Objective:To evaluate the effects of testosterone(T)on the maintenance of corpus cavernosum(CC)structure and apoptosis.Methods:Animals were divided into three groups:sham operation group(n Z 8)underwent sham operation...Objective:To evaluate the effects of testosterone(T)on the maintenance of corpus cavernosum(CC)structure and apoptosis.Methods:Animals were divided into three groups:sham operation group(n Z 8)underwent sham operation;Orchiectomized(Orchiec)t oily vehicle group(n Z 8)underwent bilateral orchiectomy and received a single dose of oily vehicle by intramuscular injection(i.m.)30 days after orchiectomy;and Orchiec t T group(n Z 8)underwent bilateral orchiectomy and received a single dose of T undecanoate 100 mg/kg i.m.30 days after the surgery.Animals were euthanized 60 days after the beginning of the experiment with an anesthetic overdose of ketamine and xylazine.Blood samples and penile tissue were collected on euthanasia.展开更多
BACKGROUND Obesity and comorbidities onset encompass gut dysbiosis,altered intestinal permeability,and endotoxemia.Treatments that target gut dysbiosis can cope with obesity and nonalcoholic fatty liver disease(NAFLD)...BACKGROUND Obesity and comorbidities onset encompass gut dysbiosis,altered intestinal permeability,and endotoxemia.Treatments that target gut dysbiosis can cope with obesity and nonalcoholic fatty liver disease(NAFLD)management.Peroxisome proliferator-activated receptor(PPAR)-alpha activation and dipeptidyl-peptidase-4(DPP-4)inhibition alleviate NAFLD,but the mechanism may involve gut microbiota modulation and merits further investigation.AIM To address the effects of PPAR-alpha activation and DPP-4 inhibition(isolated or combined)upon the gut-liver axis,emphasizing inflammatory pathways in NAFLD management in high-fat-fed C57BL/6J mice.METHODS Male C57BL/6J mice were fed a control diet(C,10%of energy as lipids)or a highfat diet(HFD,50%of energy as lipids)for 12 wk,when treatments started,forming the groups:C,HF,HFA(HFD+PPAR-alpha agonist WY14643,2.5 mg/kg body mass),HFL(HFD+DPP-4 inhibitor linagliptin,15 mg/kg body mass),and HFC(HFD+the combination of WY14643 and linagliptin).RESULTS The HFD was obesogenic compared to the C diet.All treatments elicited significant body mass loss,and the HFC group showed similar body mass to the C group.All treatments tackled oral glucose intolerance and raised plasma glucagon-like peptide-1 concentrations.These metabolic benefits restored Bacteroidetes/Firmicutes ratio,resulting in increased goblet cells per area of the large intestine and reduced lipopolysaccharides concentrations in treated groups.At the gene level,treated groups showed higher intestinal Mucin 2,Occludin,and Zo-1 expression than the HFD group.The reduced endotoxemia suppressed inflammasome and macrophage gene expression in the liver of treated animals.These observations complied with the mitigation of liver steatosis and reduced hepatic triacylglycerol,reassuring the role of the proposed treatments on NAFLD mitigation.CONCLUSION PPAR alpha activation and DPP-4 inhibition(isolated or combined)tackled NAFLD in dietinduced obese mice by restoration of gut-liver axis.The reestablishment of the intestinal barrier and the rescued phylogenetic gut bacteria distribution mitigated liver steatosis through antiinflammatory signals.These results can cope with NAFLD management by providing pre-clinical evidence that drugs used to treat obesity comorbidities can help to alleviate this silent and harmful liver disease.展开更多
The coronavirus disease 2019(COVID-19)outbreak has drawn the scientific community's attention to pre-existing metabolic conditions that could aggravate the infection,causing extended viral shedding,prolonged hospi...The coronavirus disease 2019(COVID-19)outbreak has drawn the scientific community's attention to pre-existing metabolic conditions that could aggravate the infection,causing extended viral shedding,prolonged hospitalization,and high death rates.Metabolic dysfunction-associated fatty liver disease(MAFLD)emerges as a surrogate for COVID-19 severity due to the constellation of metabolic alterations it entails.This review outlines the impact MAFLD exerts on COVID-19 severity in obese subjects,besides the possible mechanistic links to the poor outcomes.The data collected showed that MAFLD patients had poorer COVID-19 outcomes than non-MAFLD obese subjects.MAFLD is generally accompanied by impaired glycemic control and systemic arterial hypertension,both of which can decompensate during the COVID-19 clinical course.Also,MAFLD subjects had higher plasma inflammatory marker concentrations than non-MAFLD subjects,which might be related to an intensified cytokine storm syndrome frequently associated with the need for mechanical ventilation and death.In conclusion,MAFLD represents a higher risk than obesity for COVID-19 severity,resulting in poor outcomes and even progression to non-alcoholic steatohepatitis.Hepatologists should include MAFLD subjects in the high-risk group,intensify preventive measurements,and prioritize their vaccination.展开更多
基金We thank Urogenital Research Unit staff,UERJ,for technical support and UFCSPA,CNPq(MCT/CNPq 15/2007),Coordenac¸a˜o de Aperfeic¸oamento de Pessoal de Nıvel Superior e CAPES and FAPERGS(11/1003-5 e 02/2011)for financial support.
