Expression Analysis of Long Noncoding RNA-MALAT1 and Interleukin-6 in Inflammatory Bowel Disease Patients.

 Inflammatory bowel disease (IBD) manifests as chronic inflammation within the gastrointestinal tract. The study focuses on a long noncoding RNA (lncRNA) known as Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). MALAT1's misregulation has been linked with various autoimmune diseases and regulates proinflammatory cytokines. The role of IL6 in immune-triggered conditions, including IBD, is another focal point. In this research, the expression of MALAT1 and IL6 in IBD patients was meticulously analyzed to uncover potential interactions. The study involved 33 IBD patients (13 with Crohn's disease and 20 with ulcerative colitis) and 20 healthy counterparts. Quantitative real-time polymerase chain reaction determined the MALAT1 and IL6 gene expression levels. The competitive endogenous RNA (ceRNA) regulatory network was constructed using several tools, including LncRRIsearch and Cytoscape. A deep dive into the Inflammatory Bowel Disease database was undertaken to understand IL6's role in IBD. Drugs potentially targeting these genes were also pinpointed using DGIdb. Results indicated a notable elevation in the expression levels of MALAT1 and IL6 in IBD patients versus healthy controls. MALAT1 and IL6 did not show a direct linear correlation, but IL6 could serve as MALAT1's target. Analyses unveiled interactions between MALAT1 and IL6, regulated by hsa-miR-202-3p, hsa-miR-1-3p, and has-miR-9-5p. IL6's pivotal role in IBD-associated inflammation, likely interacting with other cytokines, was accentuated. Moreover, potential drugs like CILOBRADINE for MALAT1 and SILTUXIMAB for IL6 were identified. This research underscored MALAT1 and IL6's potential value as targets in diagnosis and treatment for IBD patients.

Translation and cross-cultural adaptation of the Persian version of inflammatory bowel disease-fatigue (IBD-F) self-assessment questionnaire.

BACKGROUND: This study appraises the psychometrics properties of the Inflammatory bowel disease-fatigue (IBD-F) Persian version questionnaire. METHODS: The original IBD-F questionnaire was translated into the Persian version in a standard forward-back manner. The validation was performed through the face, content, and construct validity. Fifteen experts scored each item's necessity on an ordinal Likert scale of three; then, the content validity ratio was calculated using the Lawshe formula. Eight judges from pre-defined panel rated each item on an ordinal 4-point Likert scale concerning its relevancy, clarity, and simplicity for individual-CVI calculation. The mean individual-CVI was considered as the Scale-CVI for each domain. Twenty lay experts (selected from the target population) were asked to express their opinion on each item's importance by scoring on a 5-point Likert scale; subsequently, face validity was determined by the impact score formula. The questions that had minimum values of CVR, CVI, and impact score were retained in the final version of the questionnaire for reliability evaluation. Construct validity was evaluated via Confirmatory Factor Analysis. Internal consistency and test-retest reliability were checked using Cronbach's α and intraclass correlation coefficients (ICC). Fifty-four patients recruited based on inclusion and exclusion criteria to participate in the reliability analysis. RESULTS: All the questions received the qualified values of CVR (exceeding 0.49 points) and impact score (more than 1.5 points) and were retained in the questionnaire; however, revisions were made for questions with a CVI 0.7-0.9 for clarity and simplicity. The result demonstrated relative goodness CFA and proper internal consistency, as Cronbach's α coefficient was 0.964 for the test (0.845 and 0.963 for the first and second part of the questionnaire, respectively (and 0.888 for the re-test (0.793 and 0.876 for the first and second section of the questionnaire, respectively). The ICC values between test and re-test for the first and second part and the whole questionnaire were obtained as 0.904, 0.922, and 0.921, respectively. CONCLUSION: The Persian version of the IBD-F questionnaire was valid and reliable; thus, an appropriate scale was deemed to measure fatigue (severity, frequency, and impact on daily activities).

High prevalence of SARS-Coronavirus-2 in patients with inflammatory bowel disease and the role of soluble angiotensin converting Enzyme2.

