CASP4 (Caspase 4)

These data identify the miR-203a-CASP4/11/B axis as a critical mediator of endothelial pyroptosis in sepsis. PHN attenuates sepsis by upregulating miR-203a to inhibit CASP4/11/B-dependent pyroptosis. Therefore, PHN warrants further investigation as a potential therapeutic agent for sepsis.

Mechanistically, LPS via the autocrine/paracrine action of type-I interferon (IFN) activates caspase-4 (Casp4) to cleave the N-terminal domain of GSDMD for the formation of cell surface GSDMD pores that permit the extracellular release of unconjugated ISG15 in the absence of lytic cell death. Together, our studies have identified the IFN-Casp4-GSDMD axis as a previously unrecognized non-classical pathway for unconjugated ISG15 release from cells.

Targeting pyroptosis is a novel therapeutic avenue for PN. This review synthesizes current mechanistic understanding, evaluates preclinical therapeutic strategies, and delineates crucial future directions, including elucidating gasdermin diversity, validating PANoptosis, and bridging the translational divide, thereby accelerating their application for patients suffering from PN.

Importantly, systemic inflammation induced by LPS or bacterial infection is attenuated in Apip cKO mice but exacerbated in APIP-transgenic mice. Thus, our findings suggest that APIP is crucial in regulating both canonical and non-canonical inflammasomes, presenting a potential therapeutic target for inflammatory diseases.

In this study, the efficacy of the drug Vx-445 (Elexacaftor), used in the pharmacological treatment of cystic fibrosis, was assessed in human adenocarcinomic basal alveolar epithelial (A549) and neuronal (SH-SY5Y) cell lines, where ER stress was induced by Thapsigargin. The results obtained suggest a significant effect of Vx-445 in restoring cellular homeostasis, leading to reduced expression of inflammation-related proteins, such as IL-6, tested by ELISA. Although preliminary, these results encourage further studies to explore the potential repurpose of Vx-445 as a therapeutic candidate for conditions involving ER stress and chronic inflammatory diseases associated with protein misfolding, beyond its current use in cystic fibrosis.

The details of the molecular level along with the investigation of the physicochemical properties of Hesperetin regarding the mechanism of destabilization of Aβ1-42 fibrils introduce it as a promising therapeutic agent for AD management. Our experimental findings also indicate that Hesperetin is a compound that prevents neuronal death by reducing inflammation and inhibiting apoptosis and pyroptosis.

In vivo, bAP15 suppressed xenograft growth. Collectively, these data support proteasome-associated DUB inhibition as a potential strategy in chondrosarcoma, with bAP15 serving as a chemical tool to probe this target class.

Interestingly, addressing the expression pattern for advanced-stage FL patients, the low protein expression of both CASP4 and CASP8 was also found to be associated with progressing cases, suggesting their potential role in disease pathogenesis independent of the disease stage. With further research, the expression pattern of CASP4 and CASP8 may enable the early prediction of disease progression in FL patients, which may ultimately improve patient stratification and allow for more individualized treatment strategies.

These results indicate a novel function of CASP4 in facilitating DNA repair by regulating the balance of cytoplasmic and nuclear actin, thereby enhancing radioresistance. Overall, we uncover a novel role of CASP4 in modulating nuclear actin dynamics to promote DNA DSB repair and suggest attenuating CASP4 in tumor cells may block tumor cell resistance to ionizing radiation.

In this review, we present a comprehensive overview of inflammasomes with an emphasis on the mechanistic principles that govern inflammasome formation. We also discuss the contributions of inflammasome activation to health and disease.

Interpretation & conclusions IL-32 plays a pivotal immunoregulatory role in the GBM microenvironment by driving macrophage differentiation and M2 polarisation, contributing to tumour immune evasion. These findings highlight IL-32 as a potential therapeutic target for modulating immune responses in GBM and underscore its relevance in the design of future immunotherapeutic strategies.

Besides, the upstream TF network of the 7 differentiated expressed pyroptosis-related key genes was constructed. Our team developed a diagnostic model for pyroptosis-related signatures in Alzheimer's disease, investigating ceRNA and TF regulatory networks, which may facilitate the diagnosis of AD with blood-based biomarkers.