Iron toxicity, ferroptosis and microbiota in Parkinson’s disease: Implications for novel targets

Advances in neurotoxicology, Год журнала: 2024, Номер unknown, С. 105 - 132

Опубликована: Янв. 1, 2024

Язык: Английский

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Targeting iron-metabolism:a potential therapeutic strategy for pulmonary fibrosis

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 172, С. 116270 - 116270

Опубликована: Фев. 15, 2024

Iron homeostasisis is integral to normal physiological and biochemical processes of lungs. The maintenance iron homeostasis involves the process intake, storage output, dependening on iron-regulated protein/iron response element system operate tightly metabolism-related genes, including TFR1, DMT1, Fth, FPN. Dysregulation can lead overload, which increases virulence microbial colonisers occurrence oxidative stress, causing alveolar epithelial cells undergo necrosis apoptosis, form extracellular matrix. Accumulated drive iron-dependent ferroptosis exacerbated pulmonary fibrosis. Notably, chelator deferoxamine lipophilic antioxidant ferritin-1 have been shown attenuate inhibit lipid peroxidation in paper summarises regulatory mechanisms dysregulated metabolism development Targeting may be a potential therapeutic strategy for prevention treatment

Язык: Английский

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Ferrostatin-1 inhibits fibroblast fibrosis in keloid by inhibiting ferroptosis

PeerJ, Год журнала: 2024, Номер 12, С. e17551 - e17551

Опубликована: Июнь 14, 2024

Background Keloid is a chronic proliferative fibrotic disease caused by abnormal fibroblasts proliferation and excessive extracellular matrix (ECM) production. Numerous disorders are significantly influenced ferroptosis, targeting ferroptosis can effectively mitigate fibrosis development. This study aimed to investigate the role mechanism of in keloid Methods tissues from patients normal skin healthy controls were collected. Iron content, lipid peroxidation (LPO) level, mRNA protein expression ferroptosis-related genes including solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), transferrin receptor (TFRC), nuclear factor erythroid 2-related 2 (Nrf2) determined. Mitochondrial morphology was observed using transmission electron microscopy (TEM). (KFs) isolated tissues, treated with inhibitor ferrostatin-1 (fer-1) or activator erastin. marker levels, LPO mitochondrial membrane potential, ATP KFs detected. Furthermore, levels α-smooth muscle actin (α-SMA), collagen I, III measured whether affect KFs. Results We found that iron content level substantially elevated SLC7A11, GPX4, Nrf2 downregulated TFRC upregulated Mitochondria exhibited pathology. Fer-1 treatment reduced restrained dysfunction KFs, Moreover, α-SMA, Whereas erastin showed opposite results. Conclusion Ferroptosis exists keloid. Ferrostatin-1 ECM deposition through inhibiting induced intensifying ferroptosis.

Язык: Английский

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Identification and validation of five ferroptosis-related molecular signatures in keloids based on multiple transcriptome data analysis

Frontiers in Molecular Biosciences, Год журнала: 2025, Номер 11

Опубликована: Янв. 6, 2025

Keloids are a common skin disorder characterized by excessive fibrous tissue proliferation, which can significantly impact patients' health. Ferroptosis, form of regulated cell death, plays crucial role in the development fibrosis; however, its mechanisms keloid formation remains poorly understood. This study aimed to identify key genes associated with ferroptosis formation. Data from NCBI GEO database, including GSE145725, GSE7890, and GSE44270, were analyzed, comprising total 24 17 normal samples. Additionally, single-cell data GSE181316, included 8 samples complete expression profiles, also evaluated. Differentially expressed identified, ferroptosis-related extracted GeneCards database. LASSO regression was used select keloids. Validation performed using qRT-PCR Western blot (WB) analysis on five biopsies. A 471 differentially identified GSE145725 dataset, 225 upregulated 246 downregulated genes. Five selected through gene intersection regression. Two these upregulated, while three tissue. Further GSEA pathway enrichment, GSVA set variation, immune infiltration analysis, sequencing revealed that primarily involved fibrotic process. The WB results confirmed patterns provides novel insights into molecular could serve as potential biomarkers or therapeutic targets for treating

Язык: Английский

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A potent GPX4 degrader to induce ferroptosis in HT1080 cells

European Journal of Medicinal Chemistry, Год журнала: 2023, Номер 265, С. 116110 - 116110

Опубликована: Дек. 31, 2023

Язык: Английский

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Anti-oxidants as Therapeutic Agents for Oxidative Stress Associated Pathologies: Future Challenges and Opportunities

Free Radical Research, Год журнала: 2025, Номер unknown, С. 1 - 25

Опубликована: Янв. 7, 2025

Free radicals have been implicated in the pathogenesis of cancer along with cardiovascular, neurodegenerative, pulmonary and inflammatory disorders. Further, relationship between oxidative stress disease is distinctively established. Clinical trials using anti-oxidants for prevention progression indicated some beneficial effects. However, these failed to establish as therapeutic agents due lack efficacy. This attributed fact that living systems are under dynamic redox control wherein their behaviour compartmentalized simple aggregation couples, distributed throughout system, miniscule importance while determining overall state. free radical metabolism intriguingly complex they play plural roles segregated a spatio-temporal manner. Depending on quality, quantity site generation, exhibit or harmful Use non-specific, non-targeted, general ROS scavengers lead systemic elimination all types interferes cellular signaling. Failure act lies this oversimplification extremely environment static non-compartmentalized Rather than generalizing term "oxidative stress" if we can identify "type different diseases, targeted more specific anti-oxidant therapy may be developed. In review, discuss concept dynamics, role type conditions, current status agents. probe possibility developing novel, efficacious drug-like properties.

