miR-351 promotes atherosclerosis in diabetes by inhibiting the ITGB3/PIK3R1/Akt pathway and induces endothelial cell injury and lipid accumulation.

BACKGROUND: The miR-351 gene is significantly upregulated in diabetic mice with atherosclerosis. However, the mechanism by which its presence is important for the overall disease has not been elucidated. Therefore, this study will investigate the mechanism of miR-351 in the process of diabetes mellitus with atherosclerosis through miR-351 gene knockout mice. METHODS: In this study, miR-351-/- C57BL/6 mice were first induced to form a type 2 diabetes mellitus model with atherosclerosis by STZ injection and a high-fat diet. Pathological tests (oil red O, HE, and Masson staining) combined with biochemical indices (TC, TG, LDL-C, HDL-C, TNF-α, hs-CRP, NO, SOD, MDA, CAT, and GSH-Px) were performed to evaluate the pathological degree of atherosclerosis in each group. Mouse aortic endothelial cells were treated with oxidized low-density lipoprotein (ox-LDL) and 30 mM glucose to establish a diabetic atherosclerosis cell model. Combined with cell oil red O staining and flow cytometry, the effects of silencing miR-351 on lipid accumulation and cell apoptosis in the diabetic atherosclerosis cell model were determined. Fluorescence in situ hybridization was used to detect the localization and transcription levels of miR-351 in cells. The target genes of miR-351 were predicted by bioinformatics and verified by dual-luciferase activity reporting. Western blotting was used to detect the expression levels of phosphorylated inosine 3-kinase regulatory subunit 1 (PIK3R1)/serine/threonine kinase 1 (Akt) and apoptosis-related proteins after transfection with integrin subunit ß3 (ITGB3) small interfering ribonucleic acid (siRNA). RESULTS: The expression of the miR-351 gene was significantly increased in the high-fat wild-type (HWT) group, and its expression was significantly decreased in the knockout mice. Silencing miR-351 effectively alleviated atherosclerosis in mice. The levels of miR-351 expression, apoptosis, lipid accumulation, and oxidative stress in ox-LDL + high glucose-induced endothelial cells were significantly increased. These phenomena were effectively inhibited in lentivirus-infected miR-351-silenced cell lines. Bioinformatics predicted that miR-351-5p could directly target the ITGB3 gene. Transfection of ITGB3 siRNA reversed the downregulation of apoptosis, decreased oil accumulation, and decreased oxidative stress levels induced by miR-351 silencing. In addition, it inhibited the activation of the PIK3R1/Akt pathway. CONCLUSION: Silencing miR-351 upregulates ITGB3 and activates the PIK3R1/Akt pathway, thereby exerting anti-apoptosis and protective effects on endothelial cells.

Degree of obesity and gastrointestinal adverse reactions influence the weight loss effect of liraglutide in overweight or obese patients with type 2 diabetes.

Background: Liraglutide can effectively reduce the weight of patients with type 2 diabetes. Nonetheless, its weight loss effect was highly heterogeneous in different patients in the clinical practice. Objective: To identify the factors most associated with the weight loss effect of liraglutide in obese or overweight patients with type 2 diabetes with poorly controlled oral medication in northeast China. Design: A prospective study. Methods: A prospective study was performed in subjects with type 2 diabetes who were taking oral medication and had a body mass index (BMI) of ⩾24 kg/m2. Liraglutide was administered for at least 12 weeks, while the original hypoglycemic regimen was kept unchanged (Phase I). Later, liraglutide treatment was continued or stopped as necessary or as subjects thought fit in the 13-52 weeks that followed (Phase II), and the potential factors affecting the effect of weight loss of liraglutide were analyzed. Results: Of the 127 recruited subjects, 90 had comprehensive follow-up data at week 12. In Phase I, the subjects' blood sugar levels and weight decreased significantly(P < 0.001). Among all the significant factors, the gastrointestinal adverse reactions score (GARS) was more correlated with BMI change (ΔBMI; r = 0.43) and waist circumference change (ΔWC; r = 0.32) than the baseline BMI (BMI0) and WC (WC0). At week 12, linear regression showed that BMI0 independently affected ΔBMI and ΔWC, whereas WC0 only affected ΔWC. The GARS was significantly associated with ΔBMI and ΔWC, and this association continued until week 52, even after most subjects had discontinued liraglutide treatment. Conclusion: The degree of obesity and gastrointestinal adverse reactions were the most promising predictors of weight loss in liraglutide treatment.

Effects of n-3 polyunsaturated fatty acid supplementation on pregnancy outcomes: a systematic review and meta-analysis.

