168 GENE EXPRESSION ANALYSES IN THE PERIOPERATIVE ILEAL RESECTION PERIOD ILLUMINATE PATHOGENIC AND PROTECTIVE CROHN'S DISEASE CELL SUBSETS

2021 ◽  
Vol 160 (6) ◽  
pp. S-41
Author(s):  
Kyle Gettler ◽  
Ksenija Sabic ◽  
Mamta Giri ◽  
L. Philip Schumm ◽  
Talin Haritunians ◽  
...  
2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Jin-shan Feng ◽  
Jin-yu Li ◽  
Xiu-yan Chen ◽  
Zheng Yang ◽  
Shang-hai Li

Objective. To assess the benefits of different treatments that aim to prevent the endoscopic recurrence of Crohn’s disease (CD) after ileal resection. Methods. Randomized controlled trials (RCTs) were searched from MEDLINE, Embase, and the Cochrane Central Database. All the included RCTs with an endoscopic recurrence outcome which was defined as Rutgeerts’ score ≥ i2 have a duration of more than 1 year. The quality of the included RCTs was assessed by the Cochrane Risk of Bias Tool. Pairwise treatment effects were estimated through a Bayesian random effects network meta-analysis by using the OpenBUGS 1.4 software and reported as odds ratios (ORs) with a 95% credible interval (CI). Results. Fourteen RCTs (877 participants) were included. Two strategies were superior to placebo for preventing endoscopic recurrence of CD at 1 year after surgery: infliximab (d, −5.475; 95% CI, −10.47 to –1.632) and adalimumab (d, −7.273; 95% CI, −13.84 to −2.585). Nine strategies were not effective: budesnoid, mesalazine (in both high and low dose), azathioprine, Tripterygium wilfordii, mesalazine + infliximab, ornidazole, untreated intervention, and Lactobacillus GG. Conclusions. Except for infliximab and adalimumab, other strategies included in our analysis were not effective for preventing endoscopic recurrence of CD at 1 year after ileal resection.


2012 ◽  
Vol 6 ◽  
pp. S41
Author(s):  
G.W. Sewell ◽  
P.J. Smith ◽  
A.P. Levine ◽  
C.M. McDonald ◽  
S.L. Bloom ◽  
...  

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.


2018 ◽  
Vol 34 (1) ◽  
pp. 185-188 ◽  
Author(s):  
Thomas Skouras ◽  
Susanna Dodd ◽  
Yash Prasad ◽  
Joseph Rassam ◽  
Nazreen Morley ◽  
...  

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S9-S10
Author(s):  
Brooklyn McGrew ◽  
Aman Shrivastava ◽  
Philip Fernandes ◽  
Lubaina Ehsan ◽  
Yash Sharma ◽  
...  

Abstract Background Candidate markers for Crohn’s Disease (CD) may be identified via gene expression-based construction of metabolic networks (MN). These can computationally describe gene-protein-reaction associations for entire tissues and also predict the flux of reactions (rate of turnover of specific molecules via a metabolic pathway). Recon3D is the most comprehensive human MN to date. We used publicly available CD transcriptomic data along with Recon3D to identify metabolites as potential diagnostic and prognostic biomarkers. Methods Terminal ileal gene expression profiles (36,372 genes; 218 CD. 42 controls) from the RISK cohort (Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn’s Disease) and their transcriptomic abundances were used. Recon3D was pruned to only include RISK dataset transcripts which determined metabolic reaction linkage with transcriptionally active genes. Flux balance analysis (FBA) was then run using RiPTiDe with context specific transcriptomic data to further constrain genes (Figure 1). RiPTiDe was independently run on transcriptomic data from both CD and controls. From the pruned and constricted MN obtained, reactions were extracted for further analysis. Results After applying the necessary constraints to modify Recon3D, 527 CD and 537 control reactions were obtained. Reaction comparison with a publicly available list of healthy small intestinal epithelial reactions (n=1282) showed an overlap of 80 CD and 84 control reactions. These were then further grouped based on their metabolic pathways. RiPTiDe identified context specific metabolic pathway activity without supervision and the percentage of forward, backward, and balanced reactions for each metabolic pathway (Figure 2). The metabolite concentrations in the small intestine was altered among CD patients. Notably, the citric acid cycle and malate-aspartate shuttle were affected, highlighting changes in mitochondrial metabolic pathways. This is illustrated by changes in the number of reactions at equilibrium between CD and control. Conclusions The results are relevant as cytosolic acetyl-CoA is needed for fatty acid synthesis and is obtained by removing citrate from the citric acid cycle. An intermediate removal from the cycle has significant cataplerotic effects. The malate-aspartate shuttle also allows electrons to move across the impermeable membrane in the mitochondria (fatty acid synthesis location). These findings are reported by previously published studies where gene expression for fatty acid synthesis is altered in CD patients along with mitochondrial metabolic pathway changes, resulting in altered cell homeostasis. In-depth analysis is currently underway with our work supporting the utility of potential metabolic biomarkers for CD diagnosis, management and improved care.


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