Possible association between polyomaviruses and gastrointestinal complications: a narrative review.

Polyomaviruses are a group of small, double-stranded DNA viruses that are known to be associated with the development of certain human diseases, but there is evidence that these viruses might be associated with gastrointestinal (GI) cancers. Several polyomaviruses have been identified, such as JC polyomavirus (JCPyV), BK polyomavirus (BKPyV) and recently Merkel cell polyomavirus (MCPyV). Although the direct effects of polyomaviruses on transformation of human cells and cancer development are not clearly recognized, their association with certain human diseases including GI cancers has been proposed through several molecular and epidemiological studies. For example, JCPyV and BKPyV have been linked to colorectal cancer, as there is growing evidence of finding viral genomes in cancerous tissues. Nevertheless, the major role of JCPyV, BKPyV and MCPyV in colorectal cancer progression is still under extensive investigation, and further surveys is required to establish a conclusive cause-and-effect relationship. Understanding the role of these viruses in cancer development has significant implications for diagnosis, treatment, and prevention strategies. It seems that proving a causal link between polyomaviruses and GI cancers might provide a novel path for targeted therapies or design and development of specific therapeutic vaccines. In addition, performing research on the possible link can provide insights into the underlying molecular mechanisms of carcinogenesis, potentially leading to the identification of novel biomarkers. This review focuses on polyomaviruses, in particular a recently discovered polyomavirus, MCPyV, and their possible link with human gastrointestinal disorders.

Eight years experience of transanal endoscopic microsurgery

Introduction: Transanal Endoscopic Microsurgery (TEM) is a minimally invasive method for management of different proctologic conditions. Despite widespread use of this method, it is not used widely in Iran. This report is about to describe the application of TEM in managing different proctologic conditions in a tertiary colorectal referral center in Iran regarding methods and complications. Methods: All of the patients' documents such as procedure, method, early postop complications and further operations were actively reviewed and the data were entered in to the database. Results: Since 2012 till the end of 2020 chart review was done and 150 cases of TEM operation were found. The most frequent procedure that was done was resection procedure. Using different energy devices during surgery or suturing versus not suturing the defect were not associated with complication. There was a case of in hospital mortality and one case delayed perianal fistula following TEM. Measurement of lesion distance from anal verge was not significantly different using TEM or colonoscopy. Villous adenomas detected in colonoscopy were mostly associated with malignancy. In evaluated resected lesions most of cases had free base and distance from anal verge or using different energy devices were not associated with obtaining free base. Conclusion: TEM is a safe minimal invasive procedure with acceptable complications that could be helped in managing different proctologic conditions and the results of reviewing our patients revealed the same results that is reported from other colorectal centers. (AU)

Assessment of common and differentially expressed proteins between diabetes mellitus and fatty liver disease: a network analysis.

AIM: This study aimed to introduce the main biomarkers related to NFLD and diabetes II to determine common pathogenic and metabolite factors linking NFLD to diabetes II. BACKGROUND: Nonalcoholic fatty liver disease (NFLD) is chronic hepatic failure with a broad range of hepatic disorders. NFLD and diabetes type 2 coexist regularly to drive adverse outcomes such as hepatocellular carcinoma and vascular complications. METHODS: The proteins related to NFDL and diabetes mellitus were extracted from String database. Proteins related to each disease were included in protein-protein interaction networks in Cytoscape software. Obtained networks were analyzed using Cytoscape network analyzer. The central nodes were determined as top hubs based on degree value. The top hubs related to NFLD and diabetes mellites were compared. RESULTS: In total, 200 proteins related to NFDL and diabetes mellitus were found separately in String database and connected through undirected edges in individual networks. Central nodes based on degree value were determined for each disease. Ten percent of top nodes were selected based on degree value as the 20 top hubs for each disease. Target common hub proteins between NFDL and diabetes mellitus comprised INS, AKT1, ALB, PPARG, IL6, GPDPH, LEP, TNF, ADIPOQ, IGF1, TP53, MAPK3, and SIRT1. CONCLUSION: According to the results, 13 common and 14 discriminatory central dysregulated proteins were determined for NAFLD and diabetes mellitus.

Assessment of liver cancer biomarkers.

