Innovation and Technology in Iran 2 2 Scientific production of Iran’s scientists holds the needed potential and wealth to be the world’s reference in science and knowledge. Based on this and by following guidelines of the supreme leader of the Islamic revolution, preservation, per-sistence, and reinforcement of the scientific production debate has unavoidable urgency and priority in academic and scientific circles and gatherings. We must support innovative and technological institutes more than before. Even though the country has achieved regional first rank in number of published articles and enjoys noticeable ranking in the world either in basic or in clinical medicine 1,2, it seems the process of commercializing articles and other research products and transforming research into product and innovation production is still in need of more attention. It is such that Iran’s rank in international innovation indicators, or Global Innovation Index, is still not noticeable. Despite holding first rank in the region for article publication and scientific production, in regards to global innovation indicators, Iran holds 11th rank in the region, ranking which places Iran after countries like United Arab Emirates and Kuwait. In this ranking system, unfortunately, Iran holds rank of 78 among the 143 countries of the world. In the same ranking system, Iran’s rank in the world in regards to infrastructure for innovation is 91, in regards to creative output is 75, and in regards to knowledge and technology output is 65. It seems, in this field, more drive and effort should be put forth to shape a system for transforming science into innovation, commercializing research and pivoting research on production so Iran can be transformed into an innovative country with an economy pivoted on science and also in the innovation arena can acquire needed authority. 113 113 Shahin Akhondzadeh Psychiatric Research Center, Roozbeh Hospital, South Kargar Street Psychiatric Research Center, Roozbeh Hospital, South Kargar Street Iran Editorial 276.pdf Akhondzadeh S. Hippocampal synaptic plasticity and cognition. J Clin Pharm Ther 1999;24(4):241-248.##Noorbala AA, Akhondzadeh S, Davari-Ashtiani R, Amini-Nooshabadi H. Piracetam in the treatment of schizophrenia: implications for the glutamate hypothesis of schizophrenia. J Clin Pharm Ther 1999;24(5):369-374.##

Embryonic Stem Cell Conditioned Medium Supports In Vitro Maturation of Mouse Oocytes 2 2 Background: This study aimed to investigate the maturation and fertilization rates of immature mouse oocytes using Embryonic Stem Cell Conditioned Medium (ESCM). Methods: Germinal Vesicle (GV) stage oocytes were observed in 120 NMRI mice, aged 4-6 weeks. GV oocytes with or without cumulus cells were subjected to IVM in either ESCM, Embryonic Stem Cell Growth Medium (ESGM), or α-minimum essential medium (α-MEM). After recording the Metaphase II (MII) oocyte maturation rate, the oocytes were fertilized in vitro. The fertilization success rate was recorded after 24 hr. The embryos were maintained in potassium Simplex Optimization Medium (KSOM) for 96 hr and allowed to grow until the blastocyst stage. After recording developmental competence, they were transferred into the uteri of pseudopregnant mice and their birth rates were recorded. Results: No significant difference existed between the maturation rates in α-MEM (68.18%) and ESCM (64.67%; p>0.05), whereas this rate was significantly higher for both α-MEM and ESCM compared to ESGM (32.22%; p<0.05). A significant difference in IVF success rate existed for oocytes grown in α-MEM (69.44%), ESCM (61.53%), and ESGM (0%). A significantly higher developmental competence was observed at the blastocyst stage for oocytes grown in α-MEM (51.2%) compared to ESCM (35%; p<0.05). 17 days after embryo transfer into the uteri of pseudopregnant mice, there was a nonsignficant (p>0.05), similar birth rate between α-MEM and ESCM (47 vs. 40%). Conclusion: ESCM is an effective medium for preantral follicle growth, oocyte maturation, and subsequent embryo development. 