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Inflammatory Bowel Diseases: Molecular Mechanism and Therapeutics

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 February 2026 | Viewed by 4049

Special Issue Editor


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Guest Editor
Laboratory of Developmental Genetics, Department of Biomedical Sciences, Inha University College of Medicine, Incheon 22212, Republic of Korea
Interests: animal model; mini-pig; efficacy evaluation; disease; preclinical study; inflammatory bowel disease
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Special Issue Information

Dear Colleagues,

Inflammatory bowel disease (IBD) is an inflammatory disease of the gastrointestinal tract that includes ulcerative colitis (UC) and Crohn’s disease (CD) and has the potential to develop into colon cancer over the long term. The purpose of this Special Issue is to explore the molecular mechanisms and treatments of IBD to gain a deeper understanding of the pathophysiology of IBD and new therapeutic approaches to treat these diseases. Various animal models have played a key role in the study of inflammatory bowel disease. In particular, mini pigs have become valuable animal models in biomedical research because of their physiological and anatomical similarities to humans. Animal models are helpful for studying the molecular progression of the disease and evaluating treatments, as well as future research areas including drug development.

This Special Issue welcomes original papers and reviews related to the molecular mechanisms, pathophysiology, and treatment of IBD. IJMS is a journal of molecular science; therefore, pure clinical or model studies will not be suitable for our journal. But clinical or pure model submissions with biomolecular experiments are welcomed.

Dr. Woon Kyu Lee
Guest Editor

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Keywords

  • inflammatory bowel disease
  • IBD
  • ulcerative colitis
  • Crohn’s disease
  • animal models

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Published Papers (3 papers)

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Research

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17 pages, 3340 KiB  
Article
Resveratrol Mitigates Inflammation by Modulating Tumor Necrosis Factor-Alpha Receptors (TNFRs) in a 2,4,6-Trinitrobenzene Sulfonic Acid (TNBS)-Induced Rat Model of Colitis
by Médea Veszelka, József Hegyközi, Nikoletta Almási, Szilvia Török, Bence Pál Barta, Izabella Nagy, Denise Börzsei, Nikolett Bódi, Mária Bagyánszki, Renáta Szabó and Csaba Varga
Int. J. Mol. Sci. 2025, 26(12), 5779; https://doi.org/10.3390/ijms26125779 - 16 Jun 2025
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Abstract
Several substances with antioxidant and anti-inflammatory properties are currently being investigated as potential adjunctive or standalone treatments for inflammatory bowel disease (IBD). One such substance is resveratrol (RES), also known as 3,5,4′-trihydroxy-trans-stilbene, a natural dietary polyphenol with diverse health-promoting effects. In this study, [...] Read more.
Several substances with antioxidant and anti-inflammatory properties are currently being investigated as potential adjunctive or standalone treatments for inflammatory bowel disease (IBD). One such substance is resveratrol (RES), also known as 3,5,4′-trihydroxy-trans-stilbene, a natural dietary polyphenol with diverse health-promoting effects. In this study, male Wistar–Hannover rats received oral RES supplementation at doses of 5, 10, or 20 mg/kg/day for 28 days. On day 25 colitis was induced using intracolonic administration of 2,4,6-trinitrobenzene sulphonic acid (TNBS). Based on histological and planimetric analysis, the 10 mg/kg dose significantly reduced colonic ulceration and pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) expression compared to the TNBS group. Immunohistochemistry also revealed that RES at this dose attenuated the intensity of TNF-α receptors, namely TNFR1 and TNFR2. Furthermore, the concentration of lipocalin-2 (Lcn-2) was significantly elevated in TNBS-induced colitis. In conclusion, our findings suggest that RES may exert its protective effects partly through the modulation of TNF receptor signaling in TNBS-induced colitis. Full article
(This article belongs to the Special Issue Inflammatory Bowel Diseases: Molecular Mechanism and Therapeutics)
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22 pages, 2203 KiB  
Article
Proteomic Profiling of Extracellular Vesicles in Inflammatory Bowel Diseases
by Montse Baldán-Martín, Mikel Azkargorta, Ainhoa Lapitz, Lorena Ortega Moreno, Ibon Iloro, Samuel Fernández-Tomé, Ander Arbelaiz, Iraide Escobes, Alicia C. Marín, David Bernardo, Luis Bujanda, Jesús M. Bañales, Felix Elortza, Javier P. Gisbert and María Chaparro
Int. J. Mol. Sci. 2025, 26(2), 526; https://doi.org/10.3390/ijms26020526 - 9 Jan 2025
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Abstract
The proteomic analysis of serum extracellular vesicles (EVs) could be a useful tool for studying the pathophysiology of Crohn’s disease (CD) and ulcerative colitis (UC), as well as for biomarker discovery. To characterize the proteomic composition of serum EVs in patients with CD [...] Read more.
The proteomic analysis of serum extracellular vesicles (EVs) could be a useful tool for studying the pathophysiology of Crohn’s disease (CD) and ulcerative colitis (UC), as well as for biomarker discovery. To characterize the proteomic composition of serum EVs in patients with CD and UC to identify biomarkers and molecular pathways associated with pathogenesis and activity. Methods: Serum EVs were enriched and analyzed in patients with quiescent CD, active CD (aCD), quiescent UC, active UC (aUC), and healthy controls (HCs) (n = 30 per group). All groups were matched for age and sex. Disease activity was assessed by ileocolonoscopy and categorized based on the SES-CD (CD) and the endoscopic sub-score of the Mayo Score (UC). EVs were enriched by ul-tracentrifugation, and their size and concentration were determined by nanoparticle tracking analysis. The expression of CD63, CD81, and CD9 was determined using West-ern blotting. Proteomic analysis was performed by label-free nano-LC MS/MS. A total of 324 proteins were identified; 60 showed differential abundance in CD-HC, 34 in UC-HC, and 21 in CD-UC. Regarding disease activity, the abundance of 58 and 32 proteins was altered in aCD-HC and aUC-HC, respectively. Functional analyses revealed that proteins associated with aCD were involved in immune regulation, whereas those linked to aUC were enriched in oxidative stress. We have identified expressed proteins between EVs from patients with CD and UC, depending on the presence of disease, the disease type, and the disease activity. These proteins are potential candidates as disease biomarkers and open new research avenues to better understand these conditions. Full article
(This article belongs to the Special Issue Inflammatory Bowel Diseases: Molecular Mechanism and Therapeutics)
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Review

