The role of microbial indole metabolites in tumor

Gut Microbes, Journal Year: 2024, Volume and Issue: 16(1)

Published: Oct. 1, 2024

The gut microbiota can produce a variety of microbial-derived metabolites to influence tumor development. Tryptophan, an essential amino acid in the human body, be converted by microorganisms via indole pathway such as Indole-3-Lactic Acid (ILA), Indole-3-Propionic (IPA), Indole Acetic (IAA) and Indole-3-Aldehyde (IAld). Recent studies have shown that play key roles progression, they used adjuvant regimens for immunotherapy or chemotherapy. Here, we summarize recent findings on common microbial provide review mechanisms different microenvironment. We further discuss limitations current metabolite research future possibilities. It is expected will new strategies clinical therapy.

Language: Английский

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Ferroptosis: mechanisms and therapeutic targets

MedComm, Journal Year: 2024, Volume and Issue: 5(12)

Published: Nov. 20, 2024

Ferroptosis is a nonapoptotic form of cell death characterized by iron-dependent lipid peroxidation in membrane phospholipids. Since its identification 2012, extensive research has unveiled involvement the pathophysiology numerous diseases, including cancers, neurodegenerative disorders, organ injuries, infectious autoimmune conditions, metabolic and skin diseases. Oxidizable lipids, overload iron, compromised antioxidant systems are known as critical prerequisites for driving overwhelming peroxidation, ultimately leading to plasma rupture ferroptotic death. However, precise regulatory networks governing ferroptosis ferroptosis-targeted therapy these diseases remain largely undefined, hindering development pharmacological agonists antagonists. In this review, we first elucidate core mechanisms summarize epigenetic modifications (e.g., histone modifications, DNA methylation, noncoding RNAs, N6-methyladenosine modification) nonepigenetic genetic mutations, transcriptional regulation, posttranslational modifications). We then discuss association between disease pathogenesis explore therapeutic approaches targeting ferroptosis. also introduce potential clinical monitoring strategies Finally, put forward several unresolved issues which progress needed better understand hope review will offer promise application therapies context human health disease.

Language: Английский

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Gut Microbiota at the Crossroad of Hepatic Oxidative Stress and MASLD

Antioxidants, Journal Year: 2025, Volume and Issue: 14(1), P. 56 - 56

Published: Jan. 6, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic condition marked by excessive lipid accumulation in hepatic tissue. This disorder can lead to range of pathological outcomes, including metabolic steatohepatitis (MASH) and cirrhosis. Despite extensive research, the molecular mechanisms driving MASLD initiation progression remain incompletely understood. Oxidative stress peroxidation are pivotal "multiple parallel hit model", contributing cell death tissue damage. Gut microbiota plays substantial role modulating oxidative through multiple pathways: impairing intestinal barrier, which results bacterial translocation inflammation; modifying bile acid structure, impacts signaling cascades involved lipidic metabolism; influencing hepatocytes' ferroptosis, form programmed death; regulating trimethylamine N-oxide (TMAO) activating platelet function, both recently identified as pathogenetic factors MASH progression. Moreover, various exogenous impact gut its involvement MASLD-related stress, such air pollution, physical activity, cigarette smoke, alcohol, dietary patterns. manuscript aims provide state-of-the-art overview focused on intricate interplay between microbiota, peroxidation, pathogenesis, offering insights into potential strategies prevent associated complications.

Language: Английский

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The Lactate‐Primed KAT8‒PCK2 Axis Exacerbates Hepatic Ferroptosis During Ischemia/Reperfusion Injury by Reprogramming OXSM‐Dependent Mitochondrial Fatty Acid Synthesis

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Abstract Recipients often suffer from hyperlactatemia during liver transplantation (LT), but whether exacerbates hepatic ischemia‐reperfusion injury (IRI) after donor implantation remains unclear. Here, the role of in IRI is explored. In this work, found to exacerbate ferroptosis IRI. Lactate‐primed lysine acetyltransferase 8 (KAT8) determined directly lactylate mitochondrial phosphoenolpyruvate carboxykinase 2 (PCK2) at Lys100 and augments PCK2 kinase activity. By using gene‐edited mice, evidence indicating that generated. Mechanistically, acts as a critical inducer by competitively inhibiting Parkin‐mediated polyubiquitination 3‐oxoacyl‐ACP synthase (OXSM), thereby leading metabolic remodeling fatty acid synthesis (mtFAS) potentiation oxidative phosphorylation tricarboxylic cycle. More importantly, targeting demonstrated markedly ameliorate hyperlactatemia‐mediated Collectively, findings support use therapeutics suppress patients with LT.

Language: Английский

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Laminin-dystroglycan mediated ferroptosis in hemorrhagic shock and reperfusion induced-cognitive impairment through AMPK/Nrf2

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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