114 119 Saber Miraki Department of Anatomy, Faculty of Medicine, Kurdistan University of Medical Sciences Department of Anatomy, Faculty of Medicine, Kurdistan University of Medical Sciences Iran Aram Mokarizadeh Department of Immunology and Hematology, Faculty of Medicine, Kurdistan University of Medical Sciences Department of Immunology and Hematology, Faculty of Medicine, Kurdistan University of Medical Sciences Iran Omid Banafshi Cellular and Molecular Research Center, Faculty of Medicine, Kurdistan University of Medical Sciences Cellular and Molecular Research Center, Faculty of Medicine, Kurdistan University of Medical Sciences Iran Vahideh Assadollahi Cellular and Molecular Research Center, Faculty of Medicine, Kurdistan University of Medical Sciences Cellular and Molecular Research Center, Faculty of Medicine, Kurdistan University of Medical Sciences Iran Mahdad Abdi Department of Anatomy, Faculty of Medicine, Kurdistan University of Medical Sciences Department of Anatomy, Faculty of Medicine, Kurdistan University of Medical Sciences Iran Daem Roshani Social Determinants of Health Research Center, Kurdistan University of Medical Sciences Social Determinants of Health Research Center, Kurdistan University of Medical Sciences Iran Fardin Fathi Cellular and Molecular Research Center, Faculty of Medicine, Kurdistan University of Medical Sciences Cellular and Molecular Research Center, Faculty of Medicine, Kurdistan University of Medical Sciences Iran Assisted reproductive technologiesEmbryonic stem cellsMiceOocytes 277.pdf Nottola SA, Cecconi S, Bianchi S, Motta C, Rossi G, Continenza MA, et al. Ultrastructure of isolated mouse ovarian follicles cultured in vitro. Reprod Biol Endocrinol 2011;9:3.##Desai N, Alex A, AbdelHafez F, Calabro A, Goldfarb J, Fleischman A, et al. Three-dimensional in vitro follicle growth: overview of culture models, biomaterials, design parameters and future directions. Reprod Biol Endocrinol 2010;8:119.##Wang X, Catt S, Pangestu M, Temple-Smith P. Successful in vitro culture of pre-antral follicles derived from vitrified murine ovarian tissue: oocyte maturation, fertilization, and live births. Reproduction 2011;141(2):183-191.##Ling B, Feng DQ, Zhou Y, Gao T, Wei HM, Tian ZG. Effect of conditioned medium of mesenchymal stem cells on the in vitro maturation and subsequent development of mouse oocyte. Braz J Med Biol Res 2008;41(11):978-985.##Kim DH, No JG, Park JJ, Yoo JG. Successful in vitro development of preantral follicles isolated from vitrified mouse whole ovaries. Reprod Dev Biol 2012;36(4):255-260.##Hasegawa A, Hamada Y, Mehandjiev T, Koyama K. In vitro growth and maturation as well as fertilization of mouse preantral oocytes from vitrified ovaries. Fertil Steril 2004;81 Suppl 1:824-830.##Child TJ, Abdul-Jalil AK, Gulekli B, Tan SL. In vitro maturation and fertilization of oocytes from unstimulated normal ovaries, polycystic ovaries, and women with polycystic ovary syndrome. Fertil Steril 2001;76(5):936-942.##Trounson A, Wood C, Kausche A. In vitro maturation and the fertilization and developmental competence of oocytes recovered from untreated polycystic ovarian patients. Fertil Steril 1994;62(2):353-362.##Spears N, Boland NI, Murray AA, Gosden RG. Mouse oocytes derived from in vitro grown primary ovarian follicles are fertile. Hum Reprod 1994;9(3):527-532.##Chian RC, Lim JH, Tan SL. State of the art in in-vitro oocyte maturation. Curr Opin Obstet Gynecol 2004;16(3):211-219.##Moor RM, Dai Y, Lee C, Fulka J Jr. Oocyte maturation and embryonic failure. Hum Reprod Update 1998;4(3):223-226.##Trounson A, Anderiesz C, Jones G. Maturation of human oocytes in vitro and their developmental competence. Reproduction 2001;121(1):51-75.##Cha KY, Koo JJ, Ko JJ, Choi DH, Han SY, Yoon TK. Pregnancy after in vitro fertilization of human follicular oocytes collected from nonstimulated cycles, their culture in vitro and their transfer in a donor oocyte program. Fertil Steril 1991;55(1):109-113.##Child TJ, Phillips SJ, Abdul-Jalil AK, Gulekli B, Tan SL. A comparison of in vitro maturation and in vitro fertilization for women with polycystic ovaries. Obstet Gynecol 2002;100(4):665-670.##Brower PT, Schultz RM. Intercellular communication between granulosa cells and mouse oocytes: existence and possible nutritional role during oocyte growth. Dev Biol 1982;90(1):144-153.##Picton HM, Harris SE, Muruvi W, Chambers EL. The in vitro growth and maturation of follicles. Reproduction 2008;136(6):703-715.##Gilchrist RB, Thompson JG. Oocyte maturation: emerging concepts and technologies to improve developmental potential in vitro. Theriogenology 2007;67(1):6-15.##Fathi F, Altiraihi T, Mowla SJ, Movahedin M. Transplantation of retinoic acid treated embryonic stem cells & behavioural deficit in Parkinsonian rats. Indian J Med Res 2010;131:536-544.##Nichols J. Introducing embryonic stem cells. Curr Biol 2001;11(13):R503-505.