The frequency of NRAS mutation in stool samples of Iranian colorectal cancers compared to Finnish patients.

Background: Stools from colorectal cancer patients are noninvasive samples that could be used to compare the frequency of hotspot mutations between two different ethnic cohorts. Materials and Methods: We collected stool samples from the Iranian cohort (52 patients and 49 controls) and the Finnish cohort (40 patients and 14 controls). Following stool DNA extraction, we used the AmpliSeq Colon and Lung Cancer panel to prepare DNA libraries before sequencing. Results: The Iranian cohort exhibited 35 hotspot mutations in the BRAF, ERBB4, FBXW7, FGFR1, FGFR3, KRAS, MAP2K, MET, NRAS, PIK3C, SMAD4, and TP53 genes. In the Finnish cohort, 13 hotspot mutations were found in the AKT1, APC, KIT, KRAS, SMO, STK11, and TP53 genes. Mutations in NRAS and FGFR3 were observed only in the Iranian cohort, while APC mutations were exclusive for the Finnish cohort. Conclusion: Genes involved in MAPK and PI3K-MAPK pathways showed a higher frequency of mutations in Iranian patients which may have therapeutic implications.

New long noncoding RNA biomarkers and ceRNA networks on miR-616-3p in colorectal cancer: Bioinformatics-based study.

Background: Cancer development is aided by the role of long noncoding RNAs (lncRNAs) that act as competing endogenous RNAs (ceRNAs) absorbing microRNAs (miRNAs). We aimed to discover a novel regulatory axis in colorectal cancer (CRC) and potential biomarkers based on miR-616-3p. Materials and Methods: The gene expression omnibus database was mined for differentially expressed lncRNAs (DELs) and mRNAs. LncRNAs and mRNAs were predicted using the RegRNA and TargetScan databases. A combination of the ciBioPortal and Ensemble databases was used to locate the mRNAs. Cytoscape 3.7.1-built CeRNA networks. A quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to confirm the expression levels of these RNA molecules. Statistical analyses were implemented by GraphPad Prism 9. Results: qRT-PCR showed (Linc01282, lnc-MYADM-1:1, and Zinc Finger Protein 347 [ZNF347]) were overexpressed whereas, (salt-inducible kinases 1 [SIK1], and miR-616-3p) were down regulated. Conclusion: These results identify unique, unreported lncRNAs as CRC prognostic biomarkers, as well as prospective mRNAs as new treatment targets and predictive biomarkers for CRC. In addition, our study uncovered unexplored ceRNA networks that should be studied further in CRC.

Risk factors for ERCP-related complications and what is the specific role of ASGE grading system.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is one of the main therapeutic and sometimes diagnostic methods in biliary and pancreatic diseases. A grading system for the difficulty of ERCP (grade one to four, the higher grade represents the more complexity of the procedure) has been developed by the American Society for Gastrointestinal Endoscopy (ASGE). This study aimed to assess the prevalence of ERCP-related complications, their common risk factors, and specifically the role of difficulty of the procedure based on ASGE grading. Material and Methods: This cross-sectional study was performed on 620 ERCP-operated patients over 4 years in two tertiary referral centers affiliated with Isfahan University of Medical Sciences. Data about the difficulty of procedures based on the ASGE grading scale, complications including pancreatitis, bleeding, infection, perforation, arrhythmia, respiratory suppression, aspiration, and major common risk factors were collected. Results: The overall prevalence of complications was 11.6% including pancreatitis 8.2%, perforation 0.8%, gastrointestinal bleeding 1.3%, cholangitis 2.4%, and cardiopulmonary problems 0.5% (arrhythmia 0.3% and respiratory depression 0.2%). Patients with pancreatic contrast injection (66.7% vs. 11.3% P = 0.04) and sphincter of Oddi dysfunction (SOD) (44.4% vs. 11.1%; P = 0.01) showed a statistically significant higher overall complication rate. The association of these risk factors remained significant in multivariable logistic regression analysis. Patients with pancreatic contrast injection also showed a statistically significant higher prevalence of post-ERCP pancreatitis (66.7% vs. 11.3% P = 0.04). Furthermore, a significantly higher prevalence of arrhythmia (3.6% vs. 0; P = 0.008) was observed among patients with difficult cannulation. Based on the ASGE difficulty grading score, most of the patients were classified as grade 2 (74.2%) and 3 and 4 (23.4%). No statistically significant difference was noted between the difficulty-based groups in terms of complications. Conclusion: The current study showed that the most critical risk factors of ERCP-induced complications were pancreatic contrast injection and SOD. ASGE grading scale for ERCP complexity did not predict the occurrence of complications in our study population.

