Cirrhosis causes a heavy global burden.In this review,we summarized up-todate epidemiological features of cirrhosis and its complications.Recent epidemiological studies reported an increase in the prevalence of cirrho...Cirrhosis causes a heavy global burden.In this review,we summarized up-todate epidemiological features of cirrhosis and its complications.Recent epidemiological studies reported an increase in the prevalence of cirrhosis in 2017 compared to in 1990 in both men and women,with 5.2 million cases of cirrhosis and chronic liver disease occurring in 2017.Cirrhosis caused 1.48 million deaths in 2019,an increase of 8.1%compared to 2017.Disability-adjusted life-years due to cirrhosis ranked 16th among all diseases and 7th in people aged 50-74 years in 2019.The global burden of hepatitis B virus and hepatitis C virus-associated cirrhosis is decreasing,while the burden of cirrhosis due to alcohol and nonalcoholic fatty liver disease(NAFLD)is increasing rapidly.We described the current epidemiology of the major complications of cirrhosis,including ascites,variceal bleeding,hepatic encephalopathy,renal disorders,and infections.We also summarized the epidemiology of hepatocellular carcinoma in patients with cirrhosis.In the future,NAFLD-related cirrhosis will likely become more common due to the prevalence of metabolic diseases such as obesity and diabetes,and the prevalence of alcohol-induced cirrhosis is increasing.This altered epidemiology should be clinically noted,and relevant interventions should be undertaken.展开更多
AIM： To investigate the effects of KN-93, a CaMKⅡ selective inhibitor on cell proliferation and the expression of p53 or p21 protein in human hepatic stellate cells. METHODS： Human hepatic stellate cells （LX-2） w...AIM： To investigate the effects of KN-93, a CaMKⅡ selective inhibitor on cell proliferation and the expression of p53 or p21 protein in human hepatic stellate cells. METHODS： Human hepatic stellate cells （LX-2） were incubated with various concentrations （0-50 μmol/L） of KN-93 or its inactive derivative, KN-92. Cell proliferation was measured by CCK-8 assay, and the expression of two cell cycle regulators, p53 and p21, was determined by SDS-PAGE and Western blotting. RESULTS： KN-93 （5-50 μmol/L） decreased the proliferation of human hepatic stellate cells in a dosedependent manner from 81.76% （81.76% ± 2.58% vs 96.63% ± 2.69%, P 〈 0.05） to 27.15% （27.15% ± 2.86% vs 96.59% ± 2.44%, P 〈 0.01） after 24 h treatment. Incubation of 10 μmol/L KN-93 induced the cell growth reduction in a time-dependent manner from 78.27% at 8 h to 11.48% at 48 h. However, KN-92, an inactive derivative of KN-93, did not inhibit cell proliferation effectively. Moreover, analysis of cell cycle regulator expression revealed that KN-93 rather than KN-92 reduced the expression of p53 and p21. CONCLUSION： KN-93 has potent inhibitory effect on proliferation of LX-2 cells by modulating the expression of two special cell cycle regulators, p53 and p21.展开更多
文摘Cirrhosis causes a heavy global burden.In this review,we summarized up-todate epidemiological features of cirrhosis and its complications.Recent epidemiological studies reported an increase in the prevalence of cirrhosis in 2017 compared to in 1990 in both men and women,with 5.2 million cases of cirrhosis and chronic liver disease occurring in 2017.Cirrhosis caused 1.48 million deaths in 2019,an increase of 8.1%compared to 2017.Disability-adjusted life-years due to cirrhosis ranked 16th among all diseases and 7th in people aged 50-74 years in 2019.The global burden of hepatitis B virus and hepatitis C virus-associated cirrhosis is decreasing,while the burden of cirrhosis due to alcohol and nonalcoholic fatty liver disease(NAFLD)is increasing rapidly.We described the current epidemiology of the major complications of cirrhosis,including ascites,variceal bleeding,hepatic encephalopathy,renal disorders,and infections.We also summarized the epidemiology of hepatocellular carcinoma in patients with cirrhosis.In the future,NAFLD-related cirrhosis will likely become more common due to the prevalence of metabolic diseases such as obesity and diabetes,and the prevalence of alcohol-induced cirrhosis is increasing.This altered epidemiology should be clinically noted,and relevant interventions should be undertaken.
文摘AIM： To investigate the effects of KN-93, a CaMKⅡ selective inhibitor on cell proliferation and the expression of p53 or p21 protein in human hepatic stellate cells. METHODS： Human hepatic stellate cells （LX-2） were incubated with various concentrations （0-50 μmol/L） of KN-93 or its inactive derivative, KN-92. Cell proliferation was measured by CCK-8 assay, and the expression of two cell cycle regulators, p53 and p21, was determined by SDS-PAGE and Western blotting. RESULTS： KN-93 （5-50 μmol/L） decreased the proliferation of human hepatic stellate cells in a dosedependent manner from 81.76% （81.76% ± 2.58% vs 96.63% ± 2.69%, P 〈 0.05） to 27.15% （27.15% ± 2.86% vs 96.59% ± 2.44%, P 〈 0.01） after 24 h treatment. Incubation of 10 μmol/L KN-93 induced the cell growth reduction in a time-dependent manner from 78.27% at 8 h to 11.48% at 48 h. However, KN-92, an inactive derivative of KN-93, did not inhibit cell proliferation effectively. Moreover, analysis of cell cycle regulator expression revealed that KN-93 rather than KN-92 reduced the expression of p53 and p21. CONCLUSION： KN-93 has potent inhibitory effect on proliferation of LX-2 cells by modulating the expression of two special cell cycle regulators, p53 and p21.
