scholarly journals P022 Pathologic involvement of the farnesoid X receptor/fibroblast growth factor 19 axis to the Crohn’s disease early postsurgical recurrence

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S139-S140
Author(s):  
R Suau ◽  
A Garcia-Jaraquemada ◽  
V Lorén ◽  
P Torres ◽  
E Jou ◽  
...  

Abstract Background Crohn’s disease (CD) is a chronic inflammatory bowel disease that normally requires bowel surgical resection due to intra-abdominal inflammatory complications such as fistulae and stenosis. However, 90% of patients that underwent surgery and did not receive prophylaxis, suffer from postsurgical endoscopic recurrence within one year. Methods The objective of this study is to understand the de novo postsurgical lesion formation in order to stablish a potential mechanism of action and its derived predictive signals to devise preventive strategies. To achieve it, transcriptome analyses of the inflamed and macroscopically unaffected zone of the ileocecal resection from 20 patients from a hospital cohort and 10 controls were performed. Patients were classified for early postsurgical recurrence by means of Rutgeerts index (i0<i1<i2<i3<i4) and transcriptome was analysed using different comparatives and clustering strategies. In order to replicate the results from the transcriptome analyses, the statistically significant genes and rationally related genes have been tested by qPCR in a corroboration cohort formed by 24 different patients. Results The transcriptome results showed there were no differences neither between i0, i1 and i2a (anastomotic lesions) nor when comparing i2b (non-anastomotic lesions) vs ≥i3. However, when comparing i0+i1+i2a vs. i2b+i3+i4 there were differently expressed genes highlighting ADIPOQ in the inflamed zone and the FXR/FGF19 axis in the unaffected zone. When replicating the results in the corroborative cohort, we identified FXR and other xenobiotic nuclear receptors as the genes differentially expressed in i2a vs i2b, i3 and/or i4, mainly in the macroscopically unaffected zone. Specifically, the differentially expressed genes were: MOGAT2, PXR, FXR and AHR (i2a vs i4), PPARα and FXR (i2a vs i3), TMIGD1, PPARα, FXR and AHR (i2a vs i3+i4) and FXR (i2a vs i2b+i3+i4). Conclusion Nuclear receptor FXR is activated in the ileum by bile acids action and it is key in the lipid metabolism regulation and in the bile acids production by means of FGF19. Moreover, ileal FXR, as well as other xenobiotic nuclear receptors, actively participates in the enhancement of the intestinal barrier function and in the innate immunity regulation. In conclusion, the results obtained in this study suggest a link between bowel xenobiotic metabolism and the de novo lesion formation in previously unaffected areas in the postsurgical recurrence in CD.

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 574
Author(s):  
Claudio Fiorillo ◽  
Carlo Alberto Schena ◽  
Giuseppe Quero ◽  
Vito Laterza ◽  
Daniela Pugliese ◽  
...  

Crohn’s disease (CD) is a chronic inflammatory bowel disease with a progressive course, potentially affecting the entire gastrointestinal tract from mouth to anus. Several studies have shown an increased risk of both intestinal and extra-intestinal cancer in patients with CD, due to long-standing transmural inflammation and damage accumulation. The similarity of symptoms among CD, its related complications and the de novo onset of gastrointestinal cancer raises difficulties in the differential diagnosis. In addition, once a cancer diagnosis in CD patients is made, selecting the appropriate treatment can be particularly challenging. Indeed, both surgical and oncological treatments are not always the same as that of the general population, due to the inflammatory context of the gastrointestinal tract and the potential exacerbation of gastrointestinal symptoms of patients with CD; moreover, the overlap of the neoplastic disease could lead to adjustments in the pharmacological treatment of the underlying CD, especially with regard to immunosuppressive drugs. For these reasons, a case-by-case analysis in a multidisciplinary approach is often appropriate for the best diagnostic and therapeutic evaluation of patients with CD after gastrointestinal cancer onset.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jihye Park ◽  
Daeun Jeong ◽  
Youn Wook Chung ◽  
Seunghan Han ◽  
Da Hye Kim ◽  
...  

