Objective:To explore whether thrombopoietin can exert a protective effect against doxorubicin-induced cardiotoxicity by modulating the sirtuin 1(SIRT1)signaling pathway.Methods:H9c2 cell viability was determined by CC...Objective:To explore whether thrombopoietin can exert a protective effect against doxorubicin-induced cardiotoxicity by modulating the sirtuin 1(SIRT1)signaling pathway.Methods:H9c2 cell viability was determined by CCK-8 and cardiomyocyte apoptosis was detected by TUNEL assay.The protein expressions of SIRT1 and p38 MAPK were measured by Western blot.RT-qPCR was also used to determine SIRT1 mRNA expression.In addition,intracellular reactive oxygen species levels and antioxidant enzyme activities were evaluated.Results:Thrombopoietin treatment reversed doxorubicin-induced decline in H9c2 cell viability.It also increased SIRT1 and decreased p-p38 MAPK protein expressions.In addition,thrombopoietin significantly attenuated doxorubicin-induced apoptosis and oxidative stress,and enhanced antioxidant enzyme activities.However,silencing SIRT1 abrogated the protective effects of thrombopoietin,as evidenced by reduced cell viability and increased oxidative stress and reactive oxygen species levels.Conclusions:Thrombopoietin alleviates doxorubicin-induced cardiomyocyte injury by reducing oxidative stress and apoptosis via the SIRT1/p38 MAPK pathway.However,its protective effects need to be further verified in animal tests.展开更多
Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effec...Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effective compounds and drug targets using Chinese medicine systemic pharmacology database and analysis platform and Chinese medicine molecular mechanism bioinformatics analysis tools;and searched for DKD targets using human online Mendelian genetics and gene cards.The potential targets of GLQMP for DKD were obtained through the intersection of drug targets and disease targets.Cytoscape software was applied to build herbal medicine-active compound-target-disease networks and analyze them;protein-protein interaction networks were analyzed using the STRING database platform;gene ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene ontology and gene and genome encyclopedia to enrich potential targets using the DAVID database;and the AutoDock Vina 1.1.2 software for molecular docking of key targets with corresponding key components.In vitro experiments were validated by CCK8,oil red O staining,TC,TG,RT-qPCR,and Western blot.Results:Through network pharmacology analysis,a total of 99 potential therapeutic targets of GLQMP for DKD and the corresponding 38 active compounds were obtained,and 5 core compounds were identified.By constructing the protein-protein interaction network and performing network topology analysis,we found that PPARA and PPARG were the key targets,and then we molecularly docked these two key targets with the 38 active compounds,especially the 5 core compounds,and found that PPARA and PPARG had good binding ability with a variety of compounds.In vitro experiments showed that GLQMP was able to ameliorate HK-2 cell injury under high glucose stress,improve cell viability,reduce TC and TG levels as well as decrease the accumulation of lipid droplets,and RT-qPCR and Western blot confirmed that GLQMP was able to promote the expression levels of PPARA and PPARG.Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of GLQMP treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by GLQMP.展开更多
Background:Diabetic kidney disease(DKD)is a microvascular complication of diabetes mellitus and is the main cause of end-stage renal failure.Suoquan pills(SQP)has a variety of pharmacological activities and multiple t...Background:Diabetic kidney disease(DKD)is a microvascular complication of diabetes mellitus and is the main cause of end-stage renal failure.Suoquan pills(SQP)has a variety of pharmacological activities and multiple therapeutic effects,and it is used clinically as a basic formula for the treatment of DKD.Methods:Public databases were used to identify SQP compounds and the potential targets of SQP and DKD.A drug-component-therapeutic target network was constructed.Protein-protein interaction network analysis,Gene Ontology functional analysis,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to analyse the potential molecular mechanisms of SQP based on common targets of drugs and diseases.Molecular docking simulations were conducted to confirm the binding abity of the core compounds to key targets.The efficacy and predicted molecular mechanisms of SQP were validated using cell counting kit-8 assay,flow cytometry,and western blotting with HK-2 cells as a model.Results:Network pharmacology analysis showed that 26 compounds and 207 potential targets of SQP were involved in the treatment