Background:Xihuang pill is a kind of traditional Chinese medicine,which has been widely used in the treatment of kinds of cancer.However,there is still a lack of systematic understanding of the molecular mechanism of ...Background:Xihuang pill is a kind of traditional Chinese medicine,which has been widely used in the treatment of kinds of cancer.However,there is still a lack of systematic understanding of the molecular mechanism of Xihuang pill in the treatment of liver cancer.In this work,we aim to explore the molecular mechanism of Xihuang pill in treating liver cancer.Methods:The functional components in Xihuang pill were collected from Traditional Chinese Medicine Database and Analysis Platform.The target genes of these components were also collected using Traditional Chinese Medicine Database and Analysis Platform.The target genes of liver cancer were predicted using GeneCards database.The intersecting genes were then analyzed with Venn diagrams.Kyoto Encyclopedia of Genes and Genomes and Database for Annotation,Visualization,and Integrated Discovery were used to analyze the pathway.Then,cell counting kit-8 was used to measure the half-maximal inhibitory concentration of Xihuang pills.The living dead cell staining method was used to observe the survival of cells.HepG2 cell apoptosis was tested by flow cytometry with fluorescein isothiocyanate/propidium iodide double staining method,and then the mitochondrial damage was also detected by flow cytometry.The expression of target genes was detected by quantitative real-time polymerase chain reaction.Results:A total of 130 compounds and 198 genes were identified as potential active ingredients and putative liver cancer‑related targets.We obtained 1,899 disease targets and 297 transcriptome targets from the database.Six drug-disease intersecting genes,CCNB1,BIRC5,TOP2A,ESR1,IGF2 and IGFBP3 were obtained.They are enrichment in apoptosis,PI3K-AKT signaling pathway,MAPK signaling pathway,pathways in cancer and p53 signaling pathway.Besides,it was found that the apoptosis rate of the HepG2 cells in Xihuang pill treated group was significantly higher than that of the control group.And the apoptosis rate gradually increased in a dose dependent manner of Xihuang pill treatment.Xihuang pill also induced the mitochondrial membrane potential damage.Compared with the control group,the expression level of CCNB1 and BIRC5 was induced,while the expression level of IGF2 was reduced after Xihuang pill treatment.Conclusion:Xihuang pill may act on six proteins(CCNB1,BIRC5,TOP2A,ESR1,IGF2 and IGFBP3)and cover multiple pathways to form a therapeutic network to treat liver cancer.展开更多
Lumbar spinal stenosis is caused by the compression of the nerve root or cauda equina nerve by stenosis of the lumbar spinal canal or intervertebral foramen,and is manifested as chronic low back and leg pain.Danlu Ton...Lumbar spinal stenosis is caused by the compression of the nerve root or cauda equina nerve by stenosis of the lumbar spinal canal or intervertebral foramen,and is manifested as chronic low back and leg pain.Danlu Tongdu(DLTD)tablets can relieve chronic pain caused by lumbar spinal stenosis,but the molecular mechanism remains largely unknown.In this study,the potential molecular mechanism of DLTD tablets in the treatment of lumbar spinal stenosis was first predicted by the network pharmacology method.Results showed that DLTD functions in regulating anti-oxidative,apoptosis,and inflammation signaling pathways.Furthermore,the flow cytometry results showed that DLTD tablets efficiently reduced reactive oxygen species content and inhibited rat neural stem cell apoptosis induced by hydrogen peroxide.DLTD also inhibited the mitochondrial membrane potential damage induced by hydrogen peroxide.Elisa analysis showed that DLTD induced cell cycle-related protein,CDK2 and CDK4,and reduced CDKN1A protein expression level.Taken together,our study provided new insights of DLTD in treating lumbar spinal stenosis through reducing reactive oxygen species content,decreasing apoptosis by inhibiting CDKN1A and promoting CDK2 and CDK4 expression levels.展开更多
