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

Ferroptosis: Mechanisms and role in diabetes mellitus and its complications DOI
Pan Liu, Zhengdong Zhang, Yichen Cai

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 94, P. 102201 - 102201

Published: Jan. 19, 2024

Language: Английский

Citations

44
Comprehensive review of potential drugs with anti-pulmonary fibrosis properties DOI Open Access
Jie Ma, Gang Li, Han Wang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 173, P. 116282 - 116282

Published: Feb. 23, 2024

Pulmonary fibrosis is a chronic and progressive lung disease characterized by the accumulation of scar tissue in lungs, which leads to impaired function reduced quality life. The prognosis for idiopathic pulmonary (IPF), most common form fibrosis, generally poor. median survival patients with IPF estimated be around 3–5 years from time diagnosis. Currently, there are two approved drugs (Pirfenidone Nintedanib) treatment IPF. However, Pirfenidone Nintedanib not able reverse or cure fibrosis. There need new pharmacological interventions that can slow halt progression This review aims provide an updated overview current future drug summarize possible targets potential anti-pulmonary drugs, providing theoretical support further clinical combination therapy development drugs.

Language: Английский

Citations

18
Polystyrene microplastics induce pulmonary fibrosis by promoting alveolar epithelial cell ferroptosis through cGAS/STING signaling DOI Creative Commons

Jinming Zhang,

Jiangzhou Du,

Dongyu Liu

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 277, P. 116357 - 116357

Published: April 26, 2024

Polystyrene microplastics (PS-MPs) are new types of environmental pollutant that have garnered significant attention in recent years since they were found to cause damage the human respiratory system when inhaled. The pulmonary fibrosis is one serious consequences PS-MPs inhalation. However, impact and underlying mechanisms on not clear. In this study, we studied potential lung toxicity PS-MPs-developed by long-term intranasal inhalation PS-MPs. results showed after exposing PS-MPs, lungs model mouse had different levels fibrosis. Meanwhile, resulted a markedly decrease glutathione (GSH), an increase malondialdehyde (MDA), iron overload tissue mice alveolar epithelial cells (AECs). These findings suggested occurrence PS-MP-induced ferroptosis. Inhibitor ferroptosis (Fer-1) alleviated PS-MPs-induced Mechanically, triggered cell promoted development via activating cGAS/STING signaling pathway. Inhibition with G150/H151 attenuated exposure. Together, these data provided novel mechanistic insights therapeutic paradigm.

Language: Английский

Citations

18
Combining single-cell RNA sequencing and population-based studies reveals hand osteoarthritis-associated chondrocyte subpopulations and pathways DOI Creative Commons
Hui Li, Xiaofeng Jiang, Yongbing Xiao

et al.

Bone Research, Journal Year: 2023, Volume and Issue: 11(1)

Published: Nov. 2, 2023

Hand osteoarthritis is a common heterogeneous joint disorder with unclear molecular mechanisms and no disease-modifying drugs. In this study, we performed single-cell RNA sequencing analysis to compare the cellular composition subpopulation-specific gene expression between cartilage macroscopically confirmed (n = 5) without from interphalangeal joints of five donors. Of 105 142 cells, identified 13 subpopulations, including novel subpopulation inflammation-modulating potential annotated as inflammatory chondrocytes. Fibrocartilage chondrocytes exhibited extensive alteration patterns in osteoarthritic compared nonosteoarthritic cartilage. Both fibrocartilage showed trend toward increased numbers these two subpopulations cartilage, ferroptosis pathway was enriched, iron overload-related genes, e.g., FTH1, elevated. To verify findings, conducted Mendelian randomization study using UK Biobank population-based cross-sectional data collected Xiangya Osteoarthritis Study. Genetic predisposition higher FTH1 mRNA significantly risk hand (odds ratio 1.07, 95% confidence interval: 1.02-1.11) among participants 332 668) Biobank. High levels serum ferritin (encoded by FTH1), biomarker body overload, were associated high prevalence 1 241) Study (P-for-trend 0.037). conclusion, our findings indicate that are key may be osteoarthritis, providing new insights into pathophysiology therapeutic targets osteoarthritis.

Language: Английский

Citations

30
The emerging roles of ferroptosis in organ fibrosis and its potential therapeutic effect DOI

Xuege Huang,

Yahui Song,

Lin Wei

et al.

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 116, P. 109812 - 109812

Published: Feb. 4, 2023

Language: Английский

Citations

24
Liproxstatin-1 Alleviates Lung Transplantation-induced Cold Ischemia–Reperfusion Injury by Inhibiting Ferroptosis DOI
Jin Zhao, Jiawei Li, Wei Dong

et al.

