Genetic variability in cagL gene especially within the Helicobacter pylori CagL hypervariable motif (CagLHM) may affect the development of gastric cancer. Therefore, this study was conducted to investigate the association of CagL diversity with clinical outcomes and with H pylori virulence markers. A total of 126 patients with different gastric diseases including non‐ulcer dyspepsia (NUD), peptic ulcer disease (PUD), gastric erosion (GE), and gastric cancer (GC) were enrolled. H pylori was cultured from gastric biopsies, and the isolates were screened for the presence of cagL, cagA, vacA, babA2, sabA, and cagPAI integrity by PCR. The amino acid polymorphisms of cagL were analyzed using DNA sequencing. We isolated 61 (48.4%) H pylori strains from 36 NUD, eight PUD, 12 GE, and five GC patients. Almost all isolates were cagL positive (97%), and their RGD, RHS, and SKIIVK motifs were highly conserved. Among 10 CagLHM variants identified, NEIGQ and NKIGQ were detected as the most prevalent sequences. Interestingly, a significant association was found between the presence of NKMGK and PUD (P = 0.002). Notably, the NEIGQ isolates with multiple C‐type EPIYA repeat that carried intact cagPAI correlated with disease risk for PUD, GE, and GC (P = 0.021). In conclusion, we identified novel variants of H pylori CagLHM sequences in Iranian population such as NKMGK, which was associated with disease risk for PUD. Further studies using a large number of strains are required to better clarify the function of certain CagLHM motifs in gastric carcinogenesis and disease outcome.

method have become a research trend. The ultimate biomarkers must be easily detectable with fine sensitivity and specificity and also must discriminate PC from other benign pancreatic diseases 9. Blood is a simply reachable and rather steady sample to find alerting biomarkers. Technological advances in the recent years have provided possibilities to detect circulating biomarkers based on "omics" research, relying on proteins, cell-free DNAs, non-coding RNAs, circulating tumor cells (CTCs), and exosomes molecular contents 10. MicroRNAs (miRs) are small (~22 nucleotides) non-coding RNAs that have gene regulatory roles via targeting the 3′-untranslated region (3′-UTR) of their target mRNA and finally cause either translational repression or mRNA degradation 11,12. Up to now, a number of biomarkers have been introduced as PC biomarkers such CEA, CA19-9, CA125 and CA72-4. Nonetheless, none of these tumor markers has shown efficient sensitivity or specificity for diagnosing PC at primary stages and have been used for post resection monitoring rather than earlier detection purposes. MiRNAs seem to be truly stable in blood and several authors reported that miRNAs show dysregulation in pancreatic diseases being able to differentiate PC from pancreatitis, pancreatic benign masses as well as normal subjects 13. Furthermore, owing to advanced technologies in high-throughput molecular methods the understanding of the pathophysiology of pancreatic cancer have been improved. Various genome-wide mRNA and miRNA expression profiling studies using microarray-based and NGS approaches have provided important insights into the phenotypic characteristics of pancreatic cancer 14. In this study, using multiple bioinformatics tools, we integrated various serum expression profiles of miRNAs to find the most significant potential miRNA signatures helpful in the diagnosis of PC and constructed a novel miRNA-mRNA regulatory network in PC using bioinformatics approaches. Next, we investigated the molecular mechanisms downstream of the captured miRNA signatures and their predicted target genes correlated to PC progression and analyzed them in a logistic model. Material and method Microarray datasets search. In order to find proper miRNA expression profiles in microarray datasets, we conducted a systematic search in Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/ geo/) 15. Using the keywords "Pancreatic cancer" and "Serum", at the first step we reached 900 datasets. Then, we limited the results using 'Homo sapiens' and 'Non-coding RNA profiling by array' filters, so we reached to 16 datasets. Finally, by setting the sample count on more than 200 samples, 4 final datasets were achieved. Differentially expressed miRNAs (DEMs) detection. The DEMs were obtained using the online tool GEO2R in the GEO database 15 , which makes evaluations using the GEOquery and limma R packages from the Bioconductor project to compare two or more groups of samples in a GEO dataset. Normalization has been carried out using the RMA algorithm. To ke...

