GSDMD (Gasdermin D)

The AIM2 inflammasome-mediated pyroptosis pathway may be involved in the pathogenesis of IIM, providing a theoretical basis for further research on the etiology of IIM and the development of new therapies.

The Western blot results of tumor tissues revealed that the pyroptosis effect of PPII on liver cancer was associated with the activation of the NLRP3/Caspase1/GSDMD pathway, which upregulates the expression of NLRP3, Cleaved-Caspase 1, GSDMD-N, IL-1β, and IL-18 proteins and downregulates the expression of pro-Caspase 1 and GSDMD proteins. In summary, our findings revealed the pyroptosis effect and mechanism of PPII in HCC cells in vitro and in vivo, suggesting that PPII may be used as a potential pyroptosis inducer for HCC treatment in the future.

These findings, consistent with those of Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, revealed that TMP-Bi treatment affected key biological processes including the calcium signaling pathway, tumor necrosis factor response, inflammatory response, and apoptosis. Crucially, the low toxicity and good biocompatibility of bismuth contribute significantly to this complex, making TMP-Bi a promising candidate for cancer treatment.

β-BA exerts potent anti-GBM activity by inducing mitochondrial dysfunction and NLRP3-mediated pyroptosis, providing a mechanistic basis for developing β-BA as a promising natural therapeutic candidate for GBM. The online version contains supplementary material available at 10.1007/s13205-025-04691-x.

Concurrently, the abundant flagella of VNP activate caspase-1, which in turn cleaves the overexpressed GSDMD proteins into its active form, thereby triggering robust pyroptosis in tumor cells. Taken together, by coupling bacterial adjuvanticity with ROS-mediated stress and CRISPR-driven GSDMD upregulation, this strategy achieves efficient amplification of pyroptosis and promotes antitumor immune activation.

LA exerts potent anti-inflammatory effects by targeting HIF1α-mediated metabolic reprogramming in macrophages. Our results highlight the therapeutic potential of targeting immunometabolic pathways in inflammatory lung diseases, providing new insights into the mechanism by which LA ameliorates pulmonary inflammation.

Intriguingly, hybrid 9a exhibited cytocompatibility with healthy immune cells while enhancing immune-mediated cytotoxicity against tumor cells. Altogether, these findings establish compound 9a as a modulator of innate immune signaling through selective targeting of the NLRP3 inflammasome, demonstrating its potential as an immunomodulatory therapeutic lead for oral cancer.

Notably, molecular docking and molecular dynamics simulations demonstrate that calycosin stably binds to NLRP3 with high affinity, supporting its potential as an NLRP3 inhibitor. These findings indicate that calycosin protects against CIRI-induced BBB damage by inhibiting NLRP3-mediated pyroptosis and modulating tight junction protein expression, indicating that calycosin is a potential therapeutic option for ischemic stroke.

GSDME-mediated pyroptosis plays a pivotal role in chemotherapy-induced cell death in lung adenocarcinoma. MDM2 inhibition, which switches pyroptosis to apoptosis, can be employed to regulate chemotherapy-induced pyroptosis in lung cancer cells and normal tissue cells.

Integrated multi-omics analysis highlighted cytosolic DNA-sensing and NOD-like receptor signaling as key pathways underlying PAL's effects. Collectively, PAL mitigates ALI by inhibiting NLRP3 inflammasome activation, suppressing pyroptosis, and reprogramming metabolism, supporting its potential as a therapeutic candidate.

The pyroptosis inhibitor azalamellarin N reversed the effects induced by si-XPOT. Silencing XPOT promotes pyroptosis in BC cells and inhibits BC progression, suggesting that targeting XPOT could offer new therapeutic avenues for BC treatment.

NLRP3 or GSDMD overexpression partly counteracted DDX3X knockdown-improved OA chondrocyte pyroptosis and inflammation. Inhibiting the DDX3X/NLRP3/GSDMD axis alleviated chondrocyte pyroptosis and inflammatory response in OA in vitro, thus ameliorating chondrocyte injury.