Microbiome and Schizophrenia 2 2 Schizophrenia is a debilitating psychiatric disorder that contributes to a large cascade of emotional, occupational, and cognitive impairments. Treatment involves combination of psychosocial rehabilitation and pharmacotherapy. In most cases, chronic antipsychotic therapy is required to treat symptoms, avoid relapse and attenuate episode recurrence 1-3. Despite the growing number of pharmacologic agents for the treatment of schizophrenia, many patients do not adequately benefit from or tolerate currently available antipsychotics 1-3. Existing typical and atypical antipsychotic medications are relatively equally effective in treating what are known as the positive symptoms of schizophrenia. What has been prominently lacking, however, is an agent that also treats the negative symptoms as well as substantial cognitive impairment 1-3. Despite growing numbers of antipsychotic drugs for the treatment of schizophrenia, the management of this disorder remains to be a major challenge. Therefore, there is a need to find new strategies to improve treatment plans for schizophrenia patients. New studies have found that people with schizophrenia have differences in their gut biomes compared to people without the mental disorder 4,5. The researchers found a smaller subset of bacteria that were clearly different between schizophrenia patients and those without the disorder. They report that when they introduced samples of the subset from the schizophrenia patients into the biomes of healthy mice, the mice displayed behavior changes 6,7. The researchers claim that their results show that people with schizophrenia have differences in their gut biomes and that those differences may be associated with schizophrenia symptoms. They suggest that certain bacteria in the biome may be associated with schizophrenia-related symptoms due to interactions with microbiota gut-brain amino acids, and possibly lipid metabolic pathways. In conclusion, researchers have started to find interesting links between the naturally occurring bacteria that live in our guts, and things we’ve traditionally attributed to the brain. Things like our mood, feelings, and even thoughts 8.  269 269 Shahin Akhondzadeh Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences Iran Editorial 20402.pdf Akhondzadeh S. The 5-HT hypothesis of schizophrenia. IDrugs 2001;4(3):295-300. ##Abbasi SH, Behpournia H, Ghoreshi A, Salehi B, Raznahan M, Rezazadeh SA, et al. The effect of mirtazapine add on therapy to risperidone in the treatment of schizophrenia: a double-blind randomized placebo-controlled trial. Schizophr Res 2010;116(2-3):101-106. ##Ghajar A, Gholamian F, Tabatabei-Motlagh M, Afarideh M, Rezaei F, Ghazizadeh-Hashemi M, et al. Citicoline (CDP-choline) add-on therapy to risperidone for treatment of negative symptoms in patients with stable schizophrenia: A double-blind, randomized placebo-controlled trial. Hum Psychopharmacol 2018;33(4):e2662. ##Severance EG, Yolken RH. From infection to the microbiome: An evolving role of microbes in schizophrenia. Curr Top Behav Neurosci 2019. ##Zheng P, Zeng B, Liu M, Chen J, Pan J, Han Y, et al. The gut microbiome from patients with schizophrenia modulates the glutamate-glutamine-GABA cycle and schizophrenia-relevant behaviors in mice. Sci Adv 2019;5(2):eaau8317. ##Dinan TG, Cryan JF. Schizophrenia and the microbiome: Time to focus on the impact of antipsychotic treatment on the gut microbiota. World J Biol Psychiatry 2018;19(8):568-570. ##Cuomo A, Maina G, Rosso G, Beccarini Crescenzi B, Bolognesi S, Di Muro A, et al. The microbiome: A new target for research and treatment of schizophrenia and its resistant presentations? A systematic literature search and review. Front Pharmacol 2018;9:1040. ##Dickerson F, Severance E, Yolken R. The microbiome, immunity, and schizophrenia and bipolar disorder. Brain Behav Immun 2017;62:46-52. ##

Sortilin as a Novel Diagnostic and Therapeutic Biomarker in Chronic Lymphocytic Leukemia 2 2 Background: The overexpression of sortilin/neurotensin receptor 3 has previously been reported in various human solid tumors but not in hematological malignancies. Here, we report the overexpression of sortilin in leukemic cells from patients with Chronic Lymphocytic Leukemia (CLL). Methods: Flow cytometry was used to compare the expression of sortilin in CLL pa-tients (n=52) and healthy individuals (n=26). Also, in vitro apoptosis induction was assessed in CLL Peripheral Blood Mononuclear Cell (PBMCs) following directly targeting of sortilin. Results: The results showed a significant expression of sortilin on the surface of CLL PBMCs (range from 2.2 to 71.5%) in comparison to healthy individuals (range from 0.03 to 7.4%) (p≤0.0001). The optimal cut-off value of sortilin expression was deter-mined at 7.2% with high sensitivity and specificity. Treatment of leukemic cells with anti-sortilin antibody could induce apoptosis without any effect on normal cells. Conclusion: Apoptosis induction in CLL cells together with a significant correlation between the expression of sortilin and CD23 represent a possible functional role of sortilin in leukemogenesis of CLL cells. Therefore, sortilin might be considered as a promising novel biomarker in diagnosis, monitoring, and therapy of patients with CLL. 270 276 Lia Farahi Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Iran Fatemeh Ghaemimanesh Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Iran Saeideh Milani Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Iran Seyed Mohsen Razavi Clinic of Hematology and Oncology, Firoozgar Hospital, Faculty of Medicine, Iran University of Medical Sciences Clinic of Hematology and Oncology, Firoozgar Hospital, Faculty of Medicine, Iran University of Medical Sciences Iran Mohammad Mehdi Akhondi Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Iran Hodjattallah Rabbani Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Iran ApoptosisBiomarkerChronic lymphocytic leukemiaMonoclonal antibodySortilin 10387.pdf Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Dohner H, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the international workshop on chronic lymphocytic leukemia updating the national cancer institute-working group 1996 guidelines. Blood 2008;111(12):5446-5456.##Admoni-Elisha L, Nakdimon I, Shteinfer A, Prezma T, Arif T, Arbel N, et al. Novel biomarker proteins in chronic lymphocytic leukemia: impact on diagnosis, pro-gnosis and treatment. PLoS One 2016;11(4):e0148500.