Using instant messaging applications to promote clinical teaching of medical students.

BACKGROUND: The main purpose of this study was to evaluate the use of Telegram as an Instant messaging application in clinical teaching of medical students, especially clinical ward rounds. MATERIALS AND METHODS: In this quasi-experimental study, Telegram as an Instant messaging application was employed. To do this, a Telegram group entitled as "Lavender" was created and then selected patients were divided between students and externs daily. After that, students and externs were asked to take medical histories, perform complete physical examinations, and then share their data in the Lavender group. Ultimately, to evaluate the effects of this intervention, two quantitative and qualitative approaches were used. RESULTS: From the students' point of view the highest average was associated with "Readiness for teaching round" (3.71 ± 1.34) and the lowest average was related to "Time-saving for studying about illnesses" (2.08 ± 1.44). In addition, medical trainees mentioned that reporting patients' daily medical histories and progress notes could create a reflective process. The suggestion made by many medical trainees was to select and discuss simpler cases who have more teaching points for them, while other trainees recommended focusing on common illnesses in the Lavender group. CONCLUSION: The use of messaging software applications such as Telegram in medical education has created a new paradigm, which could facilitate interpersonal interactions among trainees.

Constructing a novel competing Endogenous RNAs network based on NR3C1 and X-linked inhibitor of apoptosis protein genes reveals potential prognostic biomarkers in colorectal cancer.

Background: Long noncoding RNAs (lncRNAs) have been recognized as the main modulatory molecules in various cancers and perform as competing endogenous RNAs (ceRNAs). The nuclear hormone receptor superfamily of ligand-activated transcription factors (NR3C1) regulates numerous proliferative and metabolic processes such as tumorigenesis and metabolic diseases. Furthermore, X-linked inhibitor of apoptosis protein (XIAP) belongs to a family of the inhibitors of apoptosis proteins, is located downstream of the glucocorticoid receptor (GR or NR3C1) pathway, and cooperates with GR to suppress apoptosis. However, the underlying mechanisms of NR3C1 and XIAP in colorectal cancer (CRC) remain mainly unclear. This research aims to clarify the potential RNA biomarkers and to construct a novel ceRNA network in CRC. Materials and Methods: Multistep bioinformatics methods such as Lnc2cancer and miRDB databases were applied to identify candidate lncRNAs and miRNAs. The interaction energy between lncRNAs, NR3C1, and XIAP genes was analyzed by the LncRRIsearch database. Plus, microRNAs and lncRNA were evaluated via the Diana tools database to select microRNAs with the most binding scores. Quantitative reverse transcription-polymerase chain reaction (QRT-PCR) was applied to verify RNA molecules' expression levels and their association with the clinicopathological factors in 30 CRC tissues compared to 30 adjacent tissues. Results: QRT-PCR showed upregulation of KCNQ1OT1, NR3C1, and XIAP and downregulation of miR-421. The ceRNA network was constructed with 17 lncRNAs, 2 mRNAs, and 42 miRNAs. Thus, we explained the potential interactions between KCNQ1OT1 and miR-421 with NR3C1 and XIAP genes. Conclusion: Our study represents potential prognostic biomarkers and a new ceRNA network for further study in CRC.

Assessment of pain between sedated and unsedated colonoscopy: Double-blind randomized clinical trail.

