Iron, Oxidative Stress, and Metabolic Dysfunction—Associated Steatotic Liver Disease

Antioxidants, Journal Year: 2024, Volume and Issue: 13(2), P. 208 - 208

Published: Feb. 7, 2024

Excess free iron is a substrate for the formation of reactive oxygen species (ROS), thereby augmenting oxidative stress. Oxidative stress well-established cause organ damage in liver, main site storage. Ferroptosis, an iron-dependent mechanism regulated cell death, has recently been gaining attention development and progression liver disease. We therefore summarize mechanisms metabolism, its close connection to ferroptosis, particular relevance disease metabolic-dysfunction-associated fatty potential targets therapy from clinical perspective.

Language: Английский

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Esculin inhibits hepatic stellate cell activation and CCl4-induced liver fibrosis by activating the Nrf2/GPX4 signaling pathway

Phytomedicine, Journal Year: 2024, Volume and Issue: 128, P. 155465 - 155465

Published: Feb. 17, 2024

Language: Английский

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SLC7A11-ROS/αKG-AMPK axis regulates liver inflammation through mitophagy and impairs liver fibrosis and NASH progression

Redox Biology, Journal Year: 2024, Volume and Issue: 72, P. 103159 - 103159

Published: April 16, 2024

The changes of inflammation and metabolism are two features in nonalcoholic steatohepatitis (NASH). However, how they interact to regulate NASH progression remains largely unknown. Our works have demonstrated the importance solute carrier family 7 member 11 (SLC7A11) metabolism. Nevertheless, whether SLC7A11 regulates through mediating is unclear. In this study, we found that expression was increased liver samples from patients with NASH. Upregulated level also detected murine models. Functional studies showed knockdown or knockout had augmented suppression inflammatory markers mice. overexpression dramatically alleviated diet-induced pathogenesis. Mechanically, decreased reactive oxygen species (ROS) promoted α-ketoglutarate (αKG)/prolyl hydroxylase (PHD) activity, which activated AMPK pathway. Furthermore, impaired NLRP3 inflammasome components AMPK-mitophagy axis. IL-1β release recruited myeloid cells hepatic stellate (HSCs) activation, contributed injury fibrosis. Anti-IL-1β anakinra might attenuate response evoked by knockdown. Moreover, upregulation lipid overload-induced JNK-c-Jun conclusions, acts as a protective factor controlling development Upregulation regulating oxidation, αKG energy metabolism, decreasing

Language: Английский

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Reactive oxygen species regulation by NCF1 governs ferroptosis susceptibility of Kupffer cells to MASH

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(8), P. 1745 - 1763.e6

Published: June 7, 2024

Language: Английский

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Metabolic Messengers: small extracellular vesicles

Nature Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

Language: Английский

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Metal Ion Signaling in Biomedicine

Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Complex multicellular organisms are composed of distinct tissues involving specialized cells that can perform specific functions, making such life forms possible. Species defined by their genomes, and differences between individuals within a given species directly result from variations in genetic codes. While alterations give rise to disease-causing acquisitions cell identities, it is now well-established biochemical imbalances also lead cellular dysfunction diseases. Specifically, nongenetic chemical events orchestrate metabolism transcriptional programs govern functional identity. Thus, signaling, which broadly defines the conversion extracellular signals into intracellular changes, contribute acquisition diseased states. Metal ions exhibit unique properties be exploited cell. For instance, metal maintain ionic balance cell, coordinate amino acid residues or nucleobases altering folding function biomolecules, catalyze reactions. metals essential signaling effectors normal physiology disease. Deciphering ion challenging endeavor illuminate pathways targeted for therapeutic intervention. Here, we review key processes where play roles describe how targeting has been instrumental dissecting biochemistry this led development effective strategies.

Language: Английский

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Ferroptosis and its interaction with tumor immune microenvironment in liver cancer

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2022, Volume and Issue: 1878(1), P. 188848 - 188848

Published: Dec. 9, 2022

Language: Английский

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Arbutin alleviates fatty liver by inhibiting ferroptosis via FTO/SLC7A11 pathway

Redox Biology, Journal Year: 2023, Volume and Issue: 68, P. 102963 - 102963

Published: Nov. 16, 2023

Non-alcoholic fatty liver disease (NAFLD) is a potentially serious that affects 30 % of the global population and poses significant risk to human health. However, date, no safe, effective appropriate treatment modalities are available. In recent years, ferroptosis has emerged as mode cell death been found play key regulatory role in development NAFLD. this study, we arbutin (ARB), natural antioxidant derived from Arctostaphylos uva-ursi (L.), inhibits onset ameliorates high-fat diet-induced NAFLD vivo vitro. Using reverse docking, identified demethylase fat mass obesity-related protein (FTO) potential target ARB. Subsequent mechanistic studies revealed ARB plays controlling methylation SLC7A11 gene through inhibition FTO. addition, demonstrated could alleviate Our findings identify FTO/SLC7A11 axis therapeutic for Specifically, show alleviates by acting on pathway inhibit ferroptosis.

Language: Английский

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Extracellular vesicles: emerging roles, biomarkers and therapeutic strategies in fibrotic diseases

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: May 24, 2023

Abstract Extracellular vesicles (EVs), a cluster of cell-secreted lipid bilayer nanoscale particles, universally exist in body fluids, as well cell and tissue culture supernatants. Over the past years, increasing attention have been paid to important role EVs effective intercellular communicators fibrotic diseases. Notably, EV cargos, including proteins, lipids, nucleic acids, metabolites, are reported be disease-specific can even contribute fibrosis pathology. Thus, considered biomarkers for disease diagnosis prognosis. Emerging evidence shows that derived from stem/progenitor cells great prospects cell-free therapy various preclinical models diseases engineered improve targeting effectiveness their treatment. In this review, we will focus on biological functions mechanisms diseases, potential novel therapeutic strategies.

Language: Английский

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Activation of Kupffer cells in NAFLD and NASH: mechanisms and therapeutic interventions

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: May 16, 2023

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are emerging as the leading causes of worldwide. These conditions can lead to cirrhosis, cancer, failure, other related ailments. At present, transplantation remains sole treatment option for end-stage NASH, a rapidly growing socioeconomic burden. Kupffer cells (KCs) dominant population macrophages that reside in liver, playing crucial role innate immunity. Their primary function includes phagocytosing exogenous substances, presenting antigens, triggering immune responses. Moreover, they interact with during pathogenesis NAFLD, this crosstalk may either delay or exacerbate progression. Stimulation by endogenous signals triggers activation KCs, resulting expression various inflammatory factors chemokines, such NLRP3, TNF-α, IL-1B, IL-6, contributing cascade. In past 5 years, significant advances have been made understanding biological properties functions KCs including their interactions tissue molecules, underlying molecular mechanisms, signaling pathways, relevant therapeutic interventions. Having comprehensive these mechanisms characteristics enormous potential guiding future strategies prevention NAFLD.

Language: Английский

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