##Akil H, Perraud A, Mélin C, Jauberteau MO, Mathonnet M. Fine-tuning roles of endogenous brain-derived neuro-trophic factor, TrkB and sortilin in colorectal cancer cell survival. PLoS One 2011;6(9):e25097.##Devader C, Roulot M, Moreno S, Minelli A, Bortolomasi M, Congiu C, et al. Serum sortilin-derived propeptides concentrations are decreased in major depressive dis-order patients. J Affect Disord 2017;208:443-447.##Roselli S, Pundavela J, Demont Y, Faulkner S, Keene S, Attia J, et al. Sortilin is associated with breast cancer aggressiveness and contributes to tumor cell adhesion and invasion. Oncotarget 2015;6(12):10473-10486.##Mazella J, Zsurger N, Navarro V, Chabry J, Kaghad M, Caput D, et al. The 100-kDa neurotensin receptor is gp95/sortilin, a non-G-protein-coupled receptor. J Biol Chem 1998;273(41):26273-26276.##Morinville A, Martin S, Lavallee M, Vincent JP, Beaudet A, Mazella J. Internalization and trafficking of neuro-tensin via NTS3 receptors in HT29 cells. Int J Biochem Cell Biol 2004;36(11):2153-2168.##Nykjaer A, Lee R, Teng KK, Jansen P, Madsen P, Nielsen MS, et al. Sortilin is essential for proNGF-induced neuronal cell death. Nature 2004;427(6977):843-848.##Tanimoto R, Morcavallo A, Terracciano M, Xu SQ, Stefanello M, Buraschi S, et al. Sortilin regulates pro-granulin action in castration-resistant prostate cancer cells. Endocrinology 2015;156(1):58-70.##Al-Akhrass H, Naves T, Vincent F, Magnaudeix A, Durand K, Bertin F, et al. Sortilin limits EGFR signaling by promoting its internalization in lung cancer. Nat Commun 2017;8(1):1182.##Truzzi F, Marconi A, Lotti R, Dallaglio K, French LE, Hempstead BL, et al. Neurotrophins and their receptors stimulate melanoma cell proliferation and migration. J Invest Dermatol 2008;128(8):2031-2040.##Ghaemimanesh F, Bayat AA, Babaei S, Ahmadian G, Zarnani AH, Behmanesh M, et al. Production and characterization of a novel monoclonal antibody against human sortilin. Monoclon Antib Immunodiagn Immunother 2015;34(6):390-395.##Ghaemimanesh F, Ahmadian G, Talebi S, Zarnani AH, Behmanesh M, Hemmati S, et al. The effect of sortilin silencing on ovarian carcinoma cells. Avicenna J Med Biotechnol 2014;6(3):169-177.##Ferrante A, Thong YH. Optimal conditions for simu-ltaneous purification of mononuclear and polymorph-onuclear leucocytes from human blood by the Hypaque-Ficoll method. J Immunol Methods 1980;36(2):109-117.##Pasha RP, Roohi A, Shokri F. Establishment of human heterohybridoma and lymphoblastoid cell lines specific for the Rh D and C antigens. Transfus Med 2003;13(2):83-92.##Farahi L, Ghaemimanesh F, Milani S, Razavi S, Hadavi R, Bayat A, et al. GPI-anchored fibromodulin as a novel target for chronic lymphocytic leukemia, diagnostic and therapeutic implications. Iran J Immunol 2019;16(2):127-141.##Amini N, Bayat AA, Zarei O, Hadavi R, Mahmoudian J, Mahmoudi AR, et al. A novel monoclonal antibody against a synthetic peptide from beta-actin can react with its corresponding protein. Protein Pept Lett 2015;22(5):419-424.##Fauchais AL, Lalloue F, Lise MC, Boumediene A, Preud'homme JL, Vidal E, et al. Role of endogenous brain-derived neurotrophic factor and sortilin in B cell survival. J Immunol 2008;181(5):3027-3038.##Mikaelsson E, Osterborg A, Jeddi-Tehrani M, Kokhaei P, Ostadkarampour M, Hadavi R, et al. A proline/arginine-rich end leucine-rich repeat protein (PRELP) variant is uniquely expressed in chronic lymphocytic leukemia cells. PLoS One 2013;8(6):e67601.##Fournier S, Yang LP, Delespesse G, Rubio M, Biron G, Sarfati M. The two CD23 isoforms display differential regulation in chronic lymphocytic leukaemia. Br J Haematol 1995;89(2):373-379.##Garcia DP, Rooney MT, Ahmad E, Davis BH. Diag-nostic usefulness of CD23 and FMC-7 antigen expres-sion patterns in B-cell lymphoma classification. Am J Clin Pathol 2001;115(2):258-265.##Wilson CM, Naves T, Vincent F, Melloni B, Bonnaud F, Lalloue F, et al. Sortilin mediates the release and transfer of exosomes in concert with two tyrosine kinase receptors. J Cell Sci 2014;127(Pt 18):3983-3997.##Beraud-Dufour S, Devader C, Massa F, Roulot M, Coppola T, Mazella J. Focal adhesion kinase-dependent role of the soluble form of neurotensin receptor-3/sortilin in colorectal cancer cell dissociation. Int J Mol Sci 2016;17(11). pii: E1860.##Faulkner S, Jobling P, Rowe CW, Rodrigues Oliveira SM, Roselli S, Thorne RF, et al. Neurotrophin receptors TrkA, p75(NTR), and sortilin are increased and targetable in thyroid cancer. Am J Pathol 2018;188(1):229-241.##Ludwig DL, Pereira DS, Zhu Z, Hicklin DJ, Bohlen P. Monoclonal antibody therapeutics and apoptosis. Oncogene 2003;22(56):9097-9106.##Martin S, Navarro V, Vincent JP, Mazella J. Neurotensin receptor-1 and -3 complex modulates the cellular signaling of neurotensin in the HT29 cell line. Gastro-enterology 2002;123(4):1135-1143.##Dal Farra C, Sarret P, Navarro V, Botto JM, Mazella J, Vincent JP. Involvement of the neurotensin receptor subtype NTR3 in the growth effect of neurotensin on cancer cell lines. Int J Cancer 2001;92(4):503-509.##Robak T, Warzocha K, Govind Babu K, Kulyaba Y, Kuliczkowski K, Abdulkadyrov K, et al. Ofatumumab plus fludarabine and cyclophosphamide in relapsed chronic lymphocytic leukemia: results from the COMPLEMENT 2 trial. Leuk Lymphoma 2017;58(5): 1084-1093.##Robak T, Blonski JZ, Robak P. Antibody therapy alone and in combination with targeted drugs in chronic lym-phocytic leukemia. Semin Oncol 2016;43(2):280-290.##

