Molecular epidemiology of Enterocytozoon bieneusi and Encephalitozoon sp., among immunocompromised and immunocompetent subjects in Iran.

Intestinal microsporidiosis is known as an opportunistic infection in immunocompromised patients. The current study aimed to investigate intestinal microsporidia infection in human subjects with/without immunodeficiency. Totally, 600 stool samples were collected from immunocompromised (254) and immunocompetent (346) subjects. DNA extraction was performed and the SSU rRNA and the ITS genes were amplified to detect and characterize microsporidia and the relevant genotypes. Phylogenetic trees were drawn using MEGA7 software to illustrate the correlation between isolates. From 600 enrolled subjects, 283 and 317 were male and female, respectively. The average age ± SD of all tested subjects was 28.85 ± 26.92. The results of PCR demonstrated the presence of E. bieneusi and Encephalitozoon sp., among 10/600 (1.67%) and 26/600 (4.33%) of samples, respectively. Accordingly, E. bieneusi was seen among 4/346 (1.15%), 1/53 (1.88%), 3/124 (2.42%), and 2/63 (3.17%), and Encephalitozoon sp., was detected from 17/346 (4.91%), 3/53 (5.36%), 4/124 (3.22%) and 2/63 (3.17%) of healthy subjects, RA patients, cancer patients, and transplantation recipients, respectively. Statistical significant correlation was not seen between the presence of microsporidia and age, gender, stool appearance, and geographical region. Molecular analysis showed that all E. bieneusi were the genotype D. Phylogenetic tree demonstrated no classification according to the presence/absence of immunodeficiency, geographical locations and presence of diarrhea. The high prevalence of Encephalitozoon sp., in comparison to E. bieneusi in this study suggested the importance of this genus alongside with E. bieneusi in Iran. In addition, predominance of the genotype D highlighted the wide distribution of this genotype in Iran.

1H NMR based metabolic profiling in Crohn's disease by random forest methodology.

The present study was designed to search for metabolic biomarkers and their correlation with serum zinc in Crohn's disease patients. Crohn's disease (CD) is a form of inflammatory bowel disease that may affect any part of the gastrointestinal tract and can be difficult to diagnose using the clinical tests. Thus, introduction of a novel diagnostic method would be a major step towards CD treatment. Proton nuclear magnetic resonance spectroscopy ((1)H NMR) was employed for metabolic profiling to find out which metabolites in the serum have meaningful significance in the diagnosis of CD. CD and healthy subjects were correctly classified using random forest methodology. The classification model for the external test set showed a 94% correct classification of CD and healthy subjects. The present study suggests Valine and Isoleucine as differentiating metabolites for CD diagnosis. These metabolites can be used for screening of risky samples at the early stages of CD diagnoses. Moreover, a robust random forest regression model with good prediction outcomes was developed for correlating serum zinc level and metabolite concentrations. The regression model showed the correlation (R(2)) and root mean square error values of 0.83 and 6.44, respectively. This model suggests valuable clues for understanding the mechanism of zinc deficiency in CD patients.

NOD2 exonic variations in Iranian Crohn's disease patients.

PURPOSE: The NOD2 gene is known to have a strong association with Crohn's disease, but different trends were reported in occurrence of NOD2 variants in distinct ethnicities. The aim of this study was to assess all exonic sequences of the NOD2 gene in Iranian Crohn's disease patients and healthy controls to identify any existing variation and evaluate their association with Crohn's disease. METHODS: A total of 90 non-related Crohn's disease patients and 120 sex- and age-matched healthy controls of Iranian origin were enrolled in this study. The participants were referred to a tertiary center in a 2-year period (2006-2008). The exonic regions of the NOD2 gene were amplified by polymerase chain reaction and evaluated by direct sequencing. RESULTS: A total of 21 sequence variations were identified among all exonic regions of the NOD2 gene, of which eight had an allele frequency of more than 5%. Eight new mutations (one in exon 2 and seven in exon 4) were observed. The three main variants (R702W, G908R, and 1007fs) showed allele frequencies of 13.3%, 2.2%, and 1.7%, respectively. Three new variations (P371T, A794P, and Q908H) and R702W mutation were significantly more frequent in Crohn's disease patients compared to controls. CONCLUSIONS: Eight novel mutations were identified in the NOD2 exons, but the pathophysiological importance of these variants remains unclear. Iranian patients with their different genetic reservoirs may demonstrate some novel characteristics for disease susceptibility.

