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Vitamin D deficiency (VDD) is associated with increased risk of type 2 diabetes mellitus (T2DM) and insulin resistance (IR). We aimed to investigate the association between the triglyceride-glucose (TyG) index that represents IR and VDD in elderly patients with T2DM. We enrolled 572 elderly participants with T2DM in this study. TyG index was calculated as ln [fasting triglyceride (TG, mg/dL) × fasting blood glucose (mg/dL)/2]. Serum 25-hydroxyvitamin D [25(OH)D] level below 50 nmol/L was defined as VDD. The association between the TyG index and the VDD risk was evaluated by multivariate logistic regression analysis. We observed a significant decreased 25(OH)D level with the increase of the TyG index in elderly diabetic patients, and a negative correlation between the TyG index and 25(OH)D level. The participants in the highest TyG quartile had a 2.40-fold higher risk of VDD than those in the lowest TyG index quartile [OR 2.40; 95% CI 1.47–3.92; P  < 0.001]. The association persisted after adjustments for age, sex, smoking, obesity, insulin therapy, hypoglycemic agents’ medication, and some biochemical parameters. TyG index may be involved in the pathophysiology of VDD, which could be a predictor for VDD in elderly diabetic patients.

Background: Vitamin D deficiency (VDD) increases the risk for type 2 diabetes mellitus (T2DM), which might be related to insulin resistance (IR). We aimed to explore the association between the triglyceride-glucose (TyG) index, a reliable indicator of IR, and VDD in patients with T2DM. Methods: There were 1034 participants with T2DM enrolled in the Second Xiangya Hospital of Central South University. The TyG index was calculated as ln (fasting triglyceride (TG, mg/dL) × fasting blood glucose (mg/dL)/2). VDD was defined as 25-hydroxyvitamin D [25(OH)D] level <50 nmol/L. Results: Correlation analysis showed a negative association between the TyG index and 25(OH)D level. After adjustments for clinical and laboratory parameters, it was revealed that when taking the Q1 quartile of TyG index as a reference, an increasing trend of VDD prevalence was presented in the other three groups divided by TyG index quartiles, where the OR (95% CI) was 1.708 (1.132–2.576) for Q2, 2.041 (1.315–3.169) for Q3, and 2.543 (1.520–4.253) for Q4 (all p < 0.05). Conclusions: Patients with higher TyG index were more likely to have an increased risk of VDD in T2DM population, which may be related to IR.

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Objective. The P2Y6 receptor has been shown to be involved in many cardiovascular diseases, including hypertension and atherosclerosis. The study is aimed at exploring the role of the P2Y6 receptor in Ang II-induced abdominal aortic aneurysm (AAA) formation in apolipoprotein E-deficient (apoE-/-) mice by using its selective antagonist. Methods. Male apoE-/- mice were fed with high-fat diet and infused with angiotensin (Ang) II (1000 ng/kg/min) for 4 weeks to induce AAA or saline as controls. Mice were divided into four groups: normal saline (NS, placebo control) group (n=8), Ang II+vehicle (Ang II) group (n=14), Ang II-low dose MRS2578 (Ang II+MRS-16 mg) group (n=14), and Ang II-high dose MRS2578 (Ang II+MRS-32 mg) group (n=14). Daily intraperitoneal injection with vehicle or MRS2578 was pretreated one week before Ang II infusion. On postoperative day 10, aorta imaging of each group was taken by ultrasonography. After 4 weeks of Ang II infusion, the excised aortas were processed for diameter measurement and quantification of aneurysm severity and tissue characteristics; the blood samples were collected for measurement of the lipid profile and levels of cytokines. Verhoeff’s Van Gieson (EVG) staining and immunochemistry staining were performed to evaluate disruption of the extracellular matrix (ECM) and infiltration of macrophages. Expression and activity of matrix metalloproteinases (MMPs) was measured by gelatin zymography. Results. Treatment with MRS2578 made no significant difference in AAA formation, and maximal aortic diameter yet caused higher AAA rupture-induced mortality from 7% (Ang II) to 21.4% (Ang II+MRS-16 mg) or 42.9% (Ang II+MRS-32 mg), respectively (p<0.05). Consistently, the severity of aneurysm tended to be more deteriorated in MRS2578-treated groups, especially the high-dosage group. The ratios of type III and IV aneurysm were much higher in the MRS2578-coadministered groups (p<0.05). Furthermore, histological analyses showed that administration of MRS2578 significantly increased infiltration of macrophages, expression of monocyte chemotactic protein 1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1), and activities of MMP-2 and MMP-9 followed by aggravating degradation elastin in vivo (p<0.05). However, the multiple effects of MRS2578 on the development of AAA are independent of changes in systolic blood pressure and lipid profiles. Conclusions. The present study demonstrated that administration of MRS2578 exacerbated the progression and rupture of experimental AAA through promoting proinflammatory response and MMP expression and activity, which indicated a crucial role of the P2Y6 receptor in AAA development. Clinical Relevance. Purinergic P2Y receptors have attracted much attention since the P2Y12 receptor antagonist had been successfully applied in clinical practice. Elucidating the underlying mechanisms of AAA and exploring potential therapeutic strategies are essential to prevent its progression and reduce the mortality rate.

In the article titled “The Role of a Selective P2Y6 Receptor Antagonist, MRS2578, on the Formation of Angiotensin II-Induced Abdominal Aortic Aneurysms” [1], there was an error in affiliation numbers 1 and 2. The address line of “The Second Xiangya Hospital” was missing in both affiliations. This error was introduced during the production of the article, and the publisher apologises for this error. The corrected affiliations appear in the affiliation list.