of DKD;boldine,denudatin B,pinocembrin,kaempferoid,and quercetin were considered core compounds,and epidermal growth factor receptor(EGFR)and proto-oncogene,non-receptor tyrosine kinase(SRC)were considered key targets.Gene Ontology enrichment analysis indicated that protein phosphorylation and negative regulation of apoptotic processes are important biological processes in the treatment of DKD by SQP.Molecular docking confirmed the excellent binding abilities of boldine,denudatin B,kaempferide,and quercetin to EGFR and SRC.The results of in vitro experiments showed that treatment with an ethanolic extract of SQP significantly protected HK-2 cells from high glucose-induced cell damage.In addition,the SQP ethanol extract inhibited the phosphorylation of EGFR and SRC,suppressed the apoptosis rate,and regulated apoptosis-related proteins in HK-2 cells under high glucose stress.Conclusion:This study systematically and intuitively illustrated the possible pharmacological mechanisms of SQP against DKD through multiple components,targets,and signalling pathways,especially the inhibition of EGFR and SRC phosphorylation and apoptosis.展开更多
Background:In this study,we analyzed the potential active components,related crucial targets and possible signaling pathway mechanisms of Alpiniae Oxyphyllae Fructus and Saposhnikoviae Radix(AOF-SR)herb pairs in the t...Background:In this study,we analyzed the potential active components,related crucial targets and possible signaling pathway mechanisms of Alpiniae Oxyphyllae Fructus and Saposhnikoviae Radix(AOF-SR)herb pairs in the treatment of diabetic kidney disease(DKD)using network pharmacology and verification experiments.Methods:The active compounds and potential targets of AOF-SR were derived from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,The Encyclopedia of Traditional Chinese Medicine,and PubChem databases,and the potential therapeutic targets of DKD were derived from the OMIM,Drugbank,and DisGeNET databases.The“compounds-diseases-targets”network was constructed using Cytoscape 3.6.0.ClusterMaker functionality in Cytoscape is being used to screen important targets for AOF-SR treatment of DKD.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of important targets were performed using DAVID database.In addition,according to the predicted results of network pharmacology,HK-2 cells were used to construct DKD model for verification experiment.HK-2 cells were divided into control group,high glucose(HG)group and AOF-SR(HG+AOF-SR)group to detect survival rate and expression of key proteins in NF-κB and PI3K/Akt signaling pathways.Results:A total of 38 compounds were selected from AOF-SR,of which 23 were Alpiniae Oxyphyllae Fructus and 15 were Saposhnikoviae Radix.Through enrichment analysis of 82 important targets,88 signaling pathways were identified;some of these pathways,such as the NF-κB,PI3K-Akt,IL-17,and JAK/STAT signaling pathways,regulate the pathological process of DKD.In verification experiment,the HK-2 cells survival rate was higher in the HG+AOF-SR group than in the HG group(P<0.05).Moreover,western blotting results showed that the expression levels of NF-κB,p-PI3K,and p-Akt in HG+AOF-SR group were significantly lower than those in HG group(P<0.05).Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of AOF-SR treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by AOF-SR.展开更多
Background:To explore the pharmacological mechanism of the anti-hepatitis B virus of Phyllanthus urinaria L.through network pharmacological analysis and experimental validation.Method:The active ingredient,target of a...Background:To explore the pharmacological mechanism of the anti-hepatitis B virus of Phyllanthus urinaria L.through network pharmacological analysis and experimental validation.Method:The active ingredient,target of action and target of action related to hepatitis B were clarified by searching the herb group identification,GeneCards and OMIM databases,and the protein interaction relationship was obtained by using the String database,and the protein interaction network map was constructed by using Cytoscape software.We also performed gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of key targets of the anti-hepatitis B action of Phyllanthus urinaria L.and predicted the core targets and pathways of Phyllanthus urinaria L.anti-hepatitis B.The main targets predicted by network pharmacology were then validated by HepG2.2.15 cell experiments.Results:By searching active ingredient targets and hepatitis B disease targets,a total of 19 active ingredients and 64 related targets of action were retrieved from Phyllanthus urinaria L.,and a total of 51 common targets were obtained by mapping the obtained hepatitis B disease targets and drug targets.protein protein interaction network analysis