Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex ster...Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs proliferation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.展开更多
This research aims to understand more closely the damage to the lake environment and the factors that cause pollution in Lake Santa Maria are the first factor of increasing urbanization, the use of the land around the...This research aims to understand more closely the damage to the lake environment and the factors that cause pollution in Lake Santa Maria are the first factor of increasing urbanization, the use of the land around the lake as a place to live, the absence of maximum control from the local government this case, the Dili municipal authority. Types of solid waste consist of iron from car accidents, motorcycles, used building materials, plastic, used drink bottles and clothes, mosquito nets, food scraps from household waste, as well as old fishing nets from residents. In addition, household waste such as bath and bath, dishwashing, detergents, and waste from tempeh and tofu factories, including burnt oil from cars and motorcycles, are thrown into the lake. Municipal waste management is based on environmental standards to determine the quality of waste management in Dili Municipality. It is possible to identify the composition of waste and waste, as well as predict its environmental impact. Human (Anthropic) factors Domestic Liquid Waste, Domestic Solid Waste: Composed of organic and inorganic waste. Synthetic Waste, Disposal of Used Oil, Disposal of Domestic Animal Waste, Shallow Drains and Septic Tanks, Mountain Garbage, Garbage Thrown by Visitors, Natural Factors, Climate change, Prolonged drought, Low rainfall, El Niño and La Niña factors, Wind speed, Heat (high daily temperature pressure), Greater water evaporation, Dry wind. The occurrence of contamination necessarily implies an ecological imbalance. The impact introduced by residual compounds and waste that may be associated with the toxicity.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.:82073906 and 82273987)Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions,and Postgraduate Research Practice Innovation Program of Jiangsu Province(Grant Nos.:KYCX22-2966 and KYCX23-2967).
文摘Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs proliferation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.
文摘This research aims to understand more closely the damage to the lake environment and the factors that cause pollution in Lake Santa Maria are the first factor of increasing urbanization, the use of the land around the lake as a place to live, the absence of maximum control from the local government this case, the Dili municipal authority. Types of solid waste consist of iron from car accidents, motorcycles, used building materials, plastic, used drink bottles and clothes, mosquito nets, food scraps from household waste, as well as old fishing nets from residents. In addition, household waste such as bath and bath, dishwashing, detergents, and waste from tempeh and tofu factories, including burnt oil from cars and motorcycles, are thrown into the lake. Municipal waste management is based on environmental standards to determine the quality of waste management in Dili Municipality. It is possible to identify the composition of waste and waste, as well as predict its environmental impact. Human (Anthropic) factors Domestic Liquid Waste, Domestic Solid Waste: Composed of organic and inorganic waste. Synthetic Waste, Disposal of Used Oil, Disposal of Domestic Animal Waste, Shallow Drains and Septic Tanks, Mountain Garbage, Garbage Thrown by Visitors, Natural Factors, Climate change, Prolonged drought, Low rainfall, El Niño and La Niña factors, Wind speed, Heat (high daily temperature pressure), Greater water evaporation, Dry wind. The occurrence of contamination necessarily implies an ecological imbalance. The impact introduced by residual compounds and waste that may be associated with the toxicity.
