Free fatty acids(FFAs)play important roles in cardiovascular disease.Studies have shown that it is an important way for FAs to exert biological effects through their own receptors besides directly participating bioche...Free fatty acids(FFAs)play important roles in cardiovascular disease.Studies have shown that it is an important way for FAs to exert biological effects through their own receptors besides directly participating biochemical reaction in body.Free fatty acid receptor 2(FFA2)can be activated by short-chain FAs and is involved in inflammatory reactions and lipid accumulation.Since the known pathological changes caused by FFA2 are also implicated in cardiac hypertrophy,we hypothesized that FFA2 might be pathogenic in cardiac hypertrophy.This paper showed that FFA2 expression significantly increased in cardiac hypertrophy in vivo and in vitro.FFA2 agonist 4-CMTB or TUG-1375 promoted the expression of the hypertrophy markers ANF and BNP and increased cell surface area in vitro,which was further strengthened by FFA2 overexpression,suggesting that FFA2 might contribute to cardiomyocyte hypertrophy.Furthermore,4-CMTB treatment or FFA2 overexpression combined with 4-CMTB treatment elevated the phosphorylation and transcriptional activity of GATA4 and STAT3,which were inhibited by an ERK1/2 inhibitor,and GATA4 and STAT3 knockdown inhibited the elevation of hypertrophy biomarkers in cardiomyocytes treated with 4-CMTB.Taken together,these data indicate that FFA2 can enhance cardiomyocyte hypertrophy by activating STAT3 and GATA4 via ERK1/2,providing a potential new target for therapy.展开更多
The coronavirus disease 2019(COVID-19)has spread globally.Although mixed liver impairment has been reported in COVID-19 patients,the association of liver injury caused by specific subtype especially chronic hepatitis ...The coronavirus disease 2019(COVID-19)has spread globally.Although mixed liver impairment has been reported in COVID-19 patients,the association of liver injury caused by specific subtype especially chronic hepatitis B(CHB)with COVID-19 has not been elucidated.In this multi-center,retrospective,and observational cohort study,109 CHB and 327 non-CHB patients with COVID-19 were propensity score matched at an approximate ratio of 3:1 on the basis of age,sex,and comorbidities.Demographic characteristics,laboratory examinations,disease severity,and clinical outcomes were compared.Furthermore,univariable and multivariable logistic and Cox regression models were used to explore the risk factors for disease severity and mortality,respectively.A higher proportion of CHB patients(30 of 109(27.52%))developed into severe status than non-CHB patients(17 of 327(5.20%)).In addition to previously reported liver impairment markers,such as alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,and total bilirubin,we identified several novel risk factors including elevated lactate dehydrogenase(≥245 U/L,hazard ratio(HR)=8.639,95%confidence interval(CI)=2.528–29.523;P<0.001)and coagulation-related biomarker D-dimer(≥0.5μg/mL,HR=4.321,95%CI=1.443–12.939;P=0.009)and decreased albumin(<35 g/L,HR=0.131,95%CI=0.048–0.361;P<0.001)and albumin/globulin ratio(<1.5,HR=0.123,95%CI=0.017–0.918;P=0.041).In conclusion,COVID-19 patients with CHB were more likely to develop into severe illness and die.The risk factors that we identified may be helpful for early clinical surveillance of critical progression.展开更多
基金supported by the National Natural Science Foundation of China(No.81760058,81560059,81660042,31800891)the Scientific Research Project of Health and Family Planning Commission of Hunan Province(No.C2017025)+1 种基金the Project of Medical and Health Science and Technology of Shaoxing City(No.2020A13063)the Startup Fund for Research of Shaoxing University(No.20205021)。
文摘Free fatty acids(FFAs)play important roles in cardiovascular disease.Studies have shown that it is an important way for FAs to exert biological effects through their own receptors besides directly participating biochemical reaction in body.Free fatty acid receptor 2(FFA2)can be activated by short-chain FAs and is involved in inflammatory reactions and lipid accumulation.Since the known pathological changes caused by FFA2 are also implicated in cardiac hypertrophy,we hypothesized that FFA2 might be pathogenic in cardiac hypertrophy.This paper showed that FFA2 expression significantly increased in cardiac hypertrophy in vivo and in vitro.FFA2 agonist 4-CMTB or TUG-1375 promoted the expression of the hypertrophy markers ANF and BNP and increased cell surface area in vitro,which was further strengthened by FFA2 overexpression,suggesting that FFA2 might contribute to cardiomyocyte hypertrophy.Furthermore,4-CMTB treatment or FFA2 overexpression combined with 4-CMTB treatment elevated the phosphorylation and transcriptional activity of GATA4 and STAT3,which were inhibited by an ERK1/2 inhibitor,and GATA4 and STAT3 knockdown inhibited the elevation of hypertrophy biomarkers in cardiomyocytes treated with 4-CMTB.Taken together,these data indicate that FFA2 can enhance cardiomyocyte hypertrophy by activating STAT3 and GATA4 via ERK1/2,providing a potential new target for therapy.
基金supported by the National Natural Science Foundation of China(No.81974400)Natural Science Foundation of Zhuhai(No.ZH22036302200081-PWC to Renli Deng).
文摘The coronavirus disease 2019(COVID-19)has spread globally.Although mixed liver impairment has been reported in COVID-19 patients,the association of liver injury caused by specific subtype especially chronic hepatitis B(CHB)with COVID-19 has not been elucidated.In this multi-center,retrospective,and observational cohort study,109 CHB and 327 non-CHB patients with COVID-19 were propensity score matched at an approximate ratio of 3:1 on the basis of age,sex,and comorbidities.Demographic characteristics,laboratory examinations,disease severity,and clinical outcomes were compared.Furthermore,univariable and multivariable logistic and Cox regression models were used to explore the risk factors for disease severity and mortality,respectively.A higher proportion of CHB patients(30 of 109(27.52%))developed into severe status than non-CHB patients(17 of 327(5.20%)).In addition to previously reported liver impairment markers,such as alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,and total bilirubin,we identified several novel risk factors including elevated lactate dehydrogenase(≥245 U/L,hazard ratio(HR)=8.639,95%confidence interval(CI)=2.528–29.523;P<0.001)and coagulation-related biomarker D-dimer(≥0.5μg/mL,HR=4.321,95%CI=1.443–12.939;P=0.009)and decreased albumin(<35 g/L,HR=0.131,95%CI=0.048–0.361;P<0.001)and albumin/globulin ratio(<1.5,HR=0.123,95%CI=0.017–0.918;P=0.041).In conclusion,COVID-19 patients with CHB were more likely to develop into severe illness and die.The risk factors that we identified may be helpful for early clinical surveillance of critical progression.