Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Дек. 10, 2023

Abstract Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other modes, plays pivotal role in regulating tumorigenesis offers new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications posttranslational (PTMs) promote resistance, cancer progression, metastasis. Accumulating studies indicate that can transcriptionally translationally determine vulnerability to ferroptosis functions as driver nervous system diseases (NSDs), cardiovascular (CVDs), liver diseases, lung kidney diseases. In this review, we first summarize the core molecular mechanisms ferroptosis. Then, roles processes, including histone PTMs, DNA methylation, noncoding RNA regulation such phosphorylation, ubiquitination, SUMOylation, acetylation, ADP-ribosylation, are concisely discussed. The PTMs genesis cancers, NSD, CVDs, well application PTM modulators therapy these then discussed detail. Elucidating mediated by will facilitate development promising combination therapeutic regimens containing or PTM-targeting agents inducers be used overcome chemotherapeutic resistance could prevent addition, highlight potential approaches chemoresistance halt

Язык: Английский

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The mechanism of ferroptosis and its related diseases

Molecular Biomedicine, Год журнала: 2023, Номер 4(1)

Опубликована: Окт. 16, 2023

Abstract Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation lipid peroxides, provides novel avenue for delving into intersection metabolism, oxidative stress, and disease pathology. We have witnessed mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, traumatic tissue injuries. By unraveling intricate underpinnings molecular machinery, contributors, signaling conduits, regulatory networks governing researchers aim bridge gap between intricacies this unique mode multifaceted implications health disease. In light rapidly advancing landscape ferroptosis research, we present comprehensive review aiming at extensive in origins progress human diseases. This concludes careful analysis potential treatment approaches carefully designed either inhibit or promote ferroptosis. Additionally, succinctly summarized therapeutic targets compounds that hold promise targeting within various facet underscores burgeoning possibilities manipulating as strategy. summary, enriched insights both investigators practitioners, while fostering an elevated comprehension latent translational utilities. revealing basic processes investigating possibilities, crucial resource scientists medical aiding deep understanding effects situations.

Язык: Английский

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GPX4, ferroptosis, and diseases

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 174, С. 116512 - 116512

Опубликована: Апрель 3, 2024

GPX4 (Glutathione peroxidase 4) serves as a crucial intracellular regulatory factor, participating in various physiological processes and playing significant role maintaining the redox homeostasis within body. Ferroptosis, form of iron-dependent non-apoptotic cell death, has gained considerable attention recent years due to its involvement multiple pathological processes. is closely associated with ferroptosis functions primary inhibitor this process. Together, contribute pathophysiology several diseases, including sepsis, nervous system ischemia reperfusion injury, cardiovascular cancer. This review comprehensively explores roles impacts development progression these aim providing insights for identifying potential therapeutic strategies future.

Язык: Английский

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Extracellular vesicles in nanomedicine and regenerative medicine: A review over the last decade

Bioactive Materials, Год журнала: 2024, Номер 36, С. 126 - 156

Опубликована: Март 2, 2024

Small extracellular vesicles (sEVs) are known to be secreted by a vast majority of cells. These sEVs, specifically exosomes, induce specific cell-to-cell interactions and can activate signaling pathways in recipient cells through fusion or interaction. nanovesicles possess several desirable properties, making them ideal for regenerative medicine nanomedicine applications. properties include exceptional stability, biocompatibility, wide biodistribution, minimal immunogenicity. However, the practical utilization particularly clinical settings at large scale, is hindered expensive procedures required their isolation, limited circulation lifetime, suboptimal targeting capacity. Despite these challenges, sEVs have demonstrated remarkable ability accommodate various cargoes found extensive applications biomedical sciences. To overcome limitations broaden potential applications, researchers should strive deepen understanding current loading, characterization techniques. Additionally, acquiring fundamental knowledge about origins employing state-of-the-art methodologies expand research scope. This review provides comprehensive overview exosome-based strategies diverse domains, encompassing cancer therapy, immunotherapy, biomarker Furthermore, we emphasize immense exosomes medicine.

Язык: Английский

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The MSC-EV-microRNAome: A Perspective on Therapeutic Mechanisms of Action in Sepsis and ARDS

Cells, Год журнала: 2024, Номер 13(2), С. 122 - 122

Опубликована: Янв. 9, 2024

Mesenchymal stromal cells (MSCs) and MSC-derived extracellular vesicles (EVs) have emerged as innovative therapeutic agents for the treatment of sepsis acute respiratory distress syndrome (ARDS). Although their potential remains undisputed in pre-clinical models, this has yet to be translated clinic. In review, we focused on role microRNAs contained EVs, EV microRNAome, contribution mechanisms action. The evidence that miRNA transfer EVs a overall effects is compelling. However, several questions remain regarding how reconcile stochiometric issue low copy numbers miRNAs present particles, different delivered simultaneously interact with targets within recipient cells, best or combination use therapy, potency markers, biomarkers efficacy Here, offer molecular genetics systems biology perspective function microRNAs, action, potential.

