Advances in Ferroptosis Research: A Comprehensive Review of Mechanism Exploration, Drug Development, and Disease Treatment

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(3), P. 334 - 334

Published: Feb. 26, 2025

In recent years, ferroptosis, as an emerging modality of programmed cell death, has captured significant attention within the scientific community. This comprehensive review meticulously canvasses pertinent literature past few spanning multiple facets. It delves into intricate mechanisms underpinning tracks evolution its inducers and inhibitors, dissects roles in a diverse array diseases, well resultant therapeutic implications. A profound exploration is conducted functional ferroptosis-related molecules, intracellular pathways, metabolic cascades, signaling transduction routes. Novel ferroptosis inhibitors are introduced detail, covering their design blueprints, synthetic methodologies, bioactivity profiles. Moreover, exhaustive account provided regarding involvement malignancies, neurodegenerative disorders, cardiovascular ailments, other pathologies. By highlighting pivotal status potential regimens various this aspires to furnish thorough reference framework for future investigations clinical translations domain.

Language: Английский

ELAVL1‐dependent SOAT2 exacerbated the pancreatitis‐like cellular injury of AR42J cells induced by hyperstimulation with caerulein

The Kaohsiung Journal of Medical Sciences, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 26, 2024

Abstract Pancreatitis is a severe inflammatory condition characterized by damage to the pancreas. Sterol o‐acyltransferase 2 (SOAT2) has been reported aggravate acute pancreatitis, however, underlying mechanism remains be elucidated. Rat pancreatic exocrine cells (AR42J) were treated with caerulein induce pancreatitis‐like cellular injury. Cell viability was determined using cell counting kit‐8 (CCK‐8) assay, while proliferation analyzed through 5‐Ethynyl‐2′‐deoxyuridine assay. apoptosis measured flow cytometry, and enzyme‐linked immunosorbent assays performed detect levels of pro‐inflammatory cytokines IL‐6 TNF‐α. Additionally, Fe 2+ colorimetric assay kit, reactive oxygen species (ROS) assessed Cellular ROS Assay lipid peroxidation malondialdehyde kit. Glutathione detection Protein mRNA expression evaluated western blotting quantitative real‐time polymerase chain reaction, respectively. Furthermore, an RNA immunoprecipitation conducted investigate association between ELAV‐like binding protein 1 (ELAVL1) SOAT2. Actinomycin D explore effect ELAVL1 depletion on transcript stability SOAT2 mRNA. upregulated in caerulein‐exposed AR42J cells. Caerulein treatment induced apoptosis, response, ferroptosis, inhibition. Silencing protected against caerulein‐induced Moreover, stabilized overexpression attenuated effects silencing knockdown activated NRF2/HO‐1 pathway downregulating from injury inactivating NRF2 pathway. In conclusion, ELAVL1‐dependent exacerbated pancreatitis. These findings provide new insights into molecular mechanisms pancreatitis offer potential therapeutic targets for this condition.

Language: Английский

Role and mechanism of myonectin in severe acute pancreatitis: a crosstalk between skeletal muscle and pancreas

Skeletal Muscle, Journal Year: 2024, Volume and Issue: 14(1)

Published: Dec. 3, 2024

Severe acute pancreatitis (SAP) is characterized by high mortality rates and various complications, including skeletal muscle atrophy, which significantly exacerbates its outcomes. Despite clinical relevance, the mechanistic understanding of relationship between pancreas in SAP remains limited. Our study aimed to elucidate this "organ crosstalk" potential implications. We established an mouse model through pancreatic duct ligation (PDL) evaluated necrosis, myonectin expression levels. Recombinant protein was administered vivo vitro assess effects on acinar cell necrosis. Mechanistic insights were gained RNA-seq data analysis experimental validation. Serum samples from AP patients healthy controls collected investigate correlation serum levels disease severity. The exhibited severe elevated levels, with administration exacerbating identified iron accumulation-induced ferroptosis as a key pathway contributing myonectin-mediated A total 22 52 varying degrees included (36.5% females, age 49.79 ± 16.53). Analysis revealed higher patients, correlating severity (R = 0.28, P 0.041). findings underscore significant role progression prognostic marker for patients. This contributes deeper pathophysiology highlights therapeutic targets intervention.

Language: Английский