Flow chart indicates the selection of studies.

<p>RCT = randomized clinical trial.</p

Connected network of the enriched differentially expressed genes following exposure to 0.2 mM H₂O₂.

<p>(A) Connected network of enriched differentially expressed genes involved in fatty acid metabolism (RM018 and RM020). (B) Partial fatty acid metabolism in <i>M</i>. <i>smegmatis</i>. Genes expressed differentially after 0.2 mM H₂O₂ treatment assigned to RM018 and RM020 are marked in red.</p

Clinical Profile of Cyclooxygenase-2 Inhibitors in Treating Non-Small Cell Lung Cancer: A Meta-Analysis of Nine Randomized Clinical Trials

<div><p>Background</p><p>Evidence on the benefits of combining cyclooxygenase-2 inhibitor (COX-2) in treating non-small cell lung cancer (NSCLC) is still controversial. We investigated the efficacy and safety profile of cyclooxygenase-2 inhibitors in treating NSCLC.</p><p>Methods</p><p>The first meta-analysis of eligible studies was performed to assess the effect of COX-2 inhibitors for patients with NSCLC on the overall response rate (ORR), overall survival (OS), progression-free survival (PFS), one-year survival, and toxicities. The fixed-effects model was used to calculate the pooled RR and HR and between-study heterogeneity was assessed. Subgroup analyses were conducted according to the type of COX-2 inhibitors, treatment pattern, and treatment line.</p><p>Results</p><p>Nine randomized clinical trials, comprising 1679 patents with NSCLC, were included in the final meta-analysis. The pooled ORR of patients who have NSCLC with COX-2 inhibitors was significantly higher than that without COX-2 inhibitors. In subgroup analysis, significantly increased ORR results were found on celecoxib (RR = 1.29, 95% CI: 1.09, 1.51), rofecoxib (RR = 1.61, 95% CI: 1.14, 2.28), chemotherapy (RR = 1.40, 95% CI: 1.20, 1.63), and first-line treatment (RR = 1.39, 95% CI: 1.19, 1.63). However, COX-2 inhibitors had no effect on the one-year survival, OS, and PFS. Increased RR of leucopenia (RR = 1.21, 95% CI: 1.01, 1.45) and thrombocytopenia (RR = 1.36, 95% CI: 1.06, 1.76) suggested that COX-2 inhibitors increased hematologic toxicities (grade ≥ 3) of chemotherapy</p><p>Conclusions</p><p>COX-2 inhibitors increased ORR of advanced NSCLC and had no impact on survival indices, but it may increase the risk of hematologic toxicities associated with chemotherapy.</p></div

RNA-sequencing mapping statistics.

<p>RNA-sequencing mapping statistics.</p

Quantitative RT-PCR validation of RNA-sequencing results.

<p>(A) Quantitative RT-PCR analysis of the mRNA expression of genes differentially expressed after treatment with different levels of H₂O₂. <i>M</i>. <i>smegmatis</i> cultures were treated with 2 mM or 7 mM H₂O₂ for 30 min before extraction of RNA for qRT-PCR. The data represent 3 independent experiments. (B) Fold changes of selected genes differentially expressed genes after treatment with 0.2 mM and 7 mM H₂O₂ obtained by the RNA-sequencing.</p

Forest plot of the (A) ORR and (B) one-year survival in patients with NSCLC randomly assigned to COX-2 inhibitors treatment versus placebo/no intervention.

<p>ORR = overall response rate.</p

Distinct Responses of <i>Mycobacterium smegmatis</i> to Exposure to Low and High Levels of Hydrogen Peroxide

<div><p>Hydrogen peroxide (H₂O₂) is a natural oxidant produced by aerobic organisms and gives rise to oxidative damage, including DNA mutations, protein inactivation and lipid damage. The genus <i>Mycobacterium</i> utilizes redox sensors and H₂O₂ scavenging enzymes for the detoxification of H₂O₂. To date, the precise response to oxidative stress has not been fully elucidated. Here, we compared the effects of different levels of H₂O₂ on transcription in <i>M</i>. <i>smegmatis</i> using RNA-sequencing. A 0.2 mM H₂O₂ treatment had little effect on the growth and viability of <i>M</i>. <i>smegmatis</i> whereas 7 mM H₂O₂ was lethal. Analysis of global transcription showed that 0.2 mM H₂O₂ induced relatively few changes in gene expression, whereas a large proportion of the mycobacterial genome was found to be differentially expressed after treatment with 7 mM H₂O₂. Genes differentially expressed following treatment with 0.2 mM H₂O₂ included those coding for proteins involved in glycolysis-gluconeogenesis and fatty acid metabolism pathways, and expression of most genes encoding ribosomal proteins was lower following treatment with 7 mM H₂O₂. Our analysis shows that <i>M</i>. <i>smegmatis</i> utilizes the sigma factor MSMEG_5214 in response to 0.2 mM H₂O₂, and the RpoE1 sigma factors MSMEG_0573 and MSMEG_0574 in response to 7 mM H₂O₂. In addition, different transcriptional regulators responded to different levels of H₂O₂: MSMEG_1919 was induced by 0.2 mM H₂O₂, while high-level induction of DevR occurred in response to 7 mM H₂O₂. We detected the induction of different detoxifying enzymes, including genes encoding KatG, AhpD, TrxB and Trx, at different levels of H₂O₂ and the detoxifying enzymes were expressed at different levels of H₂O₂. In conclusion, our study reveals the changes in transcription that are induced in response to different levels of H₂O₂ in <i>M</i>. <i>smegmatis</i>.</p></div

Funnel plot of risk ratio for studies included in the meta-analysis.

<p>analysis. (A)ORR, P = 0.43, Egger’s test; (B) one-year survival, P = 0.297, Egger’s test. ORR = overall response rate.</p

Consensus risk of bias assessments of the included studies.

<p>Green: Low risk, Yellow: Unclear, Red: High risk.</p

Overview of the differential expression profiles in response to 0.2 mM H₂O₂ in <i>M</i>. <i>smegmatis</i>.

<p>(A) Enrichment analysis. The differently colored bars indicate the gene number for the enrichment of the annotations. (B) Interaction network of the differentially expressed genes of <i>M</i>. <i>smegmatis</i> induced by 0.2 mM H₂O₂ using STRING (9.1) at confidence scores ≥ 0.4. The network is enriched among the 634 differentially expressed genes and 111 interactions were observed (p value = 0).</p