GPx1 deficiency confers increased susceptibility to ferroptosis in macrophages from individuals with active Crohn’s disease DOI
James A. Sousa, Blanca E. Callejas, Arthur Wang

et al.

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

Published: Sept. 5, 2024

Abstract Intestinal cell death is a defining feature of Crohn’s disease (CD), major form inflammatory bowel disease. The focus on this aspect enteric inflammation has mainly been epithelial cells, while other types such as stromal and myeloid cells have received less attention. Hypothesising that decreased macrophage viability in an oxidative environment could be contributing factor to the pathophysiology CD, we found monocyte-derived macrophages from individuals with active CD (but not those clinical remission) increased sensitivity induced by H2O2. Molecular biology pharmacological studies ruled out apoptosis necroptosis, lipid peroxidation surface expression transferrin receptor implicated ferroptosis mechanism H2O2-induced death: was supported suppression H2O2-cytotoxicity liproxstatin-1, inhibitor ferroptosis. Selenoproteins are important antioxidants, selenium deficiency can CD. Despite normal dietary intake selenium, intestinal had protein and/or mRNA selenoprotein, glutathione peroxidase (GPx)-1. Knockdown GPx1 healthy volunteers resulted reminiscent observed In summary, susceptibility death, may facilitated, at least part, reduced antioxidant GPx1. We suggest monocytes recruited gut renders these vulnerable reactive oxygen species-evoked unravelling participation pathway reveal novel therapeutic approaches chronic condition.

Language: Английский

Hesperetin Alleviated Experimental Colitis via Regulating Ferroptosis and Gut Microbiota DOI Open Access
Jinzhi Wang, Yuanyuan Yao, Ting Yao

et al.

Nutrients, Journal Year: 2024, Volume and Issue: 16(14), P. 2343 - 2343

Published: July 19, 2024

Hesperetin (HT) is a type of citrus flavonoid with various pharmacological activities, including anti-tumor, anti-inflammation, antioxidant, and neuroprotective properties. However, the role mechanism HT in ulcerative colitis (UC) have been rarely studied. Our study aimed to uncover beneficial effects its detailed UC. Experimental was induced by 2.5% dextran sodium sulfate (DSS) for seven days. ameliorated DSS-induced mice, showing marked improvement weight loss, colon length, colonic pathological severity, levels TNFα IL6 serum. A combination informatics, network pharmacology, molecular docking identified eight key targets multi-pathways influenced As highlight, experimental validation demonstrated that PTGS2, marker ferroptosis, along other indicators ferroptosis (such as ACSL4, Gpx4, lipid peroxidation), were regulated vivo vitro. Additionally, supplement increased diversity gut microbiota, decreased relative abundance Proteobacteria Gammaproteobacteria, restored bacteria (Lachnospiraceae_NK4A136_group Prevotellaceae_UCG-001). In conclusion, an effective nutritional against suppressing modulating microbiota.

Language: Английский

Citations

9
Coix Seed Oil Alleviates DSS-Induced Ulcerative Colitis via Intestinal Barrier Repair and Ferroptosis Regulation DOI Creative Commons

Yi-Xuan Zeng,

N. Li,

Bing-Ying Deng

et al.

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 2557 - 2581

Published: Feb. 1, 2025

Ulcerative colitis is a chronic intestinal disease linked to barrier damage, ferroptosis and dysbiosis. Coix lacryma-jobi natural food with food-medicine homology, whose seed-derived oil (Coix seed oil, CSO) has been shown anti-inflammatory activity in vitro. Here, the effects mechanisms of CSO on ulcerative (UC) vivo are systematically investigated. Firstly, UC mice was replicated by 3% DSS, assessed efficacy observing fecal occult blood, colon length, DAI score pathological histomorphological changes tissues. The barrier-protective were observed AB staining qRT-PCR. Secondly, biological targets obtained from TCMSP database Swiss Target Prediction database, downloaded FerrDb platform, UC-related GEO intersection above three taken obtain "CSO-UC-Ferroptosis" targets, which analysed GO KEGG enrichment, GSEA analysis, immune cell infiltration validation. Finally, core genes molecular docking potential active components CSO. In order further verify effect ferroptosis, GPX4 agonist RSL-3 used stimulate vivo, levels Iron, MDA SOD measured, immunohistochemistry detect tight junction proteins protein mice. Besides, evaluated intercellular junctions tissues each group under electron microscope. addition, 16sRNA sequencing performed contents observe flora improved physiological parameters, reduced inflammation response regulated restored gut microbiota balance Bioinformatics results showed that G6PD, ABCC1 at CSO, also demonstrated similar expression DSS-induced models vivo. Our findings demonstrate for first time ameliorated regulating mice, suggesting as promising candidate treatment warranting investigation.