C-reactive protein as a possible marker for severity and mortality of COVID-19 infection.

AIM: The present study aimed to introduce a possible biomarker to differentiate between severe and fatal conditions of COVID-19. BACKGROUND: The COVID-19 pandemic, appearing as a complicated health problem, has changed the lifestyle of people in recent years. Clinical findings indicate mild, severe, and fatal conditions of this disease. Prediction of disease severity is a significant point in managing COVID-19 infection. METHODS: In this study, 195 differentially expressed genes (DEGs) that discriminate between fatal and severe conditions in patients were extracted from the literature and screened to determine the significant ones. The significant DEGs plus the 90 first neighbors added from the STRING database were included in the interactome using Cytoscape software v 3.7.2. The central nodes of the analyzed network were identified and assessed. RESULTS: Ten significant DEGs were candidates for assessment, of which 9 were recognized by the STRING database. IL6, ALB, TNF, CRP, INS, MPO, C3, CXCL8, TTR, and TLR4 were determined as central nodes; IL6, CRP, and TTR were highlighted as the critical genes related to the severity of COVID-19 infection. CONCLUSION: CRP was identified as the best possible biomarker with levels related to the severity and fatality of COVID-19 infection.

Increased inflammatory markers correlate with liver damage and predict severe COVID-19: a systematic review and meta-analysis.

AIM: This study aimed to determine whether patients with elevated CRP, TNFα, and IL-6 levels may be at increased risk for severe infection and liver damage of COVID-19. BACKGROUND: The COVID-19 outbreak is a serious health problem to human beings. The evidence suggests that inflammatory markers related to liver damage increase in severe forms of COVID-19 compared to mild cases. METHODS: The electronic databases ISI Web of Science, EMBASE, and Cochrane Library were comprehensively searched for articles published up to May, 2020. Data from each identified study was combined using the random effects model to estimate standardized mean difference (SMD) and 95% confidence intervals (95% CIs). Sensitivity and publication bias were also calculated. RESULTS: Totally, 23 studies were included in this meta-analysis comprising 4313 patients with COVID-19. The random effects results demonstrated that patients with severe COVID-19 had significantly higher levels of CRP [SMD = 3.26 mg/L; (95% CI 2.5, 3.9); p<0.05; I2 = 98.02%; PHeterogeneity = 0.00], TNFα [SMD = 1.78 ng/mL; (95% CI 0.39, 3.1); p=0.012; I2 = 98.2%; PHeterogeneity = 0.00], and IL-6 [ SMD = 3.67 ng/mL; (95% CI 2.4, 4.8); p<0.05; I2 = 97.8%; PHeterogeneity = 0.00] compared with those with the mild form of the disease. Significant heterogeneity was present. No significant publication bias was observed in the meta-analysis. Sensitivity analyses showed a similar effect size while reducing the heterogeneity. CONCLUSION: The data suggests that enhanced inflammation may be associated with COVID-19-related liver damage, possibly involving inflammatory marker-related mechanisms.

Evaluation of CXCR1 as a possible diagnostic biomarker in acute appendicitis.

AIM: The present study was conducted to determine the genes with common expression in blood and appendix tissue samples in order to introduce them as possible diagnostic biomarkers. BACKGROUND: Diagnosis of acute appendicitis (AA) without applying computed tomographytomography (CT), subjecting the patient to significant radiation, can be surprisingly difficult. Blood circulation may have conscious alterations in its RNA, protein, or metabolite composition. METHODS: The genes related to appendix tissue and blood samples of the patients with AA were extracted from public databases. Fold change (FC) ≥ 2 in blood and FC ≥ 5 in appendix tissue samples were considered to screen differentially expressed genes (DEGs). A protein-protein interaction network was organized using the search tool for retrieval of interacting genes and proteins (STRING) database as a plugin of Cytoscape software version 3.6.0. The main genes were enriched by DAVID Bioinformatics Resources to find the related biochemical pathways. RESULTS: Among the DEGs in blood and appendix tissue samples, C-X-C motif chemokine receptor 1(CXCR1), leukocyte immunoglobulin-like receptor A3 (LILRA3), low-affinity immunoglobulin gamma Fc region receptor III (FCGR3), and superoxide dismutase 2(SOD2) were common in both sources. CXCR1 was found as only hub gene upregulated in both blood and tissue of the patients with AA compared to controls and those with other abdominal pain. CONCLUSION: CXCR1, FCGR3, LILRA3, and SOD2 were determined as a suitable possible biomarker panel for diagnosis of AA disease.