BACKGROUND: Colonoscopy plays a vital role for the diagnosis and treatment of colonic diseases but can be associated with anxiety and discomfort or pain. We tested whether unsedated colonoscopy impacts quality indicators and investigated predictors of pain during colonoscopy. MATERIALS AND METHODS: This randomized controlled trial was performed on candidates for elective colonoscopy at AL Zahra Hospital, Isfahan at 2018-2019. Balanced block randomization was used to allocate 275 cases into two groups. At finally, 124 patients in case and 122 patients in control group enrolled in analysis. Patients in the sedation group received midazolam with/out pethidine before colonoscopy. Pain intensity in rectal examination (PIREX), preprocedural anxiety, pain intensity during colonoscopy, hemodynamics, duration of colonoscopy, polyp detection rate, cecal intubation rate, bloating within 24 h after colonoscopy, and willingness to repeat colonoscopy were assessed and compared between two groups. RESULTS: Compared to the group with sedation, cecal intubation time was shorter and bloating was less frequent (7% vs. 16%, P = 0.02) in the unsedated group. There was no difference between the two groups regarding polyp detection rate, cecal detection rate, and willingness to repeat colonoscopy. Pain during rectal examination was significantly associated with pain during colonoscopy (P < 0.001, 95% confidence interval; 0.5-1.3). CONCLUSION: The assessment of pain intensity during rectal examination may help to identify patients who can benefit from sedation during colonoscopy. Colonoscopy with sedation does not seem to have a negative impact on colonoscopy quality indicators, and may even reduce cecal intubation time and bloating following procedure.

Diagnostic Value of Pyruvate Kinase Isoenzyme Type M2 in Colon Cancer Proven with Colonoscopy.

BACKGROUND: Colonoscopy is the gold standard for colon cancer screening; it is also associated with a high cost and complication. Proliferating cells, in particular tumor cells, express a dimeric isoenzyme of pyruvate kinase, termed M2 pyruvate kinase (M2-PK). The aim of this study was to determine the diagnostic accuracy of fecal M2-PK for colon cancer. MATERIALS AND METHODS: Forty-nine patients with colon cancers and 49 healthy controls were selected consecutively among individuals undergoing screening colonoscopy for various indications. The diagnosis was confirmed by histology. M2-PK measurements were done by enzyme-linked immunosorbent assay of fecal occult blood test (FOBT) and immunological FOBT (IFOBT) according to the manufacturer's instructions. RESULTS: M2-PK > 9 (U/mL) was the best cutoff point in the detection of colon cancers. In this cutoff point, sensitivity and specificity were 87.8% and 91.8%, respectively, and accuracy was 89.8%. The sensitivity and specificity of IFOBT were 93.9% and 100%, respectively, and accuracy was 96.9%. The sensitivity and specificity of FOBT were 65.3% and 100%, respectively, and accuracy was 82.6%. CONCLUSION: IFOBT with high sensitivity and specificity and accuracy and low cost is the best fecal screening test. The current study suggests that fecal M2-PK can be used for high-risk colon cancer patients and negative IFOBT that refused colonoscopy as a precolonoscopy screening test.

The interleukin 28B gene polymorphism, rs8099917, in patients with chronic hepatitis C and response to the treatment with pegylated interferon and ribavirin.

BACKGROUND: The present study aimed to determine the frequency of the IL28B polymorphism rs8099917 in patients with genotype 1 hepatitis C virus (HCV) infection treated with pegylated-interferon-α2b (PEG-IFN-α2b) and ribavirin (RBV) and its treatment outcome. MATERIALS AND METHODS: The IL28B rs8099917 genotypes were determined among 100 HCV-infected patients and the viral load was also estimated. PEG-IFN-α2b and RBV combination were administrated to the patients for 48 weeks and the treatment outcome was defined. RESULTS: Sixty-seven (67%), 27 (27%), and 6 (6%) of 100 patients were determined as TT, GT, and GG genotype, respectively. The response rate to treatment was significantly higher in patients with TT genotype. CONCLUSION: According to the results of the present study, patients with IL28B rs8099917 TT genotype achieve higher sustained virological response than the GT and GG genotypes. Thus, when there are no alternatives, treatment with PEG-IFN-α2b and RBV combination can be suggested in patients with IL28B TT genotype.