indicated that targets including TNF,JUN,AKT1,IL-10,IL-1B,CAT,HMOX1,NFE2L2,and CASP3 and other targets may be the core targets.gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that the treatment of hepatitis B by Phyllanthus urinaria L.mainly included inflammation and oxidation-related processes,and the signaling pathways mainly included fluid shear stress and atherosclerosis,VEGF,and hepatocellular carcinoma.The results of the in vitro test showed that after the action of different concentrations of the extracts of the Phyllanthus urinaria L.in the safe concentration range on cells HepG2.2.15,HBsAg,HBeAg and hepatitis B virus DNA levels were significantly inhibited,and NFE2L2 and HMOX1 were affecting hepatitis B virus transcription and replication by regulating the oxidative stress response.Conclusion:Using an integrated network pharmacology approach,this study revealed the active components and potential targets of Phyllanthus urinaria L.for the treatment of the hepatitis B virus,providing a theoretical basis for the research and clinical application of Phyllanthus urinaria L..展开更多
The study aims to reveal the mechanism of traditional Chinese medicine in the treatment of endometriosis and provide support for further research on traditional Chinese medicine and its active ingredients.The literatu...The study aims to reveal the mechanism of traditional Chinese medicine in the treatment of endometriosis and provide support for further research on traditional Chinese medicine and its active ingredients.The literature survey was conducted using PubMed,Web of Science,CNKI and other databases with“endometriosis”,“Chinese medicine”,“Chinese herbal medicine”and“natural plants”as the main keywords.Traditional Chinese medicine can exert their therapeutic effects on endometriosis by inhibiting inflammation through multiple pathways and multiple targets,regulating cell proliferation and apoptosis,angiogenesis,cell adhesion and oxidative stress.Traditional Chinese medicine can intervene in endometriosis in multiple ways and with multiple targets.In-depth study of Chinese medicine for endometriosis can provide new ideas for exploring the pathogenesis of endometriosis and developing new drugs.展开更多
[Objectives]The purpose of this paper was to study the effects of Suoquan Yishen formula on mice with diabetic nephropathy(DN).[Methods]The mice were randomly divided into normal group,model group,irbesartan group,and...[Objectives]The purpose of this paper was to study the effects of Suoquan Yishen formula on mice with diabetic nephropathy(DN).[Methods]The mice were randomly divided into normal group,model group,irbesartan group,and high and low-dose Suoquan Yishen formula groups.The blood glucose level,BUN,Scr excretion and GSH activity and CAT activity were detected.[Results]The blood glucose levels of mice in the irbesartan group and high and low-dose Suoquan Yishen formula groups decreased.The BUN,PRO and Scr levels were higher and the GSH and CAT activity was lower in the model group compared with the normal group.After administration of Suoquan Yishen formula,the BUN,PRO and Scr levels of the DN mice decreased significantly,and the GSH and CAT activity increased significantly.[Conclusions]Suoquan Yishen formula can reduce blood glucose level,reduce PRO,BUN and Scr levels,and increase CAT and GSH activity in DN mice,thus protecting the ND mice.展开更多
Multicoloured languages play an irreplaceable role in the whole world as a useful communication tool. With the development of technology and science, varieties of languages have an ideal prospective tendency to evolut...Multicoloured languages play an irreplaceable role in the whole world as a useful communication tool. With the development of technology and science, varieties of languages have an ideal prospective tendency to evolution during the long and wonderful history. Will they be thriving or decaying? To begin with, aimed to gain general tendency about the quantity of languages' speakers, we employ the Grey prediction to capture associative curve which can be seen in Figure 1. From the trend of this vivid figure, we not only can come to the conclusion that the number of English and Chinese users tend to increase but also find that Spanish development will reach the period of stagnation. Secondly, for further improvement, we take birth rate, death rate, economic factors and the immigration into consideration and establish the language communication model. This model is deduced from the population prediction model and virus transmission model. After data normalization, the eventual curve indicates that current top-ten languages seem to be replaced by other languages. This transformation phenomenon also occurs among such top-ten languages. For instance, Hindustani will replace Spanish in the future