Chick Early Amniotic Fluid Alleviates Dextran-Sulfate-Sodium-Induced Colitis in Mice via T-Cell Receptor Pathway

Antioxidants, Год журнала: 2025, Номер 14(1), С. 51 - 51

Опубликована: Янв. 4, 2025

Ulcerative colitis (UC) is a chronic immune disease that difficult to cure. We recently found chick early amniotic fluid (ceAF) has notable anti-inflammatory and antioxidative properties, through its active components. This study demonstrates the potential of ceAF as protective agent against UC. UPLC-MS mass spectrometry identified key components ceAF, including various fatty acids nucleosides. In vitro, improved viability in DSS-induced Caco-2 cells, reduced pro-inflammatory cytokines IL-1β TNF-α, increased cytokine IL-10. It also upregulated tight junction proteins ZO-1 occludin. UC mice, treatment alleviated weight loss, colon shortening, activity, while improving histopathology, crypt depth, colonic fibrosis. Mechanistically, ceAF's effects are mediated by inhibiting overactivation TCR signaling LCK/ZAP70/LAT pathway. Our findings suggest could be valuable nutritional intervention for UC, potentially enhancing existing functional foods aimed at managing this condition.

Язык: Английский

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Drug Development in Inflammatory Bowel Diseases: What Is Next?

Pharmaceuticals, Год журнала: 2025, Номер 18(2), С. 190 - 190

Опубликована: Янв. 30, 2025

Background/Objectives: Inflammatory bowel diseases (IBDs), which include Crohn's disease (CD) and ulcerative colitis (UC), are chronic conditions requiring long-term therapy to maintain remission improve quality of life. Despite the approval numerous drugs, IBD continues present treatment challenges. This review aims summarize novel therapeutic target agents in phases II III development, including sphingosine-1-phosphate receptor modulators (S1P), anti-interleukin-23 (IL-23), other small molecules monoclonal antibodies currently under investigation (e.g., anti-TL1A, obefazimod, NX-13, RIPK-inhibitors). Methods: A comprehensive literature search was conducted up December 2024 identify relevant articles published English over past three-five years, focusing on phase II/III studies for UC CD. The included databases such as PubMed, Google Scholar, ClinicalTrials.gov portal. Results: Clinical trials underline potential immunomodulators, RIPK inhibitors, anti-IL-23p19 agents, promising options IBD. Anti-IL23p19 therapies, risankizumab mirikizumab, alongside guselkumab, exemplify this class's growing clinical relevance. While some already use, others nearing approval. Conclusions: Ongoing research into safety development personalized strategies remains pivotal enhance outcomes. Patient stratification strategic positioning these therapies within expanding landscape critical optimizing their impact.

Язык: Английский

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Genetic polymorphisms impacting clinical pharmacology of drugs used to treat inflammatory bowel disease: a precursor to multi-omics approach to precision medicine

Expert Review of Clinical Immunology, Год журнала: 2025, Номер unknown, С. 1 - 12

Опубликована: Янв. 31, 2025

Inflammatory bowel diseases (IBDs), comprised of ulcerative colitis (UC) and Crohn's disease (CD), are chronic inflammatory the gastrointestinal tract. Clinicians patients must vigilantly manage these complex over course patient's lifetime to mitigate risks disease, surgical complications, progression neoplasia, complications from medical or therapies. Over past several decades, armamentarium IBD therapeutics has expanded; now with biologics advanced small molecules complementing conventional drugs such as aminosalicylates, corticosteroids thiopurines. Significant attention been paid potential precision medicine assist clinicians in tailoring based on patients' genetic signatures maximize therapeutic benefit while minimizing adverse effects. In this paper, we review published literature polymorphisms relevant each class therapeutics. Finally, envision a paradigm shift research toward an omics-based network analysis approach. Through global collaboration, organization goal setting, predict next decade will revolutionize existing frameworks by developing precise molecular diagnoses, validated biomarkers, predictive models novel molecularly targeted

Язык: Английский

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Progressing advanced therapies for inflammatory bowel disease: Current status including dual biologic therapy and discontinuation of biologics

Expert Review of Gastroenterology & Hepatology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 19, 2025

