using network pharmacology,bioinformatic techniques,and transcriptomic analysis,followed by validation through in vivo and in vitro experiments.Results:Network pharmacology and bioinformatic analyses identified five genes(Fpr1,Glul,Mme,Mmp9,and Pla2g7)as potential targets for MI treatment.Moreover,DS significantly ameliorated cardiac function,inflammatory responses,and MI-induced myocardial fibrosis in vivo.Transcriptomic and bioinformatic analyses identified Pla2g7 as the most critical target in the DS treatment of MI.Molecular docking revealed that the key active ingredient in DS has a strong affinity for this gene.Furthermore,DS reduced the expression of Pla2g7(P=.0009),NLRP3(P=.003),interleukin-18(P<.001),and interleukin-1b(P=.004)mRNAs in vivo.Conclusions:The results indicate that DS can downregulate the expression of Pla2g7 and reduce the inflammatory response.This demonstrates the potential therapeutic target of DS and the mechanism underlying its cardioprotective effects.
基金supported by the National Natural Science Foundation of China(U1804182)the Basic Research(Natural Science)Cultivation Project of Zhengzhou University(JC23852095).
文摘The aromatic Baeckea frutescens leaves(BFL)known as“Gang-Song-Cha”is a popular drink(Tea)in South China.To explore the healthcare value,a systematic and in-depth study on BFL alleviating rheumatoid arthritis(RA)was carried out by integrating network pharmacology,molecular docking,and experimental verification.The efficacy was first evaluated,and the BFL extract could ameliorate RA by inhibiting articular swelling,lowering immune organ index,improving the ankle pathologies,and regulating serum levels of tumor necrosis factorα(TNF-α),interleukin(IL)-6,and IL-10 in CIA rats.Then the anti-RA mechanism of BFL was investigated by leveraging the high-content and active component 5-hydroxy-7-methoxy-2-isopropylchromone(Chro),and the potential signaling pathway and related target proteins for Chro acting on RA were analyzed by Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment and docking simulation.Finally,the experimental validations were conducted on rheumatoid arthritis fibroblast-like synoviocytes(RAFLS),and compound Chro could inhibit cell invasion and migration,block cell cycle at G2/M phase and induce apoptosis,and reduce the secretion of inflammatory cytokines by suppressing the PI3K-Akt pathway.These results provided pharmacological basis for the folk usage of“Gang-Song-Cha”for intervening RA.
基金Supported by the National Natural Science Foundation of China,No.82260715the Middle-Aged and Young Teachers in Colleges and Universities in Guangxi Basic Ability Promotion Project,No.2024KY0302+2 种基金Guangxi Collaborative Innovation Center for Research on Functional Ingredients of Agricultural Residues,No.CICAR2016-P6the Grant of Research Project on High-Level Talents of Youjiang Medical College for Nationalities,No.YY2021SK002Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province,No.202300011.
文摘BACKGROUND Metastasis is the main reason leading to death in colorectal cancer(CRC)and about 25%of CRC patients developed metastasis when first diagnosed.Thus,unveiling biomarkers of CRC metastasis is of great significance.AIM To reveal biomarkers of CRC metastasis.METHODS Weighted gene co-expression network analysis was conducted to identify metastatic biomarkers in CRC through a systematic analysis of the GSE29621 dataset.Comprehensive validation was performed subsequently using publicly available datasets from The Cancer Genome Atlas and Gene Expression Omnibus and supplemented with experimental verification in CRC cell lines.Moreover,the identified hub gene charged multivesicular body protein 7(CHMP7)was further subjected to clinical correlation analysis via Kaplan-Meier survival curves and Gene Set Enrichment Analysis to assess its prognostic significance and potential mechanistic involvement in CRC progression.RESULTS CHMP7 was identified as a key metastatic biomarker of CRC which displayed lower expression in CRC tissues,especially in CRC patients with metastasis and CRC cell lines with high metastasis potential.The expression of CHMP7 was significantly correlated with normal,metastatic tumor,pathologic stage,and lymphatic invasion(P<0.05).CRC patients with higher expression of CHMP7 exhibited better overall survival.Besides,Gene Set Enrichment Analysis results showed that CHMP7 might be involved in metastatic related pathways.CONCLUSION Our results indicate that CHMP7 might be a prognostic biomarker correlated with CRC metastasis.