##Odorico JS, Kaufman DS, Thomson JA. Multilineage differentiation from human embryonic stem cell lines. Stem cells 2001;19(3):193-204.##Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts. Science 1998;282(5391):1145-1147.##Amit M, Carpenter MK, Inokuma MS, Chiu CP, Harris CP, Waknitz MA, et al. Clonally derived human embryonic stem cell lines maintain pluripotency and proliferative potential for prolonged periods of culture. Dev Biol 2000;227(2):271-278.##Giuffrida D, Rogers IM, Nagy A, Calogero AE, Brown TJ, Casper RF. Human embryonic stem cells secrete soluble factors that inhibit cancer cell growth. Cell Prolif 2009;42(6):788-798.##Fatma S, Selby DE, Singla RD, Singla DK. Factors released from embryonic stem cells stimulate c-kit-FLK-1(+ve) progenitor cells and enhance neovascularization. Antioxid Redox Signal 2010;13(12):1857-1865.##Guo Y, Graham‐Evans B, Broxmeyer HE. Murine embryonic stem cells secrete cytokines/growth modulators that enhance cell survival/anti‐apoptosis and stimulate colony formation of mrine hematopoietic progenitor cells. Stem Cells 2006;24(4):850-856.##LaFramboise WA, Petrosko P, Krill-Burger JM, Morris DR, McCoy AR, Scalise D, et al. Proteins secreted by embryonic stem cells activate cardiomyocytes through ligand binding pathways. J Proteomics 2010;73(5):992-1003.##Fuchs E, Tumbar T, Guasch G. Socializing with the neighbors: stem cells and their niche. Cell 2004;116(6):769-778.##Naveiras O, Daley GQ. Stem cells and their niche: a matter of fate. Cell Mol Life Sci 2006;63(7-8):760-766.##Bendall SC, Hughes C, Campbell JL, Stewart MH, Pittock P, Liu S, et al. An enhanced mass spectrometry approach reveals human embryonic stem cell growth factors in culture. Mol Cell Proteomics 2009;8(3):421-432.##Nagy A, Gertsenstein M, Vintersten K, Behringer R. Manipulating the mouse embryo: A laboratory manual. 3rd ed. USA: Cold Spring Harbor Laboratory Press; 2003. 764 p##Das K, Stout LE, Hensleigh HC, Tagatz GE, Phipps WR, Leung BS. Direct positive effect of epidermal growth factor on the cytoplasmic maturation of mouse and human oocytes. Fertil Steril 1991;55(5):1000-1004.##Gómez E, Tarín JJ, Pellicer A. Oocyte maturation in humans: the role of gonadotropins and growth factors. Fertil Steril 1993;60(1):40-46.##De La Fuente R, O'Brien MJ, Eppig JJ. Epidermal growth factor enhances preimplantation developmental competence of maturing mouse oocytes. Hum Reprod 1999;14(12):3060-3068.##Feng P, Catt KJ, Knecht M. Transforming growth factor-beta stimulates meiotic maturation of the rat oocyte. Endocrinology 1988;122(1):181-186.##Lorenzo PL, Illera JC, Silván G, Munro CJ, Illera MJ, Illera M. Steroid-level response to insulin-like growth factor-1 in oocytes matured in vitro. J Reprod Immunol 1997;35(1):11-29.##Pawshe CH, Appa Rao KB, Totey SM. Effect of insulin‐like growth factor I and its interaction with gonadotropins on in vitro maturation and embryonic development, cell proliferation, and biosynthetic activity of cumulus‐oocyte complexes and granulosa cells in buffalo. Mol Reprod Dev 1998;49(3):277-285.##Lorenzo PL, Illera MJ, Illera JC, Illera M. Influence of growth factors on the time-dependent meiotic progression of the bovine oocytes during their in vitro maturation. Rev Esp Fisiol 1995;51(2):77-83.##Lorenzo PL, Rebollar PG, Illera MJ, Illera JC, Illera M, Alvariño JM. Stimulatory effect of insulin-like growth factor I and epidermal growth factor on the maturation of rabbit oocytes in vitro. J Reprod Fertil 1996;107(1):109-117.##Lonergan P, Carolan C, Van Langendonckt A, Donnay I, Khatir H, Mermillod P. Role of epidermal growth factor in bovine oocyte maturation and preimplantation embryo development in vitro. Biol Reprod 1996;54(6):1420-1429.##Sakaguchi M, Dominko T, Yamauchi N, Leibfried-Rutledge ML, Nagai T, First NL. Possible mechanism for acceleration of meiotic progression of bovine follicular oocytes by growth factors in vitro. Reproduction 2002;123(1):135-142.##Goud PT, Goud AP, Qian C, Laverge H, Van der Elst J, De Sutter P, et al. 