Objective:Cardiac remodeling when myocardial infarction(MI)is achieved is an established prognostic factor for function-related damage and failure of hear that happen progressively.Tongguan Capsules(TGC),i.e.,a Chines...Objective:Cardiac remodeling when myocardial infarction(MI)is achieved is an established prognostic factor for function-related damage and failure of hear that happen progressively.Tongguan Capsules(TGC),i.e.,a Chinese herbal treatment with patent has been previously demonstrated its potential benefits in cardiac function,but little is known about related mechanisms.This study sought to isolate and characterize exosomal circRNA profiles from post-MI cardiac remodeling patients in response to TGC,and further explore the possible molecular mechanisms.Methods:Exosomes were isolated from the plasma and analyzed by the detection of protein marker expression and transmission electron microscopy.This study employed DESeq2 package within Bioconductor for exploring circRNAs and determining the circRNA with differential expressions.Co-expression investigation was performed with the use of a weighted correlation framework.An investigation was conducted on the molecular framework and channels of different circRNA based on the investigation system of the and Kyoto Encyclopedia of Genes and Genomes(KEGG)Gene Ontology(GO)channels.The prediction was conducted for circRNA-miRNA interactions on the basis of frequently employed target prediction software,and the framework was built with the use of Cytoscape software.Results:In total,33084 circRNAs were detected in all chromosomes and 10065 circRNAs were identified with the use of circBase.Of them,40,207 and 258 differentially expressed circRNAs were detected between the MI group and control,MI and TGC groups,and the control and TGC groups.The differentially expressed circRNAs between the MI group and control,MI group and TGC group,and control and TGC group were significantly enriched in microtubule nucleation(BP,GO:0007020),protein binding(MF,GO:0005515),regulation of natural killer cell mediated cytotoxicity(BP,GO:0042269)corresponding to the cell cycle(hsa04110),lysine degradation(hsa00310)and lysine degradation(hsa00310)in KEGG channel investigation.Module_darkorange2 indicated the most differentiation with other modules by WGCNA investigation.This study employed a total of 14 circRNAs and 8 miRNAs which have significant interactions with each other for building the circRNA-miRNA frameworks,which indicated that has-miR-619-5p,has-miR-1268a and hasmiR-1285‐3p were under the regulation of a higher amount of circRNAs as compared with other miRNAs.Conclusion:In conclusion,different mechanisms and channels participated in the pathological processes associated with cardiac remodeling following MI.The altered circRNAs are likely to be critical to the cardioprotection of TGC through the circRNA-miRNA frameworks.展开更多
BACKGROUND The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease(CVD) risk needs to be discussed. We evaluated the impact of...BACKGROUND The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease(CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project(Prediction for Atherosclerotic Cardiovascular Disease Risk in China).METHODS A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors(LFs)(smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios(HRs) and corresponding 95% confidence intervals(CIs). The risk advancement periods(RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage(PAR%) were also calculated.RESULTS A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1healthy LFs, maintaining 3–4 healthy LFs was associated with a 40% risk reduction of incident CVD(HR = 0.60, 95% CI: 0.45–0.79)and delayed CVD risk by 6.31 years(RAP:-6.31 [-9.92,-2.70] years). The PAR% of maintaining 3–4 unhealthy LFs was 22.0%compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2to 3–4 was associated with a 23% lower risk of CVD(HR = 0.77, 95% CI: 0.60–0.98).CONCLUSIONS Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.展开更多
Background:To investigate the detailed mechanism underlying the pro-metastatic effect of spleen deficiency(SD)syndrome on hepatocellular carcinoma(HCC).Methods:In the present study,our model was established based on a...Background:To investigate the detailed mechanism underlying the pro-metastatic effect of spleen deficiency(SD)syndrome on hepatocellular carcinoma(HCC).Methods:In the present study,our model was established based on an HCC mouse model induced by diethylnitrosamine using reserpine to induce SD.Exosomes were isolated and purified from mouse plasma samples using an exosome isolation kit.Subsequently,we verified the pro-metastatic effects of exosomes from the HCC mice with SD on HCC cells by transwell assays,wound healing assays,phalloidin staining in vitro,and lung metastasis assay of mice in vivo.Finally,we further explored the detailed mechanism underlying the pro-metastatic effect of exosomes from the HCC mice with SD on HCC cells.Results:We found that SD promoted the malignant progression of HCC in mice.Exosomes from HCC mice with SD enhanced the invasion and metastasis of HCC cells in vitro and in vivo.Mechanistically,upregulation of integrinα1,integrinβ1,and integrinβ5 seemed to play a key role in mediating the pro-metastatic effect of exosomes isolated from the HCC mice with SD,which was largely abrogated upon co-treatment with a broad-spectrum integrin inhibitor.Conclusion:Our findings demonstrated that exosomes promote the invasion and metastasis of HCC cells via an integrin-dependent manner in the spleen-deficient state that would contribute to our better understanding of the role of SD in HCC progression in traditional Chinese medicine,and thus management of the disease.展开更多