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The high prevalence of antibiotic resistance in Helicobacter pylori has become a great challenge in Iran. The genetic mutations that contribute to the resistance have yet to be precisely identified. This study aimed to investigate the prevalence of antibiotic resistance and virulence markers in Iranian H. pylori isolates and to analyze if there is any association between resistance and genotype. Antibiotic susceptibility patterns of 68 H. pylori isolates were investigated against metronidazole, clarithromycin, amoxicillin, rifampicin, ciprofloxacin, levofloxacin, and tetracycline by the agar dilution method. The frxA, rdxA, gyrA, gyrB, and 23S rRNA genes of the isolates were sequenced. The virulence genotypes were also determined using PCR. Metronidazole resistance was present in 82.4% of the isolates, followed by clarithromycin (33.8%), ciprofloxacin (33.8%), rifampicin (32.4%), amoxicillin (30.9%), levofloxacin (27.9%), and tetracycline (4.4%). Overall, 75% of the isolates were resistant to at least two antibiotics tested and considered as a multidrug resistance (MDR) phenotype. Most of the metronidazole-resistant isolates carried frameshift mutations in both frxA and rdxA genes, and premature termination occurred in positions Q5Stop and Q50Stop, respectively. Amino acid substitutions M191I, G208E, and V199A were predominantly found in gyrA gene of fluoroquinolone-resistant isolates. A2143G and C2195T mutations of 23S rRNA were found in four clarithromycin-resistant isolates. Interestingly, significant associations were found between resistance to metronidazole (MNZ) and cagA-, sabA-, and dupA-positive genotypes, with p = 0.0002, p = 0.0001, and p = 0.0001, respectively. Furthermore, a significant association was found between oipA “on” status and resistance to amoxicillin (AMX) (p = 0.02). The prevalence of H. pylori antibiotic resistance is high in our region, particularly that of metronidazole, clarithromycin, ciprofloxacin, and MDR. Simultaneous screening of virulence and resistance genotypes can help clinicians to choose the appropriate therapeutic regime against H. pylori infection.

Colorectal cancer (CRC) is a worldwide health concern which requires efficient therapeutic strategies. The mechanisms underlying CRC remain an essential subject of investigations in the cancer biology field. The evaluation of human microbiota can be critical in this regard, since the disruption of the normal community of gut bacteria is an important issue in the development of CRC. However, several studies have already evaluated the different aspects of the association between microbiota and CRC. The current study aimed at reviewing and summarizing most of the studies on the modifications of gut bacteria detected in stool and tissue samples of CRC cases. In addition, the importance of metabolites derived from gut bacteria, their relationship with the microbiota, and epigenetic modifications have been evaluated.

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Background and Aims: chronic HBV infection is one of the most common viral infections in worldwide which many factors such as genetic factors are involved in pathogenesis of disease. Gamma interferon (IFN-γ) and its receptor (INFGR) play a critical role in the immune response to HBV infection. Single nucleotide polymorphisms (SNPs) are effective on level of gene expression, The aim of this study is explore the effect of -56T/C(SNP) located in promoter of gamma interferon receptor1 (INFGR1)gene on chronic HBV infection. Methods: Genomic DNA from peripheral blood samples of 150 chronically HBV infected patients and 150 healthy controls was extracted by phenol-chloroform method and DNA analysis and genotyping was performed by PCR-RFLP method. Results: According to obtained genotyping and also statistical analysis, it was observed that between the patients and control group a significant difference existed and the genotypes of TC and CC were high in control group compared to the patients group. Conclusion: The host genetic factors can plays an important role in pathogenesis of HBV infection, Genetic variations in INFGR1 was related to several diseases, in this study we surveyed association between -56T/C (SNP) in INFGR1 and chronic HBV infection, the results of our study showed that presence of C and TC alleles in our population is related to decrease risk susceptibility to chronic infection.