Background: Recent clinical trials have shown that adjunctive glucocorticoids is associated with inhibiting excessive inflammatory response and modulating cytokines release offering several advantages over conventional therapy on relieving clinical symptoms, reducing mortality, and improving prognosis. However, given the severe complications triggered by glucocorticosteroid, whether similar benefits may be achieved by patients undergoing glucocorticosteroid intervention remains controversial. Our meta-analysis aimed to investigate the efficacy and safety of adjunctive glucocorticoids in the treatment of severe community acquired pneumonia. Methods: A search of PubMed, EMBASE, Cochrane Library, EBASO, Medline, Google Scholar, Science Dicet, CBM, and CNKI databases was performed to analyze all relevant randomized controlled trials (RCTs) of corticosteroids in patients with severe community acquired pneumonia (CAP) up to January 2018. All-cause mortality, C-reactive protein (CRP) level, incidence of septic shock, and requirement of mechanical ventilation were selected as efficacy outcomes. Major adverse events involving super infection, upper gastrointestinal bleeding, and hyperglycemia were safety outcomes. Meta-analysis was conducted with RevMan 5.3 software. Results: A total of 10 RCTs comprising 665 patients were included for analysis. Regarding efficacy outcomes, adjunctive corticosteroid seemed to be superior compared with conventional treatment in terms of all-cause mortality (relative risk [RR]: 0.47, 95% confidence interval [CI], 0.3–0.74, P = .001), CRP level on day 8 after administration (standard mean difference [SMD]: −0.8, 95% CI, −1.11 to −0.5, P < .001), incidence of septic shock (odds ratio [OR] 0.15, 95% CI, 0.07–0.29, P < .001) and requirement for mechanical ventilation (OR: 0.32, 95% CI, 0.20–0.52, P < .001). Meanwhile, we found that low dose (≤86 mg) (RR: 0.41, 95% CI, 0.21–0.82, P = .01) and prolonged (>5 days) (RR: 0.35, 95% CI, 0.15–0.81, P = .01) use of corticosteroids in dosage modus of a maintenance dose after a bolus (RR: 0.28, 95% CI, 0.14–0.55, P = .002) obtained better results in death through subgroup analysis. Regarding safety outcomes, no difference was observed between 2 groups in terms of upper gastrointestinal bleeding (OR: 0.83, 95% CI, 0.27–2.52, P = .74), hyperglycemia (OR: 1.3, 95% CI, 0.68–2.49, P = .42), and super infection (OR: 1.11, 95% CI, 0.14–9.13, P = .92). Conclusion: Adjunctive corticosteroid yielded favorable outcomes in the treatment of severe community acquired pneumonia (SCAP) as evidenced by decreased all-cause mortality, incidence of septic shock, and requirement for mecha...

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Initial functional studies have demonstrated that RNA‐binding motif protein 10 (RBM10) can promote apoptosis and suppress cell proliferation; however, the results of several studies suggest a tumour‐promoting role for RBM10. Herein, we assessed the involvement of RBM10 in lung adenocarcinoma cell proliferation and explored the potential molecular mechanism. We found that, both in vitro and in vivo, RBM10 overexpression suppresses lung adenocarcinoma cell proliferation, while its knockdown enhances cell proliferation. Using complementary DNA microarray analysis, we previously found that RBM10 overexpression induces significant down‐regulation of RAP1A expression. In this study, we have confirmed that RBM10 decreases the activation of RAP1 and found that EPAC stimulation and inhibition can abolish the effects of RBM10 knockdown and overexpression, respectively, and regulate cell growth. This effect of RBM10 on proliferation was independent of the MAPK/ERK and P38/MAPK signalling pathways. We found that RBM10 reduces the phosphorylation of CREB via the AKT signalling pathway, suggesting that RBM10 exhibits its effect on lung adenocarcinoma cell proliferation via the RAP1/AKT/CREB signalling pathway.

BackgroundRecent studies have indicated that the nuclear RNA-binding protein RBM5 has the ability to modulate apoptosis and suppress tumor growth. The aim of this study is to investigate the expression of RBM5 in human prostate cancer and its mechanism of tumor suppression.MethodsThe expression of RBM5 protein in cancerous prostatic tissues and normal tissues was examined by IHC. PC-3 cell line was used to determine the apoptotic function of RBM5 in vitro. PC-3 cells were transiently transfected with pcDNA3.1-RBM5. Cell viability was determined by MTT assay. Rhodamine 123 staining and Annexin V analysis were performed to observe the apoptotic activity of PC-3 cells overexpressing RBM5. Expression of apoptosis-related genes was assessed by western blot.ResultsThe expression of RBM5 protein was significantly decreased in cancerous prostatic tissues compared to the normal tissues. PC-3 cells overexpressing RBM5 showed not only significant growth inhibition compared with the vector controls, but also dysfunction of mitochondrial membrane potential and increased apoptotic activity. To further define RBM5 function in apoptotic pathways, we investigated differential expression profiles of various BH3-only proteins including Bid, Bad, and Bim, and apoptosis regulatory proteins include P53, cleaved caspase9, and cleaved caspase3. We found that the expression of both BH3-only proteins and apoptosis regulatory proteins was increased in RBM5 transfected cells.ConclusionThe expression of RBM5 protein was significantly decreased in cancerous prostatic tissues, which suggests that RBM5 plays an important role in the pathogenesis of prostate cancer. RBM5 may induce the apoptosis of prostate cancer PC-3 cells by modulating the mitochondrial apoptotic pathway, and thus RBM5 might be a promising target for gene therapy on prostate cancer.

A limited number of studies have indicated an association between isoleucyl-tRNA synthetase 2 (IARS2) and tumorigenesis. We evaluated IARS2 protein expression in lung tumor tissues and paired non-tumor tissues. We found higher IARS2 expression in the tumor tissues, which was associated with the late Tumor and Node stages of the Tumor, Node, Metastasis staging system. Silencing IARS2 inhibited the activity of A549 and H1299 cells, resulting in G0/G1 stasis of A549 cells and mitochondrial apoptosis. IARS2 silencing was also found to inhibit NSCLC tumor growth in nude mice. Complementary DNA microarray analysis revealed 742 differentially expressed genes (507 upregulated and 235 downregulated) in IARS2-silenced A549 cells compared to controls. Ingenuity Pathway Analysis of the differential expression data suggested that multiple pathways are associated with IARS2 silencing in NSCLC cells; upstream analysis predicted the activation or inhibition of transcriptional regulators. Correlation analysis revealed that AKT and MTOR activities were significantly inhibited in IARS2-silenced cells, but were partially restored by the AKT-stimulating agent SC79. IARS2 appears to regulate lung cancer cell proliferation via the AKT/MTOR pathway. Our results help clarify the complex roles of IARS2 in tumorigenesis and suggest that it may be a novel regulator of lung cancer development.