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Biosynthesis of Silver Nanoparticles using Chlorella vulgaris and Evaluation of the Antibacterial Efficacy Against Staphylococcus aureus 2 2 Background: It is well documented that Silver Nanoparticles (SNPs) are potent antimicrobial agents. However, little is known about antimicrobial effects of biologically synthesized SNPs at molecular level. In the present study, efficacy of the green microalgae Chlorella vulgaris in biosynthesis of silver nanoparticles and inhibitory effect of the biosynthesized SNPs on growth and virulence of Staphylococcus aureus (S. aureus) were investigated. Methods: Algal suspension was incubated in the presence of silver nitrate to induce formation of nanoparticles. The experiment was conducted under a pH range to evaluate pH effect on the shape and properties of nanoparticles. Characterization was performed by Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), Energy Dispersive Spectrometry (EDS) and X-ray diffraction analysis (XRD). Moreover, concentration of biosynthesized SNPs was measured by high resolution ICP-OES spectrometer. Antibacterial effect of SNPs on growth of S. aureus was evaluated by broth micro-dilution method. Inhibitory effect of SNPs on alpha hemolysin, a well-known virulence factor of S. aureus was investigated through real time PCR assay. Results: Spherical SNPs were produced with characteristic monodispersity at low and neutral pHs; however, in alkaline condition, nanorod structures were formed. SNPs inhibited growth of S. aureus at concentration of 50 μg/ml. Alpha hemolysin expression was also effectively inhibited by SNPs treatment. Conclusion: In general, results revealed formation of spherical silver nanoparticles with inhibitory effects on bacterial growth and antagonist activity on the expression of alpha hemolysin. Moreover, increase in pH to basic condition resulted in aggregation of nanoparticles and formation of rod-like nanostructures. 120 125 Mohammad Soleimani Department of Microbiology, Faculty of Medicine, AJA University of Medical Sciences Department of Microbiology, Faculty of Medicine, AJA University of Medical Sciences Iran Maziar Habibi-Pirkoohi Department of Microbiology, Faculty of Medicine, AJA University of Medical Sciences Department of Microbiology, Faculty of Medicine, AJA University of Medical Sciences Iran BiosynthesisChlorella vulgarisNanoparticlesSilver 278.pdf Cui H, Feng Y, Ren W, Zeng T, Lv H, Pan Y. Strategies of large scale synthesis of monodisperse nanoparticles. Recent Pat Nanotechnol 2009;3(1):32-41.##Prabha G, Raj V. Formation and characterization of β-cyclodextrin (β-CD)-polyethyleneglycol (PEG)-polyethyleneimine (PEI) coated Fe3O4 nanoparticles for loading and releasing 5-Fluorouracil drug. Biomed Pharmacother 2016;80:173-182.##Iravani S. Green synthesis of metal nanoparticles using plants. Green Chem 2011;13(10):2638-2650.##Manikprabhu D, Cheng J, Chen W, Sunkara AK, Mane SB, Kumar R, et al. Sunlight mediated synthesis of silver nanoparticles by a novel actinobacterium (Sinomonas mesophila MPKL 26) and its antimicrobial activity against multi drug resistant Staphylococcus aureus. J Photochem Photobiol B 2016;158:202-205.##Prasad TN, Kambala VSR, Naidu R. Phyconanotechnology: synthesis of silver nanoparticles using brown marine algae Cystophora moniliformis and their characterisation. J Appl Phycol 2013;25(1):177-182.##Nowack B, Krug HF, Height M. 120 years of nanosilver history: implications for policy makers. Environ Sci Technol 2011;45(4):1177-1183.##Edison TJI, Sethuraman MG. Instant green synthesis of silver nanoparticles using Terminalia chebula fruit extract and evaluation of their catalytic activity on reduction of methylene blue. Process Biochem 2012;47(9):1351-1357.##Ahmed S, Ahmad M, Swami BL, Ikram S. A review on plants extract mediated synthesis of silver nanoparticles for antimicrobial applications: a green expertise. J Adv Res 2016;7(1):17-28.##Mittal AK, Chisti Y, Banerjee UC. Synthesis of metallic nanoparticles using plant extracts. Biotechnol Adv 2013;31(2):346-356.##Parial D, Patra HK, Roychoudhury P, Dasgupta AK, Pal R. Gold nanorod production by cyanobacteria-a green chemistry approach. J Appl Phycol 2012;24(1):55-60.##Annamalai J, Nallamuthu T. Green synthesis of silver nanoparticles: characterization and determination of antibacterial potency. Appl Nanosci 2016;6(2):259-265.##Patel V, Berthold D, Puranik P, Gantar M. Screening of cyanobacteria and microalgae for their ability to synthesize silver nanoparticles with antibacterial activity. Biotechnol Rep 2015;5:112-119.##El-Sheekh MM, El-Kassas HY. Application of biosynthesized silver nanoparticles against a cancer promoter cyanobacterium, Microcystis aeruginosa. Asian Pac J Cancer Prev 2014;15(16):6773-6779.##Bubeck Wardenburg J, Bae T, Otto M, Deleo FR, Schneewind O. Poring over pores: alpha-hemolysin and Panton-Valentine leukocidin in Staphylococcus aureus pneumonia. Nat Med 2007;13(12):1405-1406.