when seen from Table 1. What's more, after predicting the migration pattern, we can draw the conclusion that some range of languages' dissemination has obvious change. As show in vivid Figure 14, we know English will popularize widely among neighboring countries such as Canada, Mexico, Cuba and Russia. Moreover, with regard to how to manage international offices' quantity and locations in the world, we construct the efficiency model with combination of the Bayes' probability theory and Fussy comprehensive assessment. As a result, we obtain 9 optimal plans to establish the international offices. Intelligible result is showed in Table 4 and Table 5. In short, our model is reasonable and feasible, which can accommodate to different situation.展开更多
Objective:To analyze the components and mechanisms of Wuyao(Linderae Radix)in treating diabetic nephropathy(DN)based on network pharmacology.Methods:Multiple online databases were used to search and screen out the act...Objective:To analyze the components and mechanisms of Wuyao(Linderae Radix)in treating diabetic nephropathy(DN)based on network pharmacology.Methods:Multiple online databases were used to search and screen out the active ingredients from Linderae Radix,the related targets of active components of Linderae Radix and the genes related to DN.Search the corresponding genes name of target through UniProt database.Cytoscape 3.2.1 was used to construct the corresponding target gene network of Linderae Radix compounds.Venn diagram was used to screen the intersection genes of the active components corresponding to the target and disease-related genes,and the intersection genes were constructed into the protein interaction relationship network.Finally,DAVID database was used to do GO function enrichment analysis and KEGG signaling pathway enrichment analysis for the intersection genes,and the results of GO and KEGG were visualized.Results:1.A total of 7 potential active ingredients and 100 target proteins were screened.2.There are a total of 34 intersection genes between the potential active ingredient target in Linderae Radix in DN.3.The top 10 of the interaction correlation between intersection proteins include:AR and NCOA2,NCOA2 and NR3C1,NCOA2 and PPARG,etc.4.There were 16 entries of molecular function,9 entries of cell component,47 entries of biological process and 18 entries of signaling pathway(P<0.05).Conclusion:DN was treated by Linderae Radix from multi-component,multi-target and multi-link synergies.展开更多
TRAF7 serves as a crucial intracellular adaptor and E3 ubiquitin ligase involved in signal transduction pathways,contributing to immune responses,tumor progression,and embryonic development.Somatic mutations within th...TRAF7 serves as a crucial intracellular adaptor and E3 ubiquitin ligase involved in signal transduction pathways,contributing to immune responses,tumor progression,and embryonic development.Somatic mutations within the coiled-coil(CC)domain and WD40 repeat domain of TRAF7 could cause brain tumors,while germline pathogenic mutations contribute to severe developmental abnormalities.However,the precise molecular mechanism underlying TRAF7 involvement in embryonic development remains unclear.In this study,we employed zebrafish as an in vivo model system.TRAF7 knock down caused defects in zebrafish embryonic development.We determined the crystal structure of TRAF7 CC domain at 3.3Åresolution and found that the CC region trimerization was essential for TRAF7 functionality during zebrafish embryonic development.Additionally,disease-causing mutations in TRAF7 CC region could impair the trimer formation,consequently impacting early embryonic development of zebrafish.Therefore,our study sheds light on the molecular mechanism of TRAF7 CC trimer formation and its pivotal role in embryonic development.展开更多
The base promoted three-component reaction of β-enamino imide, malononitrile and various cyclic α-diketones in acetonitrile showed interesting molecular diversity. The reactions with acenaphthylene-1,2-dione and nin...The base promoted three-component reaction of β-enamino imide, malononitrile and various cyclic α-diketones in acetonitrile showed interesting molecular diversity. The reactions with acenaphthylene-1,2-dione and ninhydrin afforded functionalized spiro[indene-2,4'-pyrrolo[3,4-b]pyridines] and spiro[acenaphthylene-1,4'-pyrrolo[3,4-b]- pyridines] in good yields. The similar reaction of phenanthrene-9,10-dione resulted in the formation of the unexpected complex phenanthro[9', 10':4,5]furo[2,3-c]pyrrolo[3,4-b]pyrroles in satisfactory yields.展开更多
基金supported by the Natural Science Foundation of Hainan Province High-level Talent Project(grant number 820RC644)Innovative Research Projects for Postgraduate Students at Hainan Medical University(grant number HYYS2022B08).