Liver cancer is the third cause of cancer-related deaths in the world. It is primarily divides into two main types, namely hepatocellular carcinoma (HC) and cholangiocarcinoma (IC). Due to the increasing number of patients with liver cancer and the high mortality rate, early diagnosis of the disease can be helpful in treatment, but most patients are diagnosed atlate stages of HC. The aim of this study is to screen and provide an overview on candidate biomarkers related to primary liver cancer to introduce the critical ones. In this study, various biomarkers related to the diagnosis of primary liver cancer have been studied. Accordingly, biomarkers are divided into different groups as blood biomarkers classified as serum and plasma biomarkers, tissue biomarkers, microRNA biomarkers, proteomic biomarkers and altered genes. Previous researches have focused on liver cells and bile ducts, the surround cellular environment, how cells differentiate, and the types of genes expressed in liver cancer. Some even have focused on the origin of tumor cells and how they differentiate and develop. In all these studies, the expression of specific proteins and genes in liver cancer has been considered. Based on available sources, biomarkers can be considered as candidates to diagnose and prognosis of various types of primary liver cancer, from sources such as blood, tissue, mic-RNA, proteome and genes. However, more investigations are required to introduce a biomarker for precise detection of early liver cancer.

TGF-ß1 polymorphisms -509 C>T and +915 G>C and risk of pancreatic cancer.

BACKGROUND: Ninety percent of pancreatic cancer patients have less than 5-year overall survival and approximately 50% of cases were diagnosed with metastasis in the time of admission. Previous evidences have demonstrated the strong association between TGF-ß1 variations and cancer susceptibility so far. METHODS: A total of 78 patients with pancreatic cancer and 94 healthy controls were enrolled in this case- control study between 2007 and 2012. Genomic DNA was isolated from peripheral blood samples according to phenol chloroform extraction. The genotypes of TGF-ß1 rs rs1800469 and rs1800471 were determined using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The mean age of cases and the control group were 64.50 ± 13.718 and 40.12 ± 16.001, respectively. For polymorphism -509 C>T, the frequency of TT genotype were 31 (33.0), CT, 47(50) and CC, 16 (17) in control and 19 (24.4), 45 (57.7) and 14 (17.9) in cases respectively. In position +915 G>C, the frequency of GG genotype was 84 (89.4) and GC, 10 (10.6) in control and 71 (91.0) and 7 (9) in cases, respectively. We did not observe any significant differences in the genotype and allele frequencies of the TGF-ß1-509 C>T (rs1800469) and codon +915 G>C (rs1800471) between the two study groups (P>0.05). CONCLUSION: we found that TGF-ß1 gene polymorphisms rs1800469 and rs1800471 might not play a role in pancreatic cancer susceptibility in Iranian population.

Polyp detection rate and pathological features in patients undergoing a comprehensive colonoscopy screening.

AIM: To identify the prevalence, and clinical and pathologic characteristic of colonic polyps among Iranian patients undergoing a comprehensive colonoscopy, and determine the polyp detection rate (PDR) and adenoma detection rate (ADR). METHODS: In this cross-sectional study, demographics and epidemiologic characteristics of 531 persons who underwent colonoscopies between 2014 and 2015 at Mehrad gastrointestinal clinic were determined. Demographics, indication for colonoscopy, colonoscopy findings, number of polyps, and histopathological characteristics of the polyps were examined for each person. RESULTS: Our sample included 295 (55.6%) women and 236 (44.4%) men, with a mean age of 50.25 ± 14.89 years. Overall PDR was 23.5% (125/531). ADR and colorectal cancer detection rate in this study were 12.8% and 1.5%, respectively. Polyps were detected more significantly frequently in men than in women (52.8% vs 47.2%, P < 0.05). Polyps can be seen in most patients after the age of 50. The average age of patients with cancer was significantly higher than that of patients with polyps (61.3 years vs 56.4 years, P < 0.05). The majority of the polyps were adenomatous. More than 50% of the polyps were found in the rectosigmoid part of the colon. CONCLUSION: The prevalence of polyps and adenomas in this study is less than that reported in the Western populations. In our patients, distal colon is more susceptible to developing polyps and cancer than proximal colon.

Diabetes mellitus and hypertension increase the risk of colorectal cancer mortality; a robust Bayesian adjustment analysis.

