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Molecular Research in Inflammatory Bowel Disease
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Molecular Research in Inflammatory Bowel Disease

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: closed (20 November 2023) | Viewed by 10258

Special Issue Editors

Prof. Dr. Loris Riccardo Lopetuso

E-Mail Website
Guest Editor
Internal Medicine and Gastroenterology Department, IRCCS Fondazione Policlinico Gemelli, Catholic University of Rome, 00168 Rome, Italy
Interests: inflammatory bowel disease (IBD); target therapy; mucosal immunology; inflammatory cytokines; gut microbiota; intestinal mucosal healing; IBD murine models; tumorigenesis associated to chronic inflammation
Special Issues, Collections and Topics in MDPI journals
Dr. Alfredo Papa

E-Mail Website
Guest Editor
1. Department of Translational Medicine and Surgery, School of Medicine, Catholic University, 00168 Rome, Italy
2. Center for Diagnosis and Treatment of Digestive Diseases, CEMAD, Gastroenterology Department, Fondazione Policlinico Gemelli, IRCCS, 00168 Rome, Italy
Interests: inflammatory bowel disease (IBD); ulcerative colitis; Crohn’s disease; target therapy; biologic agents; small molecules; adhesion antagonists; anti-TNF; IBD vascular complications; stem-cells application in IBD; intestinal mucosal healing; gut microbiota
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

In recent years, many advances in the pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, have emerged, with substantial impact on daily clinical practice. These new findings have allowed the introduction of new molecular markers and innovative drugs useful for an innovative clinical approach to IBD. This Special Issue of IJMS will publish reviews and research articles regarding recent advances in the field of basic and molecular research with translational applications in IBD.

The establishment of new goals in the management of IBD and the continuation in the understanding of the IBD pathogenic mechanisms have introduced new concepts in the area of intestinal fibrogenesis, small oral therapeutic molecules, gut microbiota, molecular markers of intestinal healing, and molecular predictive markers of response to therapy.

In this Special Issue, we welcome your contributions in the form of original research and review articles facing both basic and molecular research in IBD.

Prof. Dr. Loris Riccardo Lopetuso
Dr. Alfredo Papa
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Published Papers (4 papers)

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Research

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14 pages, 808 KiB  
Article
Development of a Prediction Model for Short-Term Remission of Patients with Crohn’s Disease Treated with Anti-TNF Drugs
by Rosario Medina-Medina, Eva Iglesias-Flores, Jose M. Benítez, Sandra Marín-Pedrosa, Isabel Salgueiro-Rodríguez, Clara I. Linares, Sandra González-Rubio, Pilar Soto-Escribano, Beatriz Gros, Manuel L. Rodríguez-Perálvarez, José L. Cabriada, María Chaparro, Javier P. Gisbert, Eduardo Chicano-Gálvez, Ignacio Ortea, Gustavo Ferrín, Valle García-Sánchez and Patricia Aguilar-Melero
Int. J. Mol. Sci. 2023, 24(10), 8695; https://doi.org/10.3390/ijms24108695 - 12 May 2023
Viewed by 2176
Abstract
Therapy with anti-tumor necrosis factor (TNF) has dramatically changed the natural history of Crohn’s disease (CD). However, these drugs are not without adverse events, and up to 40% of patients could lose efficacy in the long term. We aimed to identify reliable markers [...] Read more.
Therapy with anti-tumor necrosis factor (TNF) has dramatically changed the natural history of Crohn’s disease (CD). However, these drugs are not without adverse events, and up to 40% of patients could lose efficacy in the long term. We aimed to identify reliable markers of response to anti-TNF drugs in patients with CD. A consecutive cohort of 113 anti-TNF naive patients with CD was stratified according to clinical response as short-term remission (STR) or non-STR (NSTR) at 12 weeks of treatment. We compared the protein expression profiles of plasma samples in a subset of patients from both groups prior to anti-TNF therapy by SWATH proteomics. We identified 18 differentially expressed proteins (p ≤ 0.01, fold change ≥ 2.4) involved in the organization of the cytoskeleton and cell junction, hemostasis/platelet function, carbohydrate metabolism, and immune response as candidate biomarkers of STR. Among them, vinculin was one of the most deregulated proteins (p < 0.001), whose differential expression was confirmed by ELISA (p = 0.054). In the multivariate analysis, plasma vinculin levels along with basal CD Activity Index, corticosteroids induction, and bowel resection were factors predicting NSTR. Full article
(This article belongs to the Special Issue Molecular Research in Inflammatory Bowel Disease)
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14 pages, 2383 KiB  
Article
90K/Mac-2 BP Is a New Predictive Biomarker of Response to Infliximab Therapy in IBD Patients
by Pasqua Letizia Pesole, Marina Liso, Rossella Donghia, Vito Guerra, Antonio Lippolis, Mauro Mastronardi and Palma Aurelia Iacovazzi
Int. J. Mol. Sci. 2023, 24(4), 3955; https://doi.org/10.3390/ijms24043955 - 16 Feb 2023
Cited by 1 | Viewed by 2645
Abstract
Inflammatory bowel diseases (IBD), comprising Crohn’s disease (CD) and Ulcerative Colitis (UC), are multifactorial disorders characterized by a chronic inflammatory status with the secretion of cytokines and immune mediators. Biologic drugs targeting pro-inflammatory cytokines, such as infliximab, are broadly used in the treatment [...] Read more.
Inflammatory bowel diseases (IBD), comprising Crohn’s disease (CD) and Ulcerative Colitis (UC), are multifactorial disorders characterized by a chronic inflammatory status with the secretion of cytokines and immune mediators. Biologic drugs targeting pro-inflammatory cytokines, such as infliximab, are broadly used in the treatment of IBD patients, but some patients lose responsiveness after an initial success. The research into new biomarkers is crucial for advancing personalized therapies and monitoring the response to biologics. The aim of this single center, observational study is to analyze the relationship between serum levels of 90K/Mac-2 BP and the response to infliximab, in a cohort of 48 IBD patients (30 CD and 18 UC), enrolled from February 2017 to December 2018. In our IBD cohort, high 90K serum levels were found at baseline in patients who then developed anti-infliximab antibodies at the fifth infusion (22 weeks after the first), becoming non-responders (9.76 ± 4.65 µg/mL compared to 6.53 ± 3.29 µg/mL in responder patients, p = 0.005). This difference was significant in the total cohort and in CD, but not significant in UC. We then analyzed the relationship between serum levels of 90K, C-reactive protein (CRP), and Fecal calprotectin. A significant positive correlation was found at baseline between 90K and CRP, the most common serum inflammation marker (R = 0.42, p = 0.0032). We concluded that circulating 90K could be considered a new non-invasive biomarker for monitoring the response to infliximab. Furthermore, 90K serum level determination, before the first infliximab infusion, in association with other inflammatory markers such as CRP, could assist in the choice of biologics for the treatment of IBD patients, thereby obviating the need for a drug switch due to loss of response, and so improving clinical practice and patient care. Full article
(This article belongs to the Special Issue Molecular Research in Inflammatory Bowel Disease)
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Review