文摘Objective:Cardiac remodeling when myocardial infarction(MI)is achieved is an established prognostic factor for function-related damage and failure of hear that happen progressively.Tongguan Capsules(TGC),i.e.,a Chinese herbal treatment with patent has been previously demonstrated its potential benefits in cardiac function,but little is known about related mechanisms.This study sought to isolate and characterize exosomal circRNA profiles from post-MI cardiac remodeling patients in response to TGC,and further explore the possible molecular mechanisms.Methods:Exosomes were isolated from the plasma and analyzed by the detection of protein marker expression and transmission electron microscopy.This study employed DESeq2 package within Bioconductor for exploring circRNAs and determining the circRNA with differential expressions.Co-expression investigation was performed with the use of a weighted correlation framework.An investigation was conducted on the molecular framework and channels of different circRNA based on the investigation system of the and Kyoto Encyclopedia of Genes and Genomes(KEGG)Gene Ontology(GO)channels.The prediction was conducted for circRNA-miRNA interactions on the basis of frequently employed target prediction software,and the framework was built with the use of Cytoscape software.Results:In total,33084 circRNAs were detected in all chromosomes and 10065 circRNAs were identified with the use of circBase.Of them,40,207 and 258 differentially expressed circRNAs were detected between the MI group and control,MI and TGC groups,and the control and TGC groups.The differentially expressed circRNAs between the MI group and control,MI group and TGC group,and control and TGC group were significantly enriched in microtubule nucleation(BP,GO:0007020),protein binding(MF,GO:0005515),regulation of natural killer cell mediated cytotoxicity(BP,GO:0042269)corresponding to the cell cycle(hsa04110),lysine degradation(hsa00310)and lysine degradation(hsa00310)in KEGG channel investigation.Module_darkorange2 indicated the most differentiation with other modules by WGCNA investigation.This study employed a total of 14 circRNAs and 8 miRNAs which have significant interactions with each other for building the circRNA-miRNA frameworks,which indicated that has-miR-619-5p,has-miR-1268a and hasmiR-1285‐3p were under the regulation of a higher amount of circRNAs as compared with other miRNAs.Conclusion:In conclusion,different mechanisms and channels participated in the pathological processes associated with cardiac remodeling following MI.The altered circRNAs are likely to be critical to the cardioprotection of TGC through the circRNA-miRNA frameworks.
基金The Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences,Grant/Award Numbers:2021-I2M-1-010,2017-I2M-1-004,and 2019-I2M-2-003the National Natural Science Foundation of China,Grant/Award Numbers:82030102,12126602the Research Unit of Prospective Cohort of Cardiovascular Diseases and Cancers,Chinese Academy of Medical Sciences,Grant/Award Numbers:2019RU038.
文摘BACKGROUND The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease(CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project(Prediction for Atherosclerotic Cardiovascular Disease Risk in China).METHODS A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors(LFs)(smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios(HRs) and corresponding 95% confidence intervals(CIs). The risk advancement periods(RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage(PAR%) were also calculated.RESULTS A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1healthy LFs, maintaining 3–4 healthy LFs was associated with a 40% risk reduction of incident CVD(HR = 0.60, 95% CI: 0.45–0.79)and delayed CVD risk by 6.31 years(RAP:-6.31 [-9.92,-2.70] years). The PAR% of maintaining 3–4 unhealthy LFs was 22.0%compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2to 3–4 was associated with a 23% lower risk of CVD(HR = 0.77, 95% CI: 0.60–0.98).CONCLUSIONS Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.
基金This study was funded by the National Science Foundation of China(No.82174173,No.82104962,No.81903967 and No.81873248).
文摘Background:To investigate the detailed mechanism underlying the pro-metastatic effect of spleen deficiency(SD)syndrome on hepatocellular carcinoma(HCC).Methods:In the present study,our model was established based on an HCC mouse model induced by diethylnitrosamine using reserpine to induce SD.Exosomes were isolated and purified from mouse plasma samples using an exosome isolation kit.Subsequently,we verified the pro-metastatic effects of exosomes from the HCC mice with SD on HCC cells by transwell assays,wound healing assays,phalloidin staining in vitro,and lung metastasis assay of mice in vivo.Finally,we further explored the detailed mechanism underlying the pro-metastatic effect of exosomes from the HCC mice with SD on HCC cells.Results:We found that SD promoted the malignant progression of HCC in mice.Exosomes from HCC mice with SD enhanced the invasion and metastasis of HCC cells in vitro and in vivo.Mechanistically,upregulation of integrinα1,integrinβ1,and integrinβ5 seemed to play a key role in mediating the pro-metastatic effect of exosomes isolated from the HCC mice with SD,which was largely abrogated upon co-treatment with a broad-spectrum integrin inhibitor.Conclusion:Our findings demonstrated that exosomes promote the invasion and metastasis of HCC cells via an integrin-dependent manner in the spleen-deficient state that would contribute to our better understanding of the role of SD in HCC progression in traditional Chinese medicine,and thus management of the disease.
