We measured plasma‐derived extracellular vesicle (EV) proteins and their microRNA (miRNA) cargos in normoglycemic (NG), glucose intolerant (GI), and newly diagnosed diabetes mellitus (DM) in middle‐aged male participants of the Brazilian Longitudinal Study of Adult Health (ELSA‐Brazil). Mass spectrometry revealed decreased IGHG‐1 and increased ITIH2 protein levels in the GI group compared with that in the NG group and higher serotransferrin in EVs in the DM group than in those in the NG and GI groups. The GI group also showed increased serum ferritin levels, as evaluated by biochemical analysis, compared with those in both groups. Seventeen miRNAs were differentially expressed (DEMiRs) in the plasma EVs of the three groups. DM patients showed upregulation of miR‐141‐3p and downregulation of miR‐324‐5p and ‐376c‐3p compared with the NG and GI groups. The DM and GI groups showed increased miR‐26b‐5p expression compared with that in the NG group. The DM group showed decreased miR‐374b‐5p levels compared with those in the GI group and higher concentrations than those in the NG group. Thus, three EV proteins and five DEMiR cargos have potential prognostic importance for diabetic complications mainly associated with the immune function and iron status of GI and DM patients.
This study explored circulating miRNAs and target genes associated with metabolic syndrome (MetS) and cardiometabolic risk in obese patients. Small-RNA sequencing was used to assess the peripheral blood miRNome of 12 obese subjects (6 MetS and 6 non-MetS). Differentially expressed miRNAs and target genes were further analyzed by qPCR in a larger sample of obese patients (48 MetS and 32 non-MetS). miRNA:mRNA interactions were studied using in silico tools. miRNome analysis identified 10 downregulated miRNAs in MetS compared to non-Met patients (p < 0.05). In silico studies revealed three miRNAs (miR-155, miR-181a, and let-7a) and their predictive targets (CCAAT/enhancer-binding protein beta—CEBPB, KRAS proto-oncogene, GTPase—KRAS and suppressor of cytokine signaling 1—SOCS1) with a potential role in the insulin receptor signaling pathway. miR-155 expression was reduced and CEBPB mRNA levels were increased in MetS patients (p < 0.05), and these effects were correlated with the number of MetS diagnostic criteria (p < 0.05). Increased HOMA-IR (>7.6) was associated with low miR-155 levels, high CEBPB expression, and serum hsCRP (p < 0.05). miR-155 was negatively correlated with CEBPB, HOMA-IR, and plasma fibrinogen, and positively correlated with serum adiponectin (p < 0.05). Downregulation of circulating miR-155 is associated with insulin resistance, poor glycemic control, and increased MetS-related cardiometabolic risk, and these effects are potentially mediated by interaction with CEBPB.
Aim: To explore the association of circulating miRNAs with adiposity, metabolic status and inflammatory biomarkers in patients with metabolic syndrome (MetS). Patients & methods: Serum levels of 372 miRNAs were measured in patients with (n = 6) and without MetS (n = 6) by quantitative PCR array, and dysregulated miRNAs were validated in a larger cohort (MetS, n = 89; non-MetS, n = 144). Results: In the screening study, seven miRNAs were dysregulated in patients with MetS, and miR-421 remained increased in the validation study. miR-421 was associated with a high risk of MetS and insulin resistance and hypertension and correlated with glycated hemoglobin, triacylglycerols, high-sensitivity C-reactive protein, IL-6, resistin and adiponectin (p < 0.05). Conclusion: Circulating miR-421 is a potential biomarker for insulin resistance, metabolic dysregulation and inflammatory status in patients with MetS.
, mais que técnica do laboratório de Biologia Molecular Aplicada ao Diagnóstico da FCF/USP, sempre muito prestativa e paciente com todos os alunos do laboratório. Jéssica Cassilla dos Santos e Juliana de Freitas Germano que são amizades que fiz em São Paulo e no trabalho, que ajudou tanto no desenvolvimento dessa pesquisa na parte técnica e teórica, mas também com sua compreensão e paciência. Ao grande amigo Miguel Elias Farah Filho que apesar de morar na minha cidade natal, até hoje mantem esse companheirismo de um amigo. Ao amigo e Prof. Raimundo Antonio Gomes Oliveira por ter plantado essa semente da pesquisa na minha pessoa e hoje estou conseguindo realizar meu primeiro sonho de muitos que tenho nesse ramo. A amiga e Prof a. Elvira Maria Guerra Shinohara pelos conselhos, carinho e ajuda com suas palavras de apoio. A minha namorada Maylla Rodrigues Lucena e sua família por estar sempre ao meu lado nos momentos difíceis e sempre incentivando para eu nunca desistir dos meus objetivos. Aos meus irmãos Silvana Jozie e José Antonio Filho pela sua compreensão e companheirismo.
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