AbstractIntestinal Behçet’s disease (BD) and Crohn’s disease (CD) present similar manifestations, but there are no specific diagnostic tests to differentiate them. We used a proteomic approach to discover novel diagnostic biomarkers specific to intestinal BD. Colon mucosa tissue samples were obtained from patients with intestinal BD or CD using colonoscopy-guided biopsy of the affected bowel. Peptides from seven intestinal BD and seven CD patients were extracted and labeled using tandem mass tag (TMT) reagents. The labeled peptides were identified and quantified using liquid chromatography-tandem mass spectrometry (LC–MS/MS). The proteins were further validated using immunohistochemical (IHC) analysis with tissue samples and an ELISA test with serum samples from 20 intestinal BD and 20 CD patients. Using TMT/LC–MS/MS-based proteomic quantification, we identified 39 proteins differentially expressed between intestinal BD and CD. Beta-2 glycoprotein 1 (APOH) and maltase-glucoamylase (MGAM) showed higher intensity in the IHC staining of intestinal BD tissues than in CD tissues. The serum MGAM level was higher in intestinal BD patients. Proteomic analysis revealed that some proteins were differentially expressed in patients with intestinal BD compared with those with CD. Differential MGAM expression in intestinal BD suggests its role as a potential novel diagnostic biomarker.


2000 ◽  
Vol 51 (4) ◽  
pp. AB146
Author(s):  
Toshifumi Ashida ◽  
Atsuo Maemoto ◽  
Takanori Fujiki ◽  
Tohru Kohno ◽  
Akitoshi Kakisaka ◽  
...  

2017 ◽  
Vol 6 (2) ◽  
Author(s):  
Matilde Zamboni ◽  
Maria Grazia Sibilla ◽  
Roberto Galeotti ◽  
Massimo Pedriali ◽  
Simona Ascanelli

Crohn’s disease (CD) is a chronic inflammatory bowel disease and its pathogenesis is still not well understood. Previous studies suggested the possibility of the involvement of vascular system, but, todate, the mesenteric circulation has poor been investigated, especially in complicated CD cases requiring colectomy. We investigated the mesenteric circulation in a case-control pilot study, including 19 controls and 7 patients affected by complicated cases of CD. Cases and controls underwent selective angiography of both superior and inferior mesenteric district. Transit time was found either significantly shortened in 2/7 cases (29%), or prolonged 5/7 (71%) (P=0.0034 in the superior mesenteric district; P=0.0079 in the inferior mesenteric district), respectively due to the presence of A-V malformations and of a miscellaneous of venous abnormalities, which included thrombosis, hypoplasia and extra-truncular venous malformations. Our study demonstrates the presence of congenital or acquired vascular anomalies in a small sample of CD patients not responder to current treatment and with severe complications. The present pilot study warrants further investigations.


2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S164-S165
Author(s):  
J Park ◽  
J Daeun ◽  
C Youn Wook ◽  
C Jae Hee ◽  
R Ji-Hwan

Abstract Background Intestinal Behçet’s disease (BD) and Crohn’s disease (CD) present similar manifestations, but there are no specific pathognomonic clinical, laboratory, or histological diagnostic tests to differentiate intestinal BD from CD. We used a proteomic approach to discover a novel diagnostic biomarker specific to intestinal BD. Methods The colon mucosa tissue samples were obtained using colonoscopy-guided biopsy of the affected bowel from patients with intestinal BD or CD at the Inflammatory Bowel Disease Clinic of Severance Hospital, Seoul, Korea. Peptides from seven intestinal BD and seven CD patients were extracted and labeled using tandem mass tag (TMT) reagents. The labeled peptides were identified and quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The differentially expressed proteins were further validated using immunohistochemical (IHC) analysis with tissue samples and an ELISA test with serum samples from 20 intestinal BD and 20 CD patients. Results A total of 3,266 proteins were identified using TMT/LC-MS/MS-based proteomic quantification, including 39 candidate proteins differentially expressed between intestinal BD and CD. Beta-2 glycoprotein 1 (APOH) and maltase-glucoamylase (MGAM) showed significantly higher intensity in the IHC staining of the intestinal BD tissues than that of CD tissues. Furthermore, the serum MGAM level was significantly higher in patients with intestinal BD than in patients with CD. Conclusion Our proteomic analysis revealed that some proteins were differentially expressed in intestinal BD patients compared to CD patients. Differential MGAM expression in intestinal BD suggests its role as a potential novel diagnostic biomarker in the differentiation of intestinal BD from CD.