Risk factors of transmission and natural history of chronic hepatitis B infection in Iranian patients.

AIM: To investigate routes of transmission, demographic characteristics, and frequency of different phases of chronic hepatitis B (CHB) in 2000 Iranian patients. BACKGROUND: Knowledge about the most frequent risk factors of CHB and its different phases is very important for optimal prevention and management policy making. METHODS: In this cross-sectional study, 2000 HBsAg positive patients who were referred to Taleghani Hospital from 2011 through 2018 were enrolled. ELISA method was employed to detect serological markers of CHB. Taking into account the HBV DNA and ALT levels and HBeAg status, the patients were classified in four groups, according to AASLD 2017 guideline. RESULTS: Male and female patients had nearly equal frequencies in our study and 82.5 % of them aged more than 20 years. A great number of our patients (95%) were HBeAg negative and the most frequent risk factors of HBV infection were positive periodontal and family history (40.3% and 24.9%, respectively). The majority of our patients were inactive carriers (63.35%), while s mall number of them were in the immune tolerant group (2.15 %). CONCLUSION: Immune tolerance phase group had the minimum number of members in our study and most of them were above 20 years old. This can be due to the mass vaccination of neonates since 1993. Most of CHB patients were in inactive carrier group. Although it is recommended not to treat these patients, performing periodic liver function tests and disease severity assessment is warranted, especially in patients above 40 years old.

Comparative study on guidelines in determining HBV phases in Iranian patients.

AIM: The aim of this study was to compare the different phases of chronic Hepatitis B virus (HBV) infection with different values for normal ALT. BACKGROUND: For many years, the upper limit of 40 IU was considered normal for ALT for both sexes, but in recent years this value is challenged and some guidelines have lowered their limit. METHODS: In this cross-sectional study, 2000 HBsAg positive patients who were referred to Taleghani Hospital, Tehran, Iran, from 2011 through 2018 were classified in four groups according to American Association of the study of the liver disease (AASLD), European Association of the study of the liver (EASL) /Asian-Pacific Association of the study of the liver (APASL) and American Collage of Gastroenterology (ACG) guidelines. The frequency of each group based on 3 different guidelines was compared. RESULTS: In HBeAg positive patients (n=100), the percentage of immune tolerance phase was 43% according to AASLD cutoff for normal ALT (35 IU for men, 25 IU for women), while it was 68% and 28% with regard to EASL/APASL and ACG (30 IU for men, 19 IU for women) cutoffs respectively. In HBeAg negative patients (n=1900), 66.68% were inactive carriers according to AASLD, but the percentage changed to 82.89% and 52.42% considering EASL/APASL and ACG values, respectively. CONCLUSION: Using ACG and to a lesser extent AASLD cutoff for ALT, many patients shift from immune tolerance and inactive carrier state into the immune active phase. Thus, more patients are candidates for treatment or intensive workup to determine the extent of liver damage.

Association of vitamin D receptor gene polymorphisms in Iranian patients with inflammatory bowel disease.

