Therapeutic Effects of Mesenchymal Stem Cell-Derived Extracellular Vesicles in sepsis: a Systematic Review and Meta-Analysis of Preclinical Studies.

BACKGROUND: Sepsis is a life-threatening disorder with no definitive cure. Preclinical studies suggest that extracellular vesicles derived from mesenchymal stromal cells (EV-MSCs) can mitigate inflammatory conditions, potentially leading to increased survival and reduced organ dysfunction during sepsis. Our aim to conduct this systematic review and meta-analysis is assessing the EV-MSCs therapeutic efficacy in sepsis. METHODS: PubMed, Embase, Scopus, WOS and ProQuest databases and also Google Scholar search engine were searched for published articles. We used hazard ratio (HR) and standardized mean difference (SMD) as effect sizes to evaluate the therapeutic effect of EV-MSCs on survival rate and determine their effect on reducing organ dysfunction, respectively. Finally, we employed GRADE tool for preclinical animal studies to evaluate certainty of the evidence. RESULTS: 30 studies met the inclusion criteria for our article. Our meta-analysis results demonstrate that animals treated with MSC-EVs have better survival rate than untreated animals (HR = 0.33; 95% CI: 0.27-0.41). Our meta-analysis suggests that EV-MSCs can reduce organ dysfunctions in sepsis, such as the lung, kidney, and liver. Additionally, EV-MSCs decrease pro-inflammatory mediators like TNF-α, IL-1ß, and IL-6. CONCLUSION: Our results indicate that EV-MSCs can be as promising therapy for sepsis management in animal models and leading to increased survival rate and reduced organ dysfunction. Furthermore, our study introduces a novel tool for risk of bias assessment and provides recommendations based on various analysis. Future studies with aiming to guide clinical translation can utilize the results of this article to establish stronger evidence for EV-MSC effectiveness.

Anticancer Effects of ZnO/CNT@Fe3O4 in AML-Derived KG1 Cells: Shedding Light on Promising Potential of Metal Nanoparticles in Acute Leukemia.

Background: Therapeutic approaches for acute myeloid leukemia (AML) have remained largely unchanged for over 40 years and cytarabine and an anthracycline (e.g., daunorubicin) backbone is the main induction therapy for these patients. Resistance to chemotherapy is the major clinical challenge and contributes to short-term survival with a high rate of disease recurrence. Given the established efficacy of nanoparticles in cancer treatment, this study was designed to evaluate the anticancer property of our novel nanocomposite in the AML-derived KG1 cells. Materials and Methods: To assess the anti-leukemic effects of our nanocomposite on AML cells, we used MTT and trypan blue assays. Flow cytometric analysis and q-RT-PCR were also applied to evaluate the impact of nanocomposite on cell cycle and apoptosis. Results: Our results outlined that ZnO/CNT@Fe3O4 decreased viability and metabolic activity of KG1 cells through induction of G1 arrest by increasing the expression of p21 and p27 cyclin-dependent kinase inhibitors and decreasing c-Myc transcription. Moreover, ZnO/CNT@Fe3O4 markedly elevated the percentage of apoptotic cells which was coupled with a significant alteration of Bax and Bcl-2 expressions. Synergistic experiments showed that ZnO/CNT@Fe3O4 enhances the cytotoxic effects of Vincristine on KG1 cells. Conclusion: In conclusion, this study sheds light on the potent anti-leukemic effects of ZnO/CNT@Fe3O4 and provides evidence for the application of this agent in the treatment of acute myeloid leukemia.