RESUMO
Myocardial cell death during acute myocardial infarction occurs because of acute ischemia, persistent ischemia, reperfusion-associated injury, and the inflammatory infiltrate as a response to cell necrosis. In the present study, quantitative real-time PCR showed that lncRNA Gm4419 was highly upregulated in ischemia/reperfusion myocardial tissues and hypoxia/reoxygenation H9C2 cells, whereas miR-682 was downregulated. Knocking down Gm4419 with sh-Gm4419 resulted in the rescue of myocardial infarction and apoptosis induced by ischemia/reperfusion or hypoxia/reoxygenation. Our study further demonstrated that Gm4419 may bind with miR-682 directly. Moreover, in vitro experiments further demonstrated that miR-682 could bind to tumor necrosis factor receptor-associated factor 3 (TRAF3) directly. Most importantly, TRAF3 overexpression could counteract the effect of sh-Gm4419. Taken together, our study indicated that Gm4419 may target miR-682 via sponging to increase TRAF3 expression, thereby contributing to myocardial I/R injury. Therefore, the Gm4419/miR-682/TRAF3 axis may be an important regulatory mechanism in myocardial ischemia/reperfusion injury.
Assuntos
MicroRNAs/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio/metabolismo , RNA Longo não Codificante/metabolismo , Fator 3 Associado a Receptor de TNF/metabolismo , Animais , Linhagem Celular , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Mediadores da Inflamação/metabolismo , MicroRNAs/genética , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , RNA Longo não Codificante/genética , Ratos Sprague-Dawley , Transdução de Sinais , Fator 3 Associado a Receptor de TNF/genéticaRESUMO
UNLABELLED: To investigate the association between the polymorphism of P choose element (p. selectin, PS) and soluble P-selectin levels in atrial fibrillation (AF) thromboembolism in Han and Uigur population of Xinjiang. METHOD: Using ELISA method determination of plasma level of sPs. The frequency distributions of SNP sP-selectin gene promoter (-2123C/G) and SNP in exon region (Thr715Pro) were investigated by polymerase chain reaction (PCR)-restriction fragment length polymorphism and direct DNA sequence analysis among 302 Xinjiang Uigur and 340 age- and sex-matched Han people. RESULTS: Cases sPs exist significant difference serum level and the control group. The frequencies of the -2123C/G allele among the Uigur population had no significant differences from those of the Han population. Thr715Pro did not show any polymorphism in the two populations. CONCLUSIONS: The sP-selectin gene polymorphisms are associated with serum sP-selectin levels or thromboembolic events, suggesting that the patients with nonvalvular AF and thromboembolic events may have genetic susceptibility.
Assuntos
Fibrilação Atrial/genética , Predisposição Genética para Doença , Selectina-P/genética , Polimorfismo de Nucleotídeo Único , Tromboembolia/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Fibrilação Atrial/complicações , Fibrilação Atrial/etnologia , Fibrilação Atrial/patologia , Axônios , Sequência de Bases , China , Etnicidade , Feminino , Expressão Gênica , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Selectina-P/sangue , Regiões Promotoras Genéticas , Tromboembolia/complicações , Tromboembolia/etnologia , Tromboembolia/patologiaRESUMO
BACKGROUND: The twin epidemic of overweight/obesity and type 2 diabetes mellitus (T2DM) is a major public health problem globally, especially in China. Overweight/obese adults commonly coexist with T2DM, which is closely related to adverse health outcomes. Therefore, this study aimed to develop risk nomogram of T2DM in Chinese adults with overweight/obesity. METHODS: We used prospective cohort study data for 82938 individuals aged ≥20 years free of T2DM collected between 2010 and 2016 and divided them into a training (n = 58056) and a validation set (n = 24882). Using the least absolute shrinkage and selection operator (LASSO) regression model in training set, we identified optimized risk factors of T2DM, followed by the establishment of T2DM prediction nomogram. The discriminative ability, calibration, and clinical usefulness of nomogram were assessed. The results were assessed by internal validation in validation set. RESULTS: Six independent risk factors of T2DM were identified and entered into the nomogram including age, body mass index, fasting plasma glucose, total cholesterol, triglycerides, and family history. The nomogram incorporating these six risk factors showed good discrimination regarding the training set, with a Harrell's concordance index (C-index) of 0.859 [95% confidence interval (CI): 0.850-0.868] and an area under the receiver operating characteristic curve of 0.862 (95% CI: 0.853-0.871). The calibration curves indicated well agreement between the probability as predicted by the nomogram and the actual probability. Decision curve analysis demonstrated that the prediction nomogram was clinically useful. The consistent of findings was confirmed using the validation set. CONCLUSIONS: The nomogram showed accurate prediction for T2DM among Chinese population with overweight and obese and might aid in assessment risk of T2DM.