Язык: Английский

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ADAM17/PTGS2 Facilitates Pulmonary Fibrosis by Regulating Ferroptosis

Journal of Cellular and Molecular Medicine, Год журнала: 2025, Номер 29(5)

Опубликована: Март 1, 2025

ABSTRACT Pulmonary fibrosis (PF) is a chronic and progressive interstitial lung disease characterised by excessive deposition of extracellular matrix (ECM), resulting in high mortality rates. In this study, we provide evidence that ADAM17/PTGS2 plays crucial role inducing ferroptosis fibroblasts, promoting PF. Initially, an assessment was made ADAM17 protein levels patients diagnosed with connective tissue diseases–interstitial diseases (CTD‐ILD), using ELISA assays. Confirmation the relationship between achieved stimulating cells PMA or TAPI‐1 (the inhibitor), conjunction fibrosis‐inducing factor, TGFβ1. To further explore major downstream proteins contributing to altered PF, employed mRNA transcriptomics. investigate fibrosis, western blot assays, immunofluorescence transmission electron microscopy (TEM). Furthermore, effects ADAM17/PTGS2/ferroptosis pathway PF were verified Adeno‐associated virus (AAV)‐mediated gene knockdown mice. CTD‐ILD patients, expression significantly elevated. Upon stimulation, fibroblasts exhibited increased fibrosis‐related proteins, combined stimulation TGFβ1 synergistically promoted cellular fibrosis. Conversely, alleviated fibrotic induced Transcriptomic analysis fibroblast specimens overexpressing revealed elevated PTGS2 levels. Knockdown inhibition assays demonstrated regulates via PTGS2, ultimately deficiency bleomycin‐induced inflammation These findings first novel mechanism for regulating PF; it provides new theoretical basis exploring treatment

Язык: Английский

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Wuwei Shaji powder alleviates OVA-induced allergic asthma by protecting bronchial epithelial cells from ferroptosis via the S-sulfhydration of Keap1

Journal of Ethnopharmacology, Год журнала: 2025, Номер unknown, С. 119649 - 119649

Опубликована: Апрель 1, 2025

Язык: Английский

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Gui-zhi-fu-ling-wan alleviates bleomycin-induced pulmonary fibrosis through inhibiting epithelial-mesenchymal transition and ferroptosis

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Апрель 16, 2025

Idiopathic pulmonary fibrosis (IPF) has a higher morbidity and poor prognosis. Gui-Zhi-Fu-Ling-Wan (GFW) is traditional Chinese herbal formula which exerts anti-inflammatory anti-oxidative effects. The goal was to determine the protective effect of GFW on bleomycin (BLM)-induced fibrosis. One hundred twenty-four mice were randomly divided into eight groups, orally supplemented with (1 g/kg) in 1 week ago continuing later single BLM intratracheal injection (5.0 mg/kg). Lung tissues collected 7 days 21 after injection. BEAS-2B cells pretreated (100 μg/mL) for three consecutive before (10 exposure. Cells harvested 12 or 24 h co-culture. supplementation alleviated BLM-induced alveolar structure destruction inflammatory cell infiltration lungs. BLM-incurred collagen deposition attenuated by GFW. In addition, pretreatment repressed BLM-evoked downregulation E-cadherin, elevation N-cadherin Vimentin mouse Besides, BLM-excited GPX4 reduction, ferritin increases, lipid peroxidation, free iron overload significantly relieved lungs cells. Notably, BLM-provoked mitochondrial reactive oxygen species (mtROS) excessive production, stress markers, such as HSP70 CLPP, injury, all abolished pretreatment. lung injury partially through repressing EMT mtROS-mediated ferroptosis epithelial

Язык: Английский

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Ferroptosis in idiopathic pulmonary fibrosis: mechanisms, impact, and therapeutic opportunities

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Май 21, 2025

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by progressive scarring, alveolar destruction, and limited therapeutic options. Although the exact etiology of IPF remains unclear, emerging evidence suggests that ferroptosis, an iron-dependent form regulated cell death driven lipid peroxidation oxidative stress, plays significant role in its pathogenesis. Ferroptotic stress not only compromises epithelial integrity, but also triggers inflammatory responses profibrotic signaling cascades activate sustain fibroblast dysfunction. This review delineates core regulatory pathways iron metabolism, peroxidation, antioxidant defenses, mitochondrial remodeling, RNA editing, with emphasis on their relevance IPF. We explore how injury macrophage-derived signals initiate subsets, shaped scRNA-seq-defined heterogeneity plasticity, respond to these cues reinforcing ECM deposition stress. Therapeutic avenues targeting including supplementation, chelation, modulation are discussed alongside cell-specific interventions nanodelivery strategies. By integrating recent advances molecular profiling ferroptosis biology, this provides framework for leveraging as tractable target identifies novel directions precision antifibrotic therapy.

Язык: Английский

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