BACKGROUND AND AIMS: The vitamin D receptor (VDR) gene maps to a region on chromosome 12 shown to be linked to inflammatory bowel disease (IBD). Many studies have recognized the relation of VDR gene polymorphisms with inflammatory and autoimmune disorders. Determining the frequency of these polymorphisms and their possible relation with IBD can improve understandings about the genetic background of these diseases. The objective of this study was to assess the association of VDR gene polymorphisms (Apa I, Taq I, Bsm I, Fok I) with IBD in Iran. METHODS: In this case control designed study 150 patients with ulcerative colitis, 80 patients with Crohn's disease and 150 Age and Sex matched healthy controls from Iranian origin were enrolled. These patients were referred to a tertiary center during a two-year period (2004-2006). Assessment of VDR gene polymorphisms was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The genotype-phenotype association for these polymorphisms was analyzed. RESULTS: Only the frequency of the Fok I polymorphism was significantly higher in ulcerative colitis and Crohn's groups. The frequency of the polymorphic allele f was higher in ulcerative colitis and Crohn's patients comparing with controls (P = 0.011 and P < 0.001, respectively). The f/f genotype was also significantly more frequent (P < 0.001), while the F/F genotype was less presented in Crohn's patients compared to controls (P < 0.001). No genotype-phenotype association was observed with any mutations. CONCLUSIONS: This study suggests a probable association of the Fok I polymorphism in VDR receptor gene and Crohn's susceptibility in Iranian population.

Frequency of three common mutations of CARD15/NOD2 gene in Iranian IBD patients.

BACKGROUND: The CARD15/NOD2 gene, located on the pericentromeric region of chromosome 16 (IBD1) has been reported to have an association with IBD, especially Crohn's disease. Three common mutations of CARD15 are variably associated with Crohn's disease in different ethnic groups. We evaluated the frequency of these mutations (R702W, G908R and 1007fsinsC) in Iranian IBD patients and compared it with the healthy control population. METHODS: One hundred patients with ulcerative colitis, 40 patients with Crohn's disease, and 100 sex- and age-matched controls were enrolled from a tertiary center during a one-year period (2005-2006). The three mutations were assessed in DNA of leukocytes by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). RESULTS: The frequency of R702W mutation was significantly higher in Iranian patients with Crohn's disease (p< 0.001; OR 19.21; 95% CI 4.23-87.32) compared to healthy controls. No association was observed between the other mutations and Crohn's disease and none of these mutations was associated with ulcerative colitis. CONCLUSION: The R702W mutation of CARD15 gene was associated with Crohn's disease in the Iranian population.

Insulin dysregulation plays a critical role in colon inflammation: a bioinformatics approach.

AIM: Evaluating and screening of genes related to colorectal inflammation of mice for finding critical ones in this disease was the aim of this study. BACKGROUND: Many studies are shown direct relationship between inflammation and colorectal cancer onset and development. Several molecular aspects of inflammation are investigated to discover molecular mechanism of this disease. METHODS: Profiles of differentially expressed genes (DEGs) of mice inflamed colorectal tissue in comparison with normal samples are obtained from Gene Expression Omnibus (GEO) database. The significant and characterized DEGs were screened via protein-protein interaction (PPI) network. Hubs of the network were determined and backbone network was constructed. Moreover, action network for the critical nodes was constructed and analyzed. RESULTS: Eight central genes including IL6, ALB, PRDM10, AKT1, GAPDH, IL8, INS and TNF were determined as hub nodes. Findings indicate that insulin plays critical role in regulation of hub genes. This finding shows association between inflammation and metabolism dysregulation. Except PRDM10 and GAPDH, the other hubs show considerable regulatory effects on each other. CONCLUSION: Inflammation of colorectal tissue is strongly depended on metabolism especially to insulin function.

SRC and TP53 play critical role in low-grade dysplasia colorectal mucosa transformation into cancer.

AIM: Determination of crucial genes that are involved in onset and progress of dysplasia of colorectal mucosa is the aim of this study. BACKGROUND: Management of dysplasia as one of the risk factors of colon cancer is very challenging. Molecular studies could be helpful in this matter. Here, the transcriptome profile of low-grade dysplasia in colon tissue in comparison with normal one is studied by protein-protein interaction (PPI) network analysis. METHODS: For detecting differentially expressed genes (DEGs) of dysplasia lesion, the data was downloaded from the gene chip GSE31106, platform GPL1261, GSM770092-94 as normal colorectal mucosa group and GSM770098-100 as low-grade dysplasia colorectal mucosa from the Gene Expression Omnibus database (GEO). The expression profile is evaluated by GEO2R and a network of DEGs is constructed and analyzed by Cytoscape algorithms. RESULTS: The findings indicate that a PPI network analysis of 113 DEGs is consist of 8 nodes that 6 of them are common with inflammation state. Only SRC and TP53 were recognized as the specific makers for dysplasia. In this respect, a subnetwork of these two genes introduce a panel of 8 nodes consist of HRAS, MYC, PIK3CA, PIK3CB, PIK3CD, PIK3CG, SRC, and TP53. CONCLUSION: It can be concluded that SRC and TP53 may play prominent role in dysplasia pathogenicity after running validation tests.

