Objective:To explore the role of endothelial biomarkers in predicting damp-heat syndrome in diabetic kidney disease(DKD).Methods:A total of 183 patients with DKD were divided into 3 groups:the early DKD group,establis...Objective:To explore the role of endothelial biomarkers in predicting damp-heat syndrome in diabetic kidney disease(DKD).Methods:A total of 183 patients with DKD were divided into 3 groups:the early DKD group,established DKD group,and advanced DKD group.All patients were classified according to traditional Chinese medicine(TCM)syndrome type,and clinical indexes were collected for statistical analysis.Results:A total of 183 DKD patients were included in this study.Fibroblast growth factor 23(FGF23),chitinase-3-like protein 1(CHI3L1),endocan,tumor necrosis factor receptor 1(TNFR1),secretory leukocyte protease inhibitor(SLPI),and vascular endothelial growth factor A(VEGF-A)were increased in advanced DKD.FGF23,CHI3L1,endocan,SLPI,and TNFR1 showed a negative correlation with estimated glomerular filtration rate(eGFR),while they had a positive correlation with 24 h urine protein.After adjusting for age,gender,diabetes duration,body mass index(BMI),hemoglobin,glucose,uric acid,24 h urine protein,cholesterol,triglyceride,low-density lipoprotein,and hemoglobin A1c(HbA1c),the multiple regression analysis showed that FGF23,endocan,TNFR1,and SLPI significantly correlated with eGFR.Conclusions:FGF23,endocan,TNFR1,and SLPI are elevated in advanced DKD compared with early stage,and they may take part in the pathogenesis and progression of DKD.Our study provides useful biomarkers for predicting the appearance of damp-heat syndrome,including FGF23,endocan,TNFR1,and SLPI.展开更多
Dioxin-like molecules have been associated with endocrine disruption and liver disease.To better understand aryl hydrocarbon receptor(AHR)biology,metabolic phenotyping and liver proteomics were performed in mice follo...Dioxin-like molecules have been associated with endocrine disruption and liver disease.To better understand aryl hydrocarbon receptor(AHR)biology,metabolic phenotyping and liver proteomics were performed in mice following ligand-activation or whole-body genetic ablation of this receptor.Male wild type(WT)and Ahr^(-/-) mice(Taconic)were fed a control diet and exposed to 3,3',4,4',5-pentachlorobiphenyl(PCB126)(61 nmol/kg by gavage)or vehicle for two weeks.PCB126 increased expression of canonical AHR targets(Cyp1 a1 and Cyp1 a2)in WT but not Ahr^(-/-).Knockouts had increased adiposity with decreased glucose tolerance;smaller livers with increased steatosis and perilipin-2;and paradoxically decreased blood lipids.PCB126 was associated with increased hepatic triglycerides in Ahr^(-/-).The liver proteome was impacted more so by Ahr^(-/-) genotype than ligandactivation,but top gene ontology(GO)processes were similar.The PCB126-associated liver proteome was Ahr-dependent.Ahr principally regulated liver metabolism(e.g.,lipids,xenobiotics,organic acids)and bioenergetics,but it also impacted liver endocrine response(e.g.,the insulin receptor)and function,including the production of steroids,hepatokines,and pheromone binding proteins.These effects could have been indirectly mediated by interacting transcription factors or microRNAs.The biologic roles of the AHR and its ligands warrant more research in liver metabolic health and disease.展开更多
基金This project was supported by the Fundamental Research Funds for the Central Universities(2017-JYB-JS-075)National Key Project for Drug Discovery(2017ZX09304019).
文摘Objective:To explore the role of endothelial biomarkers in predicting damp-heat syndrome in diabetic kidney disease(DKD).Methods:A total of 183 patients with DKD were divided into 3 groups:the early DKD group,established DKD group,and advanced DKD group.All patients were classified according to traditional Chinese medicine(TCM)syndrome type,and clinical indexes were collected for statistical analysis.Results:A total of 183 DKD patients were included in this study.Fibroblast growth factor 23(FGF23),chitinase-3-like protein 1(CHI3L1),endocan,tumor necrosis factor receptor 1(TNFR1),secretory leukocyte protease inhibitor(SLPI),and vascular endothelial growth factor A(VEGF-A)were increased in advanced DKD.FGF23,CHI3L1,endocan,SLPI,and TNFR1 showed a negative correlation with estimated glomerular filtration rate(eGFR),while they had a positive correlation with 24 h urine protein.After adjusting for age,gender,diabetes duration,body mass index(BMI),hemoglobin,glucose,uric acid,24 h urine protein,cholesterol,triglyceride,low-density lipoprotein,and hemoglobin A1c(HbA1c),the multiple regression analysis showed that FGF23,endocan,TNFR1,and SLPI significantly correlated with eGFR.Conclusions:FGF23,endocan,TNFR1,and SLPI are elevated in advanced DKD compared with early stage,and they may take part in the pathogenesis and progression of DKD.Our study provides useful biomarkers for predicting the appearance of damp-heat syndrome,including FGF23,endocan,TNFR1,and SLPI.
基金supported,in part,by the National Institute of Environmental Health Sciences(R35ES028373,R01ES032189,T32ES011564,P42ES023716,P30ES030283,F31ES028982 and R21ES031510,USA)the National Institute of General Medical Sciences(P20GM113226,USA)+1 种基金the National Institute on Alcohol Abuse and Alcoholism(P50AA024337 and 1F32AA027950,USA)the Kentucky Council on Postsecondary Education(PON24151900002934,USA)。
文摘Dioxin-like molecules have been associated with endocrine disruption and liver disease.To better understand aryl hydrocarbon receptor(AHR)biology,metabolic phenotyping and liver proteomics were performed in mice following ligand-activation or whole-body genetic ablation of this receptor.Male wild type(WT)and Ahr^(-/-) mice(Taconic)were fed a control diet and exposed to 3,3',4,4',5-pentachlorobiphenyl(PCB126)(61 nmol/kg by gavage)or vehicle for two weeks.PCB126 increased expression of canonical AHR targets(Cyp1 a1 and Cyp1 a2)in WT but not Ahr^(-/-).Knockouts had increased adiposity with decreased glucose tolerance;smaller livers with increased steatosis and perilipin-2;and paradoxically decreased blood lipids.PCB126 was associated with increased hepatic triglycerides in Ahr^(-/-).The liver proteome was impacted more so by Ahr^(-/-) genotype than ligandactivation,but top gene ontology(GO)processes were similar.The PCB126-associated liver proteome was Ahr-dependent.Ahr principally regulated liver metabolism(e.g.,lipids,xenobiotics,organic acids)and bioenergetics,but it also impacted liver endocrine response(e.g.,the insulin receptor)and function,including the production of steroids,hepatokines,and pheromone binding proteins.These effects could have been indirectly mediated by interacting transcription factors or microRNAs.The biologic roles of the AHR and its ligands warrant more research in liver metabolic health and disease.
