The present meta-analysis revealed that 16 stress-related miRNAs were significantly dysregulated in T2DM. MiR-148b, miR-223, miR-130a, miR-19a, miR-26b and miR-27b were selected as potential circulating biomarkers of T2DM. In addition, miR-146a and miR-21 were identified as potential tissue biomarkers of T2DM.
Quercetin, a dietary flavonol, has been used as potential ingredient in food supplements to promote health. Its health effects are closely related to its bioavailability and further depend on its absorption, metabolism and excretion in vivo. Here, we systematically summarized the absorption and metabolism of quercetin in human intestine, liver, and kidney, highlighting the transport and metabolic pathways, intermediate metabolites, and circulation channels involving quercetin. The bioactivities of quercetin on theintestine, liver, and kidney were also considered. In general, except for passive diffusion, different transporters (e.g., SGLT1,OATPs, and MRPs) participate in the transport of quercetin and its metabolites across biological barriers. Quercetin undergoes phase II metabolism after absorption by the intestine and is finally excreted into bile through liver or urine through kidney. Quercetin can protect the intestinal barrier and modulate the microflora. Moreover, its antioxidant, anti-inflammatory, and anti-fibrotic activities protect the liver and kidney.
BackgroundChronic stress plays an important role in the development of type 2 diabetes mellitus (T2DM) and insulin resistance (IR). MicroRNAs (miRNAs) play key roles in mediating stress responses by regulating the expression of target genes. This study systematically screened and identified the neuroendocrine stress response-related circulating miRNAs which are associated with T2DM and IR.MethodsBased on the differential plasma expression profiles between individuals with and without T2DM, stress-related miRNAs were selected from those differently expressed miRNAs whose targets are involved in known neuroendocrine pathway of stress response. Candidate miRNAs were further validated by quantitative real-time polymerase chain reaction in a large sample, including 112 T2DM patients, 72 individuals with impaired fasting glucose (IFG), and 94 healthy controls. The association between miRNA expression and potential risk of T2DM and IFG was assessed by multivariate logistic regression models. The miRNA predictors of IR were identified by stepwise multiple regression analysis. The diagnostic performance for T2DM was evaluated by area under the curve (AUC) of receiver operating characteristic (ROC).Resultslet-7b, let-7i, miR-142, miR-144, miR-155, and miR-29a were selected as candidate miRNAs for validation. Increased expression of let-7b, miR-144, and miR-29a and decreased expression of miR-142 were significant independent predictors of T2DM, IFG, and IR (P < 0.0125). These miRNAs significantly correlated with stress hormone levels (P < 0.0125). A three-miRNA panel, including let-7b, miR-142, and miR-144 had a high accuracy for diagnosing T2DM (AUC = 0.871, 95% CI: 0.822–0.919).Conclusionlet-7b, miR-142, miR-144, and miR-29a in plasma may be important markers of neuroendocrine stress response and may play a role in the pathogenesis of T2DM and IR.
Chronic stress may facilitate the development of metabolic disorders including insulin resistance (IR) and type 2 diabetes mellitus (T2DM). MiR‐18a and miR‐34c modulate central cell responsiveness to stress by targeting glucocorticoid receptor (GR) and corticotropin‐releasing factor receptor type 1 (CRFR1) mRNA, which are important regulators of the hypothalamus–pituitary–adrenal (HPA) axis. This study explored the relationship between T2DM/IR and expression of miR‐18a and miR‐34c in peripheral blood mononuclear cells (PBMCs) in an occupational sample. Three groups of study subjects were involved, including T2DM patients, impaired fasting glucose (IFG) individuals and healthy controls. The degree of IR was determined using the homoeostasis model assessment of insulin resistance (HOMA‐IR). The expression of miR‐18a and miR‐34c in PBMCs was evaluated by quantitative reverse transcription polymerase chain reaction (qRT‐PCR). Expression levels of miR‐18a and miR‐34c were significantly correlated with cortisol, corticotropin‐releasing factor (CRF) and interleukin 6 (IL‐6) (P < 0.05). The increased levels of miR‐18a were associated with risk of T2DM (adjusted OR = 1.48, 95% CI: 1.25–1.75, P < 0.001) and IFG (adjusted OR = 1.33, 95% CI: 1.09–1.63, P = 0.005). By contrast, the decreased levels of miR‐34c were associated with risk of T2DM (adjusted OR = 0.81, 95% CI: 0.75–0.88, P < 0.001) and IFG (adjusted OR = 0.87, 95% CI: 0.81–0.94, P < 0.001). After adjusting for potential confounders, miR‐18a and miR‐34c were independent positive and negative predictors of HOMA‐IR, respectively (P < 0.001). The miRNA panel with the two miRNAs demonstrated high accuracy in the diagnosis of T2DM (AUC = 0.851, 95% CI: 0.786–0.800, P < 0.001). MiR‐18a and miR‐34c in PBMCs may be important marker of stress reaction and may play a role in vulnerability to T2DM as well as IR.
Aim: To explore the relationship between lipometabolism-related microRNAs (miRNAs) in peripheral blood mononuclear cells (PBMCs) and the presence of coronary artery disease (CAD).Methods: In the present study, 161 stable CAD patients and 149 health controls were enrolled. The expression levels of seven miRNAs (miR-21, miR-24, miR-29a, miR-33a, miR-34a, miR-103a, and miR-122) in PBMCs were qualified by quantitative real-time polymerase chain reaction (qRT-PCR). The miRNA markers that showed significant difference between the two groups were used for further analysis. The risk of miRNA contributing to the presence of CAD was estimated by univariate and multivariate logistic regression models. The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy.Results: The expression levels of miR-24, miR-33a, miR-103a, and miR-122 in PBMCs were significantly increased in CAD patients compared with controls and were significantly correlated with blood lipids in both CAD patients and controls. The increased levels of miR-24 (adjusted OR = 1.32, 95% CI 1.07–1.62, P = 0.009), miR-33a (adjusted OR = 1.57, 95% CI 1.35–1.81, P < 0.001), miR-103a (adjusted OR = 1.01, 95% CI 1.01–1.02, P < 0.001), and miR-122 (adjusted OR = 1.03, 95% CI 1.01–1.04, P < 0.001) were associated with risk of CAD. We identified a miRNA panel (miR-24, miR-33, miR-103a, and miR-122) that provided a high diagnostic accuracy of CAD (AUC= 0.911, 95% CI 0.880–0.942).Conclusion: The increased expression levels of miR-24, miR-33a, miR-103a, and miR-122 in PBMCs are associated with risk of CAD. A panel of the four miRNAs has considerable clinical value in diagnosing stable CAD.
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