BackgroundHeart failure with preserved ejection fraction (HFpEF) is common, yet there is a lack of effective treatments. In this meta-analysis, we assessed the efficacy and safety of inorganic nitrate in patients with HFpEF.Methods and ResultsWe systematically searched PubMed, Embase, and the Cochrane Library from the inception of the database through March 2020. We included randomized controlled trials that compared the efficacy and safety of inorganic nitrate with a placebo in the treatment of patients with HFpEF. The primary outcome of the meta-analysis was exercise capacity (measured as a change in peak oxygen uptake). We also assessed the effect of inorganic nitrate on diastolic function (measured as changes in E/A and E/e’, assessed by echocardiography), quality of life (estimated using the Kansas City Cardiomyopathy Questionnaire), and rest and exercise hemodynamics (measured by invasive cardiac catheterization). In the pooled data analysis, there were no significant differences in peak oxygen uptake (mL/kg/min) [mean difference (MD), 0.25; 95% CI, − 0.07 to 0.57], diastolic function [E/A–standardized mean difference (SMD), 0.51; 95% CI, − 0.17 to 1.20; or E/e’–SMD, 0.02; 95% CI, − 0.23 to 0.27], or quality of life. However, a significant change was observed in the rest and exercise hemodynamics between the inorganic nitrate and placebo treatment in HFpEF patients. No study has reported the effect of inorganic nitrate on hospitalization and mortality of patients with HFpEF.ConclusionsIn patients with HFpEF, the use of inorganic nitrate is not associated with improvements in exercise capacity, diastolic function, and quality of life but is associated with significant changes in rest and exercise hemodynamics.

Background It has been demonstrated that soluble epoxide hydrolase inhibitors (sEHIs) are protective against ischemia-induced lethal arrhythmias, but the mechanisms involved are unknown. Previously, we showed that sEHIs might reduce the incidence of ischemic arrhythmias by suppressing microRNA-1 (miR-1) in the myocardium. As miR-1 and miR-133 have the same proarrhythmic effects in the heart, we assumed that the beneficial effects of sEHIs might also relate to the regulation of miR-133. Methods A mouse model of myocardial infarction (MI) was established by ligating the coronary artery. The sEHI t-AUCB (trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid) was administered daily for 7 days before MI. Myocardial infarct size and cardiac function was assessed at 24 h post-MI. The miRNA expression profiles of sham and MI mice treated with or without t-AUCB were determined by microarray and verified by real-time PCR. The incidence of arrhythmias was assessed by in vivo electrophysiologic studies. The mRNA levels of miR-133, its target genes ( KCNQ1 [potassium voltage-gated channel subfamily Q member 1] and KCNH2 [potassium voltage-gated channel subfamily H member 2]), and serum response factor ( SRF ) were measured by real-time PCR; KCNQ1 , KCNH2 , and SRF protein levels were assessed by western blotting. Results We demonstrated that the treatment with sEHIs could reduce infarct size, improve cardia function, and prevent the development of cardiac arrhythmias in MI mice. The expression levels of 14 miRNAs differed between the sham and MI groups. t-AUCB treatment altered the expression of eight miRNAs: two were upregulated and six were downregulated. Of these, the muscle-specific miR-133 was downregulated in the ischemic myocardium. In line with this, up-regulation of miR-133 and down-regulation of KCNQ1 and KCNH2 mRNA/protein were observed in ischemic myocaridum, whereas administration of sEHIs produced an opposite effect. In addition, miR-133 overexpression inhibited expression of the target mRNA, whereas t-AUCB reversed the effects. Furthermore, SRF might participate in the negative regulation of miR-133 by t-AUCB. Conclusions In MI mice, sEHI t-AUCB can repress miR-133, consequently stimulating KCNQ1 and KCNH2 mRNA and protein expression, suggesting a possible mechanism for its potential therapeutic application in ischemic arrhythmias.

Long noncoding RNAs (lncRNAs) are emerging regulators of vascular diseases, yet their role in diabetic vascular calcification/aging remains poorly understood. In this study, we identified a down-expressed lncRNA SNHG1 in high glucose (HG)-induced vascular smooth muscle cells (HA-VSMCs), which induced excessive autophagy and promoted HA-VSMCs calcification/senescence. Overexpression of SNHG1 alleviated HG-induced HA-VSMCs calcification/senescence. The molecular mechanisms of SNHG1 in HA-VSMCs calcification/senescence were explored by RNA pull-down, RNA immunoprecipitation, RNA stability assay, luciferase reporter assay, immunoprecipitation and Western blot assays. In one mechanism, SNHG1 directly interacted with Bhlhe40 mRNA 3′-untranslated region and increased Bhlhe40 mRNA stability and expression. In another mechanism, SNHG1 enhanced Bhlhe40 protein SUMOylation by serving as a scaffold to facilitate the binding of SUMO E3 ligase PIAS3 and Bhlhe40 protein, resulting in increased nuclear translocation of Bhlhe40 protein. Moreover, Bhlhe40 suppressed the expression of Atg10, which is involved in the process of autophagosome formation. Collectively, the protective effect of SNHG1 on HG-induced HA-VSMCs calcification/senescence is accomplished by stabilizing Bhlhe40 mRNA and promoting the nuclear translocation of Bhlhe40 protein. Our study could provide a novel approach for diabetic vascular calcification/aging.