Background:Fuzheng Huayu capsule(FZHY)combined with antiviral treatment has been shown to significantly reduce the risk of liver cancer in patients with hepatitis B cirrhosis.However,the potential of FZHY to directly ...Background:Fuzheng Huayu capsule(FZHY)combined with antiviral treatment has been shown to significantly reduce the risk of liver cancer in patients with hepatitis B cirrhosis.However,the potential of FZHY to directly treat liver cancer remains largely unknown.This study aims to investigate the molecular mechanism underlying the potential of FZHY in treating liver cancer.Methods:A network pharmacological analysis was performed using the Traditional Chinese Medicine Systems Pharmacology database to identify FZHY compounds and targets.Disease targets were searched using the Genecards database,and transcriptome data was downloaded from the NCBI database.Gene Ontology analysis was conducted using the DAVID database,and Kyoto Encyclopedia of Genes and Genomes analysis was based on KOBAS and bioinformatics methods.The Swissdock database was used for molecular docking.In cell experiments,the half inhibitory concentration(IC50)of FZHY was determined using the CCK8 method.The effects of FZHY on cell viability,apoptosis,and mitochondrial membrane potential were evaluated using a fluorescence microscope and flow cytometry.The molecular mechanism of FZHY in treating liver cancer was verified using quantitative polymerase chain reaction.Results:A total of 127 compounds and 184 proteins were identified as potential active ingredients and putative liver cancer-related targets.Additionally,1,899 liver cancer targets,279 transcriptome targets,and 3 pathways(p53 signaling pathway,apoptosis and PI3K-Akt pathway)were collected.The FZHY-targets-liver cancer interaction network was constructed.IC50 of FZHY lyophilized powder solution to liver cancer was 5.13 mg/mL(IC50=5.13 mg/mL).FZHY treatment led to an increase in the ratio of cell apoptosis and induced mitochondrial membrane potential damage,resulting in an increase in the number of dead cells.The expression levels of CCNB1 and BIRC5 were induced with FZHY treatment,while the expression levels of AKR1C3 and IGF2 were reduced.Conclusion:FZHY promotes apoptosis of liver cancer cells by acting on the p53 signaling pathway,apoptosis,and PI3K-Akt pathway.CCNB1,BIRC5,AKR1C3,and IGF2 are potential target proteins for FZHY in treating liver cancer.展开更多
Objective:To investigate the protective effect of glucagon-like peptid-1(GLP-l) against cardiac microvascular endothelial cell(GTFCs) injured by high glucose.Methods:CMECs were isolated and cultured.Superoxide assay k...Objective:To investigate the protective effect of glucagon-like peptid-1(GLP-l) against cardiac microvascular endothelial cell(GTFCs) injured by high glucose.Methods:CMECs were isolated and cultured.Superoxide assay kit and dihydroethidine(DHE) staining were used to assess oxidative stress.TENEL staining and caspase 3 expression were used to assess the apoptosis of CMECs.H89 was used to inhibit eAMP/PKA pathway:fasudil was used to inhibit Rho/ROCK pathway.The protein expressions of Rho.ROCK uere examined by Western blol analysis.lesults:High glucose increased the production of ROS.the activity of NADPH.the apoptosis rate and the expression level of Rho/ROCK in CMECs.while GLP- 1 decreased high glucose-induced ROS production.the NADPH activity and the apoptosis rate and the expression level of Rho/ROCK in CMECs,the difference were statistically significant(P<0.05).Conclusions:GLP-1 could protect the cardiac microvessels against oxidative stress and apoptosis.The protective effects of GLP-1 are dependent on downstream inhibition of Rho through a cAMP/PKA-dependent manner,resulting in a subsequent decrease in the expression of NADPH oxidase.展开更多
Objective: To investigate the relationship between basal ganglia cerebral infarction and paroxysmal atrial fibrillation(PAF) caused by abnormal vagus nerve tension.Methods: A total of 1 483 cases of elder patients wit...Objective: To investigate the relationship between basal ganglia cerebral infarction and paroxysmal atrial fibrillation(PAF) caused by abnormal vagus nerve tension.Methods: A total of 1 483 cases of elder patients with cerebral infarction who received head CT or MRI examination during the period were enrolled, including 830 male and613 female, with the average age as 78 years. These cases were divided into basal infarction ganglia group(n = 1 045) and non-basal ganglia infarction group(n = 438)according to the anatomic site of cerebral infarction. The differences of the incidence of PAF, left atrial diameter and heart rate variability were compared between the two groups.Results: In basal ganglia infarction group, the incidence rate of PAF was significantly higher than that of non-basal ganglia infarction group(P < 0.05). The incidence trend of cerebral infarction in basal ganglia was age-related, in the >79 years basal ganglia cerebral infarction group, the