Interestingly, omega-3 nanoemulsion reversed the results above, dramatically improving renal function and histological picture. Thus, omega-3 nanoemulsion provided a notable method for suppressing colistin-induced nephrotoxicity via its antioxidant and anti-inflammatory power, inhibiting pathological autophagy and necroptosis.

Moreover, RIPK3 system reinvigorated the TIME by promoting dendritic cell (DC) maturation, polarizing the macrophages towards the M1 phenotype, and reducing the exhaustion of CD4+ and CD8+ T lymphocytes. Our study highlights the dual role of RIPK3-driven necroptotic system in improving the safety and efficacy of cancer cell-based therapy, with broader implications for cellular therapies.

The deletion of SPOP, which led to increased stability of the RIPK3 protein, intensified LPS/sMAC/zVAD-induced necroptotic cell death in colon cancer cells. These findings underscore the critical role of the SPOP-mediated RIPK3 stability regulation pathway in controlling necroptotic cell death.

Using in vitro experiments, we validated the effects of GSK872 on necroptosis in SH-SY5Y neuronal and BV2 microglial cells. Overall, our results suggest that GSK872 exerts neuroprotective and anti-inflammatory effects, and may thus have therapeutic potential for PD.

In addition, the RIPK1, RIPK3, MLKL, and caspase-8 expression levels were significantly decreased, evidenced improvement of intestinal necroptosis by VNP. Hence, VNP potently prevents intestinal injury induced by 5-FU by modulating Keap1/Nrf2/HO-1, NF-κB/TLR4/SOCS3, and RIPK1/RIPK3/MLKL signals.

Furthermore, NSCLC cells-expressing RIPK3 suppressed T cells response to ICI therapy in vitro. Therefore, RIPK3 and MLKL could induce an immunosuppressive microenvironment, resulting in low response to ICI therapy in NSCLC.

A change in the structural rigidity is also suggested by the observation of weakened signals for mouse RIPK3 upon mixing with RIPK1 to form the RIPK1/RIPK3 complex fibrils. Our results provide vital information to understand the interactions between different proteins with RHIM, which will help us further comprehend the regulation mechanism in cell necroptosis.

Caspase 8 activation and cell death were associated with increased Fas on ILC3s, and the Fas-FasL pathway was upregulated by cILC3s during enteric infection, which could restrain the abundance of intestinal ILC3s. Collectively, these data reveal that interpretation of key cytokine signals controls ILC3 survival following microbial challenge, and that an imbalance of these pathways, such as in IBD or across ILC3 subsets, provokes depletion of tissue-protective ILC3s from the inflamed intestine.

5Z treatment enhances IAV-induced cell death and slightly reduces the inflammatory response in the lungs of H1N1 virus-infected mice and prolongs the survival of IAV-infected mice. Our study provides evidence that IAV activates TAK1 to suppress RIPK1-dependent apoptosis and necroptosis, and that RIPK3 is required for IAV-induced necroptosis but not apoptosis in epithelial cells.

The sequential maturation of dendritic cells (DCs) subsequently enhanced the infiltration of CD8+ and CD4+ T cells in tumors, while inhibiting regulatory T cells (Treg cells), resulting in the effective treatment of primary and distal tumor growth and the inhibition of TNBC metastasis. This work highlights the importance of nanoparticles in mediating drug interactions during necroptotic ICD.

This review summarizes the recent research progress of the regulators of the RIPK3 signaling pathway and discusses the potential role of RIPK3/necroptosis in the aetiopathogenesis of various diseases. An in-depth understanding of the mechanisms and functions of RIPK3 may facilitate the development of novel therapeutic strategies.

We propose that OSW-1 can induce necroptosis through the RIPK1/RIPK3/MLKL signaling pathway, and that this effect is mediated by the RIPK1-p62/SQSTM1 complex, in CRC cells. These results provide a theoretical foundation for the use of OSW-1 in the clinical treatment of CRC.