How much does vaccination reduce the rate of HBV infection in Iranian population? a Bayesian adjustment analysis.

AIM: The aim of this research was to estimate the changing rate of odds ratio (OR) by varying degrees of hepatitis B virus (HBV) underreporting. BACKGROUND: Data registering is usually associated with extensive errors such as misclassification, under-reporting, missing data due to lack of co-operation, error prone factors, and in medical studies, inadequate diagnosis of physicians or low accuracy of laboratory tests. In the present study, which discuss the actual impact of vaccination on HBV prevention, exposure and response were prone to various errors. Furthermore, some people in the community are possibly infected to the virus while were not reported in the count of patients with HBV infection. METHODS: This was a case control study. Cases included patients with HBV referring to the gastroenterology and liver disease research center. The control group included patients without HBV who underwent a fatty liver test at Taleghani hospital laboratory. Bayesian approach and Gibbs sampling algorithm were used to estimate OR. RESULTS: According to results, misclassification rate was mild in raw data, but with an increase in degree of underreporting for 50 and 500 of unreported cases, OR increased by about half and more than double, respectively, while sensitivity diminished strikingly. CONCLUSION: Our analysis asserted that knowing the degree of underreporting is essential to accurately calculate OR and sensitivity. In addition, despite varying OR in different samples, overall the results were similar according to the pattern of exposure and response association.

Combination of diclofenac and aggressive hydration for the prevention of post-ERCP pancreatitis.

AIM: To investigate whether aggressive hydration can increase the efficacy of prophylactic non-steroid anti-inflammatory drugs (NSAIDs) in prevention of post-ERCP pancreatitis. BACKGROUND: NSAIDs are recommended for the prevention of PEP; however, whether aggressive hydration can have additional benefits in this regard is not known. METHODS: Patients candidate for ERCP received either pre-procedural rectal diclofenac (100 mg) alone (n = 112) or in combination with aggressive hydration by lactate ringer's (n = 107) as prophylactic method. PEP was defined based on increase in serum levels of pancreatic enzymes (from baseline to 24 hours following the procedure) accompanied with symptoms. RESULTS: PEP was occurred in 3 patients in the diclofenac only group and in 1 patient in the diclofenac + hydration group with no significant difference (2.7% vs. 0.9%, P = 0.622). Serum amylase levels decreased over time in the diclofenac + hydration group but not in the diclofenac only group. Also, serum lipase levels decreased more rapidly over time in the diclofenac + hydration group compared to the diclofenac only group. CONCLUSION: Combination prophylactic therapy with NSAIDs plus aggressive hydration does not seem to have additional clinically important benefits in preventing PEP. Studies with larger sample of patients are required in this regard.

Effect of Probiotic Administration Immediately and 1 Month after Colonoscopy in Diarrhea-predominant Irritable Bowel Syndrome Patients.

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common disorders among young adults. Various studies have demonstrated that the use of probiotics can reduce the overall symptom of IBS, and thus, our aim was to evaluate the efficacy of probiotic products in the reduction of IBS syndrome after colonoscopy. MATERIALS AND METHODS: Our patients were divided among three groups, including immediate probiotic users, start use of probiotics 1 month after colonoscopy, and placebo group. All the patients were interviewed for having common IBS symptoms (stool consistency and frequency, gas, abdominal pain, and flatulence) at baseline, 3rd month of follow-up, and 6th month of follow-up. RESULTS: The mean reduction in abdominal pain was 3.05 ± 1.21, 3.86 ± 0.94, and 3.82 ± 0.63 in the control group, immediate probiotic users, and 1 month after colonoscopy, respectively (P < 0.001). The symptoms of the disease, such as stool consistency, the frequency of defecation, and flatulence (except gas) in the first quarter, in the two treatment groups were significantly improved more than in the control group (P < 0.05). In contrast, the frequency of defecation was not significantly different in the treatment group receiving the probiotics month after colonoscopy compared to the placebo users (P > 0.05). CONCLUSION: According to our results, the use of probiotics had the beneficial effect on IBS symptoms. Furthermore, it can be said that reductions in symptoms and pain in the two treatment groups were not significantly different, but after 6 months of treatment, the effect of probiotics in patients who immediately use it after colonoscopy was more visible and more stable.