Context: Patients with inflammatory bowel disease (IBD) were found to have the higher intestinal expression of Angiotensin-Converting Enzyme2 (ACE2) that could consequently increase susceptibility to COVID-19 infection.Objective: This study reports the outcomes of COVID-19 infection in a large cohort of IBD patients. We compare levels of serum ACE and IFN-α between COVID19 patients with and without IBD. We performed a cross-sectional retrospective multicenter study.Methods: We enrolled patients with IBD screened for SARS-COV-2 in six medical centres in Iran from June to November 2020. The blood samples were drawn to measure COVID-19 IgM and IgG, and serum levels of sACE2, sACE1, and interferon-α, regardless of suspicious symptoms have done the molecular test.Results: A total of 534 IBD patients were included in the study. Of these, 109 (20.0%) cases had detectable IgG and IgM against SARS-CoV-2. sACE2 levels were higher in IBD patients than controls, whereas ACE1and IFN-α levels were similar among groups.

Serological response to SARS-CoV-2 is attenuated in patients with inflammatory bowel disease and can affect immunization.

In this study we indicated that impaired serological responses to SARS-CoV-2 infection among patients with IBD, could have significant implications for this group of patients and should be considered in vaccination program.

Evaluation of adalimumab effects on left ventricle performance by echocardiography indexes among patients with immunosuppressant refractory ulcerative colitis.

Background and aims: Inflammatory bases lead to a simultaneous flourishing of cardiovascular complications with inflammatory bowel disease (IBD). As a released cytokine, tumor necrosis factor-α (TNF-α) can either disrupt or preserve cardiovascular performance. Due to this controversy, this study aimed to appraise the short-term anti-TNF (adalimumab [ADA]) relics on cardiac function by gauging the echocardiography indexes in patients with immunosuppressant refractory ulcerative colitis (UC). Methods: All cases with a definite diagnosis of UC were included based on providing written informed consent and owning the severe form of active disease (Mayo score ≥7), which did not dampen with immunosuppressant. Patients were excluded in the case of previous cardiac ailments/risk factors and prior related surgical or pharmaceutical intervention. Transthoracic echocardiography (TTE) was carried out before and 3 months after biological regimen allocation and changes in indexes [ejection fraction (EF), left ventricular end-diastolic volume (LVEDV)/left ventricular end-systolic volume (LVESV), and global longitudinal strain (GLS) in standard parasternal short axis from mid-ventricular level, two-, three-, and four-chamber apical long axes] were compared via statistical analyses. Results: The study consisted of 13 (65%) men and 7 (35%) women, with a mean age of 36.54 ± 11.3 years. Participants mainly possessed Montreal class I (45%) and an average of 3.25 years of disease duration. The intervention significantly controlled inflammation [endoscopic Mayo score (P = 0.001), partial Mayo score (P = 0.001), and C-reactive protein (P = 0.001)]. Endoscopic and clinical remission was obtained in 7 (35%) and 9 (45%) patients, respectively; however, no significant discrepancy related to the LVEDV (P = 0.86), LVESV (P-value = 0.25), EF (P-value = 0.06), and GLS in standard parasternal short axis (P = 0.73), long axis [apical 2-chamber (P-value = 0.61), apical 3-chamber (P-value = 0.15), and apical 4-chamber (P-value = 0.19) views] was observed before and after the intervention. Furthermore, no statistically significant correlation between disease activity and cardiac function was found, neither before nor after ADA administration. Conclusion: The present perusal found no deterioration in left ventricular function indexes with ADA intervention among patients with IBD without cardiac ailment. Thus, prescribing the anti-TNF to alleviate the inflammation can be carried out with less concern about cardiac consequences and considering other adverse traces in the target group.

Efficacy and Safety of Melatonin as an Adjunctive Therapy on Clinical, Biochemical, and Quality of Life in Patients with Ulcerative Colitis.

Ulcerative colitis (UC) is characterized by recurring episodes of inflammation limited to the mucosal layer of the colon. The exact etiology of UC is unknown, but the role of autoimmunity and activated inflammatory cascade is quite clear. Melatonin possesses anti-inflammatory and immune-modulative properties in animal and clinical trials. The aim of the present study was to evaluate the efficacy and safety of oral melatonin as an adjudicative therapy in clinical, biochemical, and quality of life in UC patients. Thirty patients diagnosed with mild to moderate UC, were randomly allocated to either receive melatonin (3 mg/d) or the placebo group for three months. Simple clinical colitis activity index (SCCAI), fecal calprotectin (FC), C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), and Sf-36 questionnaire have been used for assessment at the baseline and the end of the trial. Melatonin significantly improve SCCAI score, FC, role-emotional, energy and general health relative to placebo (p = 0.03, 0.05, 0.002, 0.032, 0.004 respectively). Regarding CRP, ESR, and the other components of SF-36 there is not any significant difference between melatonin and placebo group. Melatonin supplementation over a three-month period is effective and safe in improving clinical index, FC, and some quality of life in patients with mild to moderate UC.

