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

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Ginseng-Containing Sijunzi Decoction Ameliorates Ulcerative Colitis by Orchestrating Gut Homeostasis in Microbial Modulation and Intestinal Barrier Integrity

The American Journal of Chinese Medicine, Journal Year: 2023, Volume and Issue: 51(03), P. 677 - 699

Published: Jan. 1, 2023

Ulcerative colitis (UC) has become a global epidemic, and the lack of an effective cure highlights necessity urgency to explore novel therapies. Sijunzi Decoction (SJZD), classical Chinese herbal formula, been comprehensively applied clinically proven in treating UC; however, pharmacological mechanism behind its therapeutic benefits is largely obscure. Here, we find that SJZD can restore microbiota homeostasis intestinal barrier integrity DSS-induced colitis. significantly alleviated colonic tissue damage improved goblet cell count, MUC2 secretion, tight junction protein expressions, which indicated enhanced integrity. remarkedly suppressed abundance phylum Proteobacteria genus Escherichia-Shigella, are typical features microbial dysbiosis. Escherichia-Shigella was negatively correlated with body weight colon length, positively disease activity index IL-1[Formula: see text]. Furthermore, through gut depletion, confirmed exerted anti-inflammatory activities microbiota-dependent manner, fecal transplantation (FMT) validated mediating role treatment UC. Through microbiota, modulates biosynthesis bile acids (BAs), especially tauroursodeoxycholic acid (TUDCA), identified as signature BA during treatment. Cumulatively, our findings disclose attenuates UC via orchestrating modulation integrity, thus offering promising alternative approach clinical management

Language: Английский

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The effect of the “Oral-Gut” axis on periodontitis in inflammatory bowel disease: A review of microbe and immune mechanism associations

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: Feb. 27, 2023

Periodontitis and inflammatory bowel diseases (IBD) are of the gastrointestinal tract that share common features microbial-induced ecological dysregulation host immune response. The close relationship between periodontitis IBD is characterized by a higher prevalence in patients with severity IBD, indicating different from traditional independent form an “Oral-Gut” axis two, which affect each other thus vicious circle. However, specific mechanisms leading to association two not fully understood. In this article, we describe interconnection terms microbial pathogenesis dysregulation, including ectopic colonization gut pathogenic bacteria associated promotes inflammation activating response, alteration oral microbiota due affects periodontal Among factors, such as Klebsiella , Porphyromonas gingivalis Fusobacterium nucleatum may act bridge while among mechanisms, Th17 cell responses secreted pro-inflammatory factors IL-1β, IL-6 TNF-α play key role development both diseases. This suggests future studies, can look for targets control intervene regulating or intestinal flora through immunological methods.

Language: Английский

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Corylin ameliorates chronic ulcerative colitis via regulating the gut–brain axis and promoting 5-hydroxytryptophan production in the colon

Phytomedicine, Journal Year: 2023, Volume and Issue: 110, P. 154651 - 154651

Published: Jan. 5, 2023

Language: Английский

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Elevated SPARC Disrupts the Intestinal Barrier Integrity in Crohn's Disease by Interacting with OTUD4 and Activating the MYD88/NF‐κB Pathway

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Abstract Disruption of the intestinal epithelial barrier results in increased permeability and is a key factor onset progression Crohn's disease (CD). The protein SPARC primarily involved cell interaction migration, but its specific role remains unclear. This study demonstrates that significantly overexpressed both CD patients murine models colitis. Furthermore, mice deficient exhibits resistance to chemically induced colitis, phenomenon associated with modulation barrier‐associated proteins. Mechanistically, it elucidated competitively binds OTUD4 conjunction MYD88, facilitating translocation p65 from cytoplasm nucleus subsequent activation p65‐MLCK/MLC2 pathway, thereby compromising integrity. Additionally, identified elevated expression regulated via METTL3‐YTHDF1 axis. These findings indicate levels are colitis‐induced mice, leading damage through direct MYD88/p65/MLCK/MLC2 signaling pathway. Consequently, targeting or OTUD4/MYD88/p65/MLCK/MLC2 axis may offer novel insights into molecular mechanisms underlying represent potential therapeutic strategy.