AIM: The aim of this study was to investigate the impact of diabetes and hypertension on colorectal cancer (CRC) mortality. BACKGROUND: One of the methodology in epidemiological studies is to use self-report questionnaires to gather data, this is the easiest and cheapest method but involves with misclassification bias. We use robust Bayesian adjustment to correct this bias. METHODS: One of the methodology in epidemiological studies is to use self-report questionnaires to gather data, this is the easiest and cheapest method but involves with misclassification bias. We use robust Bayesian adjustment to correct this bias. RESULTS: The effect size with ignorance misclassification bias was 0.78 for diabetes and 0.94 for hypertension respectively which both of them were not significant. After adjusting the misclassification and performing the robust Bayesian analysis, we arrived at region (0.27, 3.4) for OR of diabetes and (0.21, 2.31) for hypertension. CONCLUSION: our study demonstrated that diabetes and hypertension increase the risk of mortality in CRC patients, using robust Bayesian analysis and misclassification in diagnosis these two exposure could change or confound the results of this association.

Lack of Association between NOD2 rs3135500 and IL12B rs1368439 microRNA Binding Site SNPs and Colorectal Cancer Susceptibility in an Iranian Population.

OBJECTIVE: The purpose of this study was to evaluate the potential association between single nucleotide polymorphisms (SNPs) in microRNA (miRNA) binding sites in the NOD2 and IL12B gene 3.-untranslated regions and colorectal cancer (CRC) susceptibility in an Iranian population. METHODS: We genotyped NOD2 rs3135500 [3. untranslated region (UTR) A/G] and IL12B rs1368439 (3.UTR G /T) in a hospital-based study of 92 colorectal cancer cases and 105 healthy controls. All samples were genotyped by TaqMan assay via an ABI 7500 Real Time PCR System (Applied Biosystems) with DNA from FFPE tissue and peripheral blood. RESULTS: our results showed similar distribution of genotype and allelic frequencies of the NOD2 and IL12B polymorphisms between patients and controls. When the more common rs3135500 AA genotype was used as the reference, the rs3135500 AG and rs3135500 GG genotypes were not significantly associated with the risk of CRC (OR = 1.294, 95% CI: 0.524 -3.197; and OR = 2.230, 95% CI: 0.87 - 5.715, respectively), and The IL12B rs1368439 TG and IL12B rs1368439 GG genotypes were not significantly associated with the risk of CRC compared with the IL12B rs1368439 TT genotype (OR = 1.547 95% CI: 0.187- 12.771; and OR = 1.753, 95% CI: 0.217-14.157, respectively). CONCLUSION: NOD2 rs3135500 and IL12B rs1368439 SNPs were not genetic risk factors for colorectal cancer in the studied Iranian population.

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.

Proinflammatory cytokines and thrombomodulin in patients with peptic ulcer disease and gastric cancer, infected with Helicobacter pylori.

BACKGROUNDS: Helicobacter pylori infect more than half of the global population. It is suggested to be related with gastritis, peptic ulcer disease (PUD), and gastric cancer. AIMS: The aim of this present study was to evaluate proinflammatory cytokines including interleukin 1, 6, 8, 10, and thrombomodulin in H. pylori-infected patients with PUD and gastric cancer. PATIENTS: This cross-sectional study was conducted in Taleghani Hospital on 111 patients with H. pylori infection. MATERIALS AND METHODS: Patients were divided into three groups of PUD, cancer, and control (normal on endoscopy), according to the results of endoscopy. The serum levels of interleukins 1, 6, 8, and 10 and thrombomodulin was determined using enzyme-linked immunosorbent assay (ELISA) technique. H. pylori infection was diagnosed by histological examination of the endoscopic biopsy. RESULTS: One hundred eleven patients were included in the study; 30 as PUD group, 30 as gastric cancer group, and 51 as controls. There was no significant difference between the means of IL-1 and IL-10 levels among the three groups (P = 0.744 and 0.383, respectively). IL-6, IL-8, and thrombomodulin levels were found to be statically different among the three groups (P < 0.05). The level of IL-6, IL-8, and thrombomodulin in cancer group was significantly higher than PUD and control groups (P < 0.05). CONCLUSION: There is a significant association between H. pylori infection and serum IL-6, IL-8, and thrombomodulin but such relation is not present between H. pylori and IL-1 and IL-10. Immunity response (IL-6, IL-8 and thrombomodulin) is more severe in cancer patient than PUD.