文摘Objective:To explore whether thrombopoietin can exert a protective effect against doxorubicin-induced cardiotoxicity by modulating the sirtuin 1(SIRT1)signaling pathway.Methods:H9c2 cell viability was determined by CCK-8 and cardiomyocyte apoptosis was detected by TUNEL assay.The protein expressions of SIRT1 and p38 MAPK were measured by Western blot.RT-qPCR was also used to determine SIRT1 mRNA expression.In addition,intracellular reactive oxygen species levels and antioxidant enzyme activities were evaluated.Results:Thrombopoietin treatment reversed doxorubicin-induced decline in H9c2 cell viability.It also increased SIRT1 and decreased p-p38 MAPK protein expressions.In addition,thrombopoietin significantly attenuated doxorubicin-induced apoptosis and oxidative stress,and enhanced antioxidant enzyme activities.However,silencing SIRT1 abrogated the protective effects of thrombopoietin,as evidenced by reduced cell viability and increased oxidative stress and reactive oxygen species levels.Conclusions:Thrombopoietin alleviates doxorubicin-induced cardiomyocyte injury by reducing oxidative stress and apoptosis via the SIRT1/p38 MAPK pathway.However,its protective effects need to be further verified in animal tests.
基金supported by the grants from National Natural Science Foundation of China(No.82174334)Hainan Provincial Key Laboratory of Tropical Brain Science Research and Transformation Research Project(JCKF2021001)Innovative Research Projects for Graduate Students(HYYS2021B01).
文摘Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effective compounds and drug targets using Chinese medicine systemic pharmacology database and analysis platform and Chinese medicine molecular mechanism bioinformatics analysis tools;and searched for DKD targets using human online Mendelian genetics and gene cards.The potential targets of GLQMP for DKD were obtained through the intersection of drug targets and disease targets.Cytoscape software was applied to build herbal medicine-active compound-target-disease networks and analyze them;protein-protein interaction networks were analyzed using the STRING database platform;gene ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene ontology and gene and genome encyclopedia to enrich potential targets using the DAVID database;and the AutoDock Vina 1.1.2 software for molecular docking of key targets with corresponding key components.In vitro experiments were validated by CCK8,oil red O staining,TC,TG,RT-qPCR,and Western blot.Results:Through network pharmacology analysis,a total of 99 potential therapeutic targets of GLQMP for DKD and the corresponding 38 active compounds were obtained,and 5 core compounds were identified.By constructing the protein-protein interaction network and performing network topology analysis,we found that PPARA and PPARG were the key targets,and then we molecularly docked these two key targets with the 38 active compounds,especially the 5 core compounds,and found that PPARA and PPARG had good binding ability with a variety of compounds.In vitro experiments showed that GLQMP was able to ameliorate HK-2 cell injury under high glucose stress,improve cell viability,reduce TC and TG levels as well as decrease the accumulation of lipid droplets,and RT-qPCR and Western blot confirmed that GLQMP was able to promote the expression levels of PPARA and PPARG.Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of GLQMP treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by GLQMP.
基金supported by the grants from National Natural Science Foundation of China(No.82174334)Hainan Province in 2022 postgraduate innovation research projects(No.Qhys2022-273).
