PANoptosis is a new cell death proposed by Malireddi et al in 2019, which is characterized by pyroptosis, apoptosis and necroptosis, but cannot be explained by any of them alone. The interaction between pyroptosis, apoptosis and necroptosis is involved in PANoptosis. In this review, from the perspective of PANoptosis, we focus on the relationship between pyroptosis, apoptosis and necroptosis, the key molecules in the process of PANoptosis and the formation of PANoptosome, as well as the role of PANoptosis in diseases. We aim to understand the mechanism of PANoptosis and provide a basis for targeted intervention of PANoptosis-related molecules to treat human diseases.

Objective: Acute kidney injury (AKI) is a common complication of acute liver failure (ALF). Pyroptosis is a necrosis type related to inflammation. This study aimed to investigate the role of TNF‐α/HMGB1 pathway in pyroptosis during ALF and AKI.Methods: An ALF and AKI mouse model was generated using LPS/D‐Gal, and a TNF‐α inhibitor, CC‐5013, was used to treat the mice. THP‐1 cells were induced to differentiate into M1 macrophages, then challenged with either CC‐5013 or an HMGB1 inhibitor, glycyrrhizin. pLVX‐mCMVZsGreen‐PGK‐Puros plasmids containing TNF‐α wild‐type (WT), mutation A94T of TNF‐α and mutation P84L of TNF‐α were transfected into M1 macrophages.Results: Treatment with CC‐5013 decreased the activation of TNF‐α/HMGB1 pathway and pyroptosis in the treated mice and cells compared with the control mice and cells. CC‐5013 also ameliorated liver and kidney pathological changes and improved liver and renal functions in treated mice, and the number of M1 macrophages in the liver and kidney tissues also decreased. The activation of TNF‐α/HMGB1 pathway and pyroptosis increased in the M1 macrophage group compared with the normal group. Similarly, the activation of TNF‐α/HMGB1 pathway and pyroptosis in the LPS + WT group also increased. By contrast, the activation of the TNF‐α/HMGB1 pathway and pyroptosis decreased in the LPS + A94T and LPS + P84L groups. Moreover, glycyrrhizin inhibited pyroptosis.Conclusion: The TNF‐α/HMGB1 inflammation signalling pathway plays an important role in pyroptosis during ALF and AKI.

The purpose of this study was to investigate whether inhibition of DNA (cytosine-5)-methyltransferase 1 (DNMT-1) alleviated ferroptosis through nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy during diabetes myocardial (DM) ischemia/reperfusion (I/R) injury (IRI). Rat DM + sham (DS), I/R, and DM + I/R (DIR), H9c2 cell high glucose (HG), hypoxia reoxygenation (H/R), and high-glucose hypoxia reoxygenation (HH/R) models were established. DNMT-1 inhibitor 5-Aza-2’-deoxycytidine (5-aza-CdR) was administered to rat and cell models. The protein level of DNMT-1, NCOA4, FTH, GPX4, Beclin-1, and P62 was detected by western blotting. Compared with normal sham (NS) group, myocardial tissue was injured in DS and I/R models. The level of DNMT-1, NCOA4, and ferroptosis was increased. Moreover, the cell injury was more serious in rat DIR or HH/R model. 5-Aza-CdR could reduce NCOA4-mediated ferritinophagy and myocardial injury in DIR and HH/R models. Moreover, the siRNA for NCOA4 could also reduce the level of ferritinophagy and cell injury in HH/R model. 5-Aza-CdR enhanced the protective effect for NCOA4-siRNA in the process of cell injury. Inhibition of DNMT-1 could reduce ferroptosis during DIR, which the NCOA4-mediated ferritinophagy might be regulated.

Eukaryotic cells are stimulated by external pressure such as that derived from heat shock, oxidative stress, nutrient deficiencies, or infections, which induce the formation of stress granules (SGs) that facilitates cellular adaptation to environmental pressures. As aggregated products of the translation initiation complex in the cytoplasm, SGs play important roles in cell gene expression and homeostasis. Infection induces SGs formation. Specifically, a pathogen that invades a host cell leverages the host cell translation machinery to complete the pathogen life cycle. In response, the host cell suspends translation, which leads to SGs formation, to resist pathogen invasion. This article reviews the production and function of SGs, the interaction between SGs and pathogens, and the relationship between SGs and pathogen-induced innate immunity to provide directions for further research into anti-infection and anti-inflammatory disease strategies.

The purpose of this study was to investigate the protective mechanism of HDAC2 inhibitor CAY10683 on intestinal mucosal barrier in acute liver failure (ALF). In order to establish ALF-induced intestinal epithelial barrier disruption models, D-galactosamine/LPS and LPS were, respectively, used with rats and NCM460 cell and then administrated with CAY10683. Transepithelial electrical resistance (TEER) was measured to detect the permeability of cells. Real-time PCR and Western blotting were employed to detect the key mRNA and protein levels. The intestinal epithelial tissue pathology was detected. After interfering with CAY10683, the mRNA and protein levels of TLR4, MyD88, TRIF, and TRAF6 were decreased compared with model group (P<0.05), whereas the levels of ZO-1 and occluding were elevated (P<0.05). The permeability was elevated in CAY10683-interfered groups, when compared with model group (P<0.05). And the degree of intestinal epithelial tissue pathological damage in CAY10683 group was significantly reduced. Moreover, CAY10683 significantly decreased the TLR4 staining in animal tissue. The HDAC2 inhibitor CAY10683 could promote the damage of intestinal mucosal barrier in ALF through inhibiting LPS/TLR4/MyD88 pathway.