##Xiang H, Qiu JZ, Wang DC, Jiang YS, Xia LJ, Deng XM. Influence of magnolol on the secretion of alpha-toxin by Staphylococcus aureus. Molecules 2010;15(3):1679-1689.##Behera S, Debata A. Biomedical applications of silver nanoparticles. J Asian Sci Res 2011;1(1):27.##Mehta SK, Gaur JP. Use of algae for removing heavy metal ions from wastewater: progress and prospects. Crit Rev Biotechnol 2005;25(3):113-152.##Mahdieh M, Zolanvari A, Azimee A. Green biosynthesis of silver nanoparticles by Spirulina platensis. Sci Iran 2012;19(3):926-929.##Kannan N, Subbalaxmi S. Biogenesis of nanoparticles- A Current perspective. Rev Adv Mater Sci 2011;27:99-114.##Mandal D, Bolander ME, Mukhopadhyay D, Sarkar G, Mukherjee P. The use of microorganisms for the formation of metal nanoparticles and their application. Appl Microbiol Biotechnol 2006;69(5):485-492.##Yasin S, Liu L, Yao J. Biosynthesis of silver nanoparticles by bamboo leaves extract and their antimicrobial activity. J Fiber Bioeng Inform 2013;6(6):77-84.##Castro L, Blázquez ML, Muñoz JA, González F, García-Balboa C, Ballester A. Biosynthesis of gold nanowires using sugar beet pulp. Process Biochem 2011;46(5):1076-1082.##Dhanalakshmi PK, Azeez R, Rekha R, Poonkodi S, Nallamuthu T. Synthesis of silver nanoparticles using green and brown seaweeds. Phykos 2012;42(2):39-45.##Rai M, Yadav A, Gade A. Silver nanoparticles as a new generation of antimicrobials. 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Evaluation of Factors Affecting Size and Size Distribution of Chitosan-Electrosprayed Nanoparticles 2 2 Background: Size and size distribution of polymeric nanoparticles have important effect on their properties for pharmaceutical application. In this study, Chitosan nanoparticles were prepared by electrospray method (electrohydrodynamic atomization) and parameters that simultaneously affect size and/or size distribution of chitosan nanoparticles were optimized. Methods: Effect of formulation/processing three independent formulation/processing parameters, namely concentration, flow rate and applied voltage was investigated on particle size and size distribution of generated nanoparticles using a Box–Behnken experimental design. Results: All the studied factors showed important effects on average size and size dis-tribution of nanoparticles. A decrease in size and size distribution was obtainable with decreasing flow rate and concentration and increasing applied voltage. Eventually, a sample with minimum size and polydispersity was obtained with polymer concentration, flow rate and applied voltage values of 0.5 %w/v, 0.05 ml/hr and 15 kV, respectively. The experimentally prepared nanoparticles, expected having lowest size and size distribution values had a size of 105 nm, size distribution of 36 and Zeta potential of 59.3 mV. Conclusion: Results showed that optimum condition for production of chitosan nano-particles with the minimum size and narrow size distribution was a minimum value for flow rate and highest value for applied voltage along with an optimum chitosan concentration. 126 132 Morteza Abyadeh Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Tehran University of Medical Sciences Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Tehran University of Medical Sciences Iran Ali Akbar Karimi Zarchi Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Tehran University of Medical Sciences Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Tehran University of Medical Sciences Iran Mohammad Ali Faramarzi Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences Iran Amir Amani Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Tehran University of Medical Sciences Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Tehran University of Medical Sciences Iran ChitosanElectrosprayExperimental design NanoparticlesParticle size 279.pdf Zhang S, Kawakami K. 