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Purinergic 2X7 receptor (P2X7R) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) are expressed in macrophages in atherosclerotic lesions. However, the mechanisms through which P2X7R participates in the inflammatory response in atherosclerosis remain largely unknown. The aim of the present study was to investigate the role of P2X7R in atherosclerosis and the mechanisms of action of the NLRP3 inflammasome following stimulation with oxidized low-density lipoprotein (oxLDL). We observed the expression and distribution of P2X7R in the atherosclerotic plaque in the coronary arteries from an autopsy specimen and in that of the aortic sinuses of apoE−/− mice by immunohistochemistry and immunofluorescence staining. The specificity of short interfering RNA (siRNA) was used to suppress P2X7R and NLRP3 mRNA expression. RT-qPCR and western blot analysis were used to analyze mRNA and protein expression, respectively. Co-immunoprecipitation was used to examine the interaction between protein kinase R (PKR) phosphorylation and NLRP3. P2X7R and NLRP3 were expressed at high levels in the atherosclerotic plaque in the coronary arteries. Stimulation with oxLDL upregulated P2X7R, NLRP3 and interleukin (IL)-1β expression. P2X7R knockdown by siRNA suppressed NLRP3 inflammasome activation by inhibiting the PKR phosphorylation mediated by oxLDL. In the atherosclerotic lesions in the aortic sinuses of apoE−/− mice, P2X7R expression was found at high levels. Moreover, P2X7R siRNA attenuated the development of atherosclerosis in the apoE−/− mice. In conclusion, our results demonstrate that P2X7R plays a significant role in the development of atherosclerosis and regulates NLRP3 inflammasome activation by promoting PKR phosphorylation.

We decided to assess the prognostic value of NLRP3 inflammasome level in acute coronary syndrome (ACS) patients and whether it was related to coronary atherosclerotic severity. Study population included one-hundred and twenty-three (123) subjects. Peripheral blood monocyte NLRP3 protein level was correlated with clinical presentation, angiographic characteristics and its scoring systems as well as GRACE and TIMI risk scores. Follow-up for major adverse cardiac events (MACE) was carried out at 180 days. Peripheral blood monocyte NLRP3 was found to be elevated in ACS patients (P < 0.05) and showed positive correlation with GRACE score (r = 0.619), TIMI score (r = 0.580), SYNTAX score (r = 0.550), Clinical SYNTAX score (r = 0.564) and Gensini score (r = 0.516). NLRP3 was also increased with increasing number of vessels, the number of lesions present and the presence bifurcation lesions (P < 0.05). Multivariate Cox regression analysis showed NLRP3 to be an independent predictor of MACE (P = 0.043). Kaplan-Meier analysis and receiver operating characteristic curves for NLRP3 showed good predictive value for MACE. There is a positive correlation of NLRP3 level with severity of coronary atherosclerosis. NLRP3 level is a promising prognostic utility and is efficient in event prediction for MACE.

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BACKGROUND: Epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement may predict the outcome of targeted drug therapy and also are associated with the efficacy of chemotherapy in patients with nonsmall cell lung cancer (NSCLC). The authors of this report investigated the relation of EGFR mutation or ALK rearrangement status and the expression of DNA repair or synthesis genes, including excision repair cross-complementing 1 (ERCC1), ribonucleotide reductase subunit M1 (RRM1), thymidylate synthetase (TS), and breast cancer-early onset (BRCA1), as a potential explanation for these observations. METHODS: In total, 104 resected lung adenocarcinomas from women who were nonsmokers were analyzed concurrently for EGFR mutations, ALK rearrangements, and mRNA expression of the ERCC1, RRM1, TS, and BRCA1 genes. EGFR mutations were detected with a proprietary detection kit, ALK rearrangements were detected by polymerase chain reaction analysis, and genetic mRNA expression was detected by real-time polymerase chain reaction analysis. RESULTS: Of 104 patients, 73 (70.2%) had EGFR mutations, and 10 (9.6%) had ALK rearrangements. ERCC1 mRNA levels in patients who had EGFR mutations were 3.44 AE 1.94 Â 10 À3 , which were significantly lower than the levels in patients who were positive for ALK rearrangements and in patients who were negative for both biomarkers (4.60 AE 1.95 Â 10 À3 and 4.95 AE 2.33 Â 10 À3, respectively; P ¼ .010). However, TS mRNA levels were significantly lower in patients who had EGFR mutations ( 1. ; P ¼ .020) than in patients who were negative for both biomarkers. CONCLUSIONS: NSCLC specimens that harbored activating EGFR mutations were more likely to express low ERCC1 and TS mRNA levels, whereas patients with NSCLC who had ALK rearrangement were more likely to express low TS mRNA levels. Cancer 2012;118:5588-94. V C 2012 American Cancer Society.

