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
Primary cilium,which protrudes from the cell,is a microtubule-based structure ensheathed by a highly specialized plasma membrane(PM).It serves as a signaling hub for sensing and transducing various external stimuli in...Primary cilium,which protrudes from the cell,is a microtubule-based structure ensheathed by a highly specialized plasma membrane(PM).It serves as a signaling hub for sensing and transducing various external stimuli including fluids,light,odorants as well as extracellular molecules.Of various signal transduction pathways that act through the primary cilium,the Hedgehog(Hh)pathway draws the most attention owing to its essential role in vertebrate development and its intimate link to carcinogenesis(Bangs and Anderson,2017).The major components of the Hh pathway include the secreted ligand Hh,two transmembrane proteins Patched(Ptch)and Smoothened(Smo),and the transcription factor glioma-associated oncogene(Gli).Ptch is the receptor for Hh which,in the absence of Hh,resides at the primary cilium and prevents ciliary localization and activation of Smo.Upon Hh binding,however,Ptch is suppressed and displaced from the ciliary membrane.This permits Smo to enter the primary cilium and initiate a cascade of events that lead to the activation of Gli transcription factors and transcription of downstream target genes.展开更多
Background：The hedgehog signaling system （HHS） plays an important role in the regulation of cell proliferation and differentiation during the embryonic phases.However,little is known about the involvement of HHS in...Background：The hedgehog signaling system （HHS） plays an important role in the regulation of cell proliferation and differentiation during the embryonic phases.However,little is known about the involvement of HHS in the malignant transformation of cells.This study aimed to detect the role of HHS in the malignant transformation of human bronchial epithelial （16HBE） cells.Methods：In this study,two microfluidic chips were designed to investigate cigarette smoke extract （CSE）-induced malignant transformation of cells.Chip A contained a concentration gradient generator,while chip B had four cell chambers with a central channel.The 16HBE cells cultured in chip A were used to determine the optimal concentration of CSE for inducing malignant transformation.The 16HBE cells in chip B were cultured with 12.25% CSE （Group A）,12.25% CSE ± 5 μmol/L cyclopamine （Group B）,or normal complete medium as control for 8 months （Group C）,to establish the in vitro lung inflammatory-cancer transformation model.The transformed cells were inoculated into 20 nude mice as cells alone （Group 1） or cells with cyclopamine （Group 2） for tumorigenesis testing.Expression of HHS proteins was detected by Western blot.Data were expressed as mean ± standard deviation.The t-test was used for paired samples,and the difference among groups was analyzed using a one-way analysis of variance.Results：The optimal concentration of CSE was 12.25%.Expression of HHS proteins increased during the process of malignant transformation （Group B vs.Group A,F =7.65,P 〈 0.05）.After CSE exposure for 8 months,there were significant changes in cellular morphology,which allowed the transformed cells to grow into tumors in 40 days after being inoculated into nude mice.Cyclopamine could effectively depress the expression of HHS proteins （Group C vs.Group B,F =6.47,P 〈 0.05） and prevent tumor growth in nude mice （Group 2 vs.Group 1,t=31.59,P〈 0.01）.Conclusions：The activity of HHS is upregulated during the CSE-induced malignant transformation of 16HBE cells.Cyclopamine can effectively depress expression of HHS proteins in vitro and prevent tumor growth of the transformed cells in vivo.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.
基金the National Natural Science Foundation of China(31771568,32021003 and 91954203)the Ministry of Science and Technology of China(2016YFA0500100).
文摘Primary cilium,which protrudes from the cell,is a microtubule-based structure ensheathed by a highly specialized plasma membrane(PM).It serves as a signaling hub for sensing and transducing various external stimuli including fluids,light,odorants as well as extracellular molecules.Of various signal transduction pathways that act through the primary cilium,the Hedgehog(Hh)pathway draws the most attention owing to its essential role in vertebrate development and its intimate link to carcinogenesis(Bangs and Anderson,2017).The major components of the Hh pathway include the secreted ligand Hh,two transmembrane proteins Patched(Ptch)and Smoothened(Smo),and the transcription factor glioma-associated oncogene(Gli).Ptch is the receptor for Hh which,in the absence of Hh,resides at the primary cilium and prevents ciliary localization and activation of Smo.Upon Hh binding,however,Ptch is suppressed and displaced from the ciliary membrane.This permits Smo to enter the primary cilium and initiate a cascade of events that lead to the activation of Gli transcription factors and transcription of downstream target genes.
基金This study was supported by grants from the Natural Science Foundation of China （No. 91129733, No. 81071228, and No. 81330060） and the Special Fund for Health-Scientific Research in the Public Interest Program from National Health and Family Planning Commission （No. 201202011）.
文摘Background：The hedgehog signaling system （HHS） plays an important role in the regulation of cell proliferation and differentiation during the embryonic phases.However,little is known about the involvement of HHS in the malignant transformation of cells.This study aimed to detect the role of HHS in the malignant transformation of human bronchial epithelial （16HBE） cells.Methods：In this study,two microfluidic chips were designed to investigate cigarette smoke extract （CSE）-induced malignant transformation of cells.Chip A contained a concentration gradient generator,while chip B had four cell chambers with a central channel.The 16HBE cells cultured in chip A were used to determine the optimal concentration of CSE for inducing malignant transformation.The 16HBE cells in chip B were cultured with 12.25% CSE （Group A）,12.25% CSE ± 5 μmol/L cyclopamine （Group B）,or normal complete medium as control for 8 months （Group C）,to establish the in vitro lung inflammatory-cancer transformation model.The transformed cells were inoculated into 20 nude mice as cells alone （Group 1） or cells with cyclopamine （Group 2） for tumorigenesis testing.Expression of HHS proteins was detected by Western blot.Data were expressed as mean ± standard deviation.The t-test was used for paired samples,and the difference among groups was analyzed using a one-way analysis of variance.Results：The optimal concentration of CSE was 12.25%.Expression of HHS proteins increased during the process of malignant transformation （Group B vs.Group A,F =7.65,P 〈 0.05）.After CSE exposure for 8 months,there were significant changes in cellular morphology,which allowed the transformed cells to grow into tumors in 40 days after being inoculated into nude mice.Cyclopamine could effectively depress the expression of HHS proteins （Group C vs.Group B,F =6.47,P 〈 0.05） and prevent tumor growth in nude mice （Group 2 vs.Group 1,t=31.59,P〈 0.01）.Conclusions：The activity of HHS is upregulated during the CSE-induced malignant transformation of 16HBE cells.Cyclopamine can effectively depress expression of HHS proteins in vitro and prevent tumor growth of the transformed cells in vivo.
