Evaluation of Serum microRNAs in Patients with Diabetic Kidney Disease: A Nested Case-Controlled Study and Bioinformatics Analysis.

BACKGROUND Diabetic kidney disease (DKD) can result in end-stage kidney disease and renal failure. This study aimed to examine the expression of serum microRNAs (miRNAs), miR-20a, miR-99b, miR-122-5p, and miR-486-5p, and to use bioinformatics data to investigate the pathways involved in DKD. MATERIAL AND METHODS Serum miRNAs were obtained from 25 healthy volunteers, 50 patients with non-complicated type 2 diabetes mellitus (T2DM), and 42 patients with T2DM and DKD. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of serum miRNAs. Specificity and sensitivity of the association between serum miRNAs in DKD were evaluated by analysis of the receiver operating characteristic (ROC) area under the curve (AUC). Serum miRNAs and clinical parameters of the patients were compared. Bioinformatics data analysis accessed the miRNA targets involved in the pathways related to the pathogenesis of DKD. RESULTS Serum levels of miR-99b and miR-122 significantly increased, and mir-20a and miR-486 decreased in the DKD group compared with healthy controls. Serum levels of miR-20a, miR-99b, miR-486-5p, and miR-122-5p were significantly correlated with albuminuria, estimated glomerular filtration rate (eGFR), blood glucose and lipid profiles. ROC curve analysis showed that diagnostic accuracy of serum levels of miR-99b for DKD was superior to miR-486-5p, miR-122-5p, and miR-20a, resulting in AUCs of 0.895, 0.853, 0.80, and 0.697, respectively. These four miRNAs regulate several genes affecting oxidative stress, inflammation, and apoptosis. CONCLUSIONS Serum miR-99b, miR-486-5p, miR-122-5p, and miR-20a were differentially expressed in patients with T2DM and DKD and should be evaluated further as potential biomarkers for DKD.

High fat-induced inflammation in vascular endothelium can be improved by Abelmoschus esculentus and metformin via increasing the expressions of miR-146a and miR-155.

BACKGROUND: Obesity is associated with chronic inflammation, which contributes to cardiovascular diseases. MicroRNAs (miRNAs) are reported to be involved in vascular inflammation and atherosclerosis. Abelmoschus esculentus (AE) and metformin have been suggested to improve inflammation in vascular system. The aim of this study is to evaluate whether miRNAs are involved in high fat induced endothelial inflammation, and whether AE and metformin improve endothelial inflammation by regulating miRNAs. METHODS: We established high fat treated rats and human aortic endothelial cells (HAECs). AE and metformin were added to explore their effects on endothelial inflammation induced by high fat and the possible mechanism. RESULTS: The vascular inflammatory genes were increased in rats treated with high fat diet. The decreased miR-146a and miR-155 were involved in endothelial inflammation induced by high fat through targeting IL-1 receptor-associated kinase 1 (IRAK1), TNF receptor-associated factor 6 (TRAF6) and nuclear factor-κB p65 (NF-κB p65), respectively. While AE and metformin could ameliorate the endothelial inflammation by increasing miR-146a and miR-155. CONCLUSIONS: These results indicate that miR-146a and miR-155 play roles in the high fat induced endothelial inflammation, which could be potential therapeutic targets. AE and metformin can attenuate endothelial inflammation through regulating miR-146a and miR-155.

Low-glycemic index diets as an intervention for diabetes: a systematic review and meta-analysis.

BACKGROUND: Low-glycemic index (GI) diets are thought to reduce postprandial glycemia, resulting in more stable blood glucose concentrations. OBJECTIVE: We hypothesized that low-GI diets would be superior to other diet types in lowering measures of blood glucose control in people with type 1 or type 2 diabetes, or impaired glucose tolerance. METHODS: We searched PubMed, the Cochrane Library, EMBASE, and clinical trials registries for published and unpublished studies up until 1 March, 2019. We included 54 randomized controlled trials in adults or children with impaired glucose tolerance, type 1 diabetes, or type 2 diabetes. Continuous data were synthesized using a random effects, inverse variance model, and presented as standardized mean differences with 95% CIs. RESULTS: Low-GI diets were effective at reducing glycated hemoglobin (HbA1c), fasting glucose, BMI, total cholesterol, and LDL, but had no effect on fasting insulin, HOMA-IR, HDL, triglycerides, or insulin requirements. The reduction in fasting glucose and HbA1c was inversely correlated with body weight. The greatest reduction in fasting blood glucose was seen in the studies of the longest duration. CONCLUSIONS: Low-GI diets may be useful for glycemic control and may reduce body weight in people with prediabetes or diabetes.

In Silico Integration Approach Reveals Key MicroRNAs and Their Target Genes in Follicular Thyroid Carcinoma.

