Aims And Methods: Accurate protein measurements using formalin-fixed biopsies are needed to improve disease characterisation. This feasibility study used targeted and global mass spectrometry (MS) to interrogate a spectrum of disease severities using 19 ulcerative colitis (UC) biopsies.
Results: Targeted assays for CD8, CD19, CD132 (interleukin-2 receptor subunit gamma/common cytokine receptor gamma chain), FOXP3 (forkhead box P3) and IL17RA (interleukin 17 receptor A) were successful; however, assays for IL17A (interleukin 17A), IL23 (p19) (interleukin 23, alpha subunit p19) and IL23R (interleukin 23 receptor) did not permit target detection. Global proteome analysis (4200 total proteins) was performed to identify pathways associated with UC progression. Positive correlation was observed between histological scores indicating active colitis and neutrophil-related measurements (R=0.42-0.72); inverse relationships were detected with cell junction targets (R=0.49-0.71) and β-catenin (R=0.51-0.55) attributed to crypt disruption. An exploratory accuracy assessment with Geboes Score and Robarts Histopathology Index cut-offs produced sensitivities/specificities of 72.7%/75.0% and 100.0%/81.8%, respectively.
Conclusions: Pathologist-guided MS assessments provide a complementary approach to histological scoring systems. Additional studies are indicated to verify the utility of this novel approach.
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http://dx.doi.org/10.1136/jclinpath-2021-207718 | DOI Listing |
Inn Med (Heidelb)
December 2024
Innere Medizin I, Universitätsklinikum Tübingen, Otfried-Müller-Straße 10, 72076, Tübingen, Deutschland.
The classic therapeutic goals of chronic inflammatory bowel disease (IBD) are, on the one hand, clinical remission and, on the other, the prevention of disease progression. The introduction of additional "targets" such as normalization of laboratory inflammation values, endoscopic and, possibly, histological mucosal healing and transmural parameters (ultrasound, magnetic resonance imaging and computed tomography) is intended to improve prognosis. A good response to therapy is usually (also) evident from these targets, although the obligatory change in medication in order to improve the prognosis if the additional treatment goals are not achieved is not evidence-based.
View Article and Find Full Text PDFWorld J Exp Med
December 2024
Department of Anatomy, University of São Paulo, São Paulo 05508-000, Brazil.
The extracellular matrix (ECM) is a non-cellular three-dimensional structure present in all tissues that is essential for the intestinal maintenance, function and structure, as well as for providing physical support for tissue integrity and elasticity. ECM enables the regulation of various processes involved in tissue homeostasis, being vital for healing, growth, migration and cell differentiation. Structurally, ECM is composed of water, polysaccharides and proteins, such as collagen fibers and proteoglycans, which are specifically arranged for each tissue.
View Article and Find Full Text PDFInfect Disord Drug Targets
December 2024
Amity Institute of Pharmacy, Lucknow, Amity University Uttar Pradesh, Sector 125, Noida, 201313, India.
Ulcerative colitis is a chronic, idiopathic, inflammatory condition affecting the colon, primarily impacting individuals aged 30 to 40. It typically begins in the rectum and gradually progresses to the proximal regions of the colon, characterized by recurrent and remitting mucosal inflammation. Ulcerative colitis is categorized under inflammatory bowel disease, which encompasses various gastrointestinal tract disorders, but its underly-ing pathophysiology remains unclear.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Department of Drugs and Medicines, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, SP, Brazil. Electronic address:
Ulcerative colitis (UC) is a chronic inflammatory bowel disease initially treated with mesalazine (5-ASA). However, its effectiveness is limited by rapid absorption, low colonic concentration, and exacerbation of dysbiosis. Probiotics can mitigate dysbiosis if they survive the acidic conditions of the stomach.
View Article and Find Full Text PDFIntest Res
December 2024
Department of Gastroenterology, Mater Hospital, Brisbane, Australia.
Background/aims: Upadacitinib is a novel selective Janus kinase inhibitor approved for use in ulcerative colitis. Clinical trials had rigorous criteria and excluded many patient subgroups. Given limited real-world effectiveness data, we examined outcomes of patients treated with upadacitinib for ulcerative colitis in a real-world population.
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