The pathogenesis of late-onset Alzheimer's disease (LOAD) mainly involves abnormal accumulation of extracellular β-amyloid (Aβ) and the consequent neurotoxic effects. The triggering receptor expressed on myeloid cells 2 (TREM2) gene is associated with the pathogenesis of LOAD and plays important roles in mediating the phagocytosis of Aβ by microglia and regulating inflammation in central nervous system. However, the exact mechanisms of these processes have not yet been clarified. In this study, we investigated the mechanism by which TREM2 regulates neuroinflammation and promotes Aβ1-42 clearance by BV-2 cells and further elucidated the underlying molecular mechanisms. We either silenced or overexpressed TREM2 in BV-2 cells and evaluated the cell viability, Aβ1-42 content, and expression of inflammatory markers (IL-1β, IL-6, and TNF-α). TREM2 overexpression up-regulated cell activity, promoted clearance of Aβ1-42 by BV-2 cells, and down-regulated expression of the inflammatory factors. In addition, TREM2 overexpression downregulation the expression of the TLR family (TLR2, TLR4 and TLR6) in BV-2 cells. Moreover, LPS, as an agonist of the TLR family, up-regulated the expression of inflammatory cytokines (IL-1β, TNF-α, and IL-6) in BV-2 cells overexpressing TREM2. In conclusion, TREM2 promoted clearance of Aβ1-42 by BV-2 cells and restored BV-2 cell viability from Aβ1-42-mediated neuroinflammation by downregulating TLRs. These findings suggest that TREM2 may be a target for LOAD therapy.

Objective: This meta-analysis and systematic review were conducted to comprehensively evaluate the efficacy and safety of mesenchymal stem cells in patients with acute ischemic stroke. Method: We conducted a manual search of electronic databases, including PubMed, Embase, the Cochrane Library, and Web of Science, with a search deadline set for February 1, 2023. Data analysis was performed using Stata version 15.0. Result: A total of 9 randomized controlled studies were included, involving a total of 316 people, including 159 mesenchymal stem cells and 147 control groups. Results of meta-analysis: Compared to a placebo group, the administration of mesenchymal stem cells resulted in a significant reduction in the National Institutes of Health Stroke Scale (NIHSS) scores among patients diagnosed with acute ischemic stroke [SMD=-0.99,95% CI (-1.93, -0.05)]. Compared to placebo, barthel index [SMD = 0.48,95% CI (-0.55,1.51)], modified rankin score [SMD = 0.45, 95% CI (1.11, 0.21)], adverse events (RR = 0.68, 95% CI (0.40, 1.17)] the difference was not statistically significant. Conclusion: Based on current studies, mesenchymal stem cell transplantation can ameliorate neurological deficits in patients with ischemic stroke to a certain extent without increasing adverse reactions. However, there was no significant effect on Barthel index and Modified Rankin score.