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17 pages, 1930 KiB  
Review
Cellular and Molecular Determinants of Biologic Drugs Resistance and Therapeutic Failure in Inflammatory Bowel Disease
by Pierluigi Puca, Ivan Capobianco, Gaetano Coppola, Federica Di Vincenzo, Valentina Trapani, Valentina Petito, Lucrezia Laterza, Daniela Pugliese, Loris Riccardo Lopetuso and Franco Scaldaferri
Int. J. Mol. Sci. 2024, 25(5), 2789; https://doi.org/10.3390/ijms25052789 - 28 Feb 2024
Cited by 2 | Viewed by 2325
Abstract
The advent of biologic drugs has revolutionized the treatment of Inflammatory Bowel Disease, increasing rates of response and mucosal healing in comparison to conventional therapies by allowing the treatment of corticosteroid-refractory cases and reducing corticosteroid-related side effects. However, biologic therapies (anti-TNFα inhibitors, anti-α4β7 [...] Read more.
The advent of biologic drugs has revolutionized the treatment of Inflammatory Bowel Disease, increasing rates of response and mucosal healing in comparison to conventional therapies by allowing the treatment of corticosteroid-refractory cases and reducing corticosteroid-related side effects. However, biologic therapies (anti-TNFα inhibitors, anti-α4β7 integrin and anti-IL12/23) are still burdened by rates of response that hover around 40% (in biologic-naïve patients) or lower (for biologic-experienced patients). Moreover, knowledge of the mechanisms underlying drug resistance or loss of response is still scarce. Several cellular and molecular determinants are implied in therapeutic failure; genetic predispositions, in the form of single nucleotide polymorphisms in the sequence of cytokines or Human Leukocyte Antigen, or an altered expression of cytokines and other molecules involved in the inflammation cascade, play the most important role. Accessory mechanisms include gut microbiota dysregulation. In this narrative review of the current and most recent literature, we shed light on the mentioned determinants of therapeutic failure in order to pave the way for a more personalized approach that could help avoid unnecessary treatments and toxicities. Full article
(This article belongs to the Special Issue Molecular Research in Inflammatory Bowel Disease)
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13 pages, 321 KiB  
Review
Focus on Anti-Tumour Necrosis Factor (TNF)-α-Related Autoimmune Diseases
by Loris Riccardo Lopetuso, Claudia Cuomo, Irene Mignini, Antonio Gasbarrini and Alfredo Papa
Int. J. Mol. Sci. 2023, 24(9), 8187; https://doi.org/10.3390/ijms24098187 - 3 May 2023
Cited by 14 | Viewed by 2656
Abstract
Anti-tumour necrosis factor (TNF)-α agents have been increasingly used to treat patients affected by inflammatory bowel disease and dermatological and rheumatologic inflammatory disorders. However, the widening use of biologics is related to a new class of adverse events called paradoxical reactions. Its pathogenesis [...] Read more.
Anti-tumour necrosis factor (TNF)-α agents have been increasingly used to treat patients affected by inflammatory bowel disease and dermatological and rheumatologic inflammatory disorders. However, the widening use of biologics is related to a new class of adverse events called paradoxical reactions. Its pathogenesis remains unclear, but it is suggested that cytokine remodulation in predisposed individuals can lead to the inflammatory process. Here, we dissect the clinical aspects and overall outcomes of autoimmune diseases caused by anti-TNF-α therapies. Full article
(This article belongs to the Special Issue Molecular Research in Inflammatory Bowel Disease)
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