文摘Background:Diabetic kidney disease(DKD)is a microvascular complication of diabetes mellitus and is the main cause of end-stage renal failure.Suoquan pills(SQP)has a variety of pharmacological activities and multiple therapeutic effects,and it is used clinically as a basic formula for the treatment of DKD.Methods:Public databases were used to identify SQP compounds and the potential targets of SQP and DKD.A drug-component-therapeutic target network was constructed.Protein-protein interaction network analysis,Gene Ontology functional analysis,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to analyse the potential molecular mechanisms of SQP based on common targets of drugs and diseases.Molecular docking simulations were conducted to confirm the binding abity of the core compounds to key targets.The efficacy and predicted molecular mechanisms of SQP were validated using cell counting kit-8 assay,flow cytometry,and western blotting with HK-2 cells as a model.Results:Network pharmacology analysis showed that 26 compounds and 207 potential targets of SQP were involved in the treatment of DKD;boldine,denudatin B,pinocembrin,kaempferoid,and quercetin were considered core compounds,and epidermal growth factor receptor(EGFR)and proto-oncogene,non-receptor tyrosine kinase(SRC)were considered key targets.Gene Ontology enrichment analysis indicated that protein phosphorylation and negative regulation of apoptotic processes are important biological processes in the treatment of DKD by SQP.Molecular docking confirmed the excellent binding abilities of boldine,denudatin B,kaempferide,and quercetin to EGFR and SRC.The results of in vitro experiments showed that treatment with an ethanolic extract of SQP significantly protected HK-2 cells from high glucose-induced cell damage.In addition,the SQP ethanol extract inhibited the phosphorylation of EGFR and SRC,suppressed the apoptosis rate,and regulated apoptosis-related proteins in HK-2 cells under high glucose stress.Conclusion:This study systematically and intuitively illustrated the possible pharmacological mechanisms of SQP against DKD through multiple components,targets,and signalling pathways,especially the inhibition of EGFR and SRC phosphorylation and apoptosis.
基金the National Natural Science Foundation of China(grant No.82160897,82205087)Hainan Provincial Natural Science Foundation of China(grant No.820RC635)+1 种基金Scientific Research Foundation of Hainan Medical University(grant No.HYPY201924,HYPY2020037)Hainan Medical University 2020 National Innovation and Entrepreneurship Program for College Students(grant No.202011810006).
文摘Background:In this study,we analyzed the potential active components,related crucial targets and possible signaling pathway mechanisms of Alpiniae Oxyphyllae Fructus and Saposhnikoviae Radix(AOF-SR)herb pairs in the treatment of diabetic kidney disease(DKD)using network pharmacology and verification experiments.Methods:The active compounds and potential targets of AOF-SR were derived from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,The Encyclopedia of Traditional Chinese Medicine,and PubChem databases,and the potential therapeutic targets of DKD were derived from the OMIM,Drugbank,and DisGeNET databases.The“compounds-diseases-targets”network was constructed using Cytoscape 3.6.0.ClusterMaker functionality in Cytoscape is being used to screen important targets for AOF-SR treatment of DKD.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of important targets were performed using DAVID database.In addition,according to the predicted results of network pharmacology,HK-2 cells were used to construct DKD model for verification experiment.HK-2 cells were divided into control group,high glucose(HG)group and AOF-SR(HG+AOF-SR)group to detect survival rate and expression of key proteins in NF-κB and PI3K/Akt signaling pathways.Results:A total of 38 compounds were selected from AOF-SR,of which 23 were Alpiniae Oxyphyllae Fructus and 15 were Saposhnikoviae Radix.Through enrichment analysis of 82 important targets,88 signaling pathways were identified;some of these pathways,such as the NF-κB,PI3K-Akt,IL-17,and JAK/STAT signaling pathways,regulate the pathological process of DKD.In verification experiment,the HK-2 cells survival rate was higher in the HG+AOF-SR group than in the HG group(P<0.05).Moreover,western blotting results showed that the expression levels of NF-κB,p-PI3K,and p-Akt in HG+AOF-SR group were significantly lower than those in HG group(P<0.05).Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of AOF-SR treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by AOF-SR.
基金the support from Social Development Project(No.ZDYF2019139)Natural Science Foundation of Hainan Province(No.ZDYF2023SHFZ116).