2020 ◽  
Author(s):  
Shahan Mamoor

Inflammatory bowel diseases (IBD) include Crohn’s Disease and Ulcerative Colitis (1). We mined published microarray data to understand how gene expression in the hematopoietic compartment of patients with Crohn’s Disease is most different from that of healthy controls (2-4). Across two datasets (2, 3), we found that BAFF, also known as the B-lymphocyte stimulator (BLyS), encoded by the gene TNFSF13B (5), was differentially expressed in the blood of patients with Crohn’s Disease . Analysis of a third dataset (4) revealed that BAFF was among the genes most differentially expressed in monocyte-derived macrophages from patients with Crohn’s Disease. Serum BAFF, fecal BAFF, and BAFF expression in the intestinal mucosa has been demonstrated to be increased in patients with IBD (6, 7). We show here that expression of BAFF in the peripheral blood of patients with Crohn’s Disease is also increased.


2020 ◽  
Author(s):  
Shahan Mamoor

Crohn’s disease, an inflammatory bowel disease of the gastrointestinal tract (1), causes significant morbidity and nearly 3.5 billion dollars in lost economic productivity in the United States (2) due to complications of the disease. We mined transcriptome and methylome datasets (3, 4) to understand, in an unbiased manner, the most significant changes in gene expression and DNA methylation in the hematopoietic system of patients with Crohn’s disease (CD). We identified the zinc finger and BTB (broad complex, tramtrack, bric-à-brac) domain-containing gene ZBTB6 (5, 6) as one of the most differentially expressed genes in the whole blood of patients with Crohn’s disease. Analysis of a separate data revealed that the ZBTB6 locus was one of the most differentially methylated sites globally in the blood of patients with Crohn’s disease when compared to the blood of healthy patients. ZBTB6 is differentially methylated and differentially expressed in the blood of patients with Crohn’s disease, and more significantly so than the vast majority of the human genome. These data point to inhibition of ZBTB6 gene expression by hyper-methylation of the ZBTB6 locus and suggest that titration of some function or transcriptional target of ZBTB6 may be an important event in the pathogenesis of Crohn’s disease.


1985 ◽  
Vol 33 (12) ◽  
pp. 604-609
Author(s):  
Roberta Messner ◽  
Sylvia Gardner ◽  
Susan Lewis

Crohn's disease is a chronic, inflammatory bowel disease which may occur in single or multiple areas of the entire GI tract from the mouth to the anus. This multifaceted disorder is manifested by various unpredictable health disturbances, affecting its victims' physical and psychosocial well-being. Individuals with Crohn's disease present a multitude of nursing challenges as they often lack the positive effects of proper nutrition, physical activity, emotional expression, interpersonal relationships, and family life. Nurses are the primary care providers who can comprehensively address the varied and complex health care needs of individuals with Crohn's disease. The core theme is the belief that it is essential for these individuals to maintain a sense of control in the midst of an altered lifestyle. Occupational health nurses can assist employees with Crohn's disease to develop a variety of physical and psychosocial strategies to cope with the unpleasant, even repugnant, aspects of a disease for which there is no known cure. The promotion of optimal health, based on the nursing process, is the objective toward which the unique efforts of nursing are directed.


Sign in / Sign up

Export Citation Format

Share Document