Background S100 calcium binding protein A9 (S100A9) is a pro-inflammatory alarmin associated with several inflammation-related diseases. However, the role of S100A9 in lung injury in sepsis has not been fully investigated. Therefore, the present study aimed to determine the role of S100A9 in a lipopolysaccharide (LPS)-induced lung injury murine model and its underlying molecular mechanisms. Methods LPS was utilized to induce sepsis and lung injury in C57BL/6 or NOD-like receptor family pyrin domain containing 3 (NLRP3)−/− mice. To investigate the effects of S100A9 blockade, mice were treated with a specific inhibitor of S100A9. Subsequently, lung injury and inflammation were evaluated by histology and enzyme‑linked immunosorbent assay (ELISA), respectively. Furthermore, western blot analysis and RT-qPCR were carried out to investigate the molecular mechanisms underlying the effects of S100A9. Results S100A9 was upregulated in the lung tissues of LPS-treated mice. However, inhibition of S100A9 alleviated LPS-induced lung injury. Additionally, S100A9 blockade also attenuated the inflammatory responses and apoptosis in the lungs of LPS-challenged mice. Furthermore, the increased expression of NLRP3 was also suppressed by S100A9 blockade, while S100A9 blockade had no effect on NLRP3−/− mice. In vitro, S100A9 downregulation mitigated LPS-induced inflammation. Interestingly, these effects were blunted by NLRP3 overexpression. Conclusion The results of the current study suggested that inhibition of S100A9 could protect against LPS-induced lung injury via inhibiting the NLRP3 pathway. Therefore, S100A9 blockade could be considered as a novel therapeutic strategy for lung injury in sepsis.

Background: There is a dispute on the prognostic value of long non-coding RNA regulator of reprogramming (lncRNA ROR) in cancers. The purpose of the present study was to evaluate the prognostic significance of lncRNA ROR expression in human cancers. Methods: PubMed, Embase, and Cochrane Library were searched to look for relevant studies. The meta-analyses of prognostic and clinicopathological parameters (CPs) were conducted. Results: A total of ten studies were finally included into the meta-analysis. High lncRNA ROR expression was significantly associated with shorter overall survival (hazard ratio [HR] = 2.88, 95% confidence interval [CI] = 2.16–3.84, P<0.01) and disease-free survival (HR = 3.25, 95% CI = 2.30–4.60, P<0.01) compared with low lncRNA ROR expression. Besides, high lncRNA ROR expression was obviously related to more advanced clinical stage (P<0.01), earlier tumor metastasis (P=0.02), lymph node metastasis (P<0.01), and vascular invasion (P<0.01) compared with low lncRNA ROR expression. However, there was no significant correlation between lncRNA ROR expression and other CPs, including age (P=0.18), gender (P=0.33), tumor size (P=0.25), or tumor differentiation (P=0.13). Conclusion: High lncRNA ROR expression was associated with worse prognosis in cancers. LncRNA ROR expression could serve as an unfavorable prognostic factor in various cancers.

Background We evaluated the association between the I/D polymorphism in the ACE gene and lung cancer risk by performing a meta-analysis. Methods The heterogeneity in the study was tested using the Cochran χ2-based Q statistic test and I2 test, and then the random ratio or fixed effect was utilized to merge the odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the strength of the association between ACE polymorphisms and susceptibility to lung cancer. Sensitivity analysis was also performed. Using funnel plot and Begg’s rank test, we investigated the publication bias. All statistical analyses were performed using Stata 12.0 and RevMan 5.3. Results A total of 4307 participants (2181 patients; 2126 controls) were included in the 12 case–control studies. No significant association was found between the ACE I/D polymorphism and lung cancer risk (II vs. ID + DD: OR = 1.22, 95% CI = 0.89–1.68; II + ID vs. DD: OR = 1.21, 95% CI = 0.90–1.63; I vs. D: OR = 1.15, 95% CI = 0.95–1.39). In the subgroup analysis by ethnicity, no significant association between the ACE I/D polymorphism and lung cancer risk was found among Asian and Caucasian populations for the comparisons of II vs. ID + DD, II + ID vs. DD, and I vs. D genetic models. Conclusion The ACE I/D polymorphism is not associated with the risk of lung cancer.