Background: Gastric cancer (GC) is the second most common malignancy and the leading cause of death in Iran. . According to global statistics, these figures are highly worrying highlighting the importance of studies in this field. Given that the role of chronic inflammation in the development of cancer, especially infection-related cancers, such as GC, has been revealed for many years, evaluating the molecules involved in these processes can be helpful. Toll-like-receptors (TLRs) as the greatest family of receptors for inflammation-associated molecular Patterns, and the effect of mutations in TLR2 and TLR4 on the pathology of GC has been identified. Considering the results of previous studies and the major role of TLR2 and TLR4 in inflammatory processes of premalignancy, in this study, the mutation in the sequence of these genes and its association with GC have been investigated in both laboratory and bioinformatics stages. Materials and Methods: In this study, 30 Helicobacter pylori-positive GC samples were collected and after DNA extraction using Sanger sequencing methods, and subsequently, variant pathogenicity predictions, such as SIFT and PolyPhen, mutation pathogenicity was predicted. Following that, PyMOL was applied to model 3D structures of the wild and mutated receptor. Results: Sanger sequencing data showed a heterozygous mutation in exon 3 of TLR4 c. 1061A>G. The modeling crystal structure of the human receptor and LPS complex showed that the variant was far from the TLR4 binding sites with its ligand. Conclusion: The results of this study indicated that mutations in two important genes of the Pattern recognition system in Iranian cancer samples have no functional relevance with these two proteins.

Background: Rheumatoid arthritis (RA) is a chronic, systematic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints and it is a common rheumatic disease with many subtypes. Nuclear Magnetic resonance (1H NMR) spectrometers with high sensitivity, resolution and dynamic range has permitted the rapid, simultaneous investigation of complex mixtures of endogenous or exogenous components present in biological materials. Metabonomics is the systematic study of chemical finger print resulted from cell reactions and could be used as a new biomarker for early disease diagnosis. In the present investigation, we studied serum metabolic profile in rheumatoid arthritis (RA) in order to find out the metabolic finger print Pattern of the disease.Materials and methods: In our metabonomics study serum samples were collected from 16 patients with active RA, and from equal number of healthy subjects. They were evaluated during a one-year follow-up with the assessment of disease activity and 1H NMR spectroscopy of sera samples. In all the cases, the presence of active rheumatoid arthritis was shown by an increase in the T1 values of the synovium of the joints. We specified and classified all metabolites using PCA, PLSDA chemometrics methods. Chenomx (Trail Version) and ProMetab codes in Matlab software environments were used for our data analysis. Results were compared with the NMR metabolite data bank (www.metabolomics.ca). Anti-CCP, ANA and urea were also analyzed by ElISA and colorimetric methods respectively.Results: The most changes identified in this study were in the biosynthesis pathways of steroid hormones, biotin, fatty acids, amino acids (Leucine, Valin and isoleucine) and also linoleic acid.Conclusion: In rheumatoid arthritis disease, the activation of the immune system consumes larg amounts of energy. The main donor of free energy in cells is ATP, which is generated by both glycolysis and oxidative phosphorylation. Changes in amino acids and free fatty acids biosynthesis pathways confirm the high energy utilization. In this disease, the increase in free fatty acid metabolism leads to production of Acetyl CoA and ketone bodies. Since there are many diseases subtype in rheumatoid arthritis, more sensitive diagnostic method is required. The result of our investigation suggests that metabolome profiling method could be used as a new biomarker for early diagnosis of rheumatoid arthritis disease.

Introduction: Coronavirus infectious disease 2019 (COVID-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pathogenassociated molecular Patterns (PAMPs) can be detected by host Pattern-recognition receptors (PRRs) expressed in inherent immune cells. The polymorphisms in PRRs leads to different recognizing and immune responses against viral infections. Methods: Single-nucleotide polymorphisms of PRRs, minor allele frequency (MAF), and their geographical distribution were obtained from the Ensembl genome database. Interaction between the common polymorphic forms of PRRs (including TLR3, TLR7, RIG-1, and MDA-5) and SARS-CoV-2 virus genome (dsRNA) were predicted using the hybrid protein-RNA docking algorithm HDOCK server. Also, the global distribution of common SNPs and their MAFs were statistically analyzed using SPSS, ver. 16. Results: The wild-type TLR3 and TLR3 SNP rs73873710 had the same docking energy score (-330. 48 kcal/mol), and had lower docking energy scores compared to the other two SNPs, rs3775290 and rs3775291 (-301. 42 and-295. 81 kcal/mol, respectively). TLR7 SNP rs179008 had a higher docking energy score (-423. 03 kcal/mol), comparing to the wild-type TLR7 (-445. 46 kcal/mol). Also, there was a statistically significant direct relationship between MAF of TLR3 SNP rs3775290 and rs3775291 with SARS-CoV-2 prevalence (P=0. 021 and P=0. 023, respectively) and prevalence/population ratio of COVID-19 (P=0. 026 and P<0. 001, respectably). Conclusion: Wild-type TLR3 and TLR3 SNP rs73873710 can recognize the SARSCoV-2 dsRNA genome through a better performance compared to TLR3 SNP rs3775290 and TLR3 SNP rs3775291. Therefore, our in-silico study established that PRRs SNPs are associated with antiviral responses against SARS-CoV-2.

one of the most common and most critical mortality causes in modern society is gastrointestinal (GI) cancer. Helicobacter pylori is one of the most potent risk factors of gastric cancer. This bacterium can suppress the immune system by various pathogenic factors and mechanisms, lead to chronic inflammatory responses, and play a critical role in the induction of cancer. The first part of this article begins with a description of H. pylori carcinogenicity and in the next part, the roles of innate immunity Pattern recognition receptors (PRRs), Toll-like receptors (TLRs), cytokines, and inflammatory regulatory mechanisms in H. pylori infection are discussed. According to our current knowledge, screening and on-time diagnosis of the disease, timely treatment, and immediate eradication of H. pylori are the most critical ways to barricade gastric cancer progression. In the end, it is suggested that, considering the expensive costs of gastric cancer treatment, H. pylori diagnostic screening tests be done at least annually in middle-aged and at-risk people.

Background: Irritable bowel syndrome is a functional gastrointestinal disease of unknown etiology. Researchers have recently drawn attention to the possible role of viruses in the development of IBS and provided evidence in this regard. In this study, it was decided to investigate the possible role of rotavirus infection in the onset of IBS.Methods: Stool and serum samples were collected from 40 patients with IBS and 40 healthy individuals. To evaluate the previous exposure to rotavirus we checked the presence and concentration of anti-rotavirus IgG by ELISA. ELISA test was performed on the serum samples. Real-time PCR test was also used to measure the viral load in the stool. Finally, the data were analyzed by SPSS-22 software.Results: No significant relationship was found between anti-rotavirus IgG presence and Level in the serum of case and healthy individuals (p-value > 0.05) . Moreover, there was no significant difference between the viral genome load in the stool samples of the two groups (p-value > 0.05).Conclusion: According to the results, it seems unlikely that a link exists between rotavirus infection and the onset of irritable bowel syndrome, but the possible role of other gastrointestinal viruses, including coronavirus, remains.