In silico prediction discontinuous B cell epitope peptide vaccine against leishmaniasis

Introduction: The kinetoplastid protozoan parasites of the genus Leishmania cause diseases for which treatment is difficult and there is still no vaccine for use in humans. Leishmanolysin is the major enzymatic protein component of the promastigote surface. Because of its role as a ligand involved in the interaction of the parasite with defensive systems of the host, including components of the complement system and the macrophage surface is an attractive candidate for designing peptide vaccines.  Methods and Results: In the current study, PEPOP was used to predict peptides from Leishmanolysin in the form of discontinuous B-cell epitopes. PEPOP identified segments comprised of accessible and sequence continuous amino acids. These segments were clustered according to their spatial distances using method of extensions: Optimized Nearest Neighbor (ONN), Optimized Flanking Nearest Neighbor (OFN), Optimized Patched segments Path (OPP), Traveling Salesman Problem (TSP), and Shortest Path (SHP). Each peptide sequence has been generally comprised of several segments. From 3D structure of Leishmanolysin, PEPOP identified 100 segments gathered in three clusters according to their spatial distances. In this study, we wanted to predict peptides from a specific region of the protein, the residue 264-345 on the active site of Leishmanolysin. It corresponds to the segments S34 to S48. The predicted peptides, which did not relate to this region (264-345) were removed and at last 29 peptides were selected. Conclusions: These results using bioinformatics analyses could be conducted in vaccine design against Leishmania infections

The effect of nisin on biofilm-forming and pathogenic bacteria using micro titer plate method

چکیده: زمینه و هدف: بعضی از باکتریهای پاتوژن و فاسد کننده مواد غذایی قادر می‌باشند به سطوح در تماس با مواد غذایی متصل شده و تشکیل بیوفیلم ‌دهند، از این جهت به ‌عنوان منبع آلودگی محصولات غذایی و انتقال بیماری ها در نظر گرفته می‌شوند. نیزین، باکتریوسین پپتیدی می‌باشد که برای کنترل بیولوژیکی بیوفیلم های میکروبی استفاده می‌گردد. همچنین امروزه نیزین در ادغام با مواد بسته‌بندی، مواد غذایی را از خطر فساد و ورود عوامل بیماریزا محافظت می‌کند. هدف از این مطالعه بررسی اثر غلظت های مختلف نیزین بر روی برخی از باکتریهای بیماریزای غذایی بوده است. روش بررسی: در این تحقیق تجربی اثرات غلظت های مختلف نیزین بر باکتریهای تشکیل‌دهنده بیوفیلم و بیماریزای Staphylococcus aureus، Listeria monocytogenes و Salmonella enteritidis با روش میکروتیترپلیت بررسی شد. میزان کاهش سلول های تشکیل‌دهنده بیوفیلم با استفاده از دستگاه الیزا ریدر و میزان کشته‌ شدن سلول ها با به‌کاربردن رنگ TTC (Triphenyl Tetrazolium Chloride) تعیین شد. داده ها با استفاده از آزمون های آنالیز واریانس و آزمون مقایسه ای Kramer-Tukey و به کمک نرم افزار Minitab تجزیه و تحلیل شد. یافته‌ها: نتایج نشان داد نیزین در غلظتی که مصرف آن مجاز است (IU/ml103´4)، بر بیوفیلم S. enteritidis نسبت به بیوفیلم باکتری های L. monocytogenes و Staph. aureus به ترتیب با 87، 57 و 30 درصد موثرتر می‌باشد (05/0

Identification of B and T cell epitope peptide vaccines from IGF-1 Receptor in breast cancer

Introduction: The insulin-like growth factor-1 receptor (IGF-1R) plays a key role in proliferation, growth, differentiation, and development of several human malignancies including breast and pancreatic adenocarcinoma. IGF-1R targeted immunotherapeutic approaches are particularly attractive, as they may potentially elicit even stronger antitumor responses than traditional targeted approaches. Cancer peptide vaccines can produce immunologic responses against cancer cells by triggering helper T cell (Th) or cytotoxic T cells (CTL) in association with Major Histocompatibility Complex (MHC) class I or II molecules on the cell surface of antigen presenting cells.  Methods and Results: In our previous study, we set a technique based on molecular docking in order to find the best MHC class I and II binder peptides using GOLD. In the present work, molecular docking analyses on a library consisting of 30 peptides mimicking discontinuous epitopes from IGF-1R extracellular domain identified peptides 249 and 86, as the best MHC binder peptides to both MHC class I and II molecules. The receptors most often targeted by peptide 249 are HLA-DR4, HLA-DR3 and HLA-DR2 and those most often targeted by peptide 86 are HLA-DR4, HLA-DP2 , and HLA-DR3. Conclusions: These findings, based on bioinformatics analyses, can be conducted in further experimental analyses in cancer therapy and vaccine design