CagA status and VacA subtypes of Helicobacter pylori in relation to histopathologic findings in Iranian population.

BACKGROUND/OBJECTIVE: The aim of this study was to detect dominant cagA/vacA genotypes of Helicobacter Pylori (H. pylori) and determine correlations between different cagA/vacA genotypes and histologic features of chronic gastritis in Iranian patients. METHODS: Gastric biopsy was taken from 166 patients with nonulcer dyspepsia. The specimens were processed and DNA from each H. pylori isolate was extracted from multiple colony sweeps for identification of glmM gene. The vacA subtypes and cagA gene were tested by PCR . Histopathological features were recorded and graded according to partial Sydney system. RESULTS: Of the 86 strains, 66 (76.7%) were cagA positive. The proportions of vacA gene subtypes s1, s2, m1 and m2 in the 78 strains isolated were 70.5%, 29.5%, 37.2% and 62.8%, respectively. About 83.3% of the vacA-positive strains had s1 allele. Twenty-six strains (33.3%) were positive for both cagA and m1 allele. Positive cagA status and vacA subtypes were not associated significantly with presence of neutrophil infiltration, intestinal metaplasia or H. pylori density. Only vacA s1 was significantly associated with more severe inflammation (P=0.02). The dominant genotype of H. pylori was vacA plus s1/m2. CagA gene positivity rate was not closely associated with severity of the disease. CONCLUSION: H. pylori strains showing vacA s1 genotype were associated with more severe gastritis. These findings show that vacA genotyping may have clinical relevance in Iran.

Pattern of tobacco use among the Iranian adult population: results of the national Survey of Risk Factors of Non-Communicable Diseases (SuRFNCD-2007).

BACKGROUND: Previous studies report on smoking in Iran but recent national data on tobacco use (including cigarette, water-pipe and pipe) have not been reported. METHODS: In 2007, 5287 Iranians aged 15-64 years were sampled from all provinces as part of a national cross-sectional survey of non-communicable disease (NCD) risk factors. Data were collected using the standardised stepwise protocol for NCD risk factor surveillance of the World Health Organization. Use of tobacco products was calculated as the sum of smoking cigarettes/cigars (smoking currently or daily any amount of factory/hand-made cigarettes or cigars), pipes (daily) and water pipes (daily). RESULTS: Total current and daily tobacco use was 14.8% (burden 7.3 million) and 13.7% (burden 6.7 million) when extrapolated to the Iranian population aged 15-64. The prevalence of current and daily cigarette smoking was 12.5% (6.1 million; 23.4% males and 1.4% females) and 11.3% (5.6 million; 21.4 males and 1.4 females); former smokers comprised 1.7 million or 3.4% of the Iranian population (6.2% males and 0.6% females; mean cessation age 34.1). The mean age of starting to smoke was 20.5 years (24.2 males and 20.4 females). The prevalence of water-pipe smoking was 2.7% (burden 1.3 million; 3.5% males and 1.9% females). Water-pipe smokers used the water-pipe on average 3.5 times a day (2.8 males and 4.5 females). CONCLUSION: The prevalence of tobacco use has not escalated over the past two decades. Nonetheless, the burden is high and therefore warrants preventive public health policies.

Association between physical activity and insulin resistance in Iranian adults: National Surveillance of Risk Factors of Non-Communicable Diseases (SuRFNCD-2007).

BACKGROUND: Insulin resistance is an underlying mechanism of metabolic syndrome. We attempted to determine the association between physical activity and insulin resistance in Iranian adults. METHODS: The data of the third national Surveillance of Risk Factors of Non-Communicable Diseases (SuRFNCD-2007) in Iran were used. We ran the Global Physical Activity Questionnaire (GPAQ) over a nationally representative sample of 3101 adults. Total physical activity (TPA) was calculated using metabolic equivalents (MET) for intensity of physical activities. Insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: When physical activity was classified into high, moderate, and low categories, HOMA-IR values significantly increased from the high category to the moderate and low categories (p<0.01). After adjustment for age, area of residence, smoking, and body mass index (BMI), TPA (r=-0.26, p<0.01 in males and r=-0.21, p<0.01 in females), duration of vigorous-intensity activity (r=-0.28, p<0.01 in males and r=-0.18, p=0.01 in females), duration of moderate-intensity activity (r=-0.16, p=0.01 in males and r=-0.17, p<0.01 in females), and the time spent on sedentary behaviors (r=0.16, p=0.01 in males and r=-0.22, p<0.01 in females) were significantly correlated to HOMA-IR. The prevalence of physical inactivity increased linearly with increasing HOMA-IR quintiles. CONCLUSIONS: Our findings indicate a significant relationship between physical inactivity and insulin resistance. For communities in a transition phase of lifestyle, encouraging physical activity may help prevent insulin resistance and its adverse consequences.