Language: Английский

Citations

1
Mitochondrial Dynamics and Metabolism in Macrophages for Cardiovascular Disease: a review DOI

Yi-lang Zhong,

Chenqin Xu,

Ji Li

et al.

Phytomedicine, Journal Year: 2025, Volume and Issue: 140, P. 156620 - 156620

Published: March 7, 2025

Language: Английский

Citations

1
GPX4 restricts ferroptosis of NKp46+ILC3s to control intestinal inflammation DOI Creative Commons
Xinyao Li, Junyu He, Xiang Gao

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(9)

Published: Sept. 19, 2024

Language: Английский

Citations

4
Influence of Mesalazine on Ferroptosis-Related Gene Expression in In Vitro Colorectal Cancer Culture DOI Creative Commons

Joanna Słoka,

Barbara Strzałka‐Mrozik, Sebastian Kubica

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(1), P. 219 - 219

Published: Jan. 16, 2025

Background/Objectives: Colorectal cancer (CRC) is one of the most common oncological disorders. Its fundamental treatments include surgery and chemotherapy, predominantly utilizing 5-fluorouracil (5-FU). Despite medical advances, CRC continues to present a high risk recurrence, metastasis low survival rates. Consequently, significant emphasis has been directed towards exploring novel types cell death, particularly ferroptosis. Ferroptosis characterized by iron imbalance accumulation lipid peroxides reactive oxygen species (ROS), leading cellular damage death. Thus, discovery safe inducers ferroptosis, offering new hope in struggle against CRC, remains crucial. In this study, we applied concept drug repositioning, selecting mesalazine (MES), non-steroidal anti-inflammatory (NSAID), for investigation. Methods: The study was conducted on colon line DLD-1 normal intestinal epithelial cells from CCD 841 CoN line. Both lines were treated with MES solutions at concentrations 10, 20, 30, 40, 50 mM. Cytotoxicity assessed using MTT assay, while ferroptosis-related gene expression analysis performed oligonucleotide microarrays, RT-qPCR used validation. Results: effectively reduces viability minimally affecting cells. Subsequent microarray revealed that significantly alters 56 genes associated Conclusions: Our results suggest may induce ferroptosis providing foundation further research area.

Language: Английский

Citations

0
Scutellaria baicalensis Extracts Restrict Intestinal Epithelial Cell Ferroptosis by Regulating Lipid Peroxidation and GPX4/ACSL4 in Colitis DOI
Jingyan Zhang,

Bingyan Tan,

Hong Wu

et al.

Phytomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 156708 - 156708

Published: March 1, 2025

Language: Английский

Citations

0
Enzymatic Oxidants, Antioxidants, and Inflammatory Bowel Disease DOI Creative Commons
R. Steven Esworthy

Applied Biosciences, Journal Year: 2025, Volume and Issue: 4(2), P. 19 - 19

Published: April 1, 2025

The role of oxidants and antioxidants in inflammatory bowel disease (IBD) has been actively explored since the early 1980s, starting with respiratory burst neutrophils ischemia pathology. Since that time, enzymatic components contributing to pool reactive oxygen species, including superoxide, H2O2, lipid hydroperoxides, counteracting antioxidants—catalase, glutathione peroxidases (Gpx), peroxiredoxins (PRDX), superoxide dismutases, others—have fleshed out. My perspective on IBD is from balance or imbalance oxidant sources process. I will present evidence involvement antioxidant processes based, as much possible, my experiences Gpxs. This be discussed terms both immune system local systems. As Gpxs are generally selenium-dependent, possible deficiencies selenium uptake active impact Gpx expression explored. more recently introduced ferroptosis, an iron-dependent peroxidation-based pathological process, reviewed for its IBD.

Language: Английский

Citations

0
Coixol inhibits the IL17A signaling pathway and promotes mitophagy to improve ulcerative colitis DOI
Jian Chen, Dantong Li, Ya Gao

et al.

Journal of Functional Foods, Journal Year: 2025, Volume and Issue: 128, P. 106798 - 106798

Published: April 9, 2025

Language: Английский

Citations

0
Focusing on ferroptosis in alveolar bone loss during periodontitis: From mechanisms to therapies DOI
Y J Tang, Jianhang Leng, Yankun Luo

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 156, P. 114683 - 114683

Published: April 18, 2025

Language: Английский

Citations

0
Disrupting the immune homeostasis: the emerging role of macrophage ferroptosis in autoimmune diseases DOI
Tian‐Fu Liu, Yichen Huang, Yizhe Wang

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 157, P. 114745 - 114745

Published: May 3, 2025

Language: Английский

Citations

0