Expression of Toll-Like receptors in metabolic syndrome: A systematic review

Introduction: Toll-Like Receptors (TLRs) of innate immune system have documented roles in the pathogenesis of metabolic disorders. This study aims to systematically review the expression of TLRs on metabolic syndrome (MetS). Materials and methods: We systematically searched PubMed/Medline, ISI web of Science, Scopus, Google Scholar, EMBASE, and OVID databases until February 2017. The terms ‘‘Metabolic Syndrome’’ OR ‘‘Mets’’ AND ‘‘Toll like receptor’’ OR ‘‘Toll like’’ OR ‘‘TLRs’’ OR ‘‘TLR’’ were used. “Expression” advertently was not used in our search and was considered in the selection process. Three steps for selecting the articles and then their qualification were conducted. Results: First, 1373 articles were found in the international databases. After removing duplicates, 963 papers remained and after two steps of selection, this number reached 410 and then 27, respectively. After full text screening and qualifying processes, we finally included 13 articles consisting of five animal and eight human studies. All human studies reported overexpression of TLRs (types 2, 4, 5, 9) in MetS, and most animal studies documented an increased TLRs expression. Conclusion: This systematic review provides evidence for the relation of innate immune system with MetS. Its findings regarding overexpression of special TLRs (e.g. types 2, 4, 5, 9) in MetS and their basic mechanisms and clinical implications might be investigated in further studies

Preventing Colorectal Cancer through Prebiotics

Colorectal cancer (CRC), the third most common cancer in the world, has been recently rising in emerging countries due to environmental and lifestyle factors. Many of these factors are brought up by industrialization, which includes lack of physical activity, poor diet, circadian rhythm disruption, and increase in alcohol consumption. They can increase the risk of CRC by changing the colonic environment and by altering gut microbiota composition, a state referred to as gut dysbiosis. Prebiotics, which are nutrients that can help maintain intestinal microbial homeostasis and mitigate dysbiosis, could be beneficial in preventing inflammation and CRC. These nutrients can hinder the effects of dysbiosis by encouraging the growth of beneficial bacteria involved in short-chain fatty acids (SCFA) production, anti-inflammatory immunity, maintenance of the intestinal epithelial barrier, pro-apoptotic mechanisms, and other cellular mechanisms. This review aims to summarize recent reports about the implication of prebiotics, and probable mechanisms, in the prevention and treatment of CRC. Various experimental studies, specifically in gut microbiome, have effectively demonstrated the protective effect of prebiotics in the progress of CRC. Hence, comprehensive knowledge is urgent to understand the clinical applications of prebiotics in the prevention or treatment of CRC

In silico analysis of A novel pathogenic variant in an Iranian Mucopolysaccharidosis IIIB patient identified by targeted next-generation sequencing

Mucopolysaccharidosis IIIB (MPS IIIB) (Sanfilippo Syndrome Type B; OMIM 252920) is an autosomal recessive metabolic disorder caused by mutations in the NAGLU gene which encode for lysosomal enzyme N-acetyl-glucosaminidase, involved in degradation of complex polysaccharide, heparan sulfate. The disease characterized by progressive cognitive decline and behavioral difficulties and motor function retardation. In this study, using targeted exome sequencing, we identified a novel heterozygote deletion variant (c.1294-1304 del CTCTTCCCCAA, p.432LeufsX25) in the NAGLU gene in consanguineous parent of a child who was dying in her 14 years old where the diagnosis of death was Mucopolysaccharidosis. Sanger sequencing was used to confirm the candidate pathogenic variants in extended family members and segregation analysis. Computational docking using the Molegro Virtual Docker (MVD) 6.0.1 software confirmed different affinity binding of truncated protein for its ligand-Acetyl-D-Glucosamine. Moreover, with I-TASSER software functional alterations between wild and mutant proteins evaluated. The variant was classified as pathogenic based on the American College of Medical Genetics and Genomics guideline. This study expands the spectrum of NAGLU pathogenic variants and confirms the utility of targeted NGS sequencing in genetic diagnosis and also the utility and power of additional family information

Association of Polymorphism in Fatty Acid Desaturase Gene with the Risk of Type 2 Diabetes in Iranian Population

Background: The type 2 diabetes is one of the most common autoimmune diseases. Due to a key role in the metabolism of unsaturated fatty acids such as arachidonic acid, one of the most important precursors of immunity mediators, fatty acid desaturase (FADS) genes could have an important impact in the development of type 2 diabetes. Materials and Methods: This study aimed to determine the relationship between polymorphisms rs174537 in FADS1 gene and rs174575 in FADS2 gene with type 2 diabetes in Iranian population. After extracting genomic DNA, the locations of mutations and allele types were identified with high-resolution melting (HRM)-polymerase chain reaction method. Then, association between these mutations with metabolic syndrome, dyslipidemia, and type 2 diabetes was investigated using χ2 correlation coefficients for variables and logistic regression. Results: The results showed that among 50 diabetic participants, 68% of patients have the mutant allele for rs174537 in FADS1 gene. This rate is 26% for rs174575 in FADS2 gene. Based on the results, it seems that participants having rs174537 mutant allele are more prone to become diabetic but it has a beneficial effect on total and low-density lipoprotein cholesterol and participants having rs174575 mutant are less prone to become diabetic, and also, it leads to higher triglycerides and body mass index (obesity). Conclusions: Detecting FADS1 and FADS2, gene polymorphisms using HRM can be an anticipating tool for making decision on initiating lifestyle modifications to prevent type 2 diabetes