Acute lung injury (ALI) is a pulmonary disorder that causes acute respiratory failure, thus leading to relative high mortality worldwide. However, the molecular mechanisms of ALI remain largely unknown. MicroRNA (miRNA)-dependent control of gene expression at a post-transcriptional level has been recently reported. Herein, we identify a candidate miRNA, miR-495, that affects the progression of ALI. Alveolar macrophages (NR8383) were treated with 1 mg/mL lipopolysaccharide (LPS) to establish a cell-injury model. Combined with the data from western blot, methylation-specific PCR, methylated DNA immunoprecipitation, and chromatin immunoprecipitation assays, NLRP3 inflammasome activation and methylation-dependent repression of miR-495 were found in LPS-exposed NR8383 cells. Dual-luciferase reporter gene assay and miR-495 gain-offunction experiments confirmed that NLRP3 was a target of miR-495. Next, the expression of miR-495 and NLRP3 was overexpressed or silenced to assess their effects on NLRP3 inflammasome activation, alveolar macrophage inflammation, and pyroptosis in vitro. As demonstrated, overexpressed miR-495 alleviated alveolar macrophage inflammation and pyroptosis and inhibited NLRP3 inflammasome activation by negatively regulating the NLRP3 gene. Consistently, elevated miR-495 alleviated lung injury and reduced the neutrophil infiltration and inflammation in rat models of LPS-induced ALI. Taken together, the data in our study demonstrated that methylation of the miR-495 promoter could downregulate miR-495, whose elevation could attenuate the activation of the NLRP3 inflammasome to protect against ALI, which provides novel therapeutic targets for ALI treatment.

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One hundred and seventeen adult sheep of both sexes, each weighing 15.2-42.4 kg, were used for this study. The purpose of this study was to investigate the relationship of the physical parameters of the waves to internal organ injury by exposing sheep to weak blast waves in TNT (trinitrotoluene) explosions, biological shock tube, and gun muzzle blasts. The results showed that the organ most sensitive to the TNT explosion was the lungs, whereas the upper respiratory tract was most sensitive to muzzle blast waves. The injury thresholds of overpressure were 29.0, 29.5, and 41.2 kPa for upper respiratory tract, lungs, and gastrointestinal tract respectively at a single exposure. Repeated exposure to 60 blasts reduced the injury threshold of the internal organs. The injury thresholds for upper respiratory tract, lungs, and gastrointestinal tract were 21.0, 18.0, and 40.4 kPa, respectively. The duration of overpressure of weak blast waves was 2.4-4.2 milliseconds, which did not significantly affect the severity of injury. The safety limits of weak blast waves to internal organ injury of human body were as follows: Ps = 37-3Ln.Tc.N/4(Tc.N< or = 1000) and Ps = 20.4(Tc.N > 1000). The results suggest that repeated exposures decrease the injury threshold of the internal organs. The safety limits proposed could protect 90% of the exposed population against internal organ injury caused by weak blast waves.

The findings of the study suggested that RGDS could act to block the laminin-integrin α7β1-signaling pathway, ultimately contributing to the inhibition of the progression of MV-induced pulmonary fibrosis.

BackgroundThe purpose of the study is to investigate the role and mechanisms of hydrogen-saturated saline (HSS) in the acute lung injury (ALI) induced by oleic acid (OA) in rats.MethodsRats were treated with OA (0.1 mL/kg) to induce ALI and then administered with HSS (5 mL/kg) by intravenous (iv) and intraperitoneal (ip) injection, respectively. Three hours after the injection with OA, the arterial oxygen partial pressure (PaO2), arterial oxygen saturation (SaO2), carbon dioxide partial pressure (PaCO2), and bicarbonate (HCO3 −) levels were analyzed using blood gas analyzer. In addition, the levels of malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and interleukin 1β (IL-1β) and myeloperoxidase (MPO) activity were measured by commercial kits, and pathological changes of lung tissue were examined by HE staining. Finally, the correlations of MPO activity or MDA level with the levels of TNF-α or IL-1β were analyzed by Pearson’s correlation analysis.ResultsWe found decreased PaO2 levels and the pathological changes of lung tissue of ALI after OA injection. In addition, OA increased the levels of MDA, TNF-α, and IL-1β, as well as MPO activity in lung tissues (P < 0.05). However, after treatment with HSS, all of these changes were alleviated (P < 0.05), and these changes were mitigated when treated with HSS by ip then iv injection (P < 0.05). Furthermore, MDA level and MPO activity were positively correlated with TNF-α and IL-1β levels in the lung tissue, respectively (P < 0.01).ConclusionHSS attenuated ALI induced by OA in rats and might protect against ALI through selective resistance to oxidation and inhibiting inflammatory infiltration.