Exosomes from senescent epithelial cells activate pulmonary fibroblasts via the miR-217-5p/Sirt1 axis in paraquat-induced pulmonary fibrosis.

BACKGROUND: Paraquat (PQ) is a widely used and highly toxic herbicide that poses a significant risk to human health. The main consequence of PQ poisoning is pulmonary fibrosis, which can result in respiratory failure and potentially death. Our research aims to uncover a crucial mechanism in which PQ poisoning induces senescence in epithelial cells, ultimately regulating the activation of pulmonary fibroblasts through the exosomal pathway. METHODS: Cellular senescence was determined by immunohistochemistry and SA-ß-Gal staining. The expression of miRNAs was measured by qPCR. Pulmonary fibroblasts treated with specific siRNA of SIRT1 or LV-SIRT1 were used to analysis senescent exosomes-mediated fibroblasts activation. Luciferase reporter assay and western blot were performed to elucidated the underlying molecular mechanisms. The effects of miR-217-5p antagomir on pulmonary fibrosis were assessed in PQ-poisoned mice models. RESULTS: Impairing the secretion of exosomes effectively mitigates the harmful effects of senescent epithelial cells on pulmonary fibroblasts, offering protection against PQ-induced pulmonary fibrosis in mice. Additionally, we have identified a remarkable elevation of miR-217-5p expression in the exosomes of PQ-treated epithelial cells, which specifically contributes to fibroblasts activation via targeted inhibition of SIRT1, a protein involved in cellular stress response. Remarkably, suppression of miR-217-5p effectively impaired senescent epithelial cells-induced fibroblasts activation. Further investigation has revealed that miR-217-5p attenuated SIRT1 expression and subsequently resulted in enhanced acetylation of ß-catenin and Wnt signaling activation. CONCLUSION: These findings highlight a potential strategy for the treatment of pulmonary fibrosis induced by PQ poisoning. Disrupting the communication between senescent epithelial cells and pulmonary fibroblasts, particularly by targeting the miR-217-5p/SIRT1/ß-catenin axis, may be able to alleviate the effects of PQ poisoning on the lungs.

Diagnostic value of mean platelet volume for neonatal sepsis: A systematic review and meta-analysis.

BACKGROUND: An increasing number of studies in recent years have identified mean platelet volume (MPV) as a predictive marker for neonatal sepsis. However, most of these studies focused on single regions, and therefore, the findings remain inconclusive. We, in this study, aimed to evaluate the potential of MPV as a biological indicator of neonatal sepsis through a systematic review and meta-analysis. METHODS: We searched PubMed, the Cochrane Library, Embase, and WanFang database for articles on MPV and neonatal sepsis, published from January 1, 1990 to December 31, 2018. We included 11 studies on 932 neonates with sepsis in this meta-analysis. RESULTS: The overall meta-analysis showed that MPV was significantly higher in patients with neonatal sepsis compared with healthy controls. Subgroup analysis revealed that the type of diagnostic criteria, analyzer, analyte, and controls used in the studies affected the difference in MPV between patients and healthy controls. CONCLUSION: MPV was significantly higher in the neonatal sepsis group compared to the control group. Therefore, in clinical practice, MPV could be used as an indicator for the early diagnosis of neonatal sepsis.