Background:
The systemic use of corticosteroids for patients in severe community-acquired pneumonia (CAP) remains disputed in clinical practice. We undertook a systematic review and meta-analysis to assess the efficacy and safety of corticosteroids in patients with severe CAP.
Methods:
We searched MEDLINE (1946 to June 2018), EMBASE (1966 to June 2018), and the Cochrane Library database for randomized controlled trials (RCTs) conducted for severe CAP. The endpoints of the study included total mortality, length of intensive care unit (ICU) stay and mechanical ventilation.
Results:
Nine trials which contained 914 patients were included for final meta-analysis. Of the 488 patients in the corticosteroid group, there were 37 deaths (7.58%) and 56 deaths occurred in 426 patients in the control group (13.1%). Corticosteroid therapy was associated with a lower rate of all-cause mortality compared to control (odd ratio [OR] 0.63, 95% confidence interval [CI] 0.42–0.95,
P
= .03). Subgroup analysis was conducted to show that the drug type modified the effect of steroids for mortality rate: prednisolone or methylprednisolone therapy (OR 0.37, 95% CI 0.19–0.72) reduced total mortality, whereas hydrocortisone use did not (OR 0.90, 95% CI 0.54–1.49). We found the length of ICU stay was significantly shorter in the steroid group compared to control (MD −2.52 days, 95% CI −4.88 to −0.15;
P
= .04). And there was a reduction trend in the need for mechanical ventilation in corticosteroid group (OR 0.53, 95% CI 0.28–1.02;
P
= .06). There was no trend towards more adverse events in the corticosteroid arm compared to control (OR 0.92, 95% CI 0.58–1.47;
P
= .74).
Conclusion:
Overall, adjunctive systemic corticosteroids therapy was effective and safe for patients with severe CAP. In addition, the effects of mortality may differ according to the type of corticosteroids.
Curzerene is a sesquiterpene and component used in oriental medicine. It was originally isolated from the traditional Chinese herbal medicine rhizomes. In this study, anticancer activity of curzerene was examined in both and models. The result of the MTT assay showed that curzerene exhibited antiproliferative effects in SPC-A1 human lung adenocarcinoma cells in a time-dependent and dose-dependent manner. The anticancer ICs were 403.8, 154.8, and 47.0 µM for 24, 48, and 72 hours, respectively. The flow cytometry analysis indicated curzerene arrested the cells in the G2/M cell cycle and promoted or induced apoptosis of SPC-A1 cells. The percentage of cells arrested in the G2/M phase increased from 9.26 % in the control group cells to 17.57 % in the cells treated with the highest dose (100 µM) of curzerene. Western blot and RT-PCR analysis demonstrated that curzerene induced the downregulation of GSTA1 protein and mRNA expressions in SPC-A1 cells. Tumor growth was significantly inhibited in SPC-A1 cell-bearing nude mice by using curzerene (135 mg/kg daily), meanwhile, curzerene did not significantly affect body mass and the organs of the mice, which may indicate that curzerene has limited toxicity and side effects . In conclusion, curzerene could inhibit the proliferation of SPC-A1 human lung adenocarcinoma cells line in both and models. Focusing on its relationship with GSTA1, curzerene could induce the downregulation of GSTA1 protein and mRNA expressions in SPC-A1 cells. Curzerene might be used as an anti-lung adenocarcinoma drug candidate compound for further development.
Curcumol is a sesquiterpene originally isolated from curcuma rhizomes, a component of herbal remedies commonly used in oriental medicine. Its beneficial pharmacological activities have attract significant interest recently. In this study, anti-cancer activity of curcumol was examined with both in vitro and in vivo models. It was found that curcumol exhibited time-and concentration-dependent anti-proliferative effects in SPC-A-1 human lung adenocarcinoma cells with cell cycle arrest in the G0/G1 phase while apoptosis-induction was also confirmed with flow cytometry and morphological analyses. Interestingly, curcumol did not display growth inhibition in MRC-5 human embryonic lung fibroblasts, suggesting the anti-proliferative effects of curcumol were specific to cancer cells. Anti-neoplastic effects of curcumol were also confirmed in tumor bearing mice. Curcumol (60 mg/ kg daily) significantly reduced tumor size without causing notable toxicity. In conclusion, curcumol appears a favorable anti-cancer candidate for further development.
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