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BackgroundIncreasing evidence shows that alterations in gut microbiome (GM) contribute to the development of type 2 diabetes mellitus (T2DM), and fecal microbiota transplantation (FMT) successfully treats various human diseases. However, the benefits of FMT therapy to T2DM patients remain unknown.MethodsWe enrolled 17 patients with T2DM for nonblinded, one-armed intervention trial of FMT. A total of 20 healthy individuals were recruited as the baseline control. HbA1c% and metabolic parameter change were evaluated in 17 T2DM patients 12 weeks after they received FMT from healthy donors. The GM composition was characterized by 16S rRNA gene amplicon sequencing from fecal samples prior to and 12 weeks after FMT treatment.ResultsWe found that the GM of T2DM patients was reconstituted by FMT. We observed a statistically significant decrease in HbA1c% (from 7.565 ± 0.148 to 7.190 ± 0.210, p

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are critical processes that are involved in atherosclerosis. The aim of this study was to explore the role of microRNA-491-5p (miR-491-5p) in the progression of atherosclerosis by regulating the growth and migration of VSMCs. In this study, we showed that the expression of miR-491-5p was downregulated in the atherosclerotic plaque tissues and plasma samples of the patients with atherosclerosis. The bioinformatic analysis and dual-luciferase reporter assay identified that matrix metallopeptidase-9 (MMP-9) was a target gene of miR-491-5p. The results showed a significant upregulation of MMP-9 in the atherosclerotic plaque tissues and plasma samples. Subsequently, the results also showed that downregulation of miR-491-5p significantly promoted the proliferation and migration of VSMCs and inhibited the apoptosis in VSMCs. Furthermore, we detected the effects of miR-491-5p mimic on the growth and migration of VSMCs, and the results illustrated that miR-491-5p mimic could inhibit the proliferation and migration of VSMCs and promote the apoptosis of VSMCs. Notably, MMP-9 plasmid could reverse all the effects of miR-491-5p mimic on VSMCs. Collectively, our study provides the first evidence that miR-491-5p inhibited the growth and migration of VSMCs by targeting MMP-9, which might provide new biomarkers and potential therapeutic targets for atherosclerosis treatment.

Objective To systematically evaluate the efficacy and safety of insulin Icodec in the treatment of type 2 diabetes mellitus (T2DM) in order to provide evidence-based guidance for the rational clinical use of drug. Methods The databases of PubMed, Embase, Cochrane Library, Web of Science, Sinomed, CNKI, Wanfang and VIP were searched by computer to identify randomized controlled trials (RCT) comparing the efficacy and safety of insulin Icodec (trial group) versus placebo or other hypoglycemic agents (control group) in the treatment of T2DM were collected from the date of database inception to August 2023. The efficacy indexes included: glycated hemoglobin A1c (HbA1c) level, HbA1c compliance rate (HbA1c<7%), fasting plasma glucose (FPG) level, body weight level, time in range (TIR) percentage. Safety indicators included: incidence of hypoglycemia events, incidence of injection site reactions, incidence of drug allergic reactions, and incidence of serious adverse events. Two evaluators independently screened the literature, extracted data from the literature and assessed the risk of bias of the studies included, and performed a meta-analysis of the data using RevMan 5.4 software. Results Seven studies with a total of 3 286 patients were included. The results of meta-analysis showed that compared with the control group, insulin Icodec reduced HbA1c (WMD=-0.16%, 95%CI -0.26%-0.07%, P<0.01), increased the rate of HbA1c compliance (OR=1.50, 95%CI 1.29-1.74, and decreased HbA1c compliance (WMD=-0.16%, 95%CI -0.26%-0.07%, P<0.01). However, there was no statistically significant difference between the two groups in reducing FPG levels (WMD=-0.05 mmol/L, 95%CI -0.29-0.20 mmol/L, P=0.71), and it increased the body weight of patients (WMD=0.52 kg, 95%CI 0.22-0.82 kg, P<0.01), but increased the percentage of TIR in patients (WMD=5.86%, 95%CI 2.02%-9.70%, P=0.003). In terms of safety, although the incidence of hypoglycemic events (OR=1.37, 95%CI 1.17-1.61, P<0.01) was higher in the insulin Icodec group than in the control group, the incidence of anaphylaxis was higher in insulin Icodec group than in the control group (OR=0.91, 95%CI 0.64-1.31, P=0.62), injection site reaction (OR=1.03, 95%CI 0.63-1.66, P=0.92) and incidence of serious adverse events (OR=0.97, 95%CI 0.75-1.24, P=0.79), there was no significant difference between insulin Icodec and control groups. Conclusions Insulin Icodec can lower HbA1c levels in patients and increase the rate of HbA1c compliance without increasing the incidence of injection site reactions, allergic events and serious adverse events. [ABSTRACT FROM AUTHOR]