Design and Fabrication of a Novel Microfluidic System for Enrichment of Circulating Tumor Cells with the Assistance of Computer Simulations 2 2 Background: Cancer is the first cause of death in developed countries. The heteroge-neous nature of cancer requires patient-specified treatment plans. One reliable ap-proach is collecting Circulating Tumour Cells (CTCs) and using them for prognosis and drug response assessment purposes. CTCs are rare and their separation from normal cell requires high-accuracy methods. Methods: A microfluidic cell capture device to separate CTCs from peripheral blood is presented in this study. The CTC separation device applies hydrodynamic forces to categorize cells according to their sizes. The proposed device is designed and evaluated by numerical simulations and validated experimentally. The simulation modified design was fabricated by soft lithography which allows prototyping the device in a few hours. For experimental setup two solutions: 1) fixed cells spiked in Phosphate Buffered Saline (PBS), and 2) fixed cells in blood were used. The CTC separation device was validated by tracking the flow and separation of cancer cell lines in the solutions. Results: It is demonstrated that the setup is capable of CTC enrichment up to 50 times. Conclusion: The presented CTC enrichment method reduces costs by eliminating the use of antibodies. The high-throughput method has the potential to be used in pre-clinical studies of cancer. 277 284 Dina Dorrigiv Department of Chemical Engineering, Sharif University of Technology Department of Chemical Engineering, Sharif University of Technology Iran Manouchehr Vossoughi Department of Chemical Engineering, Sharif University of Technology Department of Chemical Engineering, Sharif University of Technology Iran Iran Alemzadeh Department of Chemical Engineering, Sharif University of Technology Department of Chemical Engineering, Sharif University of Technology Iran Circulating tumor cellsComputer simulationMicrofluidicsPrognosis 10396.pdf Top 10 causes of death [Internet]. World Health Organization. 2016. Available from: https://www.who.int /news-room/fact-sheets/detail/the-top-10-causes-of-death##Shamloo A, Ahmad S, Momeni M. Design and parameter study of integrated microfluidic platform for CTC isolation and enquiry; A numerical approach. Biosensors 2018;8(2):8. ##Kozminsky M, Nagrath S. Circulating tumor cells, cancer stem cells, and emerging microfluidic detection technologies with clinical applications. In: Liu H, Lathia JD. Cancer Stem Cells. 1st ed. USA: Academic Press; 2016. p.473-497.##Sequist LV, Nagrath S, Toner M, Haber DA, Lynch TJ The CTC-chip an exciting new tool to detect circulating tumor cells in lung cancer patients. J Thorac Oncol 2009;4(3):281-283. ##Williams SC. Circulating tumor cells. Proc Natl Acad Sci USA 2013;110(13):4861. ##Plaks V, Koopman CD, Werb Z. Circulating tumor cells. Science 2013;341(6151):1186-1188. ##Dong Y, Skelley AM, Merdek KD, Sprott KM, Jiang C, Pierceall WE, et al. Microfluidics and circulating tumor cells. J Mol Diagn 2013;15(2):149-157.##Alix-Panabières C. EPISPOT assay: detection of viable DTCs/CTCs in solid tumor patients. Recent Results Cancer Res 2012;195:69-76. ##Hou HW, Ebrahimi Warkiani M, Khoo BL, Li ZR, Soo RA, Shao-Weng Tan D, et al. Isolation and retrieval of circulating tumor cells using centrifugal forces. Scientific Reports 2013;3(1259).##Autebert J, Coudert B, Bidard FC, Pierga JY, Descroix S, Malaquin L, et al. Microfluidic: an innovative tool for efficient cell sorting. Methods 2012 ;57(3):297-307. ##Di Carlo D, Irimia D, Tompkins RG, Toner M. Continuous inertial focusing, ordering, and separation of particles in microchannels. Proc Natl Acad Sci USA 2007; 104(48):18892-18897. ##Kuntaegowdanahalli SS, Bhagat AA, Kumar G, Papautsky I. Inertial microfluidics for continuous par-ticle separation in spiral microchannels. Lab Chip 2009;9(20):2973-2980. ##Di Carlo D, Edd JF, Humphry KJ, Stone HA, Toner M. Particle segregation and dynamics in confined flows. Phys Rev Lett 2009;102(9):094503.##Moon HS, Kwon K, Kim SI, Han H, Sohn J, Lee S, Jung HI. Continuous separation of breast cancer cells from blood samples using multi-orifice flow fractionation (MOFF) and dielectrophoresis (DEP). Lab Chip 2011; 11(6):1118-1125.##Lee MG, Choi S, Park JK. Rapid laminating mixer using a contraction-expansion array microchannel. Appl Phys Lett 2009;95(051902).##Lee MG, Shin JH, Bae CY, Choi S, Park JK. Label-free cancer cell separation from human whole blood using inertial microfluidics at low shear stress. Anal Chem 2013;85(13):6213-6218. ##Vona G, Sabile A, Louha M, Sitruk V, Romana S, Schütze K, Capron F, et al. Isolation by size of epithelial tumor cells: a new method for the immunomorphological and molecular characterization of circulatingtumor cells. Am J Pathol 2000 ;156(1):57-63. ##Di Carlo D. Inertial microfluidics. Lab Chip 2009;9(21):3038-3046. ##Martel JM, Toner M. Inertial focusing in microfluidics. Annu Rev Biomed Eng. 2014;16:371-396. ##Zhang J, Yan Sh, Yuan D, Alici G, Nguyen NT, Eb-rahimi Warkianic M, et al. Fundamentals and appli-cations of inertial microfluidics: a review. Lab Chip 2016 ;16(1):10-34 ##Warkiani ME, Khoo BL, Wu L, Tay AK, Bhagat AA, Han J, et al. Ultra-fast, label-free isolation of cir-culating tumor cells from blood using spiral microfluidics. Nat Protoc 2016;11(1):134-148. ##Lee MG, Choi S, Park JK. Inertial separation in a contraction–expansion array microchannel. J Chromatogr A 2011;1218(27):4138-4143. ##Lee MG, Choi S, Park JK. Rapid multivortex mixing in an alternately formed contraction-expansion array micro-channel. Biomed Microdevices 2010;12(6):1019-1026. ##Lee MG, Shin JH, Choi S, Park JK. Enhanced blood plasma separation by modulation of inertial lift force. Sensors and Actuators B: Chemical 2014;190:311-317.##Shamsi A, Amiri A, Heydari P, Hajghasem H, Mohta-shamifar M, Esfandiar Mi. Low cost method for hot embossing of microstructures on PMMA by SU-8 masters. Microsystem Technologies 2014;20(10-11):1925-1931.##

Anti-Influenza Virus Activity and Phenolic Content of Pomegranate (Punica granatum L.) Peel Extract and Fractions 2 2 Background: Influenza virus, associated with high level of morbidity and mortality, has been recently considered a public health concern while the choices for the control and treatment of the disease are limited. The present study was conducted to evaluate activity of pomegranate peel extract and its fractions against Influenza A virus in vitro.  