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Acute lung injury (ALI) is often associated with inflammation. Increasing evidence has identified the role for ubiquitin-specific protease 7 (USP7) in activating the expression of inflammatory factors in macrophages. The present study evaluated whether USP7 also mediates histone acetyltransferase Tat-interactive protein 60 (Tip60) in the development of ALI inflammation. An ALI mouse model was induced by intratracheal lipopolysaccharide (LPS) administration. Next, lung myeloperoxidase (MPO) activity and the ratio of dry weight/wet weight of lung were examined to evaluate tissue damage. In addition, RAW 264.7 cells were treated with LPS to induce an in vitro LPS-induced inflammatory cell model. ELISA was performed to measure expression of IL-1β, TNF-α, IL-6, and IL-8 in cells and tissues. TUNEL was used to detect LPS-induced cell apoptosis. Furthermore, the interaction between USP7 and Tip60 was identified by IP, Western blot analysis, and cycloheximide (CHX) treatment. The enrichment of Tip60 and H3K27ac in the promoter region of IL-6 and IL-8 was assessed by ChIP. USP7 was highly expressed in LPS-endotoxin-induced ALI mouse models and silencing of USP7 delayed the progression of ALI in mice. Silencing of USP7 protected RAW 264.7 cells against LPS-induced inflammation and apoptosis by downregulating IL-1β, TNF-α, IL-6, and IL-8. USP7 enhanced Tip60 protein stability, and Tip60 increased the enrichment of H3K27ac on IL-6 and IL-8 promoter region and activated NF-κB p65 to increase IL-6 and IL-8 expression. These findings reveal a new post-transcriptional role for USP7 in inflammation by stabilizing Tip60 and increasing the release of the pro-inflammatory cytokines, and implicate USP7 inhibitors as potential therapeutic agents for ALI. Key messages: USP7 expresses highly in an acute lung injury (ALI) mouse models. Silencing of USP7 inhibits inflammation and cell apoptosis in ALI mouse. USP7 stabilizes Tip60 to boost the release of IL-6 and IL-8. Tip60 increases IL-6 and IL-8 expression by acetylating NF-κB p65. Silencing of USP7 alleviates ALI by repressing NF-κB p65 and Tip60. [ABSTRACT FROM AUTHOR]

Aim: The present meta-nalysis investigates the prognostic value of osteopontin. (OPN) expression in patients with non-small-cell lung cancer. (NSCLC).Materials and Methods: The Web of Science (1945 ~ 2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966 ~ 2013), EMBASE (1980 ~ 2013), CINAHL (1982 ~ 2013), and the Chinese Biomedical Database (CBM) (1982 ~ 2013) were searched, without language restrictions, to retrieve studies related to OPN and NSCLC. We compiled carefully selected data and a meta-analysis was conducted using STATA software (Version 12.0, Stata Corporation, and College Station, Texas USA). Hazard ratios (HR) with corresponding 95% confidence interval (95%CI) were calculated.Results: Ten clinical cohort studies were selected for statistical analysis, representing a total of 1,133 NSCLC patients. The main findings of our meta-analysis are that patients who were OPN-positive had significantly shorter overall survival than OPN-negative patients. (HR = 1.47, 95%CI = 1.15. ~ 1.79,P< 0.001). Ethnicity.stratified analysis revealed a significant correlation between expression levels of OPN and poor prognosis of NSCLC patients among both Caucasians and Asians. (Asians: HR = 1.53, 95%CI = 0.95. ~ 2.11, P < 0.001; Caucasians: HR = 1.56, 95%CI = 1.08. ~ 2.03, P < 0.001; respectively).Conclusions: The present meta-analysis is consistent with the hypothesis that increased expression of OPN protein may be significantly associated with poor prognosis in patients with NSCLC. [ABSTRACT FROM AUTHOR]

The mesenchymal stem cell (MSC) is a potential strategy in the pretreatment of traumatic acute lung injury (ALI), a disease that causes inflammation and oxidative stress. This study aimed to investigate whether MSC-exosomal microRNA-124-3p (miR-124-3p) affects traumatic ALI. Initially, a traumatic ALI rat model was established using the weight-drop method. Then, exosomes were obtained from MSCs of Sprague-Dawley rats, which were injected into the traumatic ALI rats. We found that miR-124-3p was abundantly-expressed in MSCs-derived exosomes and could directly target purinergic receptor P2X ligand-gated ion channel 7 (P2X7), which was overexpressed in traumatic ALI rats. After that, a loss- and gain-of-function study was performed in MSCs and traumatic ALI rats to investigate the role of miR-124-3p and P2X7 in traumatic ALI. MSC-derived exosomal miR-124-3p or silenced P2X7 was observed to increase the survival rate of traumatic ALI rats and enhance the glutathione/superoxide dismutase activity in their lung tissues. However, the wet/dry weight of lung tissues, activity of methylenedioxyamphetamine and H 2 O 2 , and levels of inflammatory factors (TNF-a, IL-6, and IL-8) were reduced. Similarly, the numbers of total cells, macrophages, neutrophils, and lymphocytes in bronchoalveolar lavage fluid were also reduced when treated with exosomal miR-124-3p or silenced P2X7. In conclusion, the results provide evidence that miR-124-3p transferred by MSC-derived exosomes inhibited P2X7 expression, thus improving oxidative stress injury and suppressing inflammatory response in traumatic ALI, highlighting a potential pretreatment for traumatic ALI.