scholarly journals P041 CDKN2B-AS1 (ANRIL) expression is decreased in Inflammatory Bowel Disease epithelia and in Celiac, and its reduction is linked with induced cells proliferation

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S152-S152
Author(s):  
M Benshoshan ◽  
K E Sosnovski ◽  
T Braun ◽  
A Amir ◽  
Y Anikster ◽  
...  
Keyword(s):  
Large Fraction ◽  
Suppressor Gene ◽  
Rt Pcr ◽  
Cell Index ◽  
Immune Mediated ◽  
Treatment Naïve ◽  
Transcriptomics Data ◽  
Inflammatory Bowel ◽  
Contrast Reduction ◽  
Ht 29

Abstract Background Long non-coding RNAs (lncRNAs) have attenuated expression in several immune-mediated disorders. Using mRNAseq of intestinal biopsies, we identified a widespread dysregulation of 459 lncRNAs in the ileum of treatment-naïve pediatric Crohn Disease (CD) patients. We noted that large fraction of downregulated lncRNAs were correlated with epithelial functions. CDKN2B-AS1 (ANRIL) is one of the top most down-regulated lncRNA in CD, and showed decreased expression in Ulcerative Colitis (UC) colon tissues in recent studies. Methods Transcriptomics data is used to evaluate CDKN2B-AS1 expression in mucosal biopsies datasets and in gut epithelia. siRNA oligonucleotides targeting most CDKN2B-AS1 transcripts using Lipofectamine RNAiMAX is used to modulate CDKN2B-AS1 function, and RT-PCR to evaluate mRNA expression. xCELLigence system with gold microelectrodes in plate base is used to measure the impedance as an indicator for cell index. Results CDKN2B-AS1 is down-regulated in bulk mucosal biopsies obtained from CD ileum [fold change (FC) -8, corrected p=1.6E-5], in UC rectum (FC -9.4, corrected p=3.9E-18), and in celiac duodenum (FC -2.3, corrected p=0.03) in comparison to controls. CDKN2B-AS1 is detected under basal conditions in HT-29 cells. Two sets of CDKN2B-AS1 siRNA oligonucleotides (targeting most transcripts) achieved up to 60% reduction in CDKN2B-AS1 expression in HT-29 cells (p=1E-04) as confirmed by RT-PCR using two sets of primers. CDKN2B-AS1 reduction significantly increased cell index as measured by xCELLigence (doubled the index, p=1.7E-03). mRNAseq of the CDKN2B-AS1 reduced HT-29, showed reduction of the tumor suppressor gene APC in CDKN2B-AS1 siRNA treated cells (FC=-1.75, p=0.04) and of TGFBR2 (FC=-1.75, p=0.04). In contrast, reduction of CDKN2B-AS1 resulted in increase in WNT11 (FC=2.1, p=0.02) and TGFB1 (FC=1.9, p=0.04), and induction of the replication associated topoisomerase TOP1MT (FC=2.7, p=0.001). We confirmed these mRNAseq results using RT-PCR. Finally, mimicking inflammation by treating HT-29 with IL1β and LPS, reduced CDKN2B-AS1 expression (by 70%, p=6.3E-04) and doubled the cell index (p=1.8E-03). Conclusion We detected reduced CDKN2B-AS1 expression in three inflammatory disease affecting the gut in different location along the GI tract. Using HT-29 model system we were able to show, as was previously shown, an increase in cell index in CDKN2B-AS1 siRNA treated cells. We supplement those showing effect on down-stream genes that may be relevant in controlling cell proliferation. We further show that upon inflammatory triggering of HT-29 cells, CDKN2B-AS1 expression is reduced and cell index is increased, which may suggest a potential role in epithelial renewal in inflammation.

scholarly journals Procoagulatory State in Inflammatory Bowel Diseases Is Promoted by Impaired Intestinal Barrier Function

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Luca Pastorelli ◽  
Elena Dozio ◽  
Laura Francesca Pisani ◽  
Massimo Boscolo-Anzoletti ◽  
Elena Vianello ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Intestinal Barrier ◽  
Systemic Circulation ◽  
Intestinal Barrier Function ◽  
Inflammatory Conditions ◽  
Immune Mediated ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Molecular Patterns ◽  
D Dimer

Inflammatory and immune mediated disorders are risk factors for arterial and venous thromboembolism. Inflammatory bowel diseases (IBD) confer an even greater risk of thromboembolic events than other inflammatory conditions. It has been shown that IBD patients display defective intestinal barrier functions. Thus, pathogen-associated molecular patterns (PAMPs) coming from the intestinal bacterial burden might reach systemic circulation and activate innate immunity receptors on endothelial cells and platelets, promoting a procoagulative state. Aim of the study was to test this hypothesis, correlating the presence of circulating PAMPs with the activation of innate immune system and the activation of the coagulatory cascade in IBD patients. Specifically, we studied lipopolysaccharide (LPS), Toll-like receptor (TLR) 2, TLR4, and markers of activated coagulation (i.e., D-Dimer and prothrombin fragmentF1+2) in the serum and plasma of IBD patients. We found that LPS levels are increased in IBD and correlate with TLR4 concentrations; although a mild correlation between LPS and CRP levels was detected, clinical disease activity does not appear to influence circulating LPS. Instead, serum LPS correlates with both D-Dimer andF1+2measurements. Taken together, our data support the role of an impairment of intestinal barrier in triggering the activation of the coagulatory cascade in IBD.