Methods: In this research, ethyl alcohol extract of pomegranate peel was prepared and subjected to fractionation with different polarities. The potential in vitro anti-influenza A virus activity of the extract and fractions was assessed using Cytopathic Effect (CPE) reduction assay, Hemagglutinin Assay (HA), and 50% Tissue Culture In-fectious Doses (TCID50) method in Madin-Darby Canine Kidney (MDCK) cells. Results: The crude pomegranate peel extract and its n-butanol and ethyl acetate fractions had the highest inhibitory effect against influenza A virus with IC50 value of 6.45, 6.07 and 5.6 μg/ml in MDCK cells, respectively. Our results also showed that, the production of virus was significantly reduced upon treatment with crude extract, n-butanol and ethyl acetate fractions in a dose-dependent manner (p<0.05). Conclusion: Based on our results, the ethyl alcohol extract and its polar fractions of pomegranate peel can inhibit influenza A virus replication in vitro. Therefore, further characterization of its active ingredients and the mechanism of action should be carried out.  285 291 Mohammad-Taghi Moradi Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences Iran Ali Karimi Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences Iran Mehrdad Shahrani Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences Iran Leila Hashemi Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences Iran Mohammad-saleh Ghaffari-goosheh Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences Iran Antiviral AgentsPomegranatePunica granatum L 10395.pdf Elyatem SM, Kader AA. Post-harvest physiology and storage behaviour of pomegranate fruits. Scientia Horticulturae 1984;24(3):287-298.##Asmaa MJ, Ali AJ, Farid JM, Azman S. Growth inhibitory effects of crude pomegranate peel extract on chronic myeloid leuke-mia, K562 cells. Int J Appl Basic Med Res 2015;5(2):100-105. ##Haber SL, Joy JK, Largent R. Antioxidant and antiatherogenic effects of pomegranate. Am J Health Syst Pharm 2011;68(14):1302-1305. ##Ismail T, Sestili P, Akhtar S. Pomegranate peel and fruit extracts: a review of potential anti-inflammatory and anti-infective ef-fects. J Ethnopharmacol 2012;143(2):397-405. ##Ibrahium MI. Efficiency of pomegranate peel extract as antimicrobial, antioxidant and protective agents. World J Agricultural Sci 2010;6(4):338-344.##Colombo E, Sangiovanni E, Dell'agli M. A review on the anti-inflammatory activity of pomegranate in the gastrointestinal tract. Evid Based Complement Alternat Med 2013;2013:247145. ##Plumb GW, de Pascual-Teresa S, Santos-Buelga C, Rivas-Gonzalo JC, Williamson G. Antioxidant properties of gallocatechin and prodelphinidins from pomegranate peel. Redox Rep 2002;7(1):41-46. ##Lansky EP, Newman RA. Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer. J Ethnopharmacol 2007;109(2):177-206.##Hayden FG. Respiratory viral threats. Curr Opin Infect Dis 2006;19(2):169-178. ##Jackson RJ, Cooper KL, Tappenden P, Rees A, Simpson EL, Read RC, et al. Oseltamivir, zanamivir and amantadine in the prevention of influenza: a systematic review. J Infect 2011;62(1):14-25. ##van der Vries E, Schutten M, Fraaij P, Boucher C, Osterhaus A. Influenza virus resistance to antiviral therapy. Adv Pharmacol 2013;67:217-246. ##Dapat C, Kondo H, Dapat IC, Baranovich T, Suzuki Y, Shobugawa Y, et al. Neuraminidase inhibitor susceptibility profile of pandemic and seasonal influenza viruses during the 2009-2010 and 2010-2011 influenza seasons in Japan. Antiviral Res 2013;99(3):261-269. ##Moradi MT, Karimi A, Alidadi S, Ghasemi-Dehkordi P, Ghaffari-Goosheh MS. Cytotoxicity and in vitro antioxidant potential of Quercus Brantii acorn extract and the corresponding fractions. Int J Pharmacogn Phytochem Res 2016;8(4):558-562.##Folin O, Ciocalteu V. On tyrosine and tryptophane deter-minations in proteins. J Biol Chem 1927;73(2):627-650.##Chang CC, Yang MH, Wen HM, Chern JC. Estimation of total flavonoid content in propolis by two complementary colometric methods. J Food Drug Anal 2002;10(3): 178-182.##Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983;65(1-2):55-63. ##Jang YJ, Achary R, Lee HW, Lee HJ, Lee CK, Han SB, et al. Synthesis and anti-influenza virus activity of 4-oxo- or thioxo-4,5-dihydrofuro[3,4-c]pyridin-3(1H)-ones. Antiviral Res 2014;107:66-75. ##Kim Y, Narayanan S, Chang KO. Inhibition of influenza virus replication by plant-derived isoquercetin. Antiviral Res 2010;88(2):227-235. ##WHO. Manual for the Laboratory Diagnosis and Virological Surveillance of Influenza. Global Influenza Surveillance and Re-sponse System (GISRS) 2011. http:// apps.who.int/iris/bitstream/handle/10665/44518/9789241548090_eng.pdf;jsessionid=06602DB20D114E1880E85A1CF842476B?sequence=1##Matusevich OV, Egorov VV, Gluzdikov IA, Titov MI, Zarubaev VV, Shtro AA, et al. Synthesis and antiviral activity of PB1 component of the influenza A RNA polymerase peptide fragments. Antiviral Res 2015;113:4-10. ##Reed LJ, Muench H. A simple method of estimating fifty per cent endpoints. Am J Epidemiol 1938;27(3):493-497.##Kim ND, Mehta R, Yu W, Neeman I, Livney T, Amichay A, et al. Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica granatum) for human breast cancer. Breast Cancer Res Treat 2002;71(3):203-217. ##Reddy MK, Gupta SK, Jacob MR, Khan SI, Ferreira D. Antioxidant, antimalarial and antimicrobial activities of tannin-rich frac-tions, ellagitannins and phenolic acids from Punica granatum L. Planta Med 2007;73(5):461-467. ##Howell AB, D'Souza DH. The pomegranate: effects on bacteria and viruses that influence human health. Evid Based Comple-ment Alternat Med 2013;2013:606212. ##Haidari M, Ali M, Ward Casscells S, Madjid M. Pomegranate (Punica granatum) purified polyphenol extract inhibits influenza virus and has a synergistic effect with oseltamivir. Phytomedicine 2009;16(12):1127-1136. ##Cos P, Vlietinck AJ, Berghe DV, Maes L. Anti-infective potential of natural products: How to develop a stronger in vitro ‘proof-of-concept’. J Ethnopharmacol 2006;106 (3):290-302. ##Debiaggi M, Tateo F, Pagani L, Luini M, Romero E. Effects of propolis flavonoids on virus infectivity and re-plication. Microbiologica 1990;13(3):207-213. ##

G2 Dendrimer as a Carrier Can Enhance Immune Responses Against HCV-NS3 Protein in BALB/c Mice 2 2 Background: Hepatitis C virus (HCV) infection is a major issue of public health. It seems of paramount importance to find an effective vaccine against HCV infection. The best vaccine candidate should induce robust cellular responses. The aim of the current study was to evaluate immunogenicity effects of novel conjugated dendrimer G2 with the recombinant NS3 antigen as a vaccine candidate for eliciting Th1-oriented cellular responses. Methods: Female BALB/c mice were immunized with different regimes especially with NS3 conjugated with G2 dendrimer. The humoral responses (Total IgG and IgG isotyping) and cellular responses (Ex vivo IFN-γ and IL-4 ELISpot assays, in vitro CTL assay and proliferation) were evaluated and compared in immunized mice. Results: The results indicated that induced specific total IgG in all mice groups im-munized with rNS3 formulated with different adjuvants and IgG2a subclass was the predominant isotype in rNS3-G2 (p≤0.05). For preliminary evaluation of cellular re-sponse, ex vivo ELISpot assay has shown that the higher frequency of IFN-γ producing cells was in groups immunized with rNS3+M720 and rNS3-G2 (p= 0.0012) than control groups. Finally, the rNS3-specific CTLs activity showed the highest percentage of speciﬁc lysis (LDH release) of the target cells in rNS3-G2 and rNS3+M720 groups.  