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15 pages, 856 KiB  
Review
TL1A as a Target in Inflammatory Bowel Disease: Exploring Mechanisms and Therapeutic Potential
by Enrico Tettoni, Roberto Gabbiadini, Arianna Dal Buono, Giuseppe Privitera, Vincenzo Vadalà, Giulia Migliorisi, Peter Bertoli, Alessandro Quadarella, Cristina Bezzio and Alessandro Armuzzi
Int. J. Mol. Sci. 2025, 26(11), 5017; https://doi.org/10.3390/ijms26115017 - 23 May 2025
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Abstract
Inflammatory bowel diseases (IBD) are chronic disorders characterized by persistent inflammation of the gastrointestinal tract. Despite advances in treatment, a significant proportion of patients remain refractory to current therapies and develop complications, particularly fibrosis, leading to strictures and fistulae. Tumor necrosis factor-like ligand [...] Read more.
Inflammatory bowel diseases (IBD) are chronic disorders characterized by persistent inflammation of the gastrointestinal tract. Despite advances in treatment, a significant proportion of patients remain refractory to current therapies and develop complications, particularly fibrosis, leading to strictures and fistulae. Tumor necrosis factor-like ligand 1A (TL1A) has emerged as a promising new target for IBD treatment, due to its dual role in inflammatory and fibrotic pathways. TL1A, acting through its receptor death receptor 3 (DR3), orchestrates mucosal inflammation by enhancing T-cell activation and promoting pro-inflammatory mediator secretion. TL1A also drives intestinal fibrosis by activating fibroblasts and increasing collagen deposition. Clinical trials evaluating anti-TL1A monoclonal antibodies have shown encouraging efficacy and safety, with significant improvements in clinical remission rates, endoscopic healing, and histologic outcomes. Beyond IBD, TL1A overexpression has been implicated in other immune-mediated inflammatory diseases, highlighting its broader therapeutic potential. This review explores TL1A’s role in IBD pathogenesis, the latest clinical trial data, and its involvement in extraintestinal inflammatory disorders, underscoring its potential as a novel precision-medicine target across multiple diseases. Full article
(This article belongs to the Special Issue Inflammatory Bowel Diseases: Molecular Mechanism and Therapeutics)
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