Browsing by Subject "Inflammatory bowel disease (IBD)"

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    APE1/Ref-1 as a Therapeutic Target for Inflammatory Bowel Disease
    (MDPI, 2023-10-24) Sahakian, Lauren; Robinson, Ainsley M.; Sahakian, Linda; Stavely, Rhian; Kelley, Mark R.; Nurgali, Kulmira; Pediatrics, School of Medicine
    Inflammatory bowel disease (IBD) is characterized by chronic relapsing inflammation of the gastrointestinal tract. The prevalence of IBD is increasing with approximately 4.9 million cases reported worldwide. Current therapies are limited due to the severity of side effects and long-term toxicity, therefore, the development of novel IBD treatments is necessitated. Recent findings support apurinic/apyrimidinic endonuclease 1/reduction-oxidation factor 1 (APE1/Ref-1) as a target in many pathological conditions, including inflammatory diseases, where APE1/Ref-1 regulation of crucial transcription factors impacts significant pathways. Thus, a potential target for a novel IBD therapy is the redox activity of the multifunctional protein APE1/Ref-1. This review elaborates on the status of conventional IBD treatments, the role of an APE1/Ref-1 in intestinal inflammation, and the potential of a small molecule inhibitor of APE1/Ref-1 redox activity to modulate inflammation, oxidative stress response, and enteric neuronal damage in IBD.
  • Thumbnail Image
    Item
    Clinical Decision Making in Inflammatory Bowel Disease Mimics: Practice Management from Inflammatory Bowel Disease LIVE
    (Oxford University Press, 2024-04-11) Fiske, Hannah W.; Ward, Christopher; Shah, Samir A.; Holubar, Stefan D.; Al-Bawardy, Badr; Barnes, Edward L.; Binion, David; Bohm, Matthew; Brand, Myron; Clarke, Kofi; Cohen, Benjamin L.; Cross, Raymond K.; Dueker, Jeffrey; Engels, Michael; Farraye, Francis A.; Fine, Sean; Forster, Erin; Gaidos, Jill; Ginsburg, Philip; Goyal, Alka; Hanson, John; Herfath, Hans; Hull, Tracy; Kelly, Colleen R.; Lazarev, Mark; Levy, L. Campbell; Melia, Joanna; Philpott, Jessica; Qazi, Taha; Siegel, Corey A.; Watson, Andrew; Wexner, Steven D.; Williams, Emmanuelle D.; Regueiro, Miguel; Medicine, School of Medicine
    Background: Since 2009, inflammatory bowel disease (IBD) specialists have utilized "IBD LIVE," a weekly live video conference with a global audience, to discuss the multidisciplinary management of their most challenging cases. While most cases presented were confirmed IBD, a substantial number were diseases that mimic IBD. We have categorized all IBD LIVE cases and identified "IBD-mimics" with consequent clinical management implications. Methods: Cases have been recorded/archived since May 2018; we reviewed all 371 cases from May 2018-February 2023. IBD-mimics were analyzed/categorized according to their diagnostic and therapeutic workup. Results: Confirmed IBD cases made up 82.5% (306/371; 193 Crohn's disease, 107 ulcerative colitis, and 6 IBD-unclassified). Sixty-five (17.5%) cases were found to be mimics, most commonly medication-induced (n = 8) or vasculitis (n = 7). The evaluations that ultimately resulted in correct diagnosis included additional endoscopic biopsies (n = 13, 21%), surgical exploration/pathology (n = 10, 16.5%), biopsies from outside the GI tract (n = 10, 16.5%), genetic/laboratory testing (n = 8, 13%), extensive review of patient history (n = 8, 13%), imaging (n = 5, 8%), balloon enteroscopy (n = 5, 8%), and capsule endoscopy (n = 2, 3%). Twenty-five patients (25/65, 38%) were treated with biologics for presumed IBD, 5 of whom subsequently experienced adverse events requiring discontinuation of the biologic. Many patients were prescribed steroids, azathioprine, mercaptopurine, or methotrexate, and 3 were trialed on tofacitinib. Conclusions: The diverse presentation of IBD and IBD-mimics necessitates periodic consideration of the differential diagnosis, and reassessment of treatment in presumed IBD patients without appropriate clinical response. The substantial differences and often conflicting treatment approaches to IBD versus IBD-mimics directly impact the quality and cost of patient care.