Conclusion: In the present study, as our knowledge, this is first time that the immunogenicity of nanodendrimer G2 as a biocompatible adjuvant with the HCV-NS3 antigen was evaluated. The results showed high capability of the regimen to induce strong Th1-orinted cellular response in mice model, indicating the dendrimer G2 as a novel adjuvant candidate for HCV vaccine studies.  292 298 Foozieh Javadi Department of Hepatitis and AIDS, Pasteur Institute of IranDepratment of Biology, Science and Research Branch, Islamic Azad University Department of Hepatitis and AIDS, Pasteur Institute of IranDepratment of Biology, Science and Research Branch, Islamic Azad University IranIran Pooneh Rahimi Department of Hepatitis and AIDS, Pasteur Institute of Iran Department of Hepatitis and AIDS, Pasteur Institute of Iran Iran Mohammad Hossien Modarresi Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences Iran Azam Bolhassani Department of Hepatitis and AIDS, Pasteur Institute of Iran Department of Hepatitis and AIDS, Pasteur Institute of Iran Iran Mehdi Shafiee-Ardestani Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences Iran Seyed Mehdi Sadat Department of Hepatitis and AIDS, Pasteur Institute of Iran Department of Hepatitis and AIDS, Pasteur Institute of Iran Iran DendrimersHepatitic C virusMiceVaccines 10398.pdf Ashkani-Esfahani S, Alavian SM, Salehi-Marzijarani M. Prevalence of hepatitis C virus infection among hemodialysis patients in the Middle-East: A systematic review and meta-analysis. World J Gastroenterol 2017;7;23(1):151-166.##Hekmat S, Siadat SD, Aghasadeghi MR, Sadat SM, Bahramali G, Mahdavi M, et al. From in-silico immunogenicity veriﬁcation to in vitro expression of recombinant Core-NS3 fusion protein of HCV. Bratisl Lek Listy 2017;118(4):189-195. ##de Oliveria Andrade LJ, D'Oliveira Junior A, Rosangela Carvalho Melo, De Souza EC, Costa Silva CA, Paraná R. Association between hepatitis C and hepatocellular carcinoma. J Glob Infect Dis 2009;1(1):33-37. ##Jakobsen JC, Nielsen EE, Feinberg J, Katakam KK, Fobian K, Hauser G, et al. Direct-acting antivirals for chronic hepatitis C. Cochrane Database Syst Rev 2017;18;9:CD012143. ##Strahotin CS, Babich M. Hepatitis C variability, patterns of resistance, and impact on therapy. Adv Virol 2012;2012:267483. ##Baghbani-arani F, Roohvand F, Aghasadeghi MR, Eidi A, Amini S, Motevalli F, et al. 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Pharm Res 2001;18(3):352-360. ##Khosravy MS, Shafiee Ardestani M, Ahangari Cohan R, Doroud D, Amini S, Momen SB, et al. Design, synthesis, physicochem-ical and immunological characterization of dendrimer-HBsAg conjugate. Vac Res 2014;1(2):24-28. ##Wendorf J, Chesko J, Kazzaz J, Ugozzoli M, Vajdy M, O'Hagan D, et al. A comparison of anionic nanoparticles and microparti-cles as vaccine delivery systems. Hum Vaccin 2008;4(1):44-49. ##Xu Y, Tang H, Liu JH, Wang H, Liu Y. Evaluation of the adjuvant effect of silver nanoparticles both in vitro and in vivo. Toxi-col Lett 2013;219(1):42-48. ##Asgary V, Kord Mafi O, Khosravy MS, Janani AR, Namvar Asl N, Bashar R, et al. Evaluation of the effect of silver nanoparti-cles on induction of neutralizing antibodies against inactivated rabies Virus. Vac Res 2014;1(1):33-34. ##Ardestani MS, Fordoei AS, Abdoli A, Ahangari Cohan R, Bahramali G, Sadat SM, et al. Nanosilver based anionic linear globular dendrimer with a special significant antiretroviral activity. J Mater Sci Mater Med 2015;26(5):179. ##Javadi F, Rahimi R, Modaressi MH, Shafiee Ardestani M, Bolhassani A, Aghasadeghi MR, et al. Synthesis and characterization of physicochemical and immunological properties of recombinant NS3-G2 dendrimer conjugate. Vac Res 2016;2(1 and 2):97-100. ##Nanjwade BK, Bechra HM, Derkar GK, Manvi FV, Nanjwade VK. Dendrimers: emerging polymers for drug-delivery systems. Eur J Pharm Sci 2009;8;38(3):185-196. ##Javadi F, Rahimi P, Modarressi MH, Bolhassani A, Ardestani MS, Sadat SM, et al. Evaluation of truncated HCV-NS3 protein for potential applications in immunization and diagnosis. Clin Lab 2016;1;62(7):1271-1278. ##Sadat SM, Zabihollahi R, Aghasadeghi MR, Vahabpour R, Siadat SD, Memarnejadian A, et al. Application of SCR priming VLP boosting as a novel vaccination strategy against HIV-1. Curr HIV Res 2011;9(3):140-147. ##Torresi J, Johnson D, Wedemeyer H. Progress in the development of preventive and therapeutic vaccines for hepatitis C virus. J Hepatol 2011;54(6):1273-1285. ##Neumann-Haefelin C, Thimme R. Adaptive immune re-sponses in hepatitis C virus infection. Curr Top Microbiol Immunol 2013;369:243-262. ##Verstrepen BE, Verschoor EJ, Fagrouch ZC, Mooij P, de Groot NG, Bontrop RE, et al. Strong vaccine-induced CD8 T-cell re-sponses have cytolytic function in a chimpanzee clearing HCV infection. PLoS One 2014;9(4):e95103. ##Lang Kuhs KA, Ginsberg AA, Yan J, Wiseman RW, Khan AS, Sardesai NY, et al. Hepatitis C virus NS3/NS4A DNA vaccine induces multiepitope T cell responses in rhesus macaques mimicking human immune responses [corrected]. Mol Ther 2012;20(3):669-678. ##Ahlen G, Holmstrom F, Gibbs A, Alheim M, Frelin L. Long-term functional duration of immune responses to HCVNS3/4A in-duced by DNA vaccination. 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A Metabolomic Study to Identify Potential Tissue Biomarkers for Indomethacin-Induced Gastric Ulcer in Rats 2 2 Background: Gastric Ulcer (GU) is the most prevalent gastrointestinal disorder in-duced by various factors and Non-Steroid Anti-Inflammatory Drugs (NSAIDs) as one of the most common reasons. Due to the absence of appropriate molecular markers for GU, the aim of this study was to utilize a metabolomics approach in order to find potential metabolite markers for the disease.  