[Effect of Liraglutide on platelet distribution width and carotid intima-media thickness in type 2 diabetic mellitus patients with obesity].

Objective: To investigate the effect of Liraglutide on platelet distribution width(PDW) and carotid intima-media thickness(cIMT) in type 2 diabetic mellitus patients with obesity. Methods: Randomized controlled trial. A total of 80 type 2 diabetes mellitus (T2DM) obese patients with unsatisfactory glucose control were prospectively enrolled in this study from the Department of Endocrinology of Yuhuangding Hospital Affiliated to Qingdao University from January to December 2021. All the participants were treated with metformin or sulfonylureas. They were randomly divided into two groups: Liraglutide treatment group (Li group, n=40) and Control group (Con group, n=40).The Li group started the treatment with Liraglutide on the basis of the original hypoglycemic agents and the Con group was treated with metformin and sulfonylurea. After 16 weeks of treatment, the changes of PDW, cIMT and body mass index (BMI) in the two groups were observed, multiple linear regression was uesd to analyze the influencing factors of cIMT variation, and the effect of liraglutide on PDW and cIMT in obese patients with type 2 diabetes was analyzed. Results: Finally, 38 patients completed the study in Li group, including 23 males and 15 females, aged 30-69(56±11) years. All 40 patients in Con group completed the study, including 18 males and 22 females, aged 39-67(59±7) years. After 16 weeks of treatment, the levels of PDW and cIMT in Li group were (12.8±1.6) fl and (0.85±0.08) mm, respectively, lower than those before treatment (15.0±1.6) fl and (1.14±0.10) mm (t=18.61 and 20.37, respectively, both P<0.001); The PDW and cIMT in Con group were (13.6±1.5) fl and (1.05±0.10) mm, respectively, lower than those before treatment (15.0±1.5) fl and (1.13±0.13) mm (t=17.42 and 9.65, respectively, both P<0.001). The levels of fasting plasma glucose (FPG) and total cholesterol (TC) in both groups were lower than those before treatment(all P<0.001). After the treatment, the levels of PDW, cIMT, FPG and TC in Li group were lower than those in Con group (all P<0.05). The changes of PDW and cIMT before and after the treatment in Li group were (2.2±0.7) fl and (0.30±0.09) mm, respectively, higher than those in the Con group [(1.4±0.5) fl and (0.09±0.06) mm], with a statistically significant difference (both P<0.001). The changes of FPG and TC in Li group were significantly higher than those in Con group (all P<0.05). Multiple linear regression analysis showed that liraglutide, the changes of TC and systolic blood pressure (SBP) were the influencing factors for the changes of cIMT [ß (95%CI) were 0.20 (0.17-0.23), 0.03 (0.01-0.06), 0.01 (0.00-0.01), respectively, all P<0.05] Conclusion: Liraglutide treatment could reduce PDW and cIMT, thus contributing to cardiovascular benefits.

MiR-296-5p suppresses papillary thyroid carcinoma cell growth via targeting PLK1.

OBJECTIVE: Our study aimed to explore the effects of miRNA-296-5p on the biological behaviors of papillary thyroid carcinoma (PTC) cells and its potential mechanism. PATIENTS AND METHODS: Twenty-eight PTC tissues and the corresponding non-cancerous tissues were collected. Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) analysis was performed to detect the expression levels of miR-296-5p in PTC tissues and the adjacent non-cancerous tissues. Besides, the different endogenous expression levels of miR-296-5p in PTC cell line (K1) and normal thyroid gland cell line (Nthy-ori3-1) were also detected by RT-qPCR. Bioinformatics analysis, Western blot and Dual-Luciferase reporter gene assay were performed to demonstrate whether polo-like kinase 1 (PLK-1) was a downstream target of miR-296-5p. Subsequently, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay, flow cytometry analysis, colony formation assay and TUNEL assay were performed to estimate whether PLK1 down-regulation could attenuate the malignant behaviors of PTC cells in vitro. RESULTS: RT-qPCR results showed that the expression level of miR-296-5p was significantly down-regulated in PTC tissues and cells, indicating that miR-296-5p may participate in PTC development. We predicted target genes of miR-296-5p by bioinformatics and identified PLK1 as a target gene of miR-296-5p. By Western blot and Dual-Luciferase reporter gene assay, we confirmed that miR-296-5p was partially complement to PLKl mRNA 3'UTR sequence and inhibited PLK1 expression at the post-transcriptional level. In vitro experiments suggested that the transfection of miR-296-5p mimics into K1 cells suppressed cell proliferation, inhibited cell clone formation, arrest the cell cycle in G2/M phase and induced apoptosis. Importantly, PLK1 reversed the inhibitory effects of miR-296-5p on biological behaviors of PTC. CONCLUSIONS: MiR-296-5p influences the biological behaviors of PTC by regulating PLK1. These findings provide a new perspective for the molecular mechanism of PTC pathogenesis and also contribute to developing new targets and methods for PTC treatment.