scholarly journals Management of Acute Severe Ulcerative Colitis in a Pregnant Woman With COVID-19 Infection: A Case Report and Review of the Literature

2020 ◽  
Vol 26 (7) ◽  
pp. 971-973 ◽  
Author(s):  
Melissa H Rosen ◽  
Jordan Axelrad ◽  
David Hudesman ◽  
David T Rubin ◽  
Shannon Chang
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
First Trimester ◽  
Review Of The Literature ◽  
Severe Ulcerative Colitis ◽  
Immune Mediated ◽  
First Trimester Of Pregnancy ◽  
Inflammatory Bowel ◽  
High Level

Abstract First detected in Wuhan, China, the novel 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped RNA beta-coronavirus responsible for an unprecedented, worldwide pandemic caused by COVID-19. Optimal management of immunosuppression in inflammatory bowel disease (IBD) patients with COVID-19 infection currently is based on expert opinion, given the novelty of the infection and the corresponding lack of high-level evidence in patients with immune-mediated conditions. There are limited data regarding IBD patients with COVID-19 and no data regarding early pregnancy in the era of COVID-19. This article describes a patient with acute severe ulcerative colitis (UC) during her first trimester of pregnancy who also has COVID-19. The case presentation is followed by a review of the literature to date on COVID-19 in regard to inflammatory bowel disease and pregnancy, respectively.

scholarly journals Combining Biologics in Inflammatory Bowel Disease and Other Immune Mediated Inflammatory Disorders

2018 ◽  
Vol 16 (9) ◽  
pp. 1374-1384 ◽  
Author(s):  
Robert P. Hirten ◽  
Marietta Iacucci ◽  
Shailja Shah ◽  
Subrata Ghosh ◽  
Jean-Frederic Colombel
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Inflammatory Disorders ◽  
Immune Mediated ◽  
Inflammatory Bowel

scholarly journals Biológiai terápia szisztémás alkalmazása a szemészetben

2019 ◽  
Vol 160 (44) ◽  
pp. 1744-1750
Author(s):  
Fruzsina Benyó ◽  
Alexandra Farkas ◽  
Hajnalka Horváth ◽  
Zoltán Zsolt Nagy ◽  
Zsuzsanna Szepessy
Keyword(s):  
Autoimmune Disease ◽  
Biological Treatment ◽  
Biological Therapy ◽  
The Third ◽  
First Case ◽  
Immune Mediated ◽  
Initial Symptoms ◽  
Inactive Period ◽  
Infectious Uveitis ◽  
Inflammatory Bowel

Abstract: We present herewith cases of non-infectious uveitis with biological treatment where the ocular complaints were the initial symptoms indicating a multi-organ autoimmune disease. The first case was a patient with panuveitis and Vogt–Koyanagi–Harada disease, the second case was also a panuveitic patient with sarcoidosis and the third case was a patient with intermediate uveitis and inflammatory bowel disease. In all cases, emerging new, biological therapy (adalimumab) was necessary to achieve permanent inactive period of uveitis and the autoimmune disease. Introducing systemic biological treatment (adalimumab) in ophthalmology is crucial in the therapy of immune-mediated, non-infectious uveitis in order to preserve visual acuity. Orv Hetil. 2019; 160(44): 1744–1750.

scholarly journals P261 Systematic review with meta-analysis: The impact of concomitant immune-mediated diseases on the disease course of inflammatory bowel disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S280-S281
Author(s):  
M Attauabi ◽  
M Zhao ◽  
F Bendtsen ◽  
J Burisch
Keyword(s):  
Biologic Therapy ◽  
Meta Analysis ◽  
Multidisciplinary Care ◽  
Disease Course ◽  
Immune Mediated ◽  
Increased Risk ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Meta Analyses ◽  
The Impact