Methods: Stomach tissue samples from indomethacin-treated rats and normal con-trols were used to perform a 1H-NMR metabolomics study. The altered metabolites were identified using random forest multivariate analysis. Results: ROC curves showed that the random forest model had a good predictive performance with AUC of 1 for the test and 0.708 for the training sets. Seventeen differentially expressed metabolites were found between GU and normal tissue sample. These metabolites included trimethylamine, betaine, carnitine, methionine, acetylcho line, choline, N,N-Dimethylglycine, cis-aconitate, tryptophan, spermidine, acetylcar-nitine, creatinine, pantothenate, taurine, isoleucine, glucose and kynurenine. Conclusion: The results of the study demonstrated that metabolomics approach could serve as a viable method to find potential markers for GU. Surely, further studies are needed for the validation of the results. 299 307 Reyhaneh Farrokhi-Yekta Proteomics Research Center, Shahid Beheshti University of Medical Sciences Proteomics Research Center, Shahid Beheshti University of Medical Sciences Iran Nasrin Amiri-Dashatan Proteomics Research Center, Shahid Beheshti University of Medical SciencesStudent Research Committee, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences Proteomics Research Center, Shahid Beheshti University of Medical SciencesStudent Research Committee, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences IranIran Mehdi Koushki Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences Iran Masoomeh Dadpay Department of Pathology, AJA University of Medical Sciences Department of Pathology, AJA University of Medical Sciences Iran Fatemeh Goshadrou Department of Basic Sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences Department of Basic Sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences Iran Gastric ulcerIndomethacin MetabolomicsNuclear magnetic resonance 10390.pdf Sabiu S, Garuba T, Sunmonu T, Ajani E, Sulyman A, Nurain I, et al. 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Menstrual Blood Stem Cell Transplantation in Mice Model of Acute Liver Failure: Does Gender of Recipient Affect the Outcome? 2 2 Background: There exists a dramatic rise in liver failure and numerous patients un-dergo liver transplant for life-saving reasons annually. Introducing alternatives to allograft transplantation is necessary due to present limitations. Recently, a noninvasive stem cell population from Menstrual blood-derived Stem Cells (MenSCs) has been identified. There is an increasing interest in the application of MenSCs in tissue engineering; however, the fact that these gender-specific stem cells are safe for use in male sex is still not well defined. Methods: In this research, a model of acute liver failure was created in male and fe-male immunocompetent Balb-C mice through intraperitoneal injection of Carbon tetrachloride (CCl4) and MenSCs were transplanted intravenously 48 hrs after induc-tion of liver injury to evaluate their therapeutic potential. All mice were sacrificed on days 1, 7, and 30 post-transplantation to examine biochemical and molecular markers and pathological appearances. Results: Results showed the liver engraftment of MenSCs by immunofluorescence staining using anti-human mitochondrial antibody in both male and female treated groups. The restoration of serum markers of liver injury, aspartate aminotransferase and alanine aminotransferase, as well as expression levels of liver-specific genes, tyrosine aminotransferase and cholesterol 7 alpha-hydroxylase, were more significant in the female treated group compared with the male treated group on day 7 (p<0.05); however, after 30 days, there were no significant differences. Furthermore, hematoxylin and eosin and periodic acid-Schiff staining of liver sections demonstrated the considerable liver regeneration post cell therapy in both groups. Notably, data has shown that MenSCs could engraft into injured liver tissues and result in the same effect in the regeneration of liver function in both genders.  Conclusion: Results of this study introduce MenSCs therapy as an attractive alterna-tive approach for liver repairing and regeneration which has no gender constraints. 308 316 Mina Fathi-Kazerooni Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Tehran University of Medical Sciences Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Tehran University of Medical Sciences Iran Gholamreza Tavoosidana Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Tehran University of Medical Sciences Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Tehran University of Medical Sciences Iran GenderFailureRegenerative medicineStem cells 10391.pdf Flores YN, Lang CM, Salmerón J, Bastani R. 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Effect of Sodium Butyrate on LHX1 mRNA Expression as a Transcription Factor of HDAC8 in Human Colorectal Cancer Cell Lines 2 2 Background: LHX1 is an important transcription factor for the HDAC8 gene. The aim of this study was to investigate the effect of Sodium Butyrate (SB), as a histone deacetylase inhibitor, on the expression of LHX1 gene in colorectal cancer cell lines.  Methods: HT-29 and HCT-116 cell lines were treated with 6.25 to 200 mM concentrations of SB at 24, 48, and 72 hr. The cytotoxicity effect on cell viability was evaluated by MTT assay. The 50% Inhibiting Concentration (IC50) was determined graphically. Quantitative real-time PCR was performed to investigate the LHX1 mRNA expression level.  Results: Our study revealed that SB inhibited the proliferation of these cell lines in a concentration and time-dependent manner. The IC50 values for HT-29 cell line were 65, 18.6, and 9.2 mM after 24, 48, and 72 hr of treatment, respectively. The IC50 values for HCT-116 cell line were 35.5, 9.6, and 10 mM after 24, 48, and 72 hr of treatment, respectively. Furthermore, real-time PCR findings demonstrated that the LHX1 mRNA expression in treated HT-29 cell line significantly increased in comparison with untreated cells (p<0.05). However, in treated HCT-116 cell line, SB led to a significant decrease in the level of LHX1 mRNA (p<0.05), as compared to untreated cells.  Conclusion: In this study, different effects of SB on LHX1 mRNA expression level were revealed in two distinct human colorectal cancer cell lines. 317 324 Mahsa Ghiaghi Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University Iran Flora Forouzesh Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University Iran Hamzeh Rahimi Department of Molecular Medicine, Pasteur Institute of Iran Department of Molecular Medicine, Pasteur Institute of Iran Iran CytokineInterleukin-10Kawasaki diseaseSingle nucleotide polymorphismsTransforming growth factor-beta 10389.pdf Haggar FA, Boushey RP. 