Full colonoscopy in patients under 50 years old with lower gastrointestinal bleeding.

BACKGROUND: Lower gastrointestinal (GI) bleeding is a common clinical problem in young patients. The management of this disease in patients is challenging. The aim of this study is to compare sigmoidoscopy with full colonoscopy in these patients. MATERIALS AND METHODS: In this cross-sectional study, 120 eligible patients under 50 years old with acute rectal bleeding were enrolled. After cleaning the colon, initially the patients underwent sigmoidoscopy. Pain, the comfort of the test by physician and patient, duration of the procedure, and pathologic findings were recorded. The procedure continued until the splenic flexure passed in the ileocecal valve, and this stage was considered as proximal colonoscopy. Pain, easy performance by physician and the patient, duration of procedure, and pathologic findings were recorded in this stage too. The variables in the two stages were compared with each other. RESULTS: There were 66 women (55%) and 54 men (45%) and the mean of age was 41 ± 7.9 years. Proximal colonoscopy from splenic flexure to reach cecum was relatively easier for the physician and the patient than sigmoidoscopy (P < 0.001). Furthermore, the time spent to carry out proximal colonoscopy was less than the time taken for sigmoidoscopy (P < 0.001). Pathologic findings recorded in full colonoscopy were more than sigmoidoscopy (P < 0.001). Therefore, full colonoscopy that includes sigmoidoscopy and proximal colonoscopy is relatively easier than sigmoidoscopy for patients, and it also proves more advantageous than sigmoidoscopy for physicians to perform in Iranian patients because of more tortuous and elongated sigmoid colon in these patients. CONCLUSION: It is advised to perform full colonoscopy than sigmoidoscopy in young patients with lower GI bleeding.

Levofloxacin-containing versus Clarithromycin-containing Therapy for Helicobacter pylori Eradication: A Prospective Randomized Controlled Clinical Trial.

BACKGROUND: This study evaluated the clinical efficacy and tolerability of a 14-day course of bismuth-based quadruple therapy including tinidazole and levofloxacin in compare to a 14-day bismuth-based quadruple therapy including clarithromycin as first-line treatment for Helicobacter pylori infection in Iranian adults. MATERIALS AND METHODS: The study was a prospective, parallel group, randomized controlled, clinical trial that conducted on 150 patients with H. pylori infection. Patients were randomly assigned to the two groups as follows: first group received pantoprazole 40 mg, bismuth subcitrate 240 mg, amoxicillin 1 g, and clarithromycin 500 mg (PBAC group), and other group received pantoprazole 40 mg, bismuth subcitrate 240 mg, amoxicillin 1 g, tinidazole 500 mg for 7 days, followed by levofloxacin 500 mg for the second 7 days (PBATL group). Main outcomes were eradication rate, tolerance of treatment, and dyspepsia severity. RESULTS: The eradication rates for PBAC regimen was 81.1% (95% confidence interval [CI]: 71.9-90.2) and for PBATL regimen was 70.8% (95% CI: 60.1-81.6), which was not significantly different (P = 0.147). Tolerance of treatment was similar between groups. The median of severity of dyspeptic after treatment in PBAC group was 10 [9-14.75], which was similar to PBATL group 10 [9-13.5] (P = 0.690). CONCLUSION: There is no significant difference between PBAC and PBATL regimen, and efficacy was similar in both groups. The overall rate of treatment failure suggests that up to 18%-30% of patients will fail bismuth-based quadruple therapy and require retreatment for the infection.

Viscous lidocaine solution versus lidocaine spray for pharyngeal local anesthesia in upper gastroesophageal endoscopy.

