Diabetic cardiomyopathy(DbCM)is a common but underrecognized complication of patients with diabetes mellitus(DM).Although the pathobiology of other cardiac complications of diabetes such as ischemic heart disease and ...Diabetic cardiomyopathy(DbCM)is a common but underrecognized complication of patients with diabetes mellitus(DM).Although the pathobiology of other cardiac complications of diabetes such as ischemic heart disease and cardiac autonomic neuropathy are mostly known with reasonable therapeutic options,the mechanisms and management options for DbCM are still not fully understood.In its early stages,DbCM presents with diastolic dysfunction followed by heart failure(HF)with preserved ejection fraction that can progress to systolic dysfunction and HF with reduced ejection fraction in its advanced stages unless appropriately managed.Apart from prompt control of DM with lifestyle changes and antidiabetic medications,disease-modifying therapy for DbCM includes prompt control of hypertension and dyslipidemia inherent to patients with DM as in other forms of heart diseases and the use of treatments with proven efficacy in HF.A basic study by Zhang et al,in a recent issue of the World Journal of Diabetes elaborates the potential pathophysiological alterations and the therapeutic role of teneligliptin in diabetic mouse models with DbCM.Although this preliminary basic study might help to improve our understanding of DbCM and offer a potential new management option for patients with the disease,the positive results from such animal models might not always translate to clinical practice as the pathobiology of DbCM in humans could be different.However,such experimental studies can encourage more scientific efforts to find a better solution to treat patients with this enigmatic disease.展开更多
BACKGROUND Aberrant activation of phosphorylated form of glycogen synthase kinase-3β[pS9 GSK-3β(Serine 9 phosphorylation)] is known to trigger Wnt/β-catenin signal cascade but its clinicohistopathological implicati...BACKGROUND Aberrant activation of phosphorylated form of glycogen synthase kinase-3β[pS9 GSK-3β(Serine 9 phosphorylation)] is known to trigger Wnt/β-catenin signal cascade but its clinicohistopathological implications in bladder carcinogenesis remain unknown.AIM To investigate the diagnostic and prognostic relevance of expressions of pS9 GSK-3β, β-catenin and its target genes in the pathobiology of bladder cancer.METHODS Bladder tumor tissues from ninety patients were analyzed for quantitative expression and cellular localization of pS9 GSK-3β by immunohistochemical(IHC) staining. Real time-quantitative polymerase chain reaction and IHC were done to check the expression of β-catenin, Cyclin D1, Snail and Slug at transcriptome and protein level respectively. Clinicohistopathological variables were obtained from histology reports, follow up and OPD visits of patients.Expressions of the markers were statistically correlated with these variables to determine their significance in clinical setting. Results were analysed using SPSS20.0 software.RESULTS Aberrant(low or no membranous/high nuclear/high cytoplasmic) expression of pS9 GSK-3β was noted in 51% patients and found to be significantly associated with tumor stage and tumor grade(P = 0.01 and 0.04; Mann Whitney U test).Thirty one percent tumors exhibited aberrant co-expression of pS9 GSK-3β andβ–catenin proteins and showed strong statistical association with tumor stage,tumor type, smoking/tobacco chewing status(P = 0.01, 0.02 and 0.04, MannWhitney U test) and shorter overall survival probabilities of patients(P = 0.02;Kaplan Meier test). Nuclear immunostaining of Cyclin D1 in tumors with altered pS9 GSK-3β/β–catenin showed relevance with tumor stage, grade and type.CONCLUSIONβ–catenin and pS9 GSK-3β proteins are identified as markers of diagnostic/prognostic significance in disease pathogenesis. Observed histopathological association of Cyclin D1 identifies it as marker of potential relevance in tumors with altered pS9 GSK-3β/β-catenin.展开更多
Nonalcoholic fatty liver disease(NAFLD)exhibits sexual dimorphism,with men being more exposed than women to the risk of simple steatosis,nonalcoholic steatohepatitis fibrosis,and hepatocellular carcinoma(HCC),while th...Nonalcoholic fatty liver disease(NAFLD)exhibits sexual dimorphism,with men being more exposed than women to the risk of simple steatosis,nonalcoholic steatohepatitis fibrosis,and hepatocellular carcinoma(HCC),while the protection conferred to women seemingly disappears with aging and reproductive senescence(i.e.,menopause).HCC,the most common primary liver cancer,which carries an ominous prognosis,may result from various genetic and non-genetic risk factors.NAFLD is now projected to become the most common cause of HCC.HCC also exhibits a definite sexual dimorphism in as much as it has a worldwide high male-to-female ratio.In this review article,we focus on sex differences in the epidemiological features of HCC.Moreover,we discuss sex differences in the clinical outcome and molecular pathobiology of NAFLD-HCC.By highlighting the research gaps to be filled,the aim of this review is to prompt future research of sex differences in HCC and facilitate developing personalized cancer prevention strategies,detection,and treatments to achieve better patient outcomes in NAFLD-HCC,considering sex differences in HCC pathobiology.展开更多