Blastocystis and Clostridioides difficile: Evidence for a Synergistic Role in Colonization Among IBD Patients with Emphasis on Ulcerative Colitis.

BACKGROUND: Regarding the controversial role of Blastocystis in inflammatory bowel diseases (IBD) patients, it seems that this protozoan may lead to an overgrowth of some non-beneficial bacteria. The current study aimed to investigate the co-existence of Blastocystis and Clostridioides difficile in IBD patients. METHODS: Stool samples of 102 IBD patients were collected and cultivated for C. difficile and Blastocystis. DNA extraction was performed on positive samples and C. difficile and Blastocystis were toxinotyped and subtyped, respectively. Fisher's exact test and logistic regression were employed to calculate the correlation between the existence of Blastocystis and its subtypes (ST) with C. difficile and its type of toxins. Also, the co-existence of Blastocystis and C. difficile with the frequency of defecations was evaluated. RESULTS: Blastocystis and C. difficile were observed in 17 (16.7%) and 26 (25.5%) of stool samples, respectively. From 26 C. difficilepositive isolates, 24 (92.3%) and 2 (7.7%) were tcdA+/B+ and tcdA+/B-, respectively. Also, 10 (58.8%) and 7 (41.2%) were Blastocystis ST1 and ST3, respectively. Statistically significant correlations between co-existence of Blastocystis and C. difficile and co-existence of these microorganisms and frequency of defecation (P < .035) were seen. There was no statistically significant correlation between subtypes of Blastocystis and colonization of C. difficile or its toxinotypes. CONCLUSION: The co-existence of Blastocystis and C. difficile in IBD patients was observed in the current study. Moreover, it can be proposed that these microorganisms may have synergistic effects on their colonization in the gastrointestinal tract.

The emerging epidemic of inflammatory bowel disease in Asia and Iran by 2035: A modeling study.

BACKGROUND: The projection studies are imperative to satisfy demands for health care systems and proper response to the public health problems such as inflammatory bowel disease (IBD). METHODS: To accomplish this, we established an illness-death model based on available data to project the future prevalence of IBD in Asia, Iran in particular, separately from 2017 to 2035. We applied two deterministic and stochastic approaches. RESULTS: In 2035, as compared to 2020, we expected a 2.5-fold rise in prevalence for Iran with 69 thousand cases, a 2.3-fold increment for North Africa and the Middle East with 220 thousand cases, quadrupling of the prevalence for India with 2.2 million cases, a 1.5-fold increase for East Asia region with 4.5 million cases, and a 1.6-fold elevation in prevalence for high-income Asia-Pacific and Southeast Asia regions with 183 and 199 thousand cases respectively. CONCLUSIONS: Our results showed an emerging epidemic for the prevalence of IBD in Asia regions and/or countries. Hence, we suggest the need for immediate action to control this increasing trend in Asia and Iran. However, we were virtually unable to use information about age groups, gender, and other factors influencing the evolution of IBD in our model due to lack of access to reliable data.

Description of the inflammatory bowel disease natural history in Tehran province, Iran: Mixed panel approaches.

AIM: Description of the inflammatory bowel disease natural history in Tehran province. BACKGROUND: Inflammatory bowel disease (IBD) is a non-homogeneous disorder with an unpredictable natural history that impairs a patient's quality of life over the course of their life. As a result, providing evidence for efficient patient management is critical. METHODS: In this case series study, 198 IBD patients who were visited in our clinic at least three times routinely from Oct 2015 to May 2020 were included. Then, two panel-based approaches, the Multi-State Model (MSM) and random-effect ordered logistic, were used to deduce the clinical course of IBD, which included remission, mild, moderate to severe, and surgical states. RESULTS: For ulcerative colitis (UC), women had a slightly poorer condition for remission but better for moderate to severe and a faster transition from moderate to severe to mild (HR=1.490, 95% CI: 1.02-2.16) compared to men. For Crohn's disease (CD), they had a better condition for remission but a slightly poorer condition for the severe state and higher transition from mild to moderate to severe (HR=1.221, 95% CI: 0.471-3.22) than men. Oral 5-ASA had better efficacy in people with remission and/or mild states but not for those with moderate to severe states, especially in CD (mild to moderate to serve, HR=1.526, 95% CI: 0.59-3.89). Immunosuppressive drugs were better for patients with lower disease severity, especially with UC (mild to remission, HR=1.258, 95% CI: 0.75-2.09). CONCLUSION: Panel approaches have the potential efficacy to tackle the unpredictable clinical course of IBD (UC/CD). Hence, we highly recommend that our findings be included into the Iranian routine clinical environment of IBD and/or that related studies be conducted in Iran and other regions to gain a better understanding of the natural history of IBD.