文摘Objective:To evaluate the effects of testosterone(T)on the maintenance of corpus cavernosum(CC)structure and apoptosis.Methods:Animals were divided into three groups:sham operation group(n Z 8)underwent sham operation;Orchiectomized(Orchiec)t oily vehicle group(n Z 8)underwent bilateral orchiectomy and received a single dose of oily vehicle by intramuscular injection(i.m.)30 days after orchiectomy;and Orchiec t T group(n Z 8)underwent bilateral orchiectomy and received a single dose of T undecanoate 100 mg/kg i.m.30 days after the surgery.Animals were euthanized 60 days after the beginning of the experiment with an anesthetic overdose of ketamine and xylazine.Blood samples and penile tissue were collected on euthanasia.
基金Supported by Coordena??o de Aperfei?oamento de Pessoal de Nível Superior–Brasil,No. CAPES–Finance Code 001Funda??o Carlos Chagas Filho de Amparo à Pesquisa do Rio de Janeiro (FAPERJ) to Souza-Mello V,No. E-26/202.657/2018 and No. E-26/010.002136/2019supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq),No. 303785/2020-9
文摘BACKGROUND Obesity and comorbidities onset encompass gut dysbiosis,altered intestinal permeability,and endotoxemia.Treatments that target gut dysbiosis can cope with obesity and nonalcoholic fatty liver disease(NAFLD)management.Peroxisome proliferator-activated receptor(PPAR)-alpha activation and dipeptidyl-peptidase-4(DPP-4)inhibition alleviate NAFLD,but the mechanism may involve gut microbiota modulation and merits further investigation.AIM To address the effects of PPAR-alpha activation and DPP-4 inhibition(isolated or combined)upon the gut-liver axis,emphasizing inflammatory pathways in NAFLD management in high-fat-fed C57BL/6J mice.METHODS Male C57BL/6J mice were fed a control diet(C,10%of energy as lipids)or a highfat diet(HFD,50%of energy as lipids)for 12 wk,when treatments started,forming the groups:C,HF,HFA(HFD+PPAR-alpha agonist WY14643,2.5 mg/kg body mass),HFL(HFD+DPP-4 inhibitor linagliptin,15 mg/kg body mass),and HFC(HFD+the combination of WY14643 and linagliptin).RESULTS The HFD was obesogenic compared to the C diet.All treatments elicited significant body mass loss,and the HFC group showed similar body mass to the C group.All treatments tackled oral glucose intolerance and raised plasma glucagon-like peptide-1 concentrations.These metabolic benefits restored Bacteroidetes/Firmicutes ratio,resulting in increased goblet cells per area of the large intestine and reduced lipopolysaccharides concentrations in treated groups.At the gene level,treated groups showed higher intestinal Mucin 2,Occludin,and Zo-1 expression than the HFD group.The reduced endotoxemia suppressed inflammasome and macrophage gene expression in the liver of treated animals.These observations complied with the mitigation of liver steatosis and reduced hepatic triacylglycerol,reassuring the role of the proposed treatments on NAFLD mitigation.CONCLUSION PPAR alpha activation and DPP-4 inhibition(isolated or combined)tackled NAFLD in dietinduced obese mice by restoration of gut-liver axis.The reestablishment of the intestinal barrier and the rescued phylogenetic gut bacteria distribution mitigated liver steatosis through antiinflammatory signals.These results can cope with NAFLD management by providing pre-clinical evidence that drugs used to treat obesity comorbidities can help to alleviate this silent and harmful liver disease.
基金Conselho Nacional de Desenvolvimento Científico e Tecnológico(Brazil),No.305867/2017-2Fundação Carlos Chagas Filho de AmparoàPesquisa do Estado do Rio de Janeiro,No.E-26/202.657/2018.
文摘The coronavirus disease 2019(COVID-19)outbreak has drawn the scientific community's attention to pre-existing metabolic conditions that could aggravate the infection,causing extended viral shedding,prolonged hospitalization,and high death rates.Metabolic dysfunction-associated fatty liver disease(MAFLD)emerges as a surrogate for COVID-19 severity due to the constellation of metabolic alterations it entails.This review outlines the impact MAFLD exerts on COVID-19 severity in obese subjects,besides the possible mechanistic links to the poor outcomes.The data collected showed that MAFLD patients had poorer COVID-19 outcomes than non-MAFLD obese subjects.MAFLD is generally accompanied by impaired glycemic control and systemic arterial hypertension,both of which can decompensate during the COVID-19 clinical course.Also,MAFLD subjects had higher plasma inflammatory marker concentrations than non-MAFLD subjects,which might be related to an intensified cytokine storm syndrome frequently associated with the need for mechanical ventilation and death.In conclusion,MAFLD represents a higher risk than obesity for COVID-19 severity,resulting in poor outcomes and even progression to non-alcoholic steatohepatitis.Hepatologists should include MAFLD subjects in the high-risk group,intensify preventive measurements,and prioritize their vaccination.
