RIPK3 (Receptor Interacting Serine/Threonine Kinase 3)

VA may exert hepatoprotection by suppressing RIG-I, reducing TNF-α, and inhibiting RIPK1/RIPK3/MLKL-mediated necroptosis.

See also the graphical abstract(Fig. 1).

Functionally, RIPK3 shaped a diverse immune environment by promoting the invasion of innate and adaptive immune cells in patient samples and experimental mice. Thus, RIPK3-mediated inflammatory signaling enhances a diverse immune microenvironment and hinders progression in lung adenocarcinoma.

This is the first study defining the function of canine RIPK3 and potentially immunostimulatory, non-lytic, cell death in canine cells. This form of cell death can be further developed to ignite immunity against virus infections and cancer.

Additionally, TSA enhanced T-cell-mediated anti-tumor immunity, as indicated by lower levels of CD8a+PD1+ and CD4+PD1+ regulatory T cells and higher levels of CD8a+Granzyme+, CD4+Granzyme+, CD8a+IFNγ+, and CD4+IFNγ+ cells in the spleen and tumor. In conclusion, TSA attenuates RIPK1/RIPK3/MLKL-signalling and reprograms the immunosuppressive TME, inhibiting OSCC progression and highlighting its potential as a therapeutic agent in clinical conditions.

To gain insights on these transitions between states of vulnerability to cell death, we developed a compartmental model explaining the emergence of drug-tolerant cell populations, and the fluxes between drug-sensitivity states. We found that drug-sensitivity states coexist in a clonal population of cancer cells with continuous transitions between them, which are sufficient to explain both the sustained resistance to repeated treatments and how alternating drug treatments ameliorates the overall treatment efficacy.

Juglone inhibits the viability of KG-1a, MV-411, THP-1 and MOLM-13 cells, and induces apoptosis of MOLM-13 cells, the mechanism of which may be related to the inhibition of RIPK1/RIPK3/MLKL signaling pathway.

Importantly, treatment with 100 µM Nec-1 or 3 µM GSK-872 notably attenuated TNF-α-induced necroptosis signaling, inflammatory cytokine expression, and the activity of ALT, AST, GGT, and GLDH. In conclusion, these data suggest that necroptosis is associated with hepatic damage, and may be a potential therapeutic target to ameliorate liver dysfunction in dairy cows with ketosis.

In cells with enforced RIPK3 expression, cisplatin treatment significantly increased phosphorylation of both RIPK3 and its target, MLKL, indicative of induction of necroptosis. Here, we identify RIPK3 as an important mediator of chemoresistance in OS and a potential pharmacologic target to improve chemotherapy efficacy in drug-resistant tumors.

The findings of this study suggested that compound 5q acts through necroptosis by overexpression of P-RIPK3 and phosphorylation of its downstream effector, MLKL. Compound 5q holds promise as a potential candidate for the development of anti-TNBC drugs.

Overexpression of RIPK3 was associated with specific subtypes of AML, such as FAB-M4/M5, normal karyotype and NPM1 mutation, and may facilitate the leukemic development. Moreover, RIPK3 overexpression was associated poor prognosis, and may guide treatment choice in AML.

However, Tasi treatment reversed all these findings. Tasi protected against brain injury through the NRF-2/HO-1 and RIPK1/RIPK3/MLKL pathways in rats with TBI.