Abstract Background Several studies have shown an association between inflammatory bowel diseases [IBD] and immune-mediated diseases [IMIDs], but data on the impact of co-occurring IMIDs on IBD course are inconsistent. The aim of this study was to investigate the impact of co-occurring IMIDs on IBD phenotype and disease course. Methods PubMed and EMBASE were searched from database inception through December 2018 and updated in October 2019 for studies reporting prevalences or odds, risks or hazard ratios of IBD-related disease outcomes in patients with and without co-existing IMIDs. Meta-analyses were performed to estimate summary prevalences and risks of the outcomes which included disease extension, IBD-related surgery and hospitalisation, malignancy, mortality and need of medication (biologic therapy, steroids and immunomodulators). IMIDs were stratified into primary sclerosing cholangitis [PSC] and ‘IMIDs other than PSC’. Results A total of 93 studies comprising 14,307 IBD patients with IMIDs and 3,409,914 IBD patients without IMIDs were included in the study. Summary risks and prevalences with 95% confidence intervals for each outcome are presented in figures 1 and 2, respectively. The following results are all significant (p < 0.05). Compared with patients without co-occurring IMIDs, patients with ulcerative colitis [UC] and co-occurring IMIDs other than PSC more frequently received immunomodulators and steroids, and patients with Crohn’s disease [CD] and concomitant IMIDs other than PSC more often received biologic therapy. UC patients with co-existing IMIDs other than PSC more often underwent IBD-related surgery, while patients with CD and PSC received fewer surgeries. In addition, UC patients with co-occurring PSC were at increased risk for having extensive colitis, pancolitis, and malignancies. Patients with UC and PSC had a higher mortality rate, but no difference was found among patients with IMIDs other than PSC. PSC did not influence hospitalisation rates among IBD patients. Conclusion This meta-analysis found that IBD patients with co-existing IMIDs have a different disease course than patients without concomitant IMIDs. This study emphasises the importance of multidisciplinary care of IBD and that physicians caring for IBD patients need to be aware of IMIDs as a prognostic factor.

scholarly journals miR-509-5p Inhibits the Proliferation and Invasion of Osteosarcoma by Targeting TRIB2

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jiekun Guo ◽  
Qiang Wu ◽  
Xiaoming Peng ◽  
Bin Yu
Keyword(s):  
Tumor Suppressor ◽  
Cell Lines ◽  
Transcriptional Activity ◽  
Preventive Intervention ◽  
Suppressor Gene ◽  
Rt Pcr ◽  
Malignant Bone Tumors ◽  
Direct Target ◽  
Proliferation And Invasion

Osteosarcoma (OS) is one of the most common malignant bone tumors in adolescents with a poor prognosis. Though miR-509-5p has been reported as a tumor suppressor in several human cancers, the role of miR-509-5p in OS remains unclear. In this study, our result of real-time PCR (RT-PCR) showed that the expression of miR-509-5p was significantly decreased in OS tissues and cell lines. Overexpression of miR-509-5p significantly suppressed cell proliferation and invasion in OS cell lines. Moreover, we identified tribbles homolog 2 (TRIB2) as the direct target of miR-509-5p. Knockdown of TRIB2 could inhibit the malignant capacity of OS cells. At last, we reported that TRIB2 could inhibit the bioactivity of the tumor suppressor gene p21 via blocking its transcriptional activity. Collectively, our study revealed that miR-509-5p functions as a tumor suppressor by targeting TRIB2 in OS and thus could affect the activity of p21, suggesting that miR-509-5p is a novel preventive intervention for OS patients.

Can We Extrapolate Data from One Immune-Mediated Inflammatory Disease to Another One?

2019 ◽  
Vol 26 (2) ◽  
pp. 248-258 ◽  
Author(s):  
Fernando Magro ◽  
Rosa Coelho ◽  
Armando Peixoto
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Diseases ◽  
Analytical Techniques ◽  
Approval Process ◽  
Homogeneous Population ◽  
Post Translational Modifications ◽  
Innovator Product ◽  
Immune Mediated ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Immune-mediated inflammatory diseases share several pathogenic pathways and this pushes sometimes to extrapolate from one disease or indication to others. A biosimilar can be defined as a biotherapeutic product which is similar in terms of quality, safety, and efficacy to an already licensed reference biotherapeutic product. We review the substrate for extrapolation, the current approval process for biosimilars and the pioneering studies on biosimilars performed in rheumatoid arthritis patients. A biosimilar has the same amino acid sequence as its innovator product. However, post-translational modifications can occur and the current analytical techniques do not allow the final structure. To test the efficacy in one indication, a homogeneous population should be chosen and immunogenicity features are essential in switching and interchangeability. CT-P13 (Remsima™; Inflectra™) is a biosimilar of reference infliximab (Remicade®). It meets most of the requirements for extrapolation. Nevertheless, in inflammatory bowel diseases (IBD) we need more studies to confirm the postulates of extrapolation from rheumatoid arthritis and ankylosing spondylitis to IBD. Furthermore, an effective pharmacovigilance schedule is mandatory to look for immunogenicity and side effects.

scholarly journals Sulfasalazine-Induced Pancytopenia in Ulcerative Colitis

2016 ◽  
Vol 6 (3) ◽  
pp. 164-165
Author(s):  
NS Neki ◽  
Ankur Jain
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Adverse Effects ◽  
Bowel Disease ◽  
Modifying Agent ◽  
Immune Mediated ◽  
Established Disease ◽  
Inflammatory Bowel ◽  
Disease Modifying

Sulfasalazine is a well-established disease-modifying agent. It is commonly used in the treatment of rheumatic disorders and inflammatory bowel disease. The most frequently reported adverse effects are gastrointestinal effects, headache, dizziness and rash; myelosuppression can also occur. Patients treated with sulfasalazine can develop thrombocytopenia which is immune mediated. We report a case of ulcerative colitis that was on sulfasalazine subsequently developing thrombocytopenia.J Enam Med Col 2016; 6(3): 164-165

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