Immunomodulation and Generation of Tolerogenic Dendritic Cells by Probiotic Bacteria in Patients with Inflammatory Bowel Disease.

In inflammatory bowel diseases (IBD), the therapeutic benefit and mucosal healing from specific probiotics may relate to the modulation of dendritic cells (DCs). Herein, we assessed the immunomodulatory effects of four probiotic strains including Lactobacillus salivarius, Bifidobacterium bifidum, Bacillus coagulans and Bacillus subtilis natto on the expression of co-stimulatory molecules, cytokine production and gene expression of signal-transducing receptors in DCs from IBD patients. Human monocyte-derived DCs from IBD patients and healthy controls were exposed to four probiotic strains. The expression of co-stimulatory molecules was assessed and supernatants were analyzed for anti-inflammatory cytokines. The gene expression of toll-like receptors (TLRs), IL-12p40 and integrin αvß8 were also analyzed. CD80 and CD86 were induced by most probiotic strains in ulcerative colitis (UC) patients whereas only B. bifidum induced CD80 and CD86 expression in Crohn's disease (CD) patients. IL-10 and TGF-ß production was increased in a dose-independent manner while TLR expression was decreased by all probiotic bacteria except B. bifidum in DCs from UC patients. TLR-4 and TLR-9 expression was significantly downregulated while integrin ß8 was significantly increased in the DCs from CD patients. IL-12p40 expression was only significantly downregulated in DCs from CD patients. Our findings point to the general beneficial effects of probiotics in DC immunomodulation and indicate that probiotic bacteria favorably modulate the expression of co-stimulatory molecules, proinflammatory cytokines and TLRs in DCs from IBD patients.

Coexistence of Clostridioides difficile and Staphylococcus aureus in gut of Iranian outpatients with underlying inflammatory bowel disease.

Clostridioides difficile and Staphylococcus aureus are two well-known pathogens both causing hospital- and community-acquired infections. However, their intestinal coexistence was not well investigated in inflammatory bowel disease (IBD). Herein, we explored the prevalence of C. difficile, S. aureus and their coexistence in the gut of Iranian patients with IBD. Fecal and colon specimens were obtained from 70 outpatients with underlying IBD, and investigated for the presence of C. difficile and S. aureus. C. difficile isolates were characterised by CE-ribotyping. PCR was used for detection of toxin-encoding genes of C. difficile and S. aureus isolates. The antimicrobial susceptibility testing of C. difficile and S. aureus isolates were examined by agar dilution and Kirby-Bauer disk diffusion methods, respectively. Totally, C. difficile and S. aureus were detected in only 5.7% and 15.8% of IBD flares. Coexistence of C. difficile and S. aureus was detected in 5.7% of IBD flares. Two different C. difficile ribotypes including RT 126 and RT 017 were identified showing toxin profiles of tcdA+B+/cdtA+B+ and tcdA+B+, respectively. In S. aureus isolates, only positivity for the presence of sea enterotoxin was detected. C. difficile isolates were susceptible to metronidazole, ceftazidime and fidaxomicin. The highest resistance of S. aureus isolates was observed against penicillin (92.3%), following amoxicillin-clavulanate (38.5%) and amikacin (30.8%). Our findings demonstrated that patients with IBD flare are more sensitive to acquire coinfection of C. difficile and S. aureus than remission. However, more robust data is required to study the crosstalk between these enteric infections and their clinical relevance in patients with IBD flare.

The value of mRNA expression of S100A8 and S100A9 as blood-based biomarkers of inflammatory bowel disease.