  • Thumbnail Image
    Item
    The JAK inhibitor ruxolitinib reduces inflammation in an ILC3-independent model of innate immune colitis
    (Springer Nature, 2018-09) Overstreet, A.M.; LaTorre, D.L.; Abernathy-Close, L.; Murphy, S.F.; Rhee, L.; Boger, A.M.; Adlaka, K.R.; Iverson, A.M.; Bakke, D.S.; Weber, C.R.; Boone, D.L.; Microbiology and Immunology, School of Medicine
    Innate immunity contributes to the pathogenesis of inflammatory bowel disease (IBD). However, the mechanisms of IBD mediated by innate immunity are incompletely understood and there are limited models of spontaneous innate immune colitis to address this question. Here we describe a new robust model of colitis occurring in the absence of adaptive immunity. RAG1-deficient mice expressing TNFAIP3 in intestinal epithelial cells (TRAG mice) spontaneously developed 100% penetrant, early-onset colitis that was limited to the colon and dependent on intestinal microbes but was not transmissible to co-housed littermates. TRAG colitis was associated with increased mucosal numbers of innate lymphoid cells (ILCs) and depletion of ILC prevented colitis in TRAG mice. ILC depletion also therapeutically reversed established colitis in TRAG mice. The colitis in TRAG mice was not prevented by interbreeding to mice lacking group 3 ILC nor by depletion of TNF. Treatment with the JAK inhibitor ruxolitinib ameliorated colitis in TRAG mice. This new model of colitis, with its predictable onset and colon-specific inflammation, will have direct utility in developing a more complete understanding of innate immune mechanisms that can contribute to colitis and in pre-clinical studies for effects of therapeutic agents on innate immune-mediated IBD.
  • Thumbnail Image
    Item
    Nutritional Profile, Disease Severity, and Quality of Life of Patients with Inflammatory Bowel Disease: A Case–Control Study
    (MDPI, 2024-06-11) Sayegh, Lea N.; Haddad, Firas; Jaoude, Layane Bou; Fakhoury-Sayegh, Nicole; Heraoui, Gessica N. H. A.; Nasrallah, Zainab; Chidiac, Charbel; Nawfal, Rashad; Francis, Fadi F.; Mourad, Fadi H.; Hashash, Jana G.; Medicine, School of Medicine
    Introduction: Diet is thought to play an important role in the clinical course and quality of life (QOL) of patients with inflammatory bowel disease (IBD). However, dietary habits of patients with IBD are still unknown. This case-control study aims to compare the dietary habits of patients with IBD to healthy controls and evaluate differences in disease severity and QOL. Materials and methods: Food frequency, severity scores using the Harvey-Bradshaw and Ulcerative colitis activity index, and QOL were assessed using online questionnaires. Dietary habits were compared for patients with active disease and remission and for those with low QOL (LQOL) and high QOL (HQOL). Results: We recruited 61 patients with IBD and 101 controls. Significance was set at p = 0.05. Controls consumed significantly more daily calories (2546 vs. 1641, p = 0.001). However, patients with IBD consumed a higher percentage of carbohydrates (50% vs. 45%, p = 0.001), more red meat (p = 0.024), and less fiber, sucrose, and lactose (p = 0.001, 0.001, and 0.036). Patients with active disease had higher lipid intake, lower protein intake, and lower QOL (47 vs. 58, p = 0.001). Dietary differences between LQOL and HQOL mirrored those between active disease and remission. Conclusion: This study is the first to provide valuable insights into the nutritional profile of Lebanese patients with IBD.