incidence of PAF was significantly higher than that of nonbasal ganglia infarction group(P < 0.05). There was no significant difference in the left atrial diameter between the basal ganglia infarction group and non-basal ganglia infarction group. Basal ganglia cerebral infarction patients with high PAF had higher heart rate variability than non-basal ganglia infarction group.Conclusion: Elderly patients with basal ganglia infarction have high incidence of PAF.Sympathetic nerve damage in cerebral basal ganglia, increased vagal tension and cardiac vagal tension are the direct causes of PAF. The results indicates that the increased central vagal nerve tension mediated PAF probably is an indication of supplying sympathetic neurotransmitter or cardiac vagal denervation treatment.展开更多
文摘Background:Xihuang pill is a kind of traditional Chinese medicine,which has been widely used in the treatment of kinds of cancer.However,there is still a lack of systematic understanding of the molecular mechanism of Xihuang pill in the treatment of liver cancer.In this work,we aim to explore the molecular mechanism of Xihuang pill in treating liver cancer.Methods:The functional components in Xihuang pill were collected from Traditional Chinese Medicine Database and Analysis Platform.The target genes of these components were also collected using Traditional Chinese Medicine Database and Analysis Platform.The target genes of liver cancer were predicted using GeneCards database.The intersecting genes were then analyzed with Venn diagrams.Kyoto Encyclopedia of Genes and Genomes and Database for Annotation,Visualization,and Integrated Discovery were used to analyze the pathway.Then,cell counting kit-8 was used to measure the half-maximal inhibitory concentration of Xihuang pills.The living dead cell staining method was used to observe the survival of cells.HepG2 cell apoptosis was tested by flow cytometry with fluorescein isothiocyanate/propidium iodide double staining method,and then the mitochondrial damage was also detected by flow cytometry.The expression of target genes was detected by quantitative real-time polymerase chain reaction.Results:A total of 130 compounds and 198 genes were identified as potential active ingredients and putative liver cancer‑related targets.We obtained 1,899 disease targets and 297 transcriptome targets from the database.Six drug-disease intersecting genes,CCNB1,BIRC5,TOP2A,ESR1,IGF2 and IGFBP3 were obtained.They are enrichment in apoptosis,PI3K-AKT signaling pathway,MAPK signaling pathway,pathways in cancer and p53 signaling pathway.Besides,it was found that the apoptosis rate of the HepG2 cells in Xihuang pill treated group was significantly higher than that of the control group.And the apoptosis rate gradually increased in a dose dependent manner of Xihuang pill treatment.Xihuang pill also induced the mitochondrial membrane potential damage.Compared with the control group,the expression level of CCNB1 and BIRC5 was induced,while the expression level of IGF2 was reduced after Xihuang pill treatment.Conclusion:Xihuang pill may act on six proteins(CCNB1,BIRC5,TOP2A,ESR1,IGF2 and IGFBP3)and cover multiple pathways to form a therapeutic network to treat liver cancer.
基金financially supported by the National Science Foundation of China(No.32271440).
文摘Lumbar spinal stenosis is caused by the compression of the nerve root or cauda equina nerve by stenosis of the lumbar spinal canal or intervertebral foramen,and is manifested as chronic low back and leg pain.Danlu Tongdu(DLTD)tablets can relieve chronic pain caused by lumbar spinal stenosis,but the molecular mechanism remains largely unknown.In this study,the potential molecular mechanism of DLTD tablets in the treatment of lumbar spinal stenosis was first predicted by the network pharmacology method.Results showed that DLTD functions in regulating anti-oxidative,apoptosis,and inflammation signaling pathways.Furthermore,the flow cytometry results showed that DLTD tablets efficiently reduced reactive oxygen species content and inhibited rat neural stem cell apoptosis induced by hydrogen peroxide.DLTD also inhibited the mitochondrial membrane potential damage induced by hydrogen peroxide.Elisa analysis showed that DLTD induced cell cycle-related protein,CDK2 and CDK4,and reduced CDKN1A protein expression level.Taken together,our study provided new insights of DLTD in treating lumbar spinal stenosis through reducing reactive oxygen species content,decreasing apoptosis by inhibiting CDKN1A and promoting CDK2 and CDK4 expression levels.