Advanced therapies (ADT) that encompass biological agents and small molecules have been approved for the treatment of inflammatory bowel disease (IBD), broadening spectrum available options. Nevertheless, a substantial proportion patients fail to achieve satisfactory responses, necessitating surgical intervention. Treatment objectives evolved beyond clinical remission, reduction inflammation, mucosal healing, shifting focus toward enhancing quality life, acknowledging profound impact IBD on physical mental well-being. This comprehensive review describes current landscape ADT IBD, including dual biologic therapy (DBT), which involves combination two biologics or single with small-molecule compound, as well considerations surrounding discontinuation biologics. is standard moderate severe while DBT appears promising specific subsets patients, those refractory extraintestinal manifestations. However, these approaches may increase risk adverse effects, malignancy. To optimize individualized strategies in further trials are needed refine ADT's predictive value, establish DBT's safety indications, define criteria, evaluate emerging biomarkers, artificial intelligence, ultrasound patient management.

Язык: Английский

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Matching-adjusted indirect comparisons of efficacy outcomes between etrasimod and ozanimod for moderately to severely active ulcerative colitis

Journal of Comparative Effectiveness Research, Год журнала: 2025, Номер unknown

Опубликована: Фев. 24, 2025

Aim: Etrasimod and ozanimod are selective sphingosine 1-phosphate receptor modulators targeting the S1P 1,4,5 , 1,5 receptors, respectively, for treatment of patients with moderately to severely active ulcerative colitis (UC). No head-to-head trial data exist between two treatments. We compared these treatments indirectly using key efficacy outcomes from pivotal trials induction maintenance phase adjusting differences in clinical design populations. Materials & methods: Individual patient etrasimod were matched published aggregate by baseline characteristics. An anchored matching-adjusted indirect comparison (MAIC) was conducted period. unanchored MAIC utilized during period due placebo arms as a result differing designs. Matching characteristics measured at age, sex, corticosteroid use, duration UC, biologic exposure, modified Mayo score, presence left-sided colitis. Outcomes response remission period, among responders Two sensitivity analyses conducted. The first on prior TNFi exposure rather than second analysis included an only (ELEVATE UC 12). Results: There no significant end remission, respectively (relative risk [RR] 0.98 [95% confidence interval (CI): 0.76–1.33], RR: 1.25 CI: 0.71–2.92]). At maintenance, demonstrated improved both (RR: 1.18 1.05–1.30]) 1.33 1.12–1.55]). In that there notable primary analyses. pooling ELEVATE 12 52 data, results similar 0.90 0.75–1.10]) but showed reduced 0.72 0.50–1.12]) analysis, though overall remained not significantly different ozanimod. Conclusion: suggest receiving have more likely Despite approach ensure similarity weighting, residual imbalance is possible, should be interpreted context assumptions.

Язык: Английский

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The Expanding Therapeutic Potential of Deucravacitinib Beyond Psoriasis: A Narrative Review

Journal of Clinical Medicine, Год журнала: 2025, Номер 14(5), С. 1745 - 1745

Опубликована: Март 5, 2025

Deucravacitinib is an allosteric, selective tyrosine kinase 2 (TYK2) inhibitor that has demonstrated significant efficacy in the treatment of psoriasis. TYK2, a member Janus (JAK) family, plays critical role intracellular signaling pathways for pro-inflammatory cytokines. Unlike traditional JAK inhibitors, which target active domains, deucravacitinib selectively binds to pseudokinase domain TYK2. This binding induces conformational change locks enzyme inactive state, ensuring superior selectivity TYK2 over 1/2/3. unique mechanism specifically inhibits key cytokines, including IL-12, IL-23, and type I interferons, pathogenesis psoriasis other immune-mediated diseases. As result, represents promising option targeted therapy diseases may reduce adverse events commonly associated with broader immunosuppressive treatments. Furthermore, its oral administration offers convenient alternative injectable biologics, potentially improving patient adherence satisfaction. review highlights recent studies suggesting also have therapeutic benefits psoriatic arthritis, palmoplantar pustulosis, systemic lupus erythematosus, Sjogren's disease, inflammatory bowel disease. Given expanding potential, provide safer more effective current therapies, offering tailored approach treatment.

Язык: Английский

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IgG4 in the gut: Gastrointestinal IgG4-related disease or a new subtype of inflammatory bowel disease

Autoimmunity Reviews, Год журнала: 2024, Номер 24(2), С. 103720 - 103720

Опубликована: Дек. 7, 2024

Язык: Английский

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