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The Effects of Melilotus officinalis Extract on Expression of Daxx, Nfkb and Vegf Genes in the Streptozotocin-Induced Rat Model of Sporadic Alzheimer's Disease 2 2 Background: Possible mechanisms of Alzheimer Disease (AD) such as inflammation and oxidative stresses in the brain led us to investigate potential AD therapeutics of Melilotus officinalis, an herbal extract, with possible role as an anti-inflammatory and anti-oxidant agent. Among different genes which had important role in Sporadic AD (SAD), three genes including DAXX, NFkB and VEGF have shown significant statistical diversity in the brains of Alzheimer patients. Methods: These genes were chosen to be investigated for neuroprotective effects of the extract by comparing the expression level in the hippocampus of Sporadic AD (SAD) rat model using quantitative polymerase chain reaction (qPCR) in the treated and untreated groups. In addition, therapeutic effects at the behavioral, learning and memory level by Morris Water Maze (MWM) test were investigated. Results: The results represented significant decreased expression in Daxx, Nfkb and Vegf genes in the SAD rat’s model treated with the herbal extract compared to the Streptozotocin-induced (STZ-induced) rats. Furthermore, no significant changes were seen in swimming distance and time for finding the hidden platform in the herbal-treated compared to the STZ-induced group. In memory level, no significant changes were observed among treated and untreated groups. Conclusion: It seems that the herbal extract may have significant effect on Alzheimer-related gene expression changes but not on clinical levels. 133 137 Niloofar Bazazzadegan Genetics Research Center, University of Social Welfare and Rehabilitation Sciences Genetics Research Center, University of Social Welfare and Rehabilitation Sciences Iran Marzieh Dehghan Shasaltaneh Laboratory of Neuro-organic Chemistry, Institute of Biochemistry and Biophysics (IBB), University of Tehran Laboratory of Neuro-organic Chemistry, Institute of Biochemistry and Biophysics (IBB), University of Tehran Iran Kioomars Saliminejad Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran Koorosh Kamali Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran Mehdi Banan Genetics Research Center, University of Social Welfare and Rehabilitation Sciences Genetics Research Center, University of Social Welfare and Rehabilitation Sciences Iran Hamid Reza Khorram Khorshid Genetics Research Center, University of Social Welfare and Rehabilitation Sciences Genetics Research Center, University of Social Welfare and Rehabilitation Sciences Iran Alzheimer diseaseGene expressionHerbal medicine 280.pdf Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. 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BMJ 1990;300(6723):495-499.##Kaduszkiewicz H, Zimmermann T, Beck-Bornholdt HP, van den Bussche H. Cholinesterase inhibitors for patients with Alzheimer's disease: systematic review of randomised clinical trials. BMJ 2005;331(7512):321-327.##Pilcher H. Alzheimer's disease could be "type 3 diabetes". Lancet Neurol 2006;5(5):388-389.##de la Monte SM, Tong M. Mechanisms of nitrosamine-mediated neurodegeneration: potential relevance to sporadic Alzheimer's disease. J Alzheimers Dis 2009;17(4):817-825.##Grünblatt E, Hoyer S, Riederer P. Gene expression profile in streptozotocin rat model for sporadic Alzheimer’s disease. J Neural Transm (Vienna) 2004;111(3):367-386.##Tian J, Shi J, Zhang X, Wang Y. Herbal therapy: a new pathway for the treatment of Alzheimer’s disease. Alzheimers Res Ther 2010;2(5):30.##Hajiaghaee R, Akhondzadeh S. Herbal medicine in the treatment of Alzheimer’s disease. J Med Plants 2012;1(41):1-7.##Molina-Jiménez MF, Sánchez-Reus MI, Cascales M, Andrés D, Benedí J. Effect of fraxetin on antioxidant defense and stress proteins in human neuroblastoma cell model of rotenone neurotoxicity. Comparative study with myricetin and N-acetylcysteine. Toxicol Appl Pharmacol 2005;209(3):214-225.##Pleşca‐Manea L, Pârvu AE, Parvu M, Taămaş M, Buia R, Puia M. Effects of Melilotus officinalis on acute inflammation. Phytother Res 2002;16(4):316-319.##Abdollahi M, Farzamfar B, Salari P, Khorram Khorshid HR, Larijani B, Farhadi M, et al. Evaluation of acute and sub-chronic toxicity of Semelil (ANGIPARSTM), a new phytotherapeutic drug for wound healing in rodents. DARU J Pharm Sci 2008;16(Suppl 1):7-14.##Larijani B, Heshmat R, Bahrami A, Delshad H, Ranjbar Omrani G, Mohammad K, et al. Effects of intravenous Semelil (ANGIPARSTM) on diabetic foot ulcers healing: A multicenter clinical trial. DARU J Pharm Sci 2008;16(Suppl 1):35-40.##Larijani, B, Hasani Ranjbar S. Overview of diabetic foot; novel treatments in diabetic foot ulcer. DARU J Pharm Sci 2008;16(Suppl 1):1-6.##Sheweita SA, Khoshhal KI. Calcium metabolism and oxidative stress in bone fractures: role of antioxidants. Curr Drug Metab 2007;8(5):519-525.##Lukiw WJ. Gene expression profiling in fetal, aged, and Alzheimer hippocampus: a continuum of stress-related signaling. Neurochem Res 2004;29(6):1287-1297.