BACKGROUND AND STUDY AIMS: Non-invasive biomarkers of inflammatory bowel diseases (IBD) are of critical importance. Here, we evaluated the S100A8 and S100A9 mRNA expression, as the heterodimers of calprotectin, in the blood leucocytes of IBD patients to find how their expression associates with the disease characteristics. PATIENTS AND METHODS: In this cross-sectional study, 59 IBD patients and 30 healthy subjects were included. The flare and remission phases of disease were identified in 46 and 13 patients, respectively. Blood leucocytes were isolated, and the S100A8 and S100A9 mRNA expression were evaluated in the isolated leucocytes using relative quantification real-time PCR. RESULTS: The mean S100A8 and S100A9 mRNA expression were significantly higher in IBD patients than in the controls (p = 0.03 and p = 0.02, respectively). The mean S100A8 and S100A9 mRNA expression were significantly higher in the flare phase of the disease compared with the remission phase (p = 0.01 and p = 0.007, respectively). S100A8 distinguished IBD patients from controls with the sensitivity and specificity of 73% and 64%, and flare phase of disease from remission with the sensitivity and specificity of 67% and 62%. On the other hand, S100A9 distinguished IBD patients from controls with the sensitivity and specificity of 81% and 70%, and flare phase of disease from remission with the sensitivity and specificity of 68% and 64%. CONCLUSION: The S100A8 and S100A9 mRNA are differentially expressed in blood leucocytes of IBD patients compared to healthy controls as well as active versus quiescent disease. Thus, they can be potentially used as a blood-based biomarker in the monitoring of IBD.

Altered fecal bacterial composition correlates with disease activity in inflammatory bowel disease and the extent of IL8 induction.

PURPOSE OF THE STUDY: In this study we investigated the presence and relative abundance of important genera of the gut microbiota in IBD patients and their role in induction of IL8 in a cell culture model. PATIENTS AND METHODS: Stool samples of IBD patients and healthy controls were collected and relative diversity of thirteen bacterial families was measured using quantitative real-time PCR assay. Moreover, filtrate of the stool samples was used for treatment of HT-29 cell line to analyze involvement of diversity of the fecal bacterial communities in the extent of IL8 induction. RESULTS: Bacteroides, Faecalibacterium prausnitzii, Prevotella spp., and Methanobrevibacterium were significantly less abundant in IBD patients (UC, N = 22; CD, N = 7) compared with control group (N = 29). Increase in relative amounts of Haemophilus, Streptococcus spp., and H. pylori were detected in IBD patients, which was not statistically significant. Relative decrease in amount of Bacteroides spp., Faecalibacterium prausnitzii, and Prevotella spp. were found in UC patients with disease activity score greater than 4; however, higher levels of Streptococcus and Haemophilus were detected in the patients who were at flares. A relationship between the reduction of Haemophilus spp. and higher BMI was shown in IBD patients. Expression of IL8 was significantly higher in the treated cells by the fecal inoculates of IBD patients. Increase in relative amounts of Enterobacteriacea showed a correlation with the higher level of IL8 induction in both groups. CONCLUSIONS: These results showed that changes in the fecal microbiota composition could affect disease activity, BMI, and IL8 induction.

Estimation the direct cost of inflammatory bowel disease in Iranian patients; the one- year follow-up.

AIM: We conducted this study to estimate the direct medical cost of Iranian IBD patients. BACKGROUND: In the economic evaluation setting, descriptive epidemiological studies can provide substantial information for health system policymakers in taking accountable decisions for diseases such as Inflammatory Bowel Disease (IBD). METHODS: To do so, we used a self-designed checklist to collect demographic and medical cost information for IBD patients. We also tried to have a national estimation of IBD costs. RESULTS: The mean annual medical cost of IBD was 18354.52 PPP$. Crohn's disease (CD) vs. ulcerative colitis (UC) and UC township patients vs. Tehran resident patients had higher medical costs (31160.79 PPP$; P<0.001) and (20840.23 PPP$, P<0.025). The largest medical cost spent in both IBD subtypes (CD/UC) was attributed to biological agents, especially in UC patients. We estimated that the mean annual cost of IBD in Iran for 2017 was 746315864 (95% CI: 602964172, 964685749) PPP$ (constant incidence) and 862776811 (95% CI: 697055402, 1115222835) PPP$ (increment incidence) respectively. CONCLUSION: Our results suggest that for management of IBD patients, policymakers should address shifting the medical costs to biological agents, the higher cost of CD, and the impact of underlying factors on the distribution of these medical costs.

