Ferroptosis in ulcerative colitis: Potential mechanisms and promising therapeutic targets

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116722 - 116722

Published: May 9, 2024

Ulcerative colitis (UC) is a complex immune-mediated chronic inflammatory bowel disease. It mainly characterized by diffuse inflammation of the colonic and rectal mucosa with barrier function impairment. Identifying new biomarkers for development more effective UC therapies remains pressing task current research. Ferroptosis newly identified form regulated cell death iron-dependent lipid peroxidation. As research deepens, ferroptosis has been demonstrated to be involved in pathological processes numerous diseases. A growing body evidence suggests that pathogenesis associated ferroptosis, regulation provides opportunities treatment. However, specific mechanisms which participates remain fully thoroughly investigated. Therefore, this review, we focus on advances mechanism recent years describe potential role UC. In addition, explore underlying crosslinked pathway between other such as macrophages, neutrophils, autophagy, endoplasmic reticulum stress, gut microbiota Finally, also summarize compounds may act inhibitors future.

Language: Английский

---

Vanillic acid restores homeostasis of intestinal epithelium in colitis through inhibiting CA9/STIM1-mediated ferroptosis

Pharmacological Research, Journal Year: 2024, Volume and Issue: 202, P. 107128 - 107128

Published: March 2, 2024

The damage of integrated epithelial epithelium is a key pathogenic factor and closely associated with the recurrence ulcerative colitis (UC). Here, we reported that vanillic acid (VA) exerted potent therapeutic effects on DSS-induced by restoring intestinal homeostasis via inhibition ferroptosis. By CETSA assay DARTS assay, identified carbonic anhydrase IX (CAIX, CA9) as direct target VA. binding VA to CA9 causes insulin-induced gene-2 (INSIG2) interact stromal interaction molecule 1 (STIM1), rather than SREBP cleavage-activating protein (SCAP), leading translocation SCAP-SREBP1 from endoplasmic reticulum (ER) Golgi apparatus for cleavage into mature SREBP1. activation SREBP1 induced then significantly facilitated transcription SCD1 exert an inhibitory effect inhibiting excessive death cells caused ferroptosis, effectively preserved integrity barrier prevented progression unresolved inflammation. In conclusion, our study demonstrated could alleviate through CA9/STIM1-mediated providing promising candidate UC.

Language: Английский

---

Ferroptosis: Biology and Role in Gastrointestinal Disease

Gastroenterology, Journal Year: 2024, Volume and Issue: 167(2), P. 231 - 249

Published: March 1, 2024

Language: Английский

---

Toxic and essential metals: metabolic interactions with the gut microbiota and health implications

Frontiers in Nutrition, Journal Year: 2024, Volume and Issue: 11

Published: July 29, 2024

Human exposure to heavy metals, which encompasses both essential and toxic varieties, is widespread. The intestine functions as a critical organ for absorption metabolism of metals. Gut microbiota plays crucial role in metal absorption, metabolism, related processes. Toxic metals (THMs), such arsenic (As), mercury (Hg), lead (Pb), cadmium (Cd), can cause damage multiple organs even at low levels exposure, it emphasize their potential high toxicity. Nevertheless, certain trace elements, including iron (Fe), copper (Cu), manganese (Mn), play vital roles the biochemical physiological organisms concentrations but exert effects on gut higher levels. Some potentially micronutrients, chromium (Cr), silicon (Si), nickel (Ni), were considered be intermediate terms essentiality toxicity, had different metabolites. Bidirectional relationships between have been found. Heavy disrupts influences its functions, contributing metabolic other disorders. Furthermore, by serving physical barrier against modulating pH, oxidative balance, detoxification enzymes or proteins involved metabolism. interactions might positive negative according valence states, concentrations, forms same metal. This paper reviews 10 common with health implications. collated information could provide novel insights into disruption intestinal caused factor human diseases.