BACKGROUND: Advantage of using local sedation during upper gastrointestinal endoscopy (UGE) is still challenging. In the current study, the effect of lidocaine spray versus lidocaine viscous solution for pharyngeal local anesthesia during UGE has been compared. MATERIALS AND METHODS: This is a randomized clinical trial conducted on 130 patients conducting UGE in 2013. Patients were randomly divided into two groups of viscous lidocaine solution (Group V) and lidocaine spray (Group S). Patients' tolerance, satisfaction, pain/discomfort, and anxiety (based on 11-point numerical score scale) and ease of endoscopy were compared. RESULTS: Ease of procedure, patients' tolerance, and patients' satisfaction were not statistically different between two groups (P > 0.05). Patients' pain/discomfort and anxiety during endoscopy were significantly different between groups (P < 0.05). CONCLUSION: As a conclusion, there was not any difference between two groups except for pain, discomfort, and anxiety that was higher in those who administered spray that might be due to the method of usage.

Detection of Minimal Hepatic Encephalopathy in Iranian Patients with Cirrhosis.

BACKGROUND Minimal hepatic encephalopathy (MHE) is the mildest type of hepatic encephalopathy in patients with cirrhosis. Patients with MHE have normal clinical and physical examination but they show some neurocognitive dysfunctions that affect their quality of life negatively. The aim of the current study is to diagnose MHE in patients with cirrhosis and its associated factors. METHODS This is a cross-sectional study on 120 known cases of cirrhosis referred to hospitals affiliated to Isfahan University of Medical Sciences during 2014-17. The patients' cirrhosis severity was evaluated using laboratory tests and physical examinations based on MELD (Model for End-stage Liver Disease) and Child-Pugh criteria. The patients' demographics were filled in a checklist. All included patients with cirrhosis were asked to respond to the questions of Psychometric Hepatic Encephalopathy Score (PHES) test. RESULTS Mean age of the patients was 51.2 ± 9.7 years. 62 (51.7%) patients were men and 58 (48.3%) patients were women. The mean score of the patients based on MELD criteria was 14.03 ± 6.09. 26.7% of the patients presented MHE. Mean age of the patients with MHE was statistically less than the patients without MHE (p value < 0.001). Mean score of MELD criteria among the patients with diagnosis of MHE was significantly higher than the other group (p value < 0.001). The patients' Child class was statistically associated with MHE (p value < 0.001). Men were significantly more affected than women (p value = 0.03). CONCLUSION MHE was associated with MELD score and Child class of the patients with cirrhosis. The noticeable point was reversible association of age with MHE. Further studies are recommended.

Gene expression analysis of colon high-grade dysplasia revealed new molecular mechanism of disease.

AIM: The aim of this research was to find a clear molecular view of dysplasia via network analysis. BACKGROUND: There are some evidence suggest the relationship between dysplasia and colorectal cancer. Understanding of high-grade dysplasia (HGD) could be beneficial for colon cancer management. METHODS: Bioinformatics study of HGD versus healthy subjects was conducted to check the status of differentially expressed genes (DEGs). GSE31106, GPL1261, GSM770092-94 and GSM770101-6 were the sources from gene expression omnibus (GEO) that queried for protein-protein interaction (PPI) network analysis via Cytoscape and its algorithms. Hubs of network were enriched for biochemical pathways and were validated via clustering analysis. RESULTS: Numbers of 46 hub nodes were determined and were included in 12 pathways. A main cluster including 76 nodes was identified containing 45 hubs. 33 hubs among 46 genes were involved in biochemical pathways. IL1B, IL6, TNF, and TRL4 were the most important critical genes. CONCLUSION: Many different genes as hub nodes might influence the trigger and development of advance condition and also colon cancer.

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.

Polymorphism (rs16917496) at the miR-502 Binding Site of the Lysine Methyltransferase 5A (SET8) and Its Correlation with Colorectal Cancer in Iranians.