Transplantation, Journal Year: 2023, Volume and Issue: 107(10), P. 2190 - 2202

Published: May 19, 2023

Background. Primary graft dysfunction, which is directly related to cold ischemia–reperfusion (CI/R) injury, a major obstacle in lung transplantation (LTx). Ferroptosis, novel mode of cell death elicited by iron-dependent lipid peroxidation, has been implicated ischemic events. This study aimed investigate the role ferroptosis LTx-CI/R injury and effectiveness liproxstatin-1 (Lip-1), inhibitor, alleviating injury. Methods. LTx-CI/R-induced signal pathway alterations, tissue death, inflammatory responses, ferroptotic features were examined human biopsies, bronchial epithelial (BEAS-2B) cells, mouse model (24-h CI/4-h R). The therapeutic efficacy Lip-1 was explored validated both vitro vivo. Results. In tissues, activated ferroptosis-related signaling pathway, increased iron content peroxidation accumulation, altered key protein (GPX4, COX2, Nrf2, SLC7A11) expression mitochondrial morphology. BEAS-2B hallmarks significantly evidenced at setting CI CI/R compared with control, effect adding only during much better than that reperfusion Cell Counting Kit-8. Furthermore, administration markedly relieved mice, as indicated significant improvement pathological changes, pulmonary function, inflammation, ferroptosis. Conclusions. revealed existence pathophysiology Using inhibit could ameliorate suggesting might be proposed new strategy for organ preservation.

Language: Английский

Citations

24
METTL3 regulates TFRC ubiquitination and ferroptosis through stabilizing NEDD4L mRNA to impact stroke DOI Creative Commons
Wenjie Su, Xiang Yu, Shan Wang

et al.

Cell Biology and Toxicology, Journal Year: 2024, Volume and Issue: 40(1)

Published: Feb. 2, 2024

Abstract Background Stroke is a major medical problem, and novel therapeutic targets are urgently needed. This study investigates the protective role potential mechanisms of N6-methyladenosine (m6A) RNA methyltransferase METTL3 against cerebral injury resulting from insufficient blood flow. Methods In this study, we constructed mouse MCAO models HT-22 cell OGD/R to mimic ischemic stroke-induced brain neuronal damage. We generated NEDD4L knockout overexpression validated effects using infarct volume, edema, neurologic scoring. performed qRT-PCR, western blotting, co-immunoprecipitation assess influence on ferroptosis markers TFRC expression. verified effect ubiquitination by detecting half-life ubiquitination. Finally, impact mRNA stability outcomes in both vitro vivo experimental models. Result find expression downregulated Overexpressing inhibits iron carrier protein upregulating E3 ubiquitin ligase NEDD4L, thereby alleviating oxidative damage protect injury. Mechanistic studies show can methylate stabilize mRNA, enhancing As downstream effector, ubiquitinates degrades TFRC, reducing accumulation ferroptosis. Conclusion summary, uncover METTL3-NEDD4L-TFRC axis critical for inhibiting post-ischemic Enhancing pathway may serve as an effective strategy stroke therapy. lays theoretical foundation developing m6A-related therapies

Language: Английский

Citations

15
Advances in Ferroptosis-Inducing Agents by Targeted Delivery System in Cancer Therapy DOI Creative Commons

Debiao Xiang,

Lili Zhou, Ruizhen Yang

et al.

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 2091 - 2112

Published: March 1, 2024

Abstract: Currently, cancer remains one of the most significant threats to human health. Treatment cancers challenging, despite implementation diverse therapies in clinical practice. In recent years, research on mechanism ferroptosis has presented novel perspectives for treatment. Ferroptosis is a regulated cell death process caused by lipid peroxidation membrane unsaturated fatty acids catalyzed iron ions. The rapid development bio-nanotechnology generated considerable interest exploiting iron-induced as new therapeutic target against cancer. This article provides comprehensive overview advancements at intersection and bionanotechnology. this respect, its relation are summarized. Furthermore, feasibility nano-drug delivery system based treatment introduced analyzed. Secondly, strategies inducing using nanodrug technology discussed, including promoting Fenton reactions, inhibiting glutathione peroxidase 4, reducing low levels, Xc − . Additionally, explores potential combined involving Finally, application prospects challenges nanoagents discussed. Keywords: cancers, ferroptosis, system,

Language: Английский

Citations

11
Targeting ferroptosis using Chinese herbal compounds to treat respiratory diseases DOI Creative Commons

Mengjiao Xu,

Di Zhang, Jun Yan

et al.

Phytomedicine, Journal Year: 2024, Volume and Issue: 130, P. 155738 - 155738

Published: June 1, 2024

Respiratory diseases pose a grave threat to human life. Therefore, understanding their pathogenesis and therapeutic strategy is important. Ferroptosis novel type of iron-dependent programmed cell death, distinct from apoptosis, necroptosis, autophagy, characterised by iron, reactive oxygen species, lipid peroxide accumulation, as well glutathione (GSH) depletion GSH peroxidase 4 (GPX4) inactivation. A close association between ferroptosis the onset progression respiratory diseases, including chronic obstructive pulmonary disease, acute lung injury, bronchial asthma, fibrosis, cancer, has been reported. Recent studies have shown that traditional Chinese medicine (TCM) compounds exhibit unique advantages in treatment owing natural properties potential efficacy. These can effectively regulate modulating several key signalling pathways such system Xc

Language: Английский

Citations

11
Suppressing Endoplasmic Reticulum Stress Alleviates LPS-Induced Acute Lung Injury via Inhibiting Inflammation and Ferroptosis DOI
Sijiao Wang, Fan Xu, Hanhan Liu

et al.

Inflammation, Journal Year: 2024, Volume and Issue: 47(4), P. 1067 - 1082

Published: Feb. 3, 2024

Language: Английский

Citations

10