Язык: Английский

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Recent advances in the use of extracellular vesicles from adipose-derived stem cells for regenerative medical therapeutics

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Июнь 6, 2024

Abstract Adipose-derived stem cells (ADSCs) are a subset of mesenchymal (MSCs) isolated from adipose tissue. They possess remarkable properties, including multipotency, self-renewal, and easy clinical availability. ADSCs also capable promoting tissue regeneration through the secretion various cytokines, factors, extracellular vesicles (EVs). ADSC-derived EVs (ADSC-EVs) act as intercellular signaling mediators that encapsulate range biomolecules. These have been found to mediate therapeutic activities donor by proliferation migration effector cells, facilitating angiogenesis, modulating immunity, performing other specific functions in different tissues. Compared themselves, ADSC-EVs offer advantages such fewer safety concerns more convenient transportation storage for application. As result, these received significant attention cell-free agents with potential future application regenerative medicine. In this review, we focus on recent research progress regarding medical use across conditions, wound healing, chronic limb ischemia, myocardial infarction, diabetic nephropathy, fat graft survival, bone regeneration, cartilage tendinopathy tendon peripheral nerve acute lung injury, among others. We discuss underlying mechanisms responsible inducing effects. believe deciphering biological effects, associated will provide foundation developing novel approach Graphical

Язык: Английский

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The crosstalk between exosomal miRNA and ferroptosis: A narrative review

Biology of the Cell, Год журнала: 2025, Номер 117(1)

Опубликована: Янв. 1, 2025

Ferroptosis is a type of cell death that multiple mechanisms and pathways contribute to the positive negative regulation it. For example, increased levels reactive oxygen species (ROS) induce ferroptosis. ferroptosis unlike apoptosis, it not dependent on caspases, but iron. Exosomes are membrane-bound vesicles with size about 30 150 nm, contain various cellular components, including DNA, RNA, microRNAs (miRNAs), lipids, proteins, which genetically similar their cells origin. found in all bodily fluids, blood, saliva, urine. Cells often release exosomes after fusion membrane. They play an important role immune cell-cell communication. miRNAs, noncoding RNAs length 18 24 nucleotides, involved regulating gene expression transcription. Emerging data suggests exosomal miRNAs implicated pathophysiological cells, metastasis, drug resistance, death. In addition, functional studies have indicated can key modulation by Therefore, this review, given importance ferroptosis, we decided elucidate relationship between diseases.

Язык: Английский

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Tangeretin alleviates sepsis-induced acute lung injury by inhibiting ferroptosis of macrophage via Nrf2 signaling pathway

Chinese Medicine, Год журнала: 2025, Номер 20(1)

Опубликована: Янв. 15, 2025

Abstract Background Sepsis-induced acute lung injury (ALI) is a severe clinical condition accompanied with high mortality. Tangeretin, which widely found in citrus fruits, has been reported to exert antioxidant and anti-inflammatory properties. However, whether tangeretin protects against sepsis-induced ALI the potential mechanisms remain unclear. Methods We established an model via intraperitoneally injected 5 mg/kg lipopolysaccharides (LPS) for 12 h. Tangeretin was applied 30 min before LPS treatment. Dexamethasone (Dex) used as positive control. Hematoxylin eosin (HE) staining protein content bronchoalveolar lavage fluid (BALF) were determined detect degree of injury. RNA-seq also explore effect on ALI. In vitro, RAW264.7 treated Nrf2 siRNA, expression ferroptosis-associated biomarkers, including glutathione peroxidase 4 (GPX4) prostaglandin-endoperoxide synthase 2 (PTGS2) assessed. Glutathione (GSH), malondialdehyde (MDA) levels, reactive oxygen species (ROS) inflammatory factors both vivo vitro. Furthermore, mice inhibitor (ML385) verify mechanism inhibiting ferroptosis. Data analyzed using one way analysis variance or two-tailed unpaired t tests. Results Our study demonstrated that significantly alleviated injury, reversed LPS-induced reduction GPX4 GSH, mitigates elevation PTGS2 MDA levels. reduced 4-HNE iron Besides, levels LPS-stimulated IL-6, IL-1β TNF-α decreased by tangeretin. bioinformatics inhibited response. Mechanistically, we identified GPX4-dependent lipid peroxidation through activation Nrf2. The silence abolished inhibitory oxidative stress, response ferroptosis cells. Additionally, all protective effects inhibitor-treated mice. Conclusion critical contributing promising therapeutic candidate, effectively upregulating signaling pathway.

Язык: Английский

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Polystyrene nanoplastics-induced lung apoptosis and ferroptosis via ROS-dependent endoplasmic reticulum stress

The Science of The Total Environment, Год журнала: 2023, Номер 912, С. 169260 - 169260

Опубликована: Дек. 10, 2023

Язык: Английский

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MCL attenuates atherosclerosis by suppressing macrophage ferroptosis via targeting KEAP1/NRF2 interaction

Redox Biology, Год журнала: 2023, Номер 69, С. 102987 - 102987

Опубликована: Дек. 7, 2023

Micheliolide (MCL), which is the active metabolite of parthenolide, has demonstrated promising clinical application potential. However, effects and underlying mechanisms MCL on atherosclerosis are still unclear.

Язык: Английский

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