文摘Background:To explore the pharmacological mechanism of the anti-hepatitis B virus of Phyllanthus urinaria L.through network pharmacological analysis and experimental validation.Method:The active ingredient,target of action and target of action related to hepatitis B were clarified by searching the herb group identification,GeneCards and OMIM databases,and the protein interaction relationship was obtained by using the String database,and the protein interaction network map was constructed by using Cytoscape software.We also performed gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of key targets of the anti-hepatitis B action of Phyllanthus urinaria L.and predicted the core targets and pathways of Phyllanthus urinaria L.anti-hepatitis B.The main targets predicted by network pharmacology were then validated by HepG2.2.15 cell experiments.Results:By searching active ingredient targets and hepatitis B disease targets,a total of 19 active ingredients and 64 related targets of action were retrieved from Phyllanthus urinaria L.,and a total of 51 common targets were obtained by mapping the obtained hepatitis B disease targets and drug targets.protein protein interaction network analysis indicated that targets including TNF,JUN,AKT1,IL-10,IL-1B,CAT,HMOX1,NFE2L2,and CASP3 and other targets may be the core targets.gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that the treatment of hepatitis B by Phyllanthus urinaria L.mainly included inflammation and oxidation-related processes,and the signaling pathways mainly included fluid shear stress and atherosclerosis,VEGF,and hepatocellular carcinoma.The results of the in vitro test showed that after the action of different concentrations of the extracts of the Phyllanthus urinaria L.in the safe concentration range on cells HepG2.2.15,HBsAg,HBeAg and hepatitis B virus DNA levels were significantly inhibited,and NFE2L2 and HMOX1 were affecting hepatitis B virus transcription and replication by regulating the oxidative stress response.Conclusion:Using an integrated network pharmacology approach,this study revealed the active components and potential targets of Phyllanthus urinaria L.for the treatment of the hepatitis B virus,providing a theoretical basis for the research and clinical application of Phyllanthus urinaria L..
文摘The study aims to reveal the mechanism of traditional Chinese medicine in the treatment of endometriosis and provide support for further research on traditional Chinese medicine and its active ingredients.The literature survey was conducted using PubMed,Web of Science,CNKI and other databases with“endometriosis”,“Chinese medicine”,“Chinese herbal medicine”and“natural plants”as the main keywords.Traditional Chinese medicine can exert their therapeutic effects on endometriosis by inhibiting inflammation through multiple pathways and multiple targets,regulating cell proliferation and apoptosis,angiogenesis,cell adhesion and oxidative stress.Traditional Chinese medicine can intervene in endometriosis in multiple ways and with multiple targets.In-depth study of Chinese medicine for endometriosis can provide new ideas for exploring the pathogenesis of endometriosis and developing new drugs.
基金Supported by Natural Science Foundation of Hainan Province(2019CXTD407)National Natural Science Foundation of China(81860836).
文摘[Objectives]The purpose of this paper was to study the effects of Suoquan Yishen formula on mice with diabetic nephropathy(DN).[Methods]The mice were randomly divided into normal group,model group,irbesartan group,and high and low-dose Suoquan Yishen formula groups.The blood glucose level,BUN,Scr excretion and GSH activity and CAT activity were detected.[Results]The blood glucose levels of mice in the irbesartan group and high and low-dose Suoquan Yishen formula groups decreased.The BUN,PRO and Scr levels were higher and the GSH and CAT activity was lower in the model group compared with the normal group.After administration of Suoquan Yishen formula,the BUN,PRO and Scr levels of the DN mice decreased significantly,and the GSH and CAT activity increased significantly.[Conclusions]Suoquan Yishen formula can reduce blood glucose level,reduce PRO,BUN and Scr levels,and increase CAT and GSH activity in DN mice,thus protecting the ND mice.
文摘Multicoloured languages play an irreplaceable role in the whole world as a useful communication tool. With the development of technology and science, varieties of languages have an ideal prospective tendency to evolution during the long and wonderful history. Will they be thriving or decaying? To begin with, aimed to gain general tendency about the quantity of languages' speakers, we employ the Grey prediction to capture associative curve which can be seen in Figure 1. From the trend of this vivid figure, we not only can come to the conclusion that the number of English and Chinese users tend to increase but also find that Spanish development will reach the period of stagnation. Secondly, for further improvement, we take birth rate, death rate, economic factors and the immigration into consideration and establish the language communication model. This model is deduced from the population prediction model and virus transmission model. After data normalization, the eventual curve indicates that current top-ten languages seem to be replaced by other languages. This transformation phenomenon also occurs among such top-ten languages. For instance, Hindustani will replace Spanish in the future when seen from Table 1. What's more, after predicting the migration pattern, we can draw the conclusion that some range of languages' dissemination has obvious change. As show in vivid Figure 14, we know English will popularize widely among neighboring countries such as Canada, Mexico, Cuba and Russia. Moreover, with regard to how to manage international offices' quantity and locations in the world, we construct the efficiency model with combination of the Bayes' probability theory and Fussy comprehensive assessment. As a result, we obtain 9 optimal plans to establish the international offices. Intelligible result is showed in Table 4 and Table 5. In short, our model is reasonable and feasible, which can accommodate to different situation.