A decision tree-based approach for determining low bone mineral density in inflammatory bowel disease using WEKA software.

BACKGROUND: Decision tree classification is a standard machine learning technique that has been used for a wide range of applications. Patients with inflammatory bowel disease (IBD) are at increased risk of developing low bone mineral density (BMD). This study aimed at developing a new approach to select truly affected IBD patients who are indicated for densitometry, hence, subjecting fewer patients for bone densitometry and reducing expenses. MATERIALS AND METHODS: Simple decision trees have been developed by means of WEKA (Waikato Environment for Knowledge Analysis) package of machine learning algorithms to predict factors influencing the bone density among IBD patients. The BMD status was the outcome variable whereas age, sex, duration of disease, smoking status, corticosteroid use, oral contraceptive use, calcium or vitamin D supplementation, menstruation, milk abstinence, BMI, and levels of calcium, phosphorous, alkaline phosphatase, and 25-OH vitamin D were all attributes. RESULTS: Testing showed the decision trees to have sensitivities of 65.7-82.8%, specificities of 95.2-96.3%, accuracies of 86.2-89.8%, and Matthews correlation coefficients of 0.68-0.79. Smoking status was the most significant node (root) for ulcerative colitis and IBD-associated trees whereas calcium status was the root of Crohn's disease patients' decision tree. CONCLUSION: BD specialists could use such decision trees to reduce substantially the number of patients referred for bone densitometry and potentially save resources.

Exploring conserved mRNA-miRNA interactions in colon and lung cancers.

AIM: The main goal of this analysis was prioritization of co-expressed genes and miRNAs that are thought to have important influences in the pathogenesis of colon and lung cancers. BACKGROUND: MicroRNAs (miRNAs) as small and endogenous noncoding RNAs which regulate gene expression by repressing mRNA translation or decreasing stability of mRNAs; they have proven pivotal roles in different types of cancers. Accumulating evidence indicates the role of miRNAs in a wide range of biological processes from oncogenesis and tumor suppressors to contribution to tumor progression. Colon and lung cancers are frequently encountered challenging types of cancers; therefore, exploring trade-off among underlying biological units such as miRNA with mRNAs will probably lead to identification of promising biomarkers involved in these malignancies. METHODS: Colon cancer and lung cancer expression data were downloaded from Firehose and TCGA databases and varied genes extracted by DCGL software were subjected to build two gene regulatory networks by parmigene R package. Afterwards, a network-driven integrative analysis was performed to explore prognosticates genes, miRNAs and underlying pathways. RESULTS: A total of 192 differentially expressed miRNAs and their target genes within gene regulatory networks were derived by ARACNE algorithm. BTF3, TP53, MYC, CALR, NEM2, miR-29b-3p and miR-145 were identified as bottleneck nodes and enriched via biological gene ontology (GO) terms and pathways chiefly in biosynthesis and signaling pathways by further screening. CONCLUSION: Our study uncovered correlated alterations in gene expression that may relate with colon and lung cancers and highlighted the potent common biomarker candidates for the two diseases.

Pancreatic adenocarcinoma protein-protein interaction network analysis.

AIM: Gene assessment of pancreatic adenocarcinoma disease via protein-protein interaction (PPI) Network Analysis. BACKGROUND: Diagnosis, especially early detection of pancreatic adenocarcinoma as a lethal disease implies more investigation. PPI Network Analysis is a suitable tool to discover new aspects of molecular mechanism of diseases. METHODS: In the present study the related genes to pancreatic adenocarcinoma are studied in the interactome unit and the key genes are highlighted. The significant clusters were introduced by Cluster-ONE application of Cytoscape software 3.4.0. The genes are retrieved from STRING date base and analyzed by Cytoscape software. The crucial genes based on analysis of central parameters were determined and enriched by ClueGO v2.3.5 via gene ontology. RESULTS: The number of 24 key genes among 794 initial genes were highlighted as crucial nodes in relationship with pancreatic adenocarcinoma. All of the key genes were organized in a cluster including 216 nodes. The main related pathways and cancer diseases were determined. CONCLUSION: It was concluded that the introduced 24 genes are possible biomarker panel of pancreatic adenocarcinoma.

