NLRP3/1-mediated pyroptosis: beneficial clues for the development of novel therapies for Alzheimer's disease.

The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis, which is a lytic, inflammatory form of cell death. There is accumulating evidence that nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3 (NLRP3) inflammasome-mediated microglial pyroptosis and NLRP1 inflammasome-mediated neuronal pyroptosis in the brain are closely associated with the pathogenesis of Alzheimer's disease. In this review, we summarize the possible pathogenic mechanisms of Alzheimer's disease, focusing on neuroinflammation. We also describe the structures of NLRP3 and NLRP1 and the role their activation plays in Alzheimer's disease. Finally, we examine the neuroprotective activity of small-molecule inhibitors, endogenous inhibitor proteins, microRNAs, and natural bioactive molecules that target NLRP3 and NLRP1, based on the rationale that inhibiting NLRP3 and NLRP1 inflammasome-mediated pyroptosis can be an effective therapeutic strategy for Alzheimer's disease.

Differences in Gut Microbiota between Healthy Individuals and Patients with Perianal Abscess before and after Surgery.

Surgery is the most important treatment for perianal abscesses. However, the gut microbiota of patients with perianal abscess and the effects of perianal abscess on the gut microbiota after surgery are unknown. In this study, significant changes in interleukin 6 and tumor necrosis factor-α in the blood of healthy subjects, patients with perianal abscesses, and patients after perianal abscess surgery were identified. 16S rRNA gene sequencing technology was used to detect the changes in the gut microbiota among 30 healthy individuals and 30 patients with perianal abscess before and after surgery. Venn diagrams and alpha diversity analyses indicated differences in the abundance and uniformity of gut microbiota between the healthy individuals and patients with perianal abscesses before and after surgery. Beta diversity analysis indicated that the grouping effects among the control, abscess, and surgery groups were good. The classification and compositional analysis showed significant differences in the gut microbiota between healthy individuals and patients with perianal abscesses before and after surgery. LEfSe analysis, random forest analysis, and ROC curve analysis showed that Klebsiella (AUC = 0.7467) and Bilophila (AUC = 0.72) could be potential biomarkers for the diagnosis of perianal abscess. The functional prediction results showed that the differential microbiota is significantly enriched in the pathways related to nutrition and drug metabolism. This study may have important implications for the clinical management and prognostic assessment of patients with perianal abscesses.