文摘Diabetic cardiomyopathy(DbCM)is a common but underrecognized complication of patients with diabetes mellitus(DM).Although the pathobiology of other cardiac complications of diabetes such as ischemic heart disease and cardiac autonomic neuropathy are mostly known with reasonable therapeutic options,the mechanisms and management options for DbCM are still not fully understood.In its early stages,DbCM presents with diastolic dysfunction followed by heart failure(HF)with preserved ejection fraction that can progress to systolic dysfunction and HF with reduced ejection fraction in its advanced stages unless appropriately managed.Apart from prompt control of DM with lifestyle changes and antidiabetic medications,disease-modifying therapy for DbCM includes prompt control of hypertension and dyslipidemia inherent to patients with DM as in other forms of heart diseases and the use of treatments with proven efficacy in HF.A basic study by Zhang et al,in a recent issue of the World Journal of Diabetes elaborates the potential pathophysiological alterations and the therapeutic role of teneligliptin in diabetic mouse models with DbCM.Although this preliminary basic study might help to improve our understanding of DbCM and offer a potential new management option for patients with the disease,the positive results from such animal models might not always translate to clinical practice as the pathobiology of DbCM in humans could be different.However,such experimental studies can encourage more scientific efforts to find a better solution to treat patients with this enigmatic disease.
文摘BACKGROUND Aberrant activation of phosphorylated form of glycogen synthase kinase-3β[pS9 GSK-3β(Serine 9 phosphorylation)] is known to trigger Wnt/β-catenin signal cascade but its clinicohistopathological implications in bladder carcinogenesis remain unknown.AIM To investigate the diagnostic and prognostic relevance of expressions of pS9 GSK-3β, β-catenin and its target genes in the pathobiology of bladder cancer.METHODS Bladder tumor tissues from ninety patients were analyzed for quantitative expression and cellular localization of pS9 GSK-3β by immunohistochemical(IHC) staining. Real time-quantitative polymerase chain reaction and IHC were done to check the expression of β-catenin, Cyclin D1, Snail and Slug at transcriptome and protein level respectively. Clinicohistopathological variables were obtained from histology reports, follow up and OPD visits of patients.Expressions of the markers were statistically correlated with these variables to determine their significance in clinical setting. Results were analysed using SPSS20.0 software.RESULTS Aberrant(low or no membranous/high nuclear/high cytoplasmic) expression of pS9 GSK-3β was noted in 51% patients and found to be significantly associated with tumor stage and tumor grade(P = 0.01 and 0.04; Mann Whitney U test).Thirty one percent tumors exhibited aberrant co-expression of pS9 GSK-3β andβ–catenin proteins and showed strong statistical association with tumor stage,tumor type, smoking/tobacco chewing status(P = 0.01, 0.02 and 0.04, MannWhitney U test) and shorter overall survival probabilities of patients(P = 0.02;Kaplan Meier test). Nuclear immunostaining of Cyclin D1 in tumors with altered pS9 GSK-3β/β–catenin showed relevance with tumor stage, grade and type.CONCLUSIONβ–catenin and pS9 GSK-3β proteins are identified as markers of diagnostic/prognostic significance in disease pathogenesis. Observed histopathological association of Cyclin D1 identifies it as marker of potential relevance in tumors with altered pS9 GSK-3β/β-catenin.
文摘Nonalcoholic fatty liver disease(NAFLD)exhibits sexual dimorphism,with men being more exposed than women to the risk of simple steatosis,nonalcoholic steatohepatitis fibrosis,and hepatocellular carcinoma(HCC),while the protection conferred to women seemingly disappears with aging and reproductive senescence(i.e.,menopause).HCC,the most common primary liver cancer,which carries an ominous prognosis,may result from various genetic and non-genetic risk factors.NAFLD is now projected to become the most common cause of HCC.HCC also exhibits a definite sexual dimorphism in as much as it has a worldwide high male-to-female ratio.In this review article,we focus on sex differences in the epidemiological features of HCC.Moreover,we discuss sex differences in the clinical outcome and molecular pathobiology of NAFLD-HCC.By highlighting the research gaps to be filled,the aim of this review is to prompt future research of sex differences in HCC and facilitate developing personalized cancer prevention strategies,detection,and treatments to achieve better patient outcomes in NAFLD-HCC,considering sex differences in HCC pathobiology.