文摘Background:Fuzheng Huayu capsule(FZHY)combined with antiviral treatment has been shown to significantly reduce the risk of liver cancer in patients with hepatitis B cirrhosis.However,the potential of FZHY to directly treat liver cancer remains largely unknown.This study aims to investigate the molecular mechanism underlying the potential of FZHY in treating liver cancer.Methods:A network pharmacological analysis was performed using the Traditional Chinese Medicine Systems Pharmacology database to identify FZHY compounds and targets.Disease targets were searched using the Genecards database,and transcriptome data was downloaded from the NCBI database.Gene Ontology analysis was conducted using the DAVID database,and Kyoto Encyclopedia of Genes and Genomes analysis was based on KOBAS and bioinformatics methods.The Swissdock database was used for molecular docking.In cell experiments,the half inhibitory concentration(IC50)of FZHY was determined using the CCK8 method.The effects of FZHY on cell viability,apoptosis,and mitochondrial membrane potential were evaluated using a fluorescence microscope and flow cytometry.The molecular mechanism of FZHY in treating liver cancer was verified using quantitative polymerase chain reaction.Results:A total of 127 compounds and 184 proteins were identified as potential active ingredients and putative liver cancer-related targets.Additionally,1,899 liver cancer targets,279 transcriptome targets,and 3 pathways(p53 signaling pathway,apoptosis and PI3K-Akt pathway)were collected.The FZHY-targets-liver cancer interaction network was constructed.IC50 of FZHY lyophilized powder solution to liver cancer was 5.13 mg/mL(IC50=5.13 mg/mL).FZHY treatment led to an increase in the ratio of cell apoptosis and induced mitochondrial membrane potential damage,resulting in an increase in the number of dead cells.The expression levels of CCNB1 and BIRC5 were induced with FZHY treatment,while the expression levels of AKR1C3 and IGF2 were reduced.Conclusion:FZHY promotes apoptosis of liver cancer cells by acting on the p53 signaling pathway,apoptosis,and PI3K-Akt pathway.CCNB1,BIRC5,AKR1C3,and IGF2 are potential target proteins for FZHY in treating liver cancer.
基金supported by Shanghai Municipal Health Bureau Youth Subject(NO.20134y116)
文摘Objective:To investigate the protective effect of glucagon-like peptid-1(GLP-l) against cardiac microvascular endothelial cell(GTFCs) injured by high glucose.Methods:CMECs were isolated and cultured.Superoxide assay kit and dihydroethidine(DHE) staining were used to assess oxidative stress.TENEL staining and caspase 3 expression were used to assess the apoptosis of CMECs.H89 was used to inhibit eAMP/PKA pathway:fasudil was used to inhibit Rho/ROCK pathway.The protein expressions of Rho.ROCK uere examined by Western blol analysis.lesults:High glucose increased the production of ROS.the activity of NADPH.the apoptosis rate and the expression level of Rho/ROCK in CMECs.while GLP- 1 decreased high glucose-induced ROS production.the NADPH activity and the apoptosis rate and the expression level of Rho/ROCK in CMECs,the difference were statistically significant(P<0.05).Conclusions:GLP-1 could protect the cardiac microvessels against oxidative stress and apoptosis.The protective effects of GLP-1 are dependent on downstream inhibition of Rho through a cAMP/PKA-dependent manner,resulting in a subsequent decrease in the expression of NADPH oxidase.
基金funded by Shanghai Health and Family Planning Commission Youth Found to Wenbo Cheng(20144Y0116)
文摘Objective: To investigate the relationship between basal ganglia cerebral infarction and paroxysmal atrial fibrillation(PAF) caused by abnormal vagus nerve tension.Methods: A total of 1 483 cases of elder patients with cerebral infarction who received head CT or MRI examination during the period were enrolled, including 830 male and613 female, with the average age as 78 years. These cases were divided into basal infarction ganglia group(n = 1 045) and non-basal ganglia infarction group(n = 438)according to the anatomic site of cerebral infarction. The differences of the incidence of PAF, left atrial diameter and heart rate variability were compared between the two groups.Results: In basal ganglia infarction group, the incidence rate of PAF was significantly higher than that of non-basal ganglia infarction group(P < 0.05). The incidence trend of cerebral infarction in basal ganglia was age-related, in the >79 years basal ganglia cerebral infarction group, the incidence of PAF was significantly higher than that of nonbasal ganglia infarction group(P < 0.05). There was no significant difference in the left atrial diameter between the basal ganglia infarction group and non-basal ganglia infarction group. Basal ganglia cerebral infarction patients with high PAF had higher heart rate variability than non-basal ganglia infarction group.Conclusion: Elderly patients with basal ganglia infarction have high incidence of PAF.Sympathetic nerve damage in cerebral basal ganglia, increased vagal tension and cardiac vagal tension are the direct causes of PAF. The results indicates that the increased central vagal nerve tension mediated PAF probably is an indication of supplying sympathetic neurotransmitter or cardiac vagal denervation treatment.