##Daneshmand P, Saliminejad K, Dehghan Shasaltaneh M, Kamali K, Riazi GH, Nazari R, et al. Neuroprotective effects of herbal extract (Rosa canina, Tanacetum vulgare and Urtics dioica) on rat model of sporadic Alzheimer’s disease. Avicenna J Med Biotechnol 2016;8(3):120-125.##Morris RG. Morris water maze. Scholarpedia 2008;3(8):6315.##Paxinos G, Watson C. The rat brain in Sterotaxic coordinates-The New Coronal Set. 5th ed. USA: Elsevier Academic Press; 2004. 209 p.##National Institutes of Health. Guide for the care and use of laboratory animals. United States Government Printing: National Academies; 1985. 81 p.##Moura AC, Lazzari VM, Agnes G, Almeida S, Giovenardi M, Veiga AB. Transcriptional expression study in the central nervous system of rats: what gene should be used as internal control? Einstein (Sao Paulo) 2014;12(3):336-341.##Silver N, Cotroneo E, Proctor G, Osailan S, Paterson KL, Carpenter GH. Selection of housekeeping genes for gene expression studies in the adult rat submandibular gland under normal, inflamed, atrophic and regenerative states. BMC Mol Biol 2008;9:64.##Salomoni P, Khelifi AF. Daxx: death or survival protein? TrendsCell Biol 2006;16(2):97-104.##Barger SW, Hörster D, Furukawa K, Goodman Y, Krieglstein J, Mattson MP. Tumor necrosis factors alpha and beta protect neurons against amyloid beta-peptide toxicity: evidence for involvement of a kappa B-binding factor and attenuation of peroxide and Ca2+ accumulation. Proc Natl Acad Sci USA 1995;92(20):9328-9332.##Grilli M, Goffi F, Memo M, Spano P. Interleukin-1beta and glutamate activate the NF-kappaB/Rel binding site from the regulatory region of the amyloid precursor protein gene in primary neuronal cultures. J Biol Chem 1996;271(25):15002-15007.##Chen Y, Tian Z, Liang Z, Sun S, Dai CL, Lee MH, et al. Brain gene expression of a sporadic (icv-STZ Mouse) and a familial mouse model (3xTg-AD mouse) of Alzheimer’s disease. PLoS One 2012;7(12):e51432.##Kalaria R, Cohen DL, Premkumar DR, Nag S, LaManna JC, Lust WD. Vascular endothelial growth factor in Alzheimer's disease and experimental cerebral ischemia. Brain Res Mol Brain Res 1998;62(1):101-105.##Tang H, Mao X, Xie L, Greenberg DA, Jin K. Expression level of vascular endothelial growth factor in hippocampus is associated with cognitive impairment in patients with Alzheimer's disease. Neurobiol Aging 2013;34(5):1412-1415.##Mateo I, Llorca J, Infante J, Rodríguez‐Rodríguez E, Fernández-Viadero C, Peña N, et al. Low serum VEGF levels are associated with Alzheimer's disease. 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Distribution of Class I Integron and smqnr Resistance Gene Among Stenotrophomonas maltophilia Isolated from Clinical Samples in Iran 2 2 Background: Stenotrophomonas maltophilia (S. maltophilia) is a multiple-antibiotic-resistant opportunistic pathogen that is being isolated with increasing frequency from patients with health-care-associated infections. S. maltophilia is inherently resistant to most of the available antimicrobial agents. Spread of resistant strains has been attributed, in part, to class I integrons. In vitro susceptibility studies have shown trimethoprim-sulfamethoxazole and new floroquinolones as two important agents with activity against these organisms. Methods: 150 isolates of S. maltophilia were isolated from clinical samples such as respiratory discharges, sputum, and catheter and hospital environments. These isolates were also subjected to susceptibility testing and polymerase chain reaction for four groups of genes including int encoding integron elements, sulI and sulII encoding trimethoprim-sulfamethoxazole resistance and smqnr encoding quinolone resistance. Results: The rate of resistance to trimethoprim-sulfamethoxazole was up to 27 (18%) and the highest resistance to quinolone family belonged to ofloxacin (20%) and the lowest rate was for gatifloxacin (16%). The results showed that 14% of isolates contained integron elements concomitantly with sulI and sulII genes. Conclusion: Resistance rate of S. maltophilia to co-trimoxazole and fluoroquinolones and detection of integron elements between isolates in this study showed that this rate corresponded to other data obtained from other studies. 