Type 1 diabetes mellitus (T1DM) is an autoimmune disorder resulted from T cell-mediated destruction of pancreatic β-cells, how to regenerate β-cells and prevent the autoimmune destruction of remnant and neogenetic β-cells is a tough problem. Immunomodulatory propertity of mesenchymal stem cell make it illuminated to overcome it. We assessed the long-term effects of the implantation of Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) from the umbilical cord for Newly-onset T1DM. Twenty-nine patients with newly onset T1DM were randomly divided into two groups, patients in group I were treated with WJ-MSCs and patients in group II were treated with normal saline based on insulin intensive therapy. Patients were followed-up after the operation at monthly intervals for the first 3 months and thereafter every 3 months for the next 21 months, the occurrence of any side effects and results of laboratory examinations were evaluated. There were no reported acute or chronic side effects in group I compared with group II, both the HbA1c and C peptide in group I patients were significantly better than either pretherapy values or group II patients during the follow-up period. These data suggested that the implantation of WJ-MSCs for the treatment of newly-onset T1DM is safe and effective. This therapy can restore the function of islet β cells in a longer time, although precise mechanisms are unknown, the implantation of WJ-MSCs is expected to be an effective strategy for treatment of type1 diabetes.

Methyltransferase-like 3 (METTL3), an RNA N6-methyladenosine (m6A) methyltransferase, is essential for the m6A mRNA modification. As a key enzyme of m6A methylation modification, METTL3 has been implicated in immune and inflammation regulation. However, little is known of the role and underlying mechanism of METTL3 in rheumatoid arthritis (RA). The aim of the present study is to elucidate the function and potential mechanism of METTL3 in RA pathogenesis. We used quantitative real-time polymerase chain reaction to detect the expression of METTL3 in RA patients and controls as well as the macrophage cell line. CCK-8 was used for cell proliferation assay. Enzyme-linked immunosorbent assay (ELISA) was adopted to estimate the generation of IL-6 and TNF-α in macrophages. Western blot and immunofluorescence were applied to evaluate the activation of NF-κB in macrophages. The expression of METTL3 was significantly elevated in patients with RA. It was positively associated with CRP and ESR, two common markers for RA disease activity. Besides, LPS could enhance the expression and biological activity of METTL3 in macrophages, while overexpression of METTL3 significantly attenuated the inflammatory response induced by LPS in macrophages. Moreover, the effect of METTL3 on LPS-induced inflammation in macrophages was dependent on NF-κB. This study firstly demonstrates the critical role of METTL3 in RA, which provides novel insights into recognizing the pathogenesis of RA and a promising biomarker for RA.

Currently available studies have suggested that a number of exosome-encapsulated microRNAs (miRNAs) are recognized as stable biomarkers for cancers. However, little is known about the effect of exosomal miRNAs on colorectal cancer (CRC). The aim of study is to identify specific miRNAs in serum exosomes, which may serve as potential diagnostic and prognostic biomarkers and therapeutic targets for CRC. Microarray analyses of miRNAs in serum exosomes from 3 primary CRC patients and 3 healthy controls were performed. Those differentially expressed exosome-encapsulated miRNAs were verified in exosome-enriched serum samples from 77 CRC patients and 20 healthy controls by quantitative real-time PCR (qRT-PCR). A total of 39 aberrantly expressed miRNAs in serum exosomes were identified by microarray analysis. After confirmation by qRT-PCR, we found that 5 exosome-encapsulated miRNAs (miR-638, miR-5787, miR-8075, miR-6869-5p and miR-548c-5p) were significantly down-regulated, while 2 exosome-encapsulated miRNAs (miR-486-5p and miR-3180-5p) were significantly up-regulated in serum. Decreased levels of miR-638 in serum exosomes were associated with increased risk of liver metastasis and later TNM stage of CRC. Networks analyses revealed that 5 aberrantly expressed miRNAs (miR-638, miR-5787, miR-8075, miR-6869-5p, and miR-548c-5p) might be involved in the process of glucose metabolism in CRC. The present study shows the specific serum profile of exosome-encapsulated miRNAs in CRC. Those specific miRNAs in serum exosomes may serve as disease biomarkers and novel therapeutic targets for CRC.

Objective: To assess the effect of long-term exposure to air pollution on type 2 diabetes risk, a meta-analysis of prospective cohort studies was performed. Methods: Literature search was conducted with Pubmed, Embase, and Web of Science for prospective cohort studies investigating the association of type 2 diabetes risk with increments in particulate matter (PM, diameter !2.5 mm (PM2.5) or !10 mm (PM10)) or nitrogen dioxide (NO 2 ). We used a random-effects model to calculate the overall relative risk (RR) with 95% CI. Results: Of 808 identified articles, ten cohort studies were finally included, which involved a total of 2 371 907 participants and 21 095 incident cases of type 2 diabetes. Elevated risk of type 2 diabetes was significantly associated with long-term exposures to high levels of PM2.5 (RRZ1.28, 95% CI 1.06-1.55, PZ0.009, I2 Z83.5%), PM10 (RRZ1.15, 95% CI 1.02-1.30, PZ0.022, I2 Z0%), and NO 2 (RRZ1.12, 95% CI 1.02-1.23, PZ0.015, I 2 Z63.5%). When using standardized risk estimates, the RRs of type 2 diabetes were significant for increments in concentrations of PM2.5 (1.39 per 10 mg/m 3 increment, 95% CI 1.14-1.68, PZ0.001), PM10 (1.34 per 10 mg/m 3 increment, 95% CI 1.22-1.47, P!0.001), and NO 2 (1.11 per 10 mg/m 3 increment, 95% CI 1.07-1.16, P!0.001). No obvious evidence of publication bias was observed. Conclusion: Long-term exposure to high levels of main air pollutants is significantly associated with elevated risk of type 2 diabetes mellitus.

Currently available studies have implicated that exosome-delivered microRNAs (miRNAs) play crucial roles in human cancer. However, the association of serum exosomal miR-638 and hepatocellular carcinoma (HCC) remains largely unknown. We aim to investigate the expression of exosomal miR-638 in serum of HCC patients and its prognostic role in this deadly disease. Kaplan-Meier and Cox regression analyses were used to determine the survival of patients histologically diagnosed with HCC. Reduced levels of exosomal miR-638 in serum samples from patients with HCC were identified by real-time PCR. Negative association of serum exosomal miR-638 with tumor size, vascular infiltration, and TNM stage was observed in HCC patients. Besides, the proliferation of Huh7 and SMCC7721 HCC cells were significantly inhibited when miR-638 was over-expressed in these cells. In addition, HCC patients with lower levels of serum exosomal miR-638 had poor overall survival than those with higher levels of exosomal miR-638 in serum. Our study strongly suggests that serum exosome-delivered miR-638 may serve as a novel circulating biomarker for HCC. Downregulation of miR-638 predicts poor prognosis for patients with HCC.