Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14
Published: Oct. 16, 2024
Pyroptosis is an inflammatory form of programmed cell death that plays a significant role in tumorigenesis. Cinobufotalin (CB), bufadienolide extracted from toad venom, associated with antitumor effects various cancers, including liver cancer. However, the CB pyroptosis and its underlying mechanisms have not been well characterized.
Language: Английский
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4537 - 4537
Published: April 20, 2024
NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) is an intracellular complex that upon external stimuli or contact with specific ligands, recruits other components, forming the inflammasome. The inflammasome mainly mediates pyroptosis, a highly inflammatory mode of regulated cell death, as well IL-18 IL-1β production. Acute chronic liver diseases are characterized by massive influx pro-inflammatory enriched in reactive oxygen species (ROS) damage-associated molecular patterns (DAMPs) promote assemblage activation As major cause cytokine storm, exacerbates diseases, even though it might exert protective effects regards to hepatitis C B virus infection (HCV HBV). Here, we summarize current knowledge concerning function both acute disease post transplant setting, focusing on mechanisms involved activity.
Language: Английский
Citations
8
Science Advances, Journal Year: 2025, Volume and Issue: 11(1)
Published: Jan. 1, 2025
The NOD-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in human acute and chronic liver diseases. However, the cell-specific contribution of NLRP3 regeneration remains unclear. Here, we found that was highly activated during early stage via 70% partial hepatectomy (PHx) mice model clinical data. Global depletion or pharmacologically blocking significantly enhanced regeneration, while overexpression impaired it after PHx. Furthermore, with myeloid-specific knockout Nlrp3 ( Δ mye ), rather than hepatocyte-specific hep showed improved compared to control fl/fl ). Mechanistically, deficiency promoted myeloid-epithelial-reproductive tyrosine kinase (MerTK)–mediated efferocytosis, thereby inducing macrophages toward pro-reparative Ly6C lo phenotype. Notably, inhibition by MCC950 effectively reversed impairment PHx fed high-fat diet. Our findings provide potential therapeutic strategy for prevention treatment post-hepatectomy failure.
Language: Английский
Citations
0
International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1493 - 1493
Published: Feb. 11, 2025
(1) Liver injury caused by an overdose of acetaminophen (APAP) represents a major public health concern. Paeoniflorin (PF) has been reported to have anti-inflammatory and liver-protective effects, but the underlying mechanisms remain unclear. This study aimed investigate effect PF on crosstalk between pyroptosis NETs in AILI. (2) APAP-treated C57BL/6J mice were used demonstrate protective liver injury. HepG2 dHL-60 cells cultured effects hepatocyte neutrophil extracellular traps (NETs) vitro. Moreover, cell co-culture experiments performed, treated with NETs-depleting agent inhibitor improvement AILI induced through regulating NETs. (3) significantly alleviated Additionally, inhibited expression pyroptosis-related proteins, high-mobility group box 1 (HMGB1), NETs-associated proteins vitro vivo. The demonstrated that not only triggered pyroptosis, also suppressed In depleted neutrophils, level notably decreased, indicating diminished impact PF. Similarly, formation was reduced receiving compared APAP group. Compared DNase I alone, reduction combined serum ALT AST levels decreased from 46.857% 39.927% 44.347% 33.419%, respectively. DSF 45.347% 36.419%, (4) therapeutic Its mechanism involves regulation research substantiates pharmacological promise as intervention for acute
Language: Английский
Citations
0
International Immunopharmacology, Journal Year: 2025, Volume and Issue: 150, P. 114299 - 114299
Published: Feb. 16, 2025
Language: Английский
Citations
0
Toxicology Research, Journal Year: 2024, Volume and Issue: 13(5)
Published: Sept. 2, 2024
Abstract Background Acute liver injury (ALI) is characterized by massive hepatocyte death and has high mortality poor prognosis. Hepatocyte pyroptosis plays a key role in the pathophysiology of ALI involved inflammatory response mediated NOD-like receptor protein 3 (NLRP3) inflammasome activation. Deltex 1 (DTX1) single transmembrane with ubiquitin E3 ligase activity closely cell growth, differentiation, apoptosis, as well intracellular signal transduction. However, little known about influence DTX1 on ALI. This study aimed to investigate inflammation induced D-galactosamine (D-GalN) tumor necrosis factoralpha (TNF-α) human hepatocytes (LO2 cells) vitro. Methods Cell was measured flow cytometry. The levels DTX1, pyroptosis-associated proteins, cytokines were detected quantitative real-time polymerase chain reaction, western blotting, enzyme-linked immunosorbent assay. Immunofluorescence staining, co-immunoprecipitation, ubiquitination, luciferase reporter chromatin immunoprecipitation assays performed detect regulation between NLRP3 or nuclear factor 4 alpha (HNF4α). Analysis variance compare groups. Results We found that decreased D-GalN/TNF-α-induced LO2 cells. overexpression significantly inhibited inflammation. interacted ubiquitination degradation. Furthermore, targeting NLRP3, knockdown In addition, HNF4α promoted transcription binding its promoter. Conclusion Our revealed suppressed regulating ubiquitination.
Language: Английский
Citations
1
Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14
Published: Oct. 16, 2024
Pyroptosis is an inflammatory form of programmed cell death that plays a significant role in tumorigenesis. Cinobufotalin (CB), bufadienolide extracted from toad venom, associated with antitumor effects various cancers, including liver cancer. However, the CB pyroptosis and its underlying mechanisms have not been well characterized.
Language: Английский
Citations
1