Association between variants of the autophagy related gene ATG16L1 in inflammatory bowel diseases and clinical statues.

AIM: In the present study, two main variants of ATG16L1 gene, rs2241880 T300A and rs2241879 C/T, were evaluated in IBD patients as well as in remission and flareup phase across an Iranian population for the first time. BACKGROUND: Inflammatory bowel disease (IBD) has found increasing global incidence and prevalence in recent years especially among pediatrics. ATG16L1 is the major gene that regulates autophagy pathway. The autophagy pathway also affects dysbiosis. METHODS: Genomic DNA was isolated from peripheral blood samples following salting out extraction method. The genotypes of ATG16L1 polymorphisms rs2241880 T300A and rs2241879 C/T were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: In this case control study, a total of 101 IBD patients (75 ulcerative colitis (UC) and 26 Crohn's disease (CD)) and 99 healthy controls were evaluated. In the present study, a significant association was found between rs2241879 single nucleotide polymorphism on ATG16L1 gene and increased risk of IBD among an Iranian population (P=0.01). There was no statistically significant relationship between rs2241880 and IBD risk (P= 0.42). The effect on these two variants was investigated in relapse and flareup phase which was not significant either, but in CD, rs2241879 and rs2241880 were difference in the relapse phase. CONCLUSION: The results showed that ATG16L1 gene rs2241879 has a significant relationship with increased risk of IBD among an Iranian population. Individuals with C allele showed a significant relationship with 1.68-fold increased risk of IBD (P=0.01; adjusted OR=1.68; 95% CI=1.13-2.50).

Interleukin 12B mRNA level and rs3212227 genotyping in peripheral blood mononuclear cells of inflammatory bowel disease patients

Background/aim: Inflammatory bowel disease (IBD) is a multifactorial disorder. Single nucleotide polymorphisms (SNPs) in the IL-12 gene, which are the main factors to regulate the immune reaction, play an important role in the production of IL-12 molecules. The aim of this study was to evaluate the correlation between the SNP on position +1188 of the 3 ' UTR region of the IL-12 p40 subunit gene and expression of the IL-12 p40 gene. Materials and methods: This case-control study was performed with 102 patients with IBD and 107 healthy people. PCR-RFLP and comparative real-time PCR were performed to assess the association between genotype and IL-12 gene expression. Results: The frequency of AA, CA, and CC genotypes of this gene at position +1188 was calculated to be 58.8%, 32.4%, and 8.8% in patients and 61.7%, 26.2%, and 12.1% in the control group, respectively, with no significant difference between the two groups (IL- 12B rs3212227: AA (Reference 1), CA (P = 0.407); OR (95% CI) 0.771 (0.418­1.424), CC (P = 0.561); OR (95% CI) 1.313 (0.524­3.292)). Also, the IL-12B mRNA expression level was compared between IBD patients and healthy controls and demonstrated a significant association (R 2 0.136, 95% CI 1.892­3.872, P < 0.0001). Conclusion: Our results show that IL-12B expression in IBD may be associated with altered immune and inflammatory responses.

Lack of Association between Interleukin 23R (IL-23R) rs10889677 Polymorphism and Inflammatory Bowel Disease Susceptibility In an Iranian Population.

BACKGROUND: Inflammatory bowel diseases (IBDs), which include ulcerative colitis (UC) and Crohn's disease (CD), are inflammatory disorders that affect the gastrointestinal tract. A combination of inflammatory cytokines has an important role in IBD development. Genome-wide association studies have shown that polymorphisms in the interleukin-23R gene (IL-23R) increase susceptibility to IBD. The aim of this study was to investigate the IL-23R 3' UTR SNP to determine a potential association between genotype distribution and IBD. METHODS: The case group included 102 IBD patients and the control group included 107 healthy individuals. IL-23R polymorphisms rs10889677 were genotyped using PCR-RFLP analysis. RFLP results were confirmed by direct sequencing. RESULTS: The allele and genotype frequencies in patients and controls were evaluated and compared, and no significant association between this functional rs10889677 polymorphism and risk of IBD was observed (P=0.587; adjusted OR: 0.89; 95% CI: 0.597-1.339). We also found no significant association between CD (14.71%) and UC (85.29%) patients in allele or genotype levels (P>0.05). CONCLUSION: Our results suggest that the rs10889677 A>C polymorphism is not a potential prognostic marker in Iranian patients with IBD.