BACKGROUND: One of the gene expression regulatory mechanisms is mediated by small noncoding RNAs called microRNA (miRNA). They interact with a recognition sequence located mostly in 3'-untranslated regions (3'-UTRs) of mRNAs. Polymorphisms in miRNAs recognition sequences could affect gene expression which in turn may alter disease susceptibility. SET8, a member of the SET domain-containing methyltransferase, acts in a variety of biological processes such as genomic stability. Here, we report correlation of rs16917496 polymorphism, located in the recognition sequence of miR-502 within 3'-UTR of SET8, with colorectal cancer (CRC) in Iranians. MATERIALS AND METHODS: One hundred and seventy CRC patients and 170 noncancer counterparts were recruited in this case-control study. Genotyping of rs16917496 was performed using polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: There was no significant association of rs16917496 with CRC in population under study (P value for genotype and allele distribution were >0.05). However, stratification analysis based on smoking status revealed that TT+TC genotypes of SET8 rs16917496 are strongly associated with increased risk of CRC (odds ratio: 5.8, 95% confidence interval: 1.37-24.34, P - 0.005) in smoker subgroup. CONCLUSION: Correlation of rs16917496 T allele with CRC in smokers is emphasizing the importance of individuals' genotype in the recruitment of adverse health hazards of smoking more profoundly for certain people compared to others.

Effects of Phlebotomy on Liver Enzymes and Histology of Patients with Nonalcoholic Fatty Liver Disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD), defined as excessive liver fat deposition and one of end-stage liver disease causes. Increased ferritin levels are associated with insulin resistance and a higher hepatic iron and fat content. Hyperferritinemia has been associated with severity of liver damage in NAFLD. The study aimed to evaluate the effects of phlebotomy on liver enzymes and histology in such patients. MATERIALS AND METHODS: Thirty-two eligible patients who had NAFLD and after 6 months of lifestyle modification still had NAFLD, and whose ferritin serum was above 250 mg/dl, were enrolled in this clinical trial study. After written informed consent was obtained, each patient's blood serum was taken for aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALK-P), complete blood count (CBC), total iron-binding capacity (TIBC), iron, and ferritin. Then the patients underwent liver biopsy. After that patients underwent phlebotomy, giving 350 cc blood monthly. Before every phlebotomy, hemoglobin and ferritin were checked. If they were in the goal range, phlebotomy was discontinued and the patient underwent liver biopsy. A serum sample was taken for testing at the beginning of the study. The results before and after phlebotomy were compared. The maximum duration of the study was 6 months. RESULTS: Thirty-two patients (26 males and 6 females) were enrolled, and the mean average age was 33.7 ± 6.74 years. Phlebotomy improved liver enzymes and histology of liver significantly (P < 0.001) and induced reduction of ferritin. CONCLUSION: Phlebotomy is effective for the improvement of liver enzymes and histology in patients with NAFLD and hyperferritinemia.

Network analysis of common genes related to esophageal, gastric, and colon cancers.

AIM: The aim of this study was to provide a biomarker panel for esophageal, gastric and colorectal cancers. It can help introducing some diagnostic biomarkers for these diseases. BACKGROUND: Gastrointestinal cancers (GICs) including esophageal, gastric and colorectal cancers are the most common cancers in the world which are usually diagnosed in the final stages and due to heterogeneity of these diseases, the treatments usually are not successful. For this reason, many studies have been conducted to discover predictive biomarkers. METHODS: In the present study, 507 genes related to esophageal, gastric and colon cancers were extracted.. The network was constructed by Cytoscape software (version 3.4.0). Then a main component of the network was analyzed considering centrality parameters including degree, betweenness, closeness and stress. Three clusters of the protein network accompanied with their seed nodes were determined by MCODE application in Cytoscape software. Furthermore, Gene Ontology (GO) analysis of the key genes in combination to the seed nodes was performed. RESULTS: The network of 17 common differential expressed genes in three esophageal, gastric and colon adenocarcinomas including 1730 nodes and 9188 edges were constructed. Eight crucial genes were determined. Three Clusters of the network were analyzed by GO analysis. CONCLUSION: The analyses of common genes of the three cancers showed that there are some common crucial genes including TP53, EGFR, MYC, AKT1, CDKN2A, CCND1 and HSP90AA1 which are tightly related to gastrointestinal cancers and can be predictive biomarkers for these cancers.