A comparison of oral omeprazole and intravenous cimetidine in reducing complications of duodenal peptic ulcer.

BACKGROUND: Gastrointestinal bleeding is a common problem and its most common etiology is peptic ulcer disease. Ulcer rebleeding is considered a perilous complication for patients. To reduce the rate of rebleeding and to fasten the improvement of patients' general conditions, most emergency departments in Iran use H2-blockers before endoscopic procedures (i.e. intravenous omeprazole is not available in Iran). The aim of this study was to compare therapeutic effects of oral omeprazole and intravenous cimetidine on reducing rebleeding rates, duration of hospitalization, and the need for blood transfusion in duodenal ulcer patients. METHODS: In this clinical trial, 80 patients with upper gastrointestinal bleeding due to duodenal peptic ulcer and endoscopic evidence of rebleeding referring to emergency departments of Imam and Sina hospitals in Tabriz, Iran were randomly assigned to two equal groups; one was treated with intravenous cimetidine 800 mg per day and the other, with 40 mg oral omeprazole per day. RESULTS: No statistically significant difference was found between cimetidine and omeprazole groups in regards to sex, age, alcohol consumption, cigarette smoking, NSAID consumption, endoscopic evidence of rebleeding, mean hemoglobin and mean BUN levels on admission, duration of hospitalization and the mean time of rebleeding. However, the need for blood transfusion was much lower in omeprazole than in cimetidine group (mean: 1.68 versus 3.58 units, respectively; p < 0.003). Moreover, rebleeding rate was significantly lower in omeprazole group (15%) than in cimetidine group (50%) (p < 0.001). CONCLUSION: This study demonstrated that oral omeprazole significantly excels intravenous cimetidine in reducing the need for blood transfusion and lowering rebleeding rates in patients with upper gastrointestinal bleeding. Though not statistically significant (p = 0.074), shorter periods of hospitalization were found for omeprazole group which merits consideration for cost minimization.

Evaluation of liver cirrhosis and hepatocellular carcinoma using Protein-Protein Interaction Networks.

AIM: In the current study, we analysised only the articles that investigate serum proteome profile of cirrhosis patients or HCC patients versus healthy controls. BACKGROUND: Increased understanding of cancer biology has enabled identification of molecular events that lead to the discovery of numerous potential biomarkers in diseases. Protein-protein interaction networks is one of aspect that could elevate the understanding level of molecular events and protein connections that lead to the identification of genes and proteins associated with diseases. METHODS: Gene expression data, including 63 gene or protein names for hepatocellular carcinoma and 29 gene or protein names for cirrhosis, were extracted from a number of previous investigations. The networks of related differentially expressed genes were explored using Cytoscape and the PPI analysis methods such as MCODE and ClueGO. Centrality and cluster screening identified hub genes, including APOE, TTR, CLU, and APOA1 in cirrhosis. RESULTS: CLU and APOE belong to the regulation of positive regulation of neurofibrillary tangle assembly. HP and APOE involved in cellular oxidant detoxification. C4B and C4BP belong to the complement activation, classical pathway and acute inflammation response pathway. Also, it was reported TTR, TFRC, VWF, CLU, A2M, APOA1, CKAP5, ZNF648, CASP8, and HSP27 as hubs in HCC. In HCC, these include A2M that are corresponding to platelet degranulation, humoral immune response, and negative regulation of immune effector process. CLU belong to the reverse cholesterol transport, platelet degranulation and human immune response. APOA1 corresponds to the reverse cholesterol transport, platelet degranulation and humoral immune response, as well as negative regulation of immune effector process pathway. CONCLUSION: In conclusion, this study suggests that there is a common molecular relationship between cirrhosis and hepatocellular cancer that may help with identification of target molecules for early treatment that is essential in cancer therapy.

