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Objective To investigate the role and mechanism of NLRP3/Caspase-1/IL-1β inflammasome pathway in the formation of aortic dissection in mice. Methods Fifty male C57BL/6 mice (3 weeks old, body weight 10~13 g) were divided into control group (n=10, normal diet), β-aminopropionitrile (BAPN) group [n=20, drink water containing 1 g/(kg·d) BAPN], and BAPN+ MCC950 group [n=20, drink water containing 1 g/(kg·d) BAPN and intraperitoneal injection of 20 mg/(kg·d) NLRP3 inhibitor, MCC950] by random sampling. Water intake, body weight, incidence of aortic dissection and aortic dissection-related mortality were recorded. The inflammatory infiltration in the aorta was observed with HE staining, elastic fiber breakage was observed by elastic Van Gieson (EVG) staining, average fluorescence intensity of NLRP3, IL-1β, α-SMA and OPN was detected by immunofluorescence assay, and protein expression levels of NLRP3, Caspase-1, ASC, IL-1β, α-SMA and OPN were measured with Western blotting. Results No aortic dissection or death was observed in the control group. The BAPN group had an incidence of aortic dissection of 80%, aortic dissection-related mortality of 35%, and obvious broken elastic fibers and inflammatory infiltrate in the aortic wall, and increased expression levels of NLRP3, Caspase-1, ASC and IL-1β, decreased contractile α-SMA and increased synthetic protein OPN when compared with the control group (P < 0.05). While MCC950 treatment decreased the incidence of aortic dissection (80% vs 35%, P=0.004) and aortic dissection-related mortality (35% vs 15%, P=0.144), alleviated the broken elastic fibers and inflammatory infiltrate in the aortic wall, and down-regulated the expression of NLRP3, Caspase-1, ASC and IL-1β, enhanced contractile α-SMA and decreased the synthetic protein when compared with the BAPN group (P < 0.05). Conclusion The occurrence of aortic dissection in mice is associated with activation of NLRP3/Caspase-1/IL-1β inflammasome pathway. NLRP3 inhibitor, MCC950, can reduce the occurrence of aortic dissection and show a protective effect on blood vessels.

Background: The overall survival (OS) for patients with recurrent glioma is meager. Also, the effect of radionecrosis and prognostic factors for recurrent glioma remains controversial. In this regard, developing effective predictive models and guiding clinical care is crucial for these patients. Methods: We screened patients with recurrent glioma after radiotherapy and those who received surgery between August 1, 2013, and December 31, 2020. Univariate and multivariate Cox regression analyses determined the independent prognostic factors affecting the prognosis of recurrent glioma. Moreover, nomograms were constructed to predict recurrent glioma risk and prognosis. Statistical methods were used to determine the prediction accuracy and discriminability of the nomogram prediction model based on the area under the curve (AUC), the C-index, the decision curve analysis (DCA), and the calibration curve. In order to distinguish high-risk and low-risk groups for OS, the X-Tile and Kaplan-Meier (K-M) survival curves were employed, and the nomogram prediction model was further validated by the X-Tile and K-M survival curves. Results: According to a Cox regression analysis, independent prognostic factors of recurrent glioma after radiotherapy with radionecrosis were World Health Organization (WHO) grade and gliosis percentage. We utilized a nomogram prediction model to analyze results visually. The C-index was 0.682 (95% CI: 0.616–0.748). According to receiver operating characteristic (ROC) analysis, calibration plots, and DCA, the nomogram prediction model was found to have a high-performance ability, and all patients were divided into low-risk and high-risk groups based on OS (P <.001). Conclusion: WHO grade and gliosis percentage are prognostic factors for recurrent glioma with radionecrosis, and a nomogram prediction model was established based on these two variables. Patients could be divided into high- and low-risk groups with different OS by this model, and it will provide individualized clinical decisions for future treatment. [ABSTRACT FROM AUTHOR]

The role of N6-methyladenosine (m6A) modification of host mRNA during bacterial infection is unclear. Here, we show that Helicobacter pylori infection upregulates host m6A methylases and increases m6A levels in gastric epithelial cells. Reducing m6A methylase activity via hemizygotic deletion of methylase-encoding gene Mettl3 in mice, or via small interfering RNAs targeting m6A methylases, enhances H. pylori colonization. We identify LOX-1 mRNA as a key m6A-regulated target during H. pylori infection. m6A modification destabilizes LOX-1 mRNA and reduces LOX-1 protein levels. LOX-1 acts as a membrane receptor for H. pylori catalase and contributes to bacterial adhesion. Pharmacological inhibition of LOX-1, or genetic ablation of Lox-1, reduces H. pylori colonization. Moreover, deletion of the bacterial catalase gene decreases adhesion of H. pylori to human gastric sections. Our results indicate that m6A modification of host LOX-1 mRNA contributes to protection against H. pylori infection by downregulating LOX-1 and thus reducing H. pylori adhesion.N6-methyladenosine (m6A) modification of mRNA regulates gene expression in eukaryotes. Here, Zeng et al. show that m6A modification of mRNAs contributes to protection against the pathogen Helicobacter pylori by downregulating a host protein that acts as receptor for the pathogen. [ABSTRACT FROM AUTHOR]