Elucidating the pathway activity and prognostic significance of diverse cell-death patterns in idiopathic pulmonary fibrosis DOI Creative Commons
Jiazheng Sun,

Yalu Sun,

Hehua Guo

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: April 19, 2024

Abstract Background Idiopathic pulmonary fibrosis (IPF) is one of the interstitial lung diseases (ILDs) with poor prognosis. Multiple regulated cell death (RCD) pathways are involved in regulating progression at different stages. Methods A total 20 RCD and crucial regulatory genes were collected from available literature. The study initially elucidated profiling kinds normal fibrotic tissues based on scRNAseq dataset bulk-RNAseq dataset. Targets associated IPF identified by Mendelian randomization analysis, univariate Cox regression was used to further identify RCD-related significantly overall survival (OS). combination 101 distinct machine-learning algorithms utilized develop a prognostic signature. In addition, we investigated relationship between signature clinical characteristics. Results By integrating data data, pathway activity patterns patients. following detailed research various patterns, developed CDI 13 genes, which combined multiple machine learning methods generate has strong predictive influence prognosis As proven independent datasets, patients high had poorer outcome. From characteristics, have impaired function. Finally, nomogram ability generated Conclusion summary, novel model that effectively forecasts patterns.

Language: Английский

Iron toxicity, ferroptosis and microbiota in Parkinson’s disease: Implications for novel targets DOI
Fernanda V. Carvalho,

Harold E. Landis,

Bruk Getachew

et al.

Advances in neurotoxicology, Journal Year: 2024, Volume and Issue: unknown, P. 105 - 132

Published: Jan. 1, 2024

Language: Английский

Citations

9
Targeting iron-metabolism:a potential therapeutic strategy for pulmonary fibrosis DOI Open Access
Yi Sun,

Yu Ren,

Liyun Song

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 172, P. 116270 - 116270

Published: Feb. 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

Language: Английский

Citations

7
Ferrostatin-1 inhibits fibroblast fibrosis in keloid by inhibiting ferroptosis DOI Creative Commons
Yang Liu,

Xiuli Li,

Yanli Wang

et al.

PeerJ, Journal Year: 2024, Volume and Issue: 12, P. e17551 - e17551

Published: June 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.

Language: Английский

Citations

7
Identification and validation of five ferroptosis-related molecular signatures in keloids based on multiple transcriptome data analysis DOI Creative Commons
Zhen Sun, Yonghong Qin, Xuanfen Zhang

et al.

Frontiers in Molecular Biosciences, Journal Year: 2025, Volume and Issue: 11

Published: Jan. 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

Language: Английский

Citations

0
Anti-oxidants as Therapeutic Agents for Oxidative Stress Associated Pathologies: Future Challenges and Opportunities DOI
Shivani R. Nandha, Rahul Checker, Raghavendra S. Patwardhan

et al.

Free Radical Research, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 25

Published: Jan. 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.

Language: Английский

Citations

0
ADAM17/PTGS2 Facilitates Pulmonary Fibrosis by Regulating Ferroptosis DOI Creative Commons

Suyan Yan,

Yaqi Zhao, Wei Xu

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(5)

Published: March 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

Language: Английский

Citations

0
Wuwei Shaji powder alleviates OVA-induced allergic asthma by protecting bronchial epithelial cells from ferroptosis via the S-sulfhydration of Keap1 DOI
Hongwei Zhao, Haiyan Zhang, Jian‐Yu Shi

et al.

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119649 - 119649

Published: April 1, 2025

Language: Английский

Citations

0
Gui-zhi-fu-ling-wan alleviates bleomycin-induced pulmonary fibrosis through inhibiting epithelial-mesenchymal transition and ferroptosis DOI Creative Commons

Z. Chen,

Mengmeng Ma, Rui Wang

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 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

Language: Английский

Citations

0
A potent GPX4 degrader to induce ferroptosis in HT1080 cells DOI

Haoze Song,

Jing Liang,

Yuanyuan Guo

et al.

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 265, P. 116110 - 116110

Published: Dec. 31, 2023

Language: Английский

Citations

8
Ginsenoside Re Alleviates Oxidative Stress Damage and Ferroptosis in Pulmonary Fibrosis Mice by Regulating the Nrf2/Keap1/GPX4 axis DOI

Huicai Lin,

Zhongyuan Wen,

Linying Feng

et al.

International Journal of Drug Discovery and Pharmacology, Journal Year: 2024, Volume and Issue: unknown, P. 100025 - 100025

Published: Dec. 17, 2024

Article Ginsenoside Re Alleviates Oxidative Stress Damage and Ferroptosis in Pulmonary Fibrosis Mice by Regulating the Nrf2/Keap1/GPX4 axis Huicai Lin 1,2,3, Zhaoqin Wen Linying Feng Xiaoyan Chen 4, Yongxiang Song 5, Jiang Deng 1,2,3,* 1 Key Laboratory of Basic Pharmacology Ministry Education Joint International Research Ethnomedicine Education, Zunyi Medical University, Zunyi563006, China 2 Guizhou Province, 3 The Second Affiliated Hospital 4 Department Pathophysiology, 5 Thoracic Surgery, * Correspondence: [email protected]; Tel.: +86-851-2864-3411; Fax: +86-851-2864-3411 Received: 30 August 2024; Revised: 28 September Accepted: Published: 17 December 2024 Abstract: fibrosis (PF) is a chronic, progressive, irreversible, fibrotic interstitial lung disease with high mortality. (G-Re) one active components ginseng, which has been proven to possess multiple pharmacological effects, including anti-inflammatory antioxidant. Thus, G-Re considered potential therapeutic agent for treating PF. present study explored protective mechanisms against bleomycin (BLM)-induced PF mice its as strategy A mouse model BLM-induced was utilized assess effect treatment, N-acetylcysteine (NAC) set positive control agent. Various parameters such function, histopathological changes, oxidative stress markers, nuclear factor erythroid 2-related (Nrf2) translocation related protein expressions, Kelch-like ECH-associated (Keap1), heme oxygenase (HO-1), NAD(P)H quinone oxidoreductase (NQO-1), ferroptosis signature glutathione peroxidase (GPX4) were evaluated. Continuous administration 14 days significantly reduced injury, enhanced antioxidant capacity, activated Nrf2/Keap1 signaling pathway, inhibited evidenced GPX4. Additionally, treatment collagen deposition, improved pulmonary alleviated tissue mice. These findings demonstrate that exerts effects modulating targeting pathways, highlighting intervention providing insights into molecular underlying effects.

Language: Английский

Citations

1