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Interleukin 10 and Transforming Growth Factor Beta Polymorphisms as Risk Factors for Kawasaki Disease: A Case-Control Study and Meta-Analysis 2 2 Background: Alteration in serum expression of Transforming Growth Factor-beta (TGF-β) and IL-10 have been suggested to play a role in the pathogenesis of Kawa-saki Disease (KD). Inconsistent reports exist on the association of IL-10 polymorphisms with KD susceptibility and Coronary Artery Aneurysms (CAA).  Methods: A number of 110 paediatric patients with KD and 140 healthy individuals were recruited to investigate the frequency of Single Nucleotide Polymorphisms (SNPs) of TGF-β C/T at codon 10 (rs1982073), C/G at codon 25 (rs1800471) and IL-10 A/G at -1082 (rs1800896), C/T at -819 (rs1800871) and A/C at -592 (rs1800872) and their respective genotype and haplotypes. A comprehensive search was performed in MEDLINE and SCOPUS using the keywords of interleukin 10, transforming growth factor beta, and Kawasaki disease. Moreover, previous studies investigating the TGF-β and IL-10 polymorphisms in KD were evaluated. Review Manager Version 5.1 Software was used to perform meta-analysis. Results: There was no significant association between allelic or genotypic variants in the mentioned polymorphisms in TGF-β or IL-10 with KD or CAA. The only significant haplotypic variant was TC variant at codon 10, and 25 of TGF-β polymorphisms were associated with higher risk of KD. Meta-analysis of a total number of 770 patients vs. 1471 healthy controls showed no difference in the frequency of any of the IL-10 genetic variants in KD patients, regardless of the presence of CAA. Conclusion: Polymorphisms of TGF-β or IL-10 are not associated with additional risk for KD in Iranian population. IL-10 polymorphisms at -1082, -819 and -592 positions are not associated with KD, nor do they predict coronary artery aneurysm formation. 325 333 Farzaneh Rahmani Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical SciencesNeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN) Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical SciencesNeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN) IranIran Vahid Ziaee Pediatric Rheumatology Research Group, Rheumatology Research Center, Tehran University of Medical SciencesDepartment of Pediatrics, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences Pediatric Rheumatology Research Group, Rheumatology Research Center, Tehran University of Medical SciencesDepartment of Pediatrics, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences IranIran Raheleh Assari Pediatric Rheumatology Research Group, Rheumatology Research Center, Tehran University of Medical SciencesDepartment of Pediatrics, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences Pediatric Rheumatology Research Group, Rheumatology Research Center, Tehran University of Medical SciencesDepartment of Pediatrics, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences IranIran Maryam Sadr Molecular Immunology Research Center, School of Medicine, Tehran University of Medical Sciences Molecular Immunology Research Center, School of Medicine, Tehran University of Medical Sciences Iran Arezou Rezaei Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Sciences Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Sciences Iran Zeinab Sadr Molecular Immunology Research Center, School of Medicine, Tehran University of Medical Sciences Molecular Immunology Research Center, School of Medicine, Tehran University of Medical Sciences Iran Seyed Reza Raeeskarami Department of Pediatrics, Vali-e-Asr Hospital, Tehran University of Medical Sciences Department of Pediatrics, Vali-e-Asr Hospital, Tehran University of Medical Sciences Iran Mohammad Hassan Moradinejad Department of Pediatrics, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences Department of Pediatrics, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences Iran Yahya Aghighi Department of Pediatrics, Imam Khomeini Hospital, Tehran University of Medical Sciences Department of Pediatrics, Imam Khomeini Hospital, Tehran University of Medical Sciences Iran Nima Rezaei Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical SciencesDepartment of Immunology, School of Medicine, Tehran University of Medical SciencesNetwork of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN) Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical SciencesDepartment of Immunology, School of Medicine, Tehran University of Medical SciencesNetwork of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN) IranIranUSA CytokineInterleukin-10Kawasaki diseaseSingle nucleotide polymorphisms 10392.pdf Dillon MJ, Eleftheriou D, Brogan PA. 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Integrity and Quantity Evaluation of Plasma Cell-Free DNA in Triple Negative Breast Cancer 2 2 Background: Triple-Negative Breast Cancer (TNBC) is a subtype of breast cancer that lacks expression of the estrogen and progesterone receptor and does not overexpress human epidermal growth factor 2 receptor protein. TNBC is associated with special characteristics, including aggressiveness, poor prognosis, and treatment response. Non-invasive blood-based molecular markers such as cell-free DNA (cfDNA) variables have been shown to be putative markers in breast cancer prognosis.  Methods: The cfDNA quantity and integrity were assessed in a case-control study of 96 breast cancer patients including 46 triple negative and 50 non-triple negative compared with 50 unaffected controls. A quantitative real-time PCR approach based on the quantification of two amplicons of the β-actin gene with different lengths (99 and 394 bp) was used to evaluate the integrity index 394/99.  Results: Both cfDNA integrity index and quality were significantly elevated in breast cancer patients but integrity index can be considered as the more reliable diagnostic marker. The statistically significant increase of cfDNA quantity and integrity was ob-served in TNBC patients, somehow associated with nodal metastasis (p<0.001).  Conclusion: Elevated cfDNA concentration and integrity index in breast cancer pa-tients compared with normal control and significant difference observed between TNBC and non-TNBC may be considered as a possible effective non-invasive diagnostic and prognostic molecular marker in breast cancer. 