Pathological and Clinical Correlation between Celiac Disease and Helicobacter Pylori Infection; a Review of Controversial Reports.

There are overwhelming reports and descriptions about celiac associated disorders. Although there is a clear genetic association between celiac disease (CD) and some gastrointestinal disorders, there are controversial reports claiming an association between CD and Helicobacter pylori (H. pylori) infection. Different studies indicated the possible association between lymphocytic gastritis and both CD and H. pylori infection, although this evidence is not consistently accepted. Also it was shown that an increase in intraepithelial lymphocytes count is associated with both H. pylori infection and celiac disease. Therefore the following questions may raise: how far is this infection actually related to CD?, which are the underlying patho-mechanisms for these associations? what are the clinical implications? what is the management? and what would be the role of gluten free diet in treating these conditions? PubMed (PubMed Central), Ovid, ISI of web knowledge, and Google scholar were searched for full text articles published between 1985 and 2015. The associated keywords were used, and papers described particularly the impact of pathological and clinical correlation between CD and H. pylori infection were identified. In this review we tried to answer the above questions and discussed some of the recent developments in the pathological and clinical aspects of CD and H. pylori infection.

Effect of vitamin D3 supplementation on TNF-α serum level and disease activity index in Iranian IBD patients.

AIM: The aim of the study was to assess the effectiveness of vitamin D3 [1, 25(OH)2D3] treatment in IBD with regard to tumor necrosis factor-alpha (TNF-α) serum level and clinical disease activity index (CDAI). BACKGROUND: Vitamin D has immune-regulatory functions in experimental inflammatory bowel disease (IBD) and vitamin D deficiency is common in IBD patients. PATIENTS AND METHODS: This was a randomized clinical trial on 108 IBD patients with serum 25-OHD levels less than 30ng/ml, which divided into vitamin D and control groups. Vitamin D group received 50000 IU vitamin D3 for 12 weeks. Before and after the study, TNF-α and 25-OHD serum levels were measured by ELISA method. Data were analyzed using paired t-test, chi-square test and Spearman correlation coefficient. P-values ​​less than 0.05 were considered statistically significant. RESULTS: Before the intervention no significant difference was found between baseline characteristics and TNF-α serum level of two groups. After intervention TNF-α serum level reduced but this reduction was not statistically significant (p= 0.07, 95% CI: -0.45 to 8.14). The mean serum 25-OHD level of vitamin D increased from 15.54 to 67.89, which was statistically significant (p= 0.00, 95% CI: -61.40 to -43.30). TNF-α level was also associated significantly with CDAI before (Spearman's rho: 0.3, p<0.0001) and after (Spearman's rho: 0.27, P=0.01) intervention. CONCLUSION: Oral supplementation vitamin D3 significantly increased serum vitamin D levels and insignificantly reduced serum TNF-α level. More studies with larger samples would be beneficial to assess vitamin D3 supplementation efficient effect in IBD.

Time trend analysis and demographic features of inflammatory bowel disease in Tehran.

AIM: This retrospective study is aimed to review demographic and clinical characteristics of IBD to elucidate the probable factors associating with IBD development in Taleghani Hospital in Iran since 2001 during a 12-year-period. BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) are two major idiopathic entities of inflammatory bowel disease (IBD). Previous studies have reported an increased incidence of IBD in Middle East countries. PATIENTS AND METHODS: In the present study 1914 patients with UC, 318 patients with CD and 25 with indeterminate colitis (IC) were included. Demographic information, clinical features, extraintestinal manifestations, complications and extension of disease were collected and interpreted for all participants. According to the time of registration, patients were divided into seven groups. Statistical analysis was performed using the chi-square test. RESULTS: In seven groups of IBD patients, disease registry was estimated for UC, CD, and total IBD during a 12-year-period. From 2001 to 2005, a relative increased registry was observed among UC patients. However, in the years 2006 and 2007 a ​​significant reduction in the number of patients was reported. Then an increasing trend was observed in UC patients. UC presented mostly with diarrhea, hematochezia and bloody diarrhea, while most of CD patients complained of abdominal pain. CONCLUSION: Evaluation of data related to registered IBD patients in Iran shows that probable incidence and prevalence of IBD (UC and CD) is increasing compared to previous decades.