Role of mesenchymal stem cell derived extracellular vesicles in autoimmunity: A systematic review.

BACKGROUND: Mesenchymal stem cells (MSCs) have been reported to possess immune regulatory effects in innate and adaptive immune reactions. MSCs can mediate intercellular communications by releasing extracellular vesicles (EVs), which deliver functional molecules to targeted cells. MSC derived EVs (MSC-EVs) confer altering effects on many immune cells, including T lymphocytes, B lymphocytes, natural killer cells, dendritic cells, and macrophages. A large number of studies have suggested that MSC-EVs participate in regulating autoimmunity related diseases. This characteristic of MSC-EVs makes them be potential biomarkers for the diagnosis and treatment of autoimmunity related diseases. AIM: To verify the potential of MSC-EVs for molecular targeted therapy of autoimmunity related diseases. METHODS: Literature search was conducted in PubMed to retrieve the articles published between 2010 and 2020 in the English language. The keywords, such as "MSCs," "EVs," "exosome," "autoimmunity," "tumor immunity," and "transplantation immunity," and Boolean operator "AND" and "NOT" coalesced admirably to be used for searching studies on the specific molecular mechanisms of MSC-EVs in many immune cell types and many autoimmunity related diseases. Studies that did not investigate the molecular mechanisms of MSC-EVs in the occurrence and development of autoimmune diseases were excluded. RESULTS: A total of 96 articles were chosen for final reference lists. After analyzing those publications, we found that it had been well documented that MSC-EVs have the ability to induce multiple immune cells, like T lymphocytes, B lymphocytes, natural killer cells, dendritic cells, and macrophages, to regulate immune responses in innate immunity and adaptive immunity. Many validated EVs-delivered molecules have been identified as key biomarkers, such as proteins, lipids, and nucleotides. Some EVs-encapsulated functional molecules can serve as promising therapeutic targets particularly for autoimmune disease. CONCLUSION: MSC-EVs play an equally important part in the differentiation, activation, and proliferation of immune cells, and they may become potential biomarkers for diagnosis and treatment of autoimmunity related diseases.

MicroRNA-15b suppresses the growth and invasion of glioma cells through targeted inhibition of cripto-1 expression.

Gliomas are the most common type of malignant brain tumor. Studies have identified that miR­15b is negatively correlated with cripto-1 expression in glioma cells, and these molecules serve an important role in cancer development and progression. The current study was undertaken to further examine the association between these two molecules. Fluorescent quantitative PCR confirmed that miR­15b expression was significantly downregulated in glioma tissue while cripto­1 expression was significantly increased. Subsequent to transfection with miR­15b mimics, cripto­1 expression was significantly suppressed, and dual luciferase reporter assays further demonstrated that miR­15b regulates cripto­1 in a targeted manner. Furthermore, miR­15b inhibited proliferation and invasion, and promoted apoptosis of glioma cells while downregulating the expression of MMP­2 and MMP­9. In contrast, cripto­1 expression had the opposite effects. Co­transfection with miR­15b mimics and the cripto­1 overexpression vector overcame the inhibitory action of miR­15b on cripto­1. Therefore, it is suggested that miR­15b modulates cell growth and invasion through targeted regulation of cripto­1 expression in glioma cells. This observation may provide novel targets for the prevention and treatment of gliomas.

[Meta-analysis of the efficacy and safety of telaprevir combined with peginterferon alfa plus ribavirin in patients with chronic hepatitis C].

OBJECTIVE: To evaluate the efficacy and safety of telaprevir combined with peginterferon alfa (Peg-IFNa) plus ribavirin (RBV) (collectively, TPR therapy) in patients with chronic hepatitis C (CHC) using a meta-analysis approach. METHODS: The Pubmed literature database was searched for randomized controlled trials of TRP therapy in CHC patients published between 2009 and 2011. The following outcome data was extracted for meta-analysis of efficacy: sustained virological response (SVR), defined as serum HCV RNA of less than 1000 copies/ml at end-of-treatment (week 24); rapid virological response (RVR), defined as serum HCV RNA of less than 1000 copies/ml at treatment week 4; recurrence, defined as serum HCV RNA of less than 1000 copies/mL at end-of-treatment and more than 1000 copies/ml at follow-up (week 24 after treatment completion). The pooled odds ratio (OR) or relative risk (RR) were calculated, with 95% confidence interval (CI). Heterogeneity was assessed by the Chi-squared test based on the Q statistic. RESULTS: Six studies of TPR triple therapy, representing a total of 2677 CHC patients, were included in the meta-analysis. Among the 1850 patients who received TPR, 56.3% (n = 1041) achieved RVR, 66.8% (n = 1235) achieved SVR, and 12.1% (n = 176/1460) experienced recurrence. Among the 827 patients who received PR double-therapy, 7.0% (n = 58) achieved RVR, 35.8% (n = 296) achieved SVR, and 32.3% (n = 145/449) experienced recurrence. The TRP group had significantly higher rates of RVR (OR = 29.83, 95% CI: 16.16 to 55.05) and SVR (OR = 3.97, 95% CI: 2.58 to 6.11) than the PR group (both P less than 0.01), and significantly lower rate of recurrence (RR = 0.36, 95% CI: 0.24 to 0.56, P less than 0.01). CONCLUSION: The therapeutic effect of research group is better than that of control group, suggesting that ornithine aspartate combined with naloxone treatment in hepatic encephalopathy is worthy of promoting.