Third national Surveillance of Risk Factors of Non-Communicable Diseases (SuRFNCD-2007) in Iran: methods and results on prevalence of diabetes, hypertension, obesity, central obesity, and dyslipidemia.

BACKGROUND: The burden of non-communicable diseases is rising globally. This trend seems to be faster in developing countries of the Middle East. In this study, we presented the latest prevalence rates of a number of important non-communicable diseases and their risk factors in the Iranian population. METHODS: The results of this study are extracted from the third national Surveillance of Risk Factors of Non-Communicable Diseases (SuRFNCD-2007), conducted in 2007. A total of 5,287 Iranian citizens, aged 15-64 years, were included in this survey. Interviewer-administered questionnaires were applied to collect the data of participants including the demographics, diet, physical activity, smoking, history of hypertension, and history of diabetes. Anthropometric characteristics were measured and serum biochemistry profiles were determined on venous blood samples. Diabetes (fasting plasma glucose >or= 126 mg/dl), hypertension (systolic blood pressure >or= 140 mmHg, diastolic blood pressure >or= 90 mmHg, or use of anti-hypertensive drugs), dyslipidemia (hypertriglyceridemia: triglycerides >or= 150 mg/dl, hypercholesterolemia: total cholesterol >or= 200 mg/dl), obesity (body mass index >or= 30 kg/m2), and central obesity (waist circumference >or= 80 cm in females and >or= 94 cm in males) were identified and the national prevalence rates were estimated. RESULTS: The prevalence of diabetes, hypertension, obesity, and central obesity was 8.7% (95%CI = 7.4-10.2%), 26.6% (95%CI = 24.4-28.9%), 22.3% (95%CI = 20.2-24.5%), and 53.6% (95%CI = 50.4-56.8%), respectively. The prevalence of hypertriglyceridemia and hypercholesterolemia was 36.4% (95%CI = 34.1-38.9%) and 42.9% (95%CI = 40.4-45.4%), respectively. All of the mentioned prevalence rates were higher among females (except hypertriglyceridemia) and urban residents. CONCLUSION: We documented a strikingly high prevalence of a number of chronic non-communicable diseases and their risk factors among Iranian adults. Urgent preventive interventions should be implemented to combat the growing public health problems in Iran.

vacA genotypes of Helicobacter pylori in relation to cagA status and clinical outcomes in Iranian populations.

Mosaicism in vacA alleles with two distinct families of vacA signal sequences (s1 and s2) and two distinct families of middle region alleles (m1 and m2) has been reported. Research suggests that the vacA s1 genotype is closely associated with duodenal ulcer disease and with high cytotoxin production. The aims of this study were to evaluate the role of vacA genotyping with respect to gastric inflammation and injury, and clinical presentation in Iranian populations. Genomic DNA of biopsy specimens from patients with gastritis, peptic ulcer disease (PUD), or gastric cancer (GC) were characterized based on ureC (glmM), cagA, and vacA genotyping by using polymerase chain reaction. Of 167 patients including 33 with PUDs, 129 with non-ulcer dyspepsia (NUD), and 5 with GC, 96 (57.5%) cases were infected by Helicobacter pylori. Among these patients, H. pylori were isolated from 19 (57.7%) PUD patients, 74 (68.7%) NUD patients, and 3 (60%) GC patients. The cagA was detected in 76% of H. pylori-positive cases. The vacA s1-m2 genotype was the most prevalent in 7/19 PUD (37%) and 30/74 NUD (40.5%) patients with H. pylori infection. The prevalence of vacA s2-m1 (8%) was high in Iranian isolates. A significant association was not found between H. pylori genotypes and clinical outcomes. The vacA genotypes and cagA status were not useful markers for gastroduodenal diseases in Tehran, Iran.