Language: Английский

---

Cr(VI) induces ferroptosis in DF-1 cells by simultaneously perturbing iron homeostasis of ferritinophagy and mitophagy

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 925, P. 171818 - 171818

Published: March 19, 2024

Language: Английский

---

Advances in research on immunocyte iron metabolism, ferroptosis, and their regulatory roles in autoimmune and autoinflammatory diseases

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(7)

Published: July 4, 2024

Abstract Autoimmune diseases commonly affect various systems, but their etiology and pathogenesis remain unclear. Currently, increasing research has highlighted the role of ferroptosis in immune regulation, with cells being a crucial component body’s system. This review provides an overview discusses relationship between ferroptosis, programmed cell death cells, autoimmune diseases. Additionally, it summarizes key targets such as GPX4 TFR, responses. Furthermore, release multiple molecules, including damage-associated molecular patterns (DAMPs), following by is examined, these molecules further influence differentiation function thereby affecting occurrence progression Moreover, secrete factors or metabolites, which also impact target organs tissues involved Iron chelators, chloroquine its derivatives, antioxidants, calreticulin have been demonstrated to be effective animal studies for certain diseases, exerting anti-inflammatory immunomodulatory effects. Finally, brief summary future perspectives on are provided, aiming guide disease treatment strategies.

Language: Английский

---

Gut microbiota in health and disease: advances and future prospects

MedComm, Journal Year: 2024, Volume and Issue: 5(12)

Published: Nov. 20, 2024

Abstract The gut microbiota plays a critical role in maintaining human health, influencing wide range of physiological processes, including immune regulation, metabolism, and neurological function. Recent studies have shown that imbalances composition can contribute to the onset progression various diseases, such as metabolic disorders (e.g., obesity diabetes) neurodegenerative conditions Alzheimer's Parkinson's). These are often accompanied by chronic inflammation dysregulated responses, which closely linked specific forms cell death, pyroptosis ferroptosis. Pathogenic bacteria trigger these death pathways through toxin release, while probiotics been found mitigate effects modulating responses. Despite insights, precise mechanisms influences diseases remain insufficiently understood. This review consolidates recent findings on impact immune‐mediated inflammation‐associated conditions. It also identifies gaps current research explores potential advanced technologies, organ‐on‐chip models microbiome–gut–organ axis, for deepening our understanding. Emerging tools, single‐bacterium omics spatial metabolomics, discussed their promise elucidating microbiota's disease development.

Language: Английский

---

Age-related alterations in gut homeostasis are microbiota dependent

npj Biofilms and Microbiomes, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 25, 2025

Accumulating data suggest that remodeling aged gut microbiota improves aging-related imbalance in intestinal homeostasis. However, evidence favor of the beneficial effect on stress and immune responses during aging is scarce. The current study revealed old mice presented impaired barrier integrity. Transcriptome sequencing coupled with bioinformatics analysis altered gene expression profiles colon mesenteric lymph nodes, which are involved mainly responses, respectively. Notably, was closely related to differentially expressed genes. Microbiota depletion ameliorated integrity partially reversed inflammatory factors upregulated mice. Furthermore, fecal transplantation from young resulted a significant improvement These findings highlight potential microbiota-targeted interventions physiological processes call for further investigation.

Language: Английский

---

Excessive dietary iron exposure increases the susceptibility of largemouth bass (Micropterus salmoides) to Aeromonas hydrophila by interfering with immune response, oxidative stress, and intestinal homeostasis

Fish & Shellfish Immunology, Journal Year: 2024, Volume and Issue: 147, P. 109430 - 109430

Published: Feb. 5, 2024

Language: Английский

---

Nutritional Support: The Use of Antioxidants in Inflammatory Bowel Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4390 - 4390

Published: April 16, 2024

The problem of treating inflammatory bowel disease continues to be a topic great interest for researchers. Despite the complexity surrounding their treatment and strategies prolong periods remission, there is promising exploration various compounds that have potential in combating inflammation alleviating symptoms. Selenium, calcium, magnesium, zinc, iron are among these compounds, offering glimpse hope IBD. These essential minerals not only hold promise reducing diseases, but also show enhance immune function possibly influence balance intestinal microflora. By potentially modulating gut microbiota, they may help support overall health. Furthermore, could play crucial role mitigating minimising complications patients with protective effect against mucosal damage IBD calcium itself osteoporosis this group notable.

Language: Английский

---