基金the Natural Science Foundation of Hainan Province(No.:2019CXTD407)the National Natural Science Foundation of China(No.:81860836).
文摘Objective:To analyze the components and mechanisms of Wuyao(Linderae Radix)in treating diabetic nephropathy(DN)based on network pharmacology.Methods:Multiple online databases were used to search and screen out the active ingredients from Linderae Radix,the related targets of active components of Linderae Radix and the genes related to DN.Search the corresponding genes name of target through UniProt database.Cytoscape 3.2.1 was used to construct the corresponding target gene network of Linderae Radix compounds.Venn diagram was used to screen the intersection genes of the active components corresponding to the target and disease-related genes,and the intersection genes were constructed into the protein interaction relationship network.Finally,DAVID database was used to do GO function enrichment analysis and KEGG signaling pathway enrichment analysis for the intersection genes,and the results of GO and KEGG were visualized.Results:1.A total of 7 potential active ingredients and 100 target proteins were screened.2.There are a total of 34 intersection genes between the potential active ingredient target in Linderae Radix in DN.3.The top 10 of the interaction correlation between intersection proteins include:AR and NCOA2,NCOA2 and NR3C1,NCOA2 and PPARG,etc.4.There were 16 entries of molecular function,9 entries of cell component,47 entries of biological process and 18 entries of signaling pathway(P<0.05).Conclusion:DN was treated by Linderae Radix from multi-component,multi-target and multi-link synergies.
基金funded by Shanghai Jiao Tong University‘Star of Jiao Tong University’Medical-Engineering Cross Research Fund(YG2019QNB01)Shanghai Municipal Key Clinical Specialty(shslczdzk06902)Shanghai Children's Hospital Fund(2022YGZM01).
文摘TRAF7 serves as a crucial intracellular adaptor and E3 ubiquitin ligase involved in signal transduction pathways,contributing to immune responses,tumor progression,and embryonic development.Somatic mutations within the coiled-coil(CC)domain and WD40 repeat domain of TRAF7 could cause brain tumors,while germline pathogenic mutations contribute to severe developmental abnormalities.However,the precise molecular mechanism underlying TRAF7 involvement in embryonic development remains unclear.In this study,we employed zebrafish as an in vivo model system.TRAF7 knock down caused defects in zebrafish embryonic development.We determined the crystal structure of TRAF7 CC domain at 3.3Åresolution and found that the CC region trimerization was essential for TRAF7 functionality during zebrafish embryonic development.Additionally,disease-causing mutations in TRAF7 CC region could impair the trimer formation,consequently impacting early embryonic development of zebrafish.Therefore,our study sheds light on the molecular mechanism of TRAF7 CC trimer formation and its pivotal role in embryonic development.
基金This work was financially supported by the National Natural Science Foundation of China (No. 21572196) and the Priority Academic Program Development of Jiangsu Higher Education Institutions. We also want to give sincerely thanks to the Analysis Center of Yangzhou University for providing all necessary instruments for characterization of structures.
文摘The base promoted three-component reaction of β-enamino imide, malononitrile and various cyclic α-diketones in acetonitrile showed interesting molecular diversity. The reactions with acenaphthylene-1,2-dione and ninhydrin afforded functionalized spiro[indene-2,4'-pyrrolo[3,4-b]pyridines] and spiro[acenaphthylene-1,4'-pyrrolo[3,4-b]- pyridines] in good yields. The similar reaction of phenanthrene-9,10-dione resulted in the formation of the unexpected complex phenanthro[9', 10':4,5]furo[2,3-c]pyrrolo[3,4-b]pyrroles in satisfactory yields.