Introduction: There are limited studies exploring the effects of n-3 PUFA supplementation on pregnancy outcomes. The goal of this study was to review relevant studies in order to determine the effect of n-3 polyunsaturated fatty acid (n-3 PUFA) supplementation on pregnancy outcomes based on eligible randomized controlled trials (RCTs). Material and methods: Qualified studies were searched by keywords in PubMed, the Cochrane library and Embase. Studies from other pertinent sources were also reviewed, and RCTs published before January 2021 were reviewed. For each study, we assessed and synthesized the outcomes by relative risk (RR) or weighted mean difference (WMD) combined with the 95% confidence interval (95% CI). Results: We included 13 studies with 9069 patients. Compared with the control group, n-3 PUFA significantly decreased the incidence of preterm delivery (RR = 0.898, 95% CI: 0.819-0.984) and low birthweight (RR = 0.797, 95% CI: 0.655-0.970), and increased the birth weight (WMD = 99.340, 95% CI: 10.503-188.177) and birth length (WMD = 0.449, 95% CI: 0.236-0.663). There was no significant difference in pregnancy-induced hypertension, preeclampsia, intrauterine growth retardation (IUIG), early preterm delivery, anti-hypertensive therapy, gestational diabetes or head circumference at birth between the two groups. Conclusions: The available evidence shows that n-3 PUFA is not beneficial in reducing the incidence of maternal pregnancy outcomes such as gestational diabetes mellitus and hypertension; but it is beneficial to neonatal health such as decreasing the incidence of preterm delivery and low birthweight and increasing birth weight and birth length.

Omentin as an Independent Predictor of Metabolic Syndrome and Obesity Among Adolescents in Northeast China.

Purpose: We investigated the association of omentin with metabolic syndrome (MetS), MetS components, and obesity in adolescents. Methods: A total of 742 middle-school students from Liaoyang City were enrolled in this cross-sectional study using the stratified cluster sampling method. Clinical information and blood samples were collected, and serum omentin levels were measured using enzyme-linked immunosorbent assay. Results: Mean plasma omentin levels were lower in male than in female participants (88.25 (interquartile range 63.02-133.61) vs 99.46 (interquartile range 69.08-188.35) ng/L, P = 0.004). The participants were divided into four groups according to the quartile (Q) values of omentin from low to high. With increasing omentin levels from Q1 to Q4, the age of adolescents and the proportion of males gradually increased (P < 0.05), whereas the body mass index (BMI) (P < 0.05) and prevalence of MetS (P > 0.05) tended to decrease. Omentin levels were significantly and negatively correlated with waist circumference and BMI (correlation coefficients of -0.099 and -0.115, respectively). Regression analysis showed that omentin level was independently associated with the risk of MetS (Odds ratio, OR = 0.639, 95% confidence interval, CI (0.432, 0.945)), which was attributed to the association with central obesity (OR = 0.775, 95% CI (0.605, 0.993)) among MetS components. Increased omentin levels also indicated a reduced risk of obesity (OR = 0.700, 95% CI (0.563, 0.870)). Conclusion: Omentin is an independent predictor of MetS and obesity among adolescents in northeast China.

Triglyceride to high-density lipoprotein cholesterol ratio in adolescence as a predictive marker of metabolic syndrome and obesity in early adulthood in China.

OBJECTIVE: To explore serum triglyceride (TG) to high-density cholesterol (HDL-C) ratio as a diagnostic marker of metabolic syndrome (MetS) in adolescents and its efficacy in predicting MetS and obesity in the early adulthood. METHODS: A stratified cluster random sampling method was used to select a total of 935 subjects from senior and junior high schools in Liaoyang, northeast China. The subjects were physically examined and laboratory evaluation was performed. A follow-up examination was performed after 5 years on some (n = 93) of the subjects who had reached adulthood. RESULTS: TG/HDL-C had significantly high diagnostic accuracy for MetS than HOMA-IR, TG or HDL-C. Subjects with the highest TG/HDL-C at baseline had higher risk of MetS (odds ratio [OR] = 11.65) and obesity (OR = 4.32) in early adulthood. CONCLUSION: TG/HDL-C ratio has a strong and independent ability in diagnosing MetS in adolescents and predicting the occurrence of MetS and obesity in their early adulthood.

Association of circulating inflammatory cells and platelets with gestational diabetes and pregnancy outcomes.

Gestational diabetes mellitus (GDM) is the most common cause of hyperglycemia during pregnancy, and its prevalence has increased over the past decades. GDM is directly related to the recent obstetric outcomes and long-term maternal and child health, which can be greatly improved by early identification and diagnosis of GDM. However, the prediction of the disease has always been a difficult problem due to the lack of simple and practical serological markers. Despite the controversy, recent studies have identified that circulating inflammatory cells and platelets, routinely included in the obstetric blood tests, are related to the development of GDM and adverse pregnancy outcomes. In this review, we summarized the studies in this field based on the recent literature. The inflammatory cell components we included were the total number of white blood cells, neutrophils, lymphocytes, monocytes and platelets, which were routinely examined in the blood tests in pregnancy. The aim of this review is not only to enrich our understanding of the pathogenesis of GDM but also to provide evidence for the value of these novel and practical serological markers in early identification of GDM and the prevention and its adverse outcomes.