An increased Bax/Bcl-2 ratio in circulating inflammatory cells predicts primary response to infliximab in inflammatory bowel disease patients.

BACKGROUND: Predicting the response of inflammatory bowel disease (IBD) patients to infliximab (IFX) is an unmet clinical need. The expression and density of transmembrane tumor necrosis factor-α in circulating leukocytes maybe directly related to response by promoting apoptosis. AIM: We tested the hypothesis that direct apoptosis assessment by real-time polymerase chain reaction evaluation of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) proteins in peripheral blood mononuclear cells (PBMCs) might be associated with response to IFX. METHODS: IFX naïve patients (Crohn's disease, 32 and ulcerative colitis, 20; 35 responders and 17 non-responders) were evaluated for Bax and Bcl-2 mRNA expression levels before and 2 weeks after the first infusion. In a subset of patients, apoptosis was also evaluated using flow cytometry. RESULTS: After the first infusion, Bax increased more in responders than in non-responders (0.7± 0.38 vs 0.81 ± 0.32 and 0.86 ± 0.37 vs 0.87 ± 0.45, respectively, p = 0.071). Bcl-2 decreased more in responders than in non-responders (0.71 ± 0.12 vs 0.63 ± 0.13 and 0.81 ± 0.28 vs 0.77 ± 0.27, respectively, p = 0.038). The Bax/Bcl-2 ratio increased more in responders than in non-responders (0.99 ± 0.5 vs 1.3 ± 0.51 and 1.03 ± 0.17 vs 1.1 ± 0.28, respectively, p = 0.005). The Bax/Bcl-2 ratio was able to predict response in 33/52 patients and was correlated to flow cytometry-assessed apoptosis (r = 0.911; p < 0.001). CONCLUSIONS: An increased Bax/Bcl-2 ratio in PBMCs was associated with therapeutic response to IFX in IBD patients.

Alterations of the human gut Methanobrevibacter smithii as a biomarker for inflammatory bowel diseases.

It is hypothesized that direct and indirect homeostasis between gut microbiota plays a key role in different intestine disorders. Archaea methanogens, an ancient domain of single-celled organism, are major archaea in the digestive system. Recent evidence has shown that the variable prevalence of methanogens in different individuals could have certain effects on inflammatory bowel diseases (IBD). We aimed to assess the prevalence of Methanobrevibacter smithii between Iranian patients suffering from IBD and healthy control subjects. Stool DNA extracts from 47 healthy controls and 61 IBD patients were investigated. Quantitative real time PCR was performed for detecting Mbb. smithii load. We found a significantly decreased the Mbb. smithii load between IBD patients and healthy subjects. It is assumed that there is a reverse association between Mbb. smithii bacterial load and susceptibility to IBD, and this association could be extended to IBD patients in remission as we found that Mbb. smithii bacterial load is markedly higher among healthy subjects in comparison to IBD patients.

Determining the degree of adherence to treatment in inflammatory bowel disease patients.

AIM: Since the inflammatory bowel disease (IBD) is a disorder which requires continuous drug intake to induce and maintain the remission phase, finding the barriers for low adherent group, may improve the disease phase and quality of life in those patients. BACKGROUND: IBD is defined as a chronic immune disorder with unpredictable flares. The common treatment of these diseases can be effective for inducing and maintaining remission courses. Therefore the use of long-term medication therapy is the crucial key to prevent surgery and complications in patients with IBD. METHODS: Morisky Medication Adherence Scales (MMAS) is used for detecting level of adherence to the medicines for 137 patients with IBD. Demographic and clinical data are recorded for all patients and quality of life has been evaluated by Short-Form 36 questionnaire in 55 patients. RESULTS: Demographic and clinical features showed no correlation with the degree of adherence. The MMAS-8 score in the low adherent group significantly different than that in the medium and high adherer group. No relation was found statistically between level of adherence and mental or physical sates (p value=0.17, 1.2) and total quality of life (p value=0.22) in patients with IBD. CONCLUSION: Designing smart reminder and the physician's explain about adverse effects and beneficial of medicines may be effective to confront with forgetfulness and feeling comfort with treatment. Improve a strategy in order to regular measurement of adherence to medication, provides enough information about stop taking medication.