334 338 Mahdieh Salimi Department of Medical Genetics, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB) Department of Medical Genetics, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB) Iran Somayeh Sedaghati-Burkhani Department of Medical Genetics, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB) Department of Medical Genetics, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB) Iran Cell-free DNAReal-time PCRTriple negative breast neoplasms 10394.pdf Pal SK, Childs BH, Pegram M. 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The diagnostic value of circulating cell free DNA quantification in non-small cell lung cancer: A systematic review with meta-analysis. Lung Cancer 2016;100:63-70. ##Agah S, Akbari A, Talebi A, Masoudi M, Sarveazad A, Mirzaei A, et al. Quantification of plasma cell-free circulating DNA at different stages of colorectal cancer. Cancer Invest 2017; 35(10):625-632. ##Kamel AM, Teama S, Fawzy A, El Deftar M. Plasma DNA integrity index as a potential molecular diagnostic marker for breast cancer. Tumour Biol 2016;37(6):7565-7572. ##Szpechcinski A, Chorostowska-Wynimko J, Struniawski R, Kupis W, Rudzinski P, Langfort R, et al. Cell-free DNA levels in plasma of patients with non-small-cell lung cancer and inflammatory lung disease. Br J Cancer 2015;113(3):476-483. ##Han X, Wang J, Sun Y. Circulating tumor DNA as biomarkers for cancer detection. Genomics Proteomics Bioinformatics 2017;15(2):59-72. ##Rave-Fränk M. 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Importance of Fluctuating Amino Acid Residues in Folding and Binding of Proteins 2 2 Background: Conformational flexibility of proteins remains as one of the major events in protein-protein/DNA/ligand/small molecule binding to achieve its biological function in the cell. The availability of high-resolution structures of protein complexes is a valuable resource for researchers to understand the mechanisms behind such interactions and it is found that the flexibility of amino acid residues at binding sites is crucial for many important functions in the cell. Methods: In this article, our statistical method (PreFRP) developed based on fluctuating amino acid residues and various amino acid indices related to flexibility/rigidity were used to study the importance of fluctuating amino acid residues in thermonuc-leases from pathogenic bacteria, cell penetrating peptides and intrinsically disordered proteins responsible for many neural disorders.  Results: The results from our analysis reveal the importance of fluctuating amino acid residues in folding and binding of proteins. The role of moderate and high fluctuating residues in themonucleases, cell penetrating peptide and disordered regions are discussed in detail. Conclusion: Therefore, our analysis will help in understanding the importance of fluc-tuating amino acid residues in proteins which undergo a conformation change phenomenon. 339 344 Renganathan Senthil Department of Bioinformatics, Faculty of Biosciences, The Marudupandiyar Institutions, Thanjavur-613403 Department of Bioinformatics, Faculty of Biosciences, The Marudupandiyar Institutions, Thanjavur-613403 India Singaravelu Usha Department of Bioinformatics, Bharathiar University, Coimbatore-641046 Department of Bioinformatics, Bharathiar University, Coimbatore-641046 India Konda Saravanan Amino acidBinding sitesCell-penetrating peptidesDNA-binding proteins 10393.pdf Kastritis PL, Bonvin AM. On the binding affinity of macromolecular interactions: daring to ask why proteins interact. J R Soc Interface 2012;10(79):20120835. ##Xie ZR, Hwang MJ. Methods for predicting protein–ligand binding sites. Methods Mol Biol 2015;1215:383-398. ##Kabsch W, Sander C. On the use of sequence homologies to predict protein structure: identical pentapeptides can have completely different conformations. Proc Natl Acad Sci 1984;81(4):1075-1078. ##Wilson IA, Haft DH, Getzoff ED, Tainer JA, Lerner RA, Brennert S. Identical short peptide sequences in unrelated proteins can have different conformations: A testing gro-und for theories of immune recognition. Proc Natl Acad Sci USA 1985;82(16):5255-5259. ##Argos P. Analysis of sequence-similar pentapeptides in unrelated protein tertiary structures. Strategies for protein folding and a guide for site-directed mutagenesis. J Mol Biol 1987;197(2):331-348. ##Minor DL, Kim PS. Context-dependent secondary structure formation of a designed protein sequence. Nature 1996;380:730-734.##Dalal S, Regan L. Understanding the sequence determinants of conformational switching using protein design. Protein Sci 2000;9(9):1651-1659.##Ruvinsky AM, Vakser IA. Sequence composition and environment effects on residue fluctuations in protein structures. J Chem Phys 2010;133(15):155101. ##Saravanan KM, Selvaraj S. Search for identical octapeptides in unrelated proteins: Structural plasticity revisited. Biopolymers 2012;98(1):11-26.##Saravanan KM, Krishnaswamy S. Dihedral angle preferences for alanine and glycine residues in alpha and beta transmembrane regions. J Biomol Struct Dyn 2015;33: 552-562. ##Saravanan KM, Senthil R. PreFRP: Prediction and visualization of fluctuation residues in proteins. J Nat Sci Biol Med 2016;7(2):124-126. ##Berman HM, Bhat TN, Bourne PE, Feng Z, Gilliland G, Weissig H, et al. The Protein Data Bank and the challenge of structural genomics. Nat Struct Biol 2000;7 Suppl:957-959. ##Piovesan D, Tabaro F, Mičetić I, Necci M, Quaglia F, Oldfield CJ, et al. DisProt 7.0: A major update of the data-base of disor-dered proteins. Nucleic Acids Res 2017; 45(Database issue):D219-227. ##Saravanan KM, Dunker AK, Krishnaswamy S. Sequence fingerprints distinguish erroneous from correct predictions of intrinsi-cally disordered protein regions. J Biomol Struct Dyn 2017;27:1-14. ##Linding R, Russell RB, Neduva V, Gibson TJ. Glob Plot: Exploring protein sequences for globularity and disorder. Nucleic Ac-ids Res 2003;31(13):3701-3708. ##Yang ZR, Thomson R, McNeil P, Esnouf RM. RONN: The bio-basis function neural network technique applied to the detection of natively disordered regions in proteins. Bioinformatics 2005;21(16):3369-3376. ##Xue B, Dunbrack RL, Williams RW, Dunker AK, Uversky VN. PONDR-FIT: A meta-predictor of intrinsically disordered amino acids. Biochim Biophys Acta 2010; 1804(4):996-1010. ##Bahramali G, Goliaei B, Minuchehr Z, Salari A. Chameleon sequences in neurodegenerative diseases. Biochem Biophys Res Commun 2016;472(1):209-216. ##