Nonalcoholic fatty liver disease(NAFLD) is one of the most common liver diseases and its prevalence is likely to reach epidemic proportions.According to the"two-stage hypothesis"proposed for the pathophysiol...Nonalcoholic fatty liver disease(NAFLD) is one of the most common liver diseases and its prevalence is likely to reach epidemic proportions.According to the"two-stage hypothesis"proposed for the pathophysiology of NAFLD,insulin resistance,oxidative stress and pro-inflammatory cytokines are among the key promoters of the disease. Here,ginger has been hypothesized to prevent NAFLD or blunt its progression via several mechanisms,such as sensitizing insulin effects,activating peroxisome proliferator-activated receptorγwhich induces adiponectin and down-regulates pro-inflammatory cytokines,changing the balance between adiponectin and tumor necrosis factor-αin favor of adiponectin,promoting considerable antioxidant effects and antidyslipidemic properties,and reducing hepatic triglyceride content which can prevent steatosis.The aforementioned mechanisms imply that ginger possesses interesting potentials for serving as a natural supplement for the prevention and treatment of NAFLD.Therefore,conducting trials to explore its benefits in clinical practice is greatly recommended.展开更多
Objective: This paper applied a transcriptomic approach to investigate the mechanisms of adriamycin(ADR) in treating proliferative vitreoretinopathy(PVR) using ARPE-19 cells. Methods: The growth inhibitory effects of ...Objective: This paper applied a transcriptomic approach to investigate the mechanisms of adriamycin(ADR) in treating proliferative vitreoretinopathy(PVR) using ARPE-19 cells. Methods: The growth inhibitory effects of ADR on ARPE-19 cells were assessed by sulforhodamine B(SRB) assay and propidium iodide(PI) staining using flow cytometry. The differentially expressed genes between ADR-treated ARPE-19 cells and normal ARPE-19 cells and the signaling pathways involved were investigated by microarray analysis. Mitochondrial function was detected by JC-1 staining using flow cytometry and the Bcl-2/Bax protein family. The phosphorylated histone H2 AX(γ-H2 AX), phosphorylated checkpoint kinase 1(p-CHK1), and phosphorylated checkpoint kinase 2(p-CHK2) were assessed to detect DNA damage and repair. Results: ADR could significantly inhibit ARPE-19 cell proliferation and induce caspasedependent apoptosis in vitro. In total, 4479 differentially expressed genes were found, and gene ontology items and the p53 signaling pathway were enriched. A protein–protein interaction analysis indicated that the TP53 protein molecules regulated by ADR were related to DNA damage and oxidative stress. ADR reduced mitochondrial membrane potential and the Bcl-2/Bax ratio. p53-knockdown restored the activation of c-caspase-3 activity induced by ADR by regulating Bax expression, and it inhibited ADR-induced ARPE-19 cell apoptosis. Finally, the levels of the γ-H2 AX, p-CHK1, and p-CHK2 proteins were up-regulated after ADR exposure. Conclusions: The mechanism of ARPE-19 cell death induced by ADR may be caspase-dependent apoptosis, and it may be regulated by the p53-dependent mitochondrial dysfunction, activating the p53 signaling pathway through DNA damage.展开更多
文摘Nonalcoholic fatty liver disease(NAFLD) is one of the most common liver diseases and its prevalence is likely to reach epidemic proportions.According to the"two-stage hypothesis"proposed for the pathophysiology of NAFLD,insulin resistance,oxidative stress and pro-inflammatory cytokines are among the key promoters of the disease. Here,ginger has been hypothesized to prevent NAFLD or blunt its progression via several mechanisms,such as sensitizing insulin effects,activating peroxisome proliferator-activated receptorγwhich induces adiponectin and down-regulates pro-inflammatory cytokines,changing the balance between adiponectin and tumor necrosis factor-αin favor of adiponectin,promoting considerable antioxidant effects and antidyslipidemic properties,and reducing hepatic triglyceride content which can prevent steatosis.The aforementioned mechanisms imply that ginger possesses interesting potentials for serving as a natural supplement for the prevention and treatment of NAFLD.Therefore,conducting trials to explore its benefits in clinical practice is greatly recommended.
基金Project supported by the Zhejiang Province Key Research and Development Program(No.2015C03042),China
文摘Objective: This paper applied a transcriptomic approach to investigate the mechanisms of adriamycin(ADR) in treating proliferative vitreoretinopathy(PVR) using ARPE-19 cells. Methods: The growth inhibitory effects of ADR on ARPE-19 cells were assessed by sulforhodamine B(SRB) assay and propidium iodide(PI) staining using flow cytometry. The differentially expressed genes between ADR-treated ARPE-19 cells and normal ARPE-19 cells and the signaling pathways involved were investigated by microarray analysis. Mitochondrial function was detected by JC-1 staining using flow cytometry and the Bcl-2/Bax protein family. The phosphorylated histone H2 AX(γ-H2 AX), phosphorylated checkpoint kinase 1(p-CHK1), and phosphorylated checkpoint kinase 2(p-CHK2) were assessed to detect DNA damage and repair. Results: ADR could significantly inhibit ARPE-19 cell proliferation and induce caspasedependent apoptosis in vitro. In total, 4479 differentially expressed genes were found, and gene ontology items and the p53 signaling pathway were enriched. A protein–protein interaction analysis indicated that the TP53 protein molecules regulated by ADR were related to DNA damage and oxidative stress. ADR reduced mitochondrial membrane potential and the Bcl-2/Bax ratio. p53-knockdown restored the activation of c-caspase-3 activity induced by ADR by regulating Bax expression, and it inhibited ADR-induced ARPE-19 cell apoptosis. Finally, the levels of the γ-H2 AX, p-CHK1, and p-CHK2 proteins were up-regulated after ADR exposure. Conclusions: The mechanism of ARPE-19 cell death induced by ADR may be caspase-dependent apoptosis, and it may be regulated by the p53-dependent mitochondrial dysfunction, activating the p53 signaling pathway through DNA damage.