To better understand the molecular mechanism for the pathogenesis of follicular thyroid carcinoma (FTC), this study aimed at identifying key miRNAs and their target genes associated with FTC, as well as analyzing their interactions. Based on the gene microarray data GSE82208 and microRNA dataset GSE62054, the differentially expressed genes (DEGs) and microRNAs (DEMs) were obtained using R and SAM software. The common DEMs from R and SAM were fed to three different bioinformatic tools, TargetScan, miRDB, and miRTarBase, respectively, to predict their biological targets. With DEGs intersected with target genes of DEMs, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed through the DAVID database. Then a protein-protein interaction (PPI) network was constructed by STRING. Finally, the module analysis for PPI network was performed by MCODE and BiNGO. A total of nine DEMs were identified, and their function might work through regulating hub genes in the PPI network especially KIT and EGFR. KEGG analysis showed that intersection genes were enriched in the PI3K-Akt signaling pathway and microRNAs in cancer. In conclusion, the study of miRNA-mRNA network would offer molecular support for differential diagnosis between malignant FTC and benign FTA, providing new insights into the potential targets for follicular thyroid carcinoma diagnosis and treatment.

Association between the expression of vascular endothelial growth factors and metabolic syndrome or its components: a systematic review and meta-analysis.

BACKGROUND: Several studies have linked vascular endothelial growth factors (VEGFs) with metabolic syndrome or its components. However, there has been no systematic appraisal of the findings of these studies to date. The current systematic review and meta-analysis was conducted to explore this association. METHODS: PubMed, EMBASE, the Cochrane library, and clinical trials registries were used to retrieve peer-reviewed clinical studies that had evaluated the association of VEGFs with metabolic syndrome or its components without applying language and date restrictions. The final search was performed on 29 September 2017. RESULTS: We included 32 studies in this systematic review and meta-analysis, of which 16 studies (19 study arms) were included in the meta-analysis and remaining studies were qualitatively assessed. Overall, VEGF-A, VEGF-B and VEGF-C were strongly associated with metabolic syndrome or its components. The components of metabolic syndrome varied in their association. Obesity was not correlated with increased VEGF-A expression (p = 0.12), whereas VEGF-B and VEGF-C expression was significantly higher in those with obesity. In contrast, hyperglycemia in type 1 diabetes was strongly associated with increased VEGF-A levels (p < 0.00001), as was type 2 diabetes (p = 0.0006). The studies included in the qualitative analysis similarly showed an increase in VEGF family expression in people with metabolic syndrome, and with its components. CONCLUSION: The increased concentrations of vascular endothelial growth factors are variably associated with metabolic syndrome or its components. Each VEGF protein has a unique set of associations with the disease state.

The role of vascular endothelial growth factor-B in metabolic homoeostasis: current evidence.

It has been shown that adipose tissue and skeletal muscles in lean individuals respond to meal-induced hyperinsulinemia by increase in perfusion, the effect not observed in patients with metabolic syndrome. In conditions of hyperglycaemia and hypertriglyceridemia, this insufficient vascularization leads to the liberation of reactive oxygen species (ROS), and disruption of nitric oxide (NO) synthesis and endothelial signalling responsible for the uptake of circulating fatty acids (FAs), whose accumulation in skeletal muscles and adipose tissue is widely associated with the impairment of insulin signalling. While the angiogenic role of VEGF-A and its increased circulating concentrations in obesity have been widely confirmed, the data related to the metabolic role of VEGF-B are diverse. However, recent discoveries indicate that this growth factor may be a promising therapeutic agent in patients with metabolic syndrome. Preclinical studies agree over two crucial metabolic effects of VEGF-B: (i) regulation of FAs uptake and (ii) regulation of tissue perfusion via activation of VEGF-A/vascular endothelial growth factor receptor (VEGFR) 2 (VEGFR2) pathway. While in some preclinical high-fat diet studies, VEGF-B overexpression reverted glucose intolerance and stimulated fat burning, in others it further promoted accumulation of lipids and lipotoxicity. Data from clinical studies point out the changes in circulating or tissue expression levels of VEGF-B in obese compared with lean patients. Potentially beneficial effects of VEGF-B, achieved through enhanced blood flow (increased availability of insulin and glucose uptake in target organs) and decreased FAs uptake (prevention of lipotoxicity and improved insulin signalling), and its safety for clinical use, remain to be clarified through future translational research.

Globalisation and income growth promote the Mediterranean diet.

OBJECTIVE: To examine global food demand patterns and how changing diets may stimulate demand for and trade of Mediterranean diet products. DESIGN: Literature review. Trends in global and US food consumption patterns are examined and trade data are reviewed to evaluate the impact of changing diets on trade of Mediterranean diet products. Market access issues are also addressed briefly to highlight the role of policy in the trade of Mediterranean diet products. RESULTS: Diets are shifting towards higher-value products such as meats, fruits and vegetables, and a wider array of packaged food products. Trade in these products has also grown in the past two decades, with several non-traditional importers and exporters becoming increasingly active in the global market. CONCLUSIONS: Income-driven demands for quality and variety are likely to increase the demand for Mediterranean diet products globally. While the middle-income countries appear to be the best growth prospects, the USA remains a potential growth market if these products can meet the growing consumer demand for variety, quality and convenience. Although consumer trends globally indicate growth in demand for Mediterranean diet products, the additional demand may not be reflected by a corresponding growth in trade. Trade in Mediterranean diet products continues to be hampered by higher than average trade barriers and high transportation costs for perishables.