Aims Accumulating evidence has suggested that airborne fine particulate matter (PM2.5) exposure is associated with an increased risk of ischemic stroke. However, the underlying mechanisms have not been fully elucidated. In this study, we aim to investigate the role and mechanisms of NLRP3 inflammasome and pyroptosis in ischemic stroke after PM2.5 exposure. Methods The BV‐2 and HMC‐3 microglial cell lines were established and subjected to oxygen–glucose deprivation and reoxygenation (OGD/R) with or without PM2.5 exposure. We used the CCK‐8 assay to explore the effects of PM2.5 on cell viability of BV‐2 and HMC‐3 cells. Then, the effects of PM2.5 exposure on NLRP3 inflammasome and pyroptosis following OGD/R were detected by western blotting, ELISA, and the confocal immunofluorescence staining. Afterwards, NLRP3 was knocked down to further validate the effects of PM2.5 on cell viability, NLRP3 inflammasome activation, and pyroptosis after OGD/R in HMC‐3 cells. Finally, the intracellular reactive oxygen species (ROS) was measured and the ROS inhibitor N‐acetyl‐L‐cysteine (NAC) was used to investigate whether ROS was required for PM2.5‐induced NLRP3 inflammasome activation and pyroptosis under ischemic conditions. Results We found that PM2.5 exposure decreased the viability of BV‐2 and HMC‐3 cells in a dose‐ and time‐dependent manner under ischemic conditions. Furthermore, PM2.5 exposure aggravated NLRP3 inflammasome activation and pyroptosis after OGD/R, as indicated by an increased expression of NLRP3, ASC, pro‐caspase‐1, Caspase‐1, GSDMD, and GSDMD‐N; increased production of IL‐1β and IL‐18; and enhanced Caspase‐1 activity and SYTOX green uptake. However, shRNA NLRP3 treatment attenuated the effects of PM2.5 on cell viability, NLRP3 inflammasome activation, and pyroptosis. Moreover, we observed that PM2.5 exposure increased the production of intracellular ROS following OGD/R, while inhibiting ROS production with NAC partially attenuated PM2.5‐induced NLRP3 inflammasome activation and pyroptosis under ischemic conditions. Conclusion These results suggested that PM2.5 exposure triggered the activation of NLRP3 inflammasome and pyroptosis under ischemic conditions, which may be mediated by increased ROS production after ischemic stroke. These findings may provide a more enhanced understanding of the interplay between PM2.5 and neuroinflammation and cell death, and reveal a novel mechanism of PM2.5‐mediated toxic effects after ischemic stroke.
Purpose. Cervical cancer (CC) is one of the most common gynecologic neoplasms. Hypoxia is an essential trigger for activating immunosuppressive activity and initiating malignant tumors. However, the determination of the role of immunity and hypoxia on the clinical outcome of CC patients remains unclear. Methods. The CC independent cohort were collected from TCGA database. Consensus cluster analysis was employed to determine a molecular subtype based on immune and hypoxia gene sets. Cox relevant analyses were utilized to set up a risk classifier for prognosis assessment. The underlying pathways of classifier genes were detected by GSEA. Moreover, we conducted CIBERSORT algorithm to mirror the immune status of CC samples. Results. We observed two cluster related to immune and hypoxia status and found the significant difference in outcome of patients between the two clusters. A total of 251 candidate genes were extracted from the two clusters and enrolled into Cox relevant analyses. Then, seven hub genes (CCL20, CXCL2, ITGA5, PLOD2, PTGS2, TGFBI, and VEGFA) were selected to create an immune and hypoxia-based risk classifier (IHBRC). The IHBRC can precisely distinguish patient risk and estimate clinical outcomes. In addition, IHBRC was closely bound up with tumor associated pathways such as hypoxia, P53 signaling and TGF β signaling. IHBRC was also tightly associated with numerous types of immunocytes. Conclusion. This academic research revealed that IHBRC can be served as predictor for prognosis assessment and cancer treatment estimation in CC.
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