Acute lung injury (ALI), is a rapidly progressing heterogenous pulmonary disorder that possesses a high risk of mortality. Accumulating evidence has implicated the activation of the p65 subunit of NF-κB [NF-κB(p65)] activation in the pathological process of ALI. microRNAs (miRNAs), a group of small RNA molecules, have emerged as major governors due to their post-transcriptional regulation of gene expression in a wide array of pathological processes, including ALI. The dysregulation of miRNAs and NF-κB activation has been implicated in human diseases. In the current study, we set out to decipher the convergence of miR-99b and p65 NF-κB activation in ALI pathology. We measured the release of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in bronchoalveolar lavage fluid using ELISA. MH-S cells were cultured and their viability were detected with cell counting kit 8 (CCK8) assays. The results showed that miR-99b was up-regulated, while PRDM1 was downregulated in a lipopolysaccharide (LPS)-induced murine model of ALI. Mechanistic investigations showed that NF-κB(p65) was enriched at the miR-99b promoter region, and further promoted its transcriptional activity. Furthermore, miR-99b targeted PRDM1 by binding to its 3’UTR, causing its downregulation. This increased lung injury, as evidenced by increased wet/dry ratio of mouse lung, myeloperoxidase activity and pro-inflammatory cytokine secretion, and enhanced infiltration of inflammatory cells in lung tissues. Together, our findings indicate that NF-κB(p65) promotion of miR-99b can aggravate ALI in mice by downregulating the expression of PRDM1.
Methyl methacrylate-butadiene-styrene (MBS) were prepared by emulsion polymerization method through grafting of styrene (St) and methyl methacrylate (MMA) with varied ratio on polybutadiene (PB) particles. The effect of St/MMA weight ratio of the shell in MBS on the property of PVC/MBS blends was investigated. It was found that when St/MMA weight ratio was 0/40 and 10/30, brittle-ductile transition occurred firstly for PVC/MBS blends. Transparency of PVC/MBS blends enhanced with the increase of St content in the shell of MBS. TEM results showed that MBS composition in the shell affected disperse morphology of MBS particles in PVC matrix and the deformation behavior of PVC/MBS blends. With the increase of MMA content of the shell in MBS, the deformation mechanism of PVC/MBS blends take place transition from debonding in the interface between MBS particle and PVC matrix to the cavitation of MBS followed by shear deformation of PVC matrix.
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