Language: Английский

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TGR5 agonist inhibits intestinal epithelial cell apoptosis via cAMP/PKA/c-FLIP/JNK signaling pathway and ameliorates dextran sulfate sodium-induced ulcerative colitis

Acta Pharmacologica Sinica, Journal Year: 2023, Volume and Issue: 44(8), P. 1649 - 1664

Published: March 30, 2023

Language: Английский

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Wheat Germ-Derived Peptide Alleviates Dextran Sulfate Sodium-Induced Colitis in Mice

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 71(42), P. 15593 - 15603

Published: Oct. 11, 2023

This study explores the protective properties and potential mechanisms of wheat-germ-derived peptide APEPEPAF (APE) against ulcerative colitis. Colitis mice induced by dextran sulfate sodium (DSS) were used as animal model. The results showed that APE could alleviate colitis symptoms including weight loss, colon shortening, histopathological changes. attenuated generation inflammatory cytokines inhibiting phosphorylation protein kinase PKCζ (Thr410) NF-κB transcriptional activity in DSS-induced mice, suggesting ameliorates inflammation regulating PKCζ/NF-κB signaling pathway. also preserved barrier function dose-dependently promoting expression tight junction proteins (claudin-1, zonula occluded-1, occludin). In addition, significantly decreased abundance Bacteroides increased Dubosiella Lachnospiraceae_UCG-006 to improve intestinal flora imbalance mice. Therefore, wheat germ can be a novel agent dietary supplement treat colitis..

Language: Английский

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Repurposing metformin as adjuvant therapy in patients with ulcerative colitis treated with mesalamine: A randomized controlled double-blinded study

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 138, P. 112541 - 112541

Published: June 25, 2024

Language: Английский

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Identifying Spatial Co-occurrence in Healthy and InflAmed tissues (ISCHIA)

Molecular Systems Biology, Journal Year: 2024, Volume and Issue: 20(2), P. 98 - 119

Published: Jan. 15, 2024

Abstract Sequencing-based spatial transcriptomics (ST) methods allow unbiased capturing of RNA molecules at barcoded spots, charting the distribution and localization cell types transcripts across a tissue. While coarse resolution these techniques is considered disadvantage, we argue that inherent proximity transcriptomes captured on spots can be leveraged to reconstruct cellular networks. To this end, developed ISCHIA (Identifying Spatial Co-occurrence in Healthy InflAmed tissues), computational framework analyze co-occurrence transcript species within spots. analysis complementary differential gene expression, as it does not depend abundance given type or expression levels, but rather their association We applied types, ligands receptors Visium dataset human ulcerative colitis patients, validated our findings single-cell matched hybridization-based data. uncover inflammation-induced networks involving M fibroblasts, well ligand-receptor interactions enriched inflamed colon, associated signatures. Our results highlight hypothesis-generating power broad applicability

Language: Английский

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An Inulin-Type Fructan CP-A from Codonopsis pilosula Alleviated 5-Fluorouracil-Induced Intestinal Mucositis via the ERK/MLCK/MLC2 Pathway and Regulation of Gut Microbiota

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(3), P. 297 - 297

Published: Feb. 26, 2024

Intestinal mucositis (IM) is a common adverse effect of chemotherapy, limiting its clinical application. Codonopsis pilosula-derived CP-A (an inulin-type fructan) an edible Chinese medicine with anti-inflammatory and gastrointestinal protective effects, which may be useful for treating IM. Here, we explored CP-A’s role in ameliorating IM induced by 5-fluorouracil (5-FU) investigated the underlying mechanism using vitro experiments rat models. Western blotting, immunohistochemistry (IHC), real-time PCR (RT-PCR) analyses were used to assess protein expression related extracellular-regulated kinases (ERK)/myosin light chain kinase (MLCK)/myosin 2 (MLC2) signaling pathway tight junction proteins. Inflammatory factors quantified enzyme-linked immunosorbent assays (ELISAs), 16S rRNA amplicon sequencing was employed cecum content analysis. The results indicated that restored body weight food intake reversed histopathological changes rats. Further, abnormal MLCK activation 5-FU attenuated via ERK/MLCK/MLC2 pathway. treatment improved levels reduced inflammatory factor expression. Moreover, intervention regulated intestinal microbiota community structure, increasing abundance Lactobacillus decreasing Shigella. In conclusion, mitigates 5-FU-induced inhibiting pathway, reducing factors, improving mucosal barrier, regulating microbial community. This study highlights therapeutic potential provides insights future research.

Language: Английский

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