The electrochemical performance of lithium-oxygen (Li-O 2 ) batteries depends largely on the architecture and catalytic effectiveness of the oxygen cathode. Herein, in this study, a graphene aerogel decorated with MoS x nanosheets (MoS x /HRG) with a three-dimensional porous framework synthesized using a one-step hydrothermal reaction followed by freeze-drying is reported. The MoS x /HRG aerogel possesses hierarchical mesopores and micropores, which could facilitate electrolyte impregnation and oxygen diffusion, and provide much more accommodation space for the reaction products. The lithium-oxygen batteries based on this MoS x /HRG aerogel cathode show improved electrochemical performance, with a high initial discharge capacity up to 6678.4 mA h g À1 at a current density of 0.05 mA cm À2 and better cycling capability with a cut-off capacity of 500 mA h g À1 at a current density of 0.1 mA cm À2 , compared with the lithium-oxygen batteries based on an HRG aerogel cathode. The enhanced performance is ascribed to the excellent catalytic activity of the MoS x nanosheets and the unique three-dimensional porous architecture.

Saikosaponins-a (Ssa) is a major bioactive extract of Radix Bupleuri which is a traditional Chinese medicine. The roles of inflammatory response and lipid transportation in the process of atherosclerosis have drawn increasing attention. We explored the regulation of lipid transportation and immune-inflammatory role of Ssa in early atherosclerosis. The antiatherogenic actions and possible molecular mechanisms of Ssa were texted in THP-1 cells. We examined the effect of Ssa on oxidized low-density lipoprotein (ox-LDL)-induced lipid uptake, cholesterol efflux, immune-inflammatory response. THP-1 macrophages were treated with Ssa followed by ox-LDL for 24 hours. Results from western blot showed that Ssa obviously reduced lipoprotein uptake to block foam cell formation and the expression of Density Lipoprotein Receptor-1 and CD36. Ssa also significantly boosted cholesterol efflux and the expression of ATP binding cassettetransporter A1 and peroxisome proliferator-activated receptor γ. The results also indicated that Ssa inhibited ox-LDL-induced activation of AKT and nuclear factor-κB, assembly of NLRP3 inflammasome and production of proinflammatory cytokines. It is suggested that the ability against immune inflammatory response of Ssa is due to modulation of the PI3K/AKT/NF-κB/NLRP3 pathway. In conclusion, this study provides new insight into Ssa's molecular mechanism and its therapeutic potential in the treatment of atherosclerosis.

Background: The further progression of credible expression profiling analysis of genes continues to expand our understanding of the biological characteristics in lung cancer. In this study, RNA sequencing (RNA-Seq) was used to contrast the transcriptomics profiling of small cell lung cancer (SCLC) that acquired partial response (PR) and stable disease (SD)/progressive disease (PD) after first-line chemotherapy. We aimed to illuminate the underlying mechanisms of long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) in the efficacy of SCLC first-line chemotherapy.Methods: Six male patients (mean age, 64.2 years) with SCLC were enrolled in this study. RNA-Seq was executed on the tumor tissues from 3 patients with PR outcome and 3 patients with SD or PD therapeutic effect after first-line chemotherapy.Results: RNA-Seq generated 26.67×10 6 (±8.7×10 6 ) reads in SCLC tissues [mean (±standard deviation)].Analysis revealed that 64 lncRNAs had higher expression and 194 had lower expression in the PR group ≥2-fold (P<0.05). Three downregulated genes in the PR group [HOXA-AS3, cancer susceptibility 9 (CASC9), and KEGG] could have a role in the insensitivity of SCLC. A total of 1,303 differential miRNAs were defined between PR and the SD or PD SCLC group, while 520 miRNAs had higher expression, and 783 had lower expression in the PR group. Two lower expressed miRNAs in the PR group (miRNA 601 and miRNA 596) might be the key genes in SCLC chemotherapy insensitivity.Conclusions: The expression of 3 gene (HOXA-AS3, CASC9, and KEGG) and 2 miRNAs (miRNA 601 and miRNA 596) were markedly decreased in SCLC patients who achieved PR. They thus might be the promising candidate genes in SCLC chemotherapy insensitivity.