138 141 Mohammadali Malekan Microbiology Research Center, Pasteur Institute of Iran Microbiology Research Center, Pasteur Institute of Iran Iran Bahman Tabaraie Kousha Faravar Giti, Industrial Research Institute of Biotechnology Kousha Faravar Giti, Industrial Research Institute of Biotechnology Iran Ladan Akhoundtabar Department of Microbiology, Azad University of Jahrom Department of Microbiology, Azad University of Jahrom Iran Parviz Afrough Microbiology Research Center, Pasteur Institute of IranDepartment of Mycobacteriology and Pulmonary Research, Pasteur Institute Microbiology Research Center, Pasteur Institute of IranDepartment of Mycobacteriology and Pulmonary Research, Pasteur Institute IranIran Ava Behrouzi Department of Mycobacteriology and Pulmonary Research, Pasteur Institute Department of Mycobacteriology and Pulmonary Research, Pasteur Institute Iran ResistanceStenotrophomonas maltophiliaTrimethoprim-sulfamethoxazole 281.pdf Berg G, Roskot N, Smalla K. Genotypic and phenotypic relationships between clinical and environmental isolates of Stenotrophomonas maltophilia. J Clin Microbiol 1999;37(11):3594-3600.##Al-Jasser AM. Stenotrophomonas maltophilia resistant to trimethoprim-sulfamethoxazole: an increasing problem. Ann Clin Microbiol Antimicrob 2006;5:23.##Avison MB, Higgins CS, Ford PJ, von Heldreich CJ, Walsh TR, Bennett PM. Differential regulation of L1 and L2 beta-lactamase expression in Stenotrophomonas maltophilia. J Antimicrob Chemother 2002;49(2):387-389.##Li XZ, Nikaido H. Efflux-mediated drug resistance in bacteria: an update. Drugs 2009;69(12):1555-1623.##Sader HS, Jones RN. Antimicrobial susceptibility of uncommonly isolated non-enteric Gram-negative bacilli. Int J Antimicrob Agents 2005;25(2):95-109.##Zelenitsky SA, Iacovides H, Ariano RE, Harding GK. Antibiotic combinations significantly more active than monotherapy in an in vitro infection model of Stenotrophomonas maltophilia. Diagn Microbiol Infect Dis 2005;51(1):39-43.##Barbolla R, Catalano M, Orman BE, Famiglietti A, Vay C, Smayevsky J, et al. Class 1 integrons increase trimethoprim-sulfamethoxazole MICs against epidemiologically unrelated Stenotrophomonas maltophilia isolates. Antimicrob Agents Chemother 2004;48(2):666-669.##Toleman MA, Bennett PM, Bennett DM, Jones RN, Walsh TR. Global emergence of trimethoprim/sulfamethoxazole resistance in Stenotrophomonas maltophilia mediated by acquisition of sul genes. Emerg Infect Dis 2007;13(4):559-565.##Brooke JS. Stenotrophomonas maltophilia: an emerging global opportunistic pathogen. Clin Microbiol Rev 2012;25(1):2-41.##Gordon NC, Wareham DW. Novel variants of the Smqnr family of quinolone resistance genes in clinical isolates of Stenotrophomonas maltophilia. J Antimicrob Chemother 2010;65(3):483-489.##Sánchez MB, Hernández A, Rodríguez-Martínez JM, Martínez-Martínez L, Martínez JL. Predictive analysis of transmissible quinolone resistance indicates Stenotrophomonas maltophilia as a potential source of a novel family of Qnr determinants. BMC Microbiol 2008;8:148.##Wareham DW, Gordon NC, Shimizu K. Two new variants of and creation of a repository for Stenotrophomonas maltophilia quinolone protection protein (Smqnr) genes. Int J Antimicrob Agents 2011;37(1):89-90.##Poirel L, Cattoir V, Nordmann P. Is plasmid-mediated quinolone resistance a clinically significant problem? Clin Microbiol Infect 2008;14(4):295-297.##Betriu C, Sánchez A, Palau ML, Gómez M, Picazo JJ. Antibiotic resistance surveillance of Stenotrophomonas maltophilia, 1993-1999. J Antimicrob Chemother 2001;48(1):152-154.##Gales AC, Jones RN, Forward KR, Liñares J, Sader HS, Verhoef J. Emerging importance of multidrug-resistant Acinetobacter species and Stenotrophomonas maltophilia as pathogens in seriously ill patients: geographic patterns, epidemiological features, and trends in the SENTRY Antimicrobial Surveillance Program (1997-1999). Clin Infect Dis 2001;32 Suppl 2:S104-113##Qureshi A, Mooney L, Denton M, Kerr KG. Stenotrophomonas maltophilia in salad. Emerg Infect Dis 2005;11(7):1157-1158.##

A Novel Variant of OCT4 Entitled OCT4B3 is Expressed in Human Bladder Cancer and Astrocytoma Cell Lines 2 2 Background: Alternative splicing is an important mechanism that regulates gene expression and function in human cells. OCT4, a crucial pluripotency marker in embryonic stem/carcinoma cells generates several spliced variants in different cell types and cancers. The expression of OCT4 in cancers has been challenged in many studies. The existence of several OCT4 spliced variants and absence of specific discriminating primers is the main reason of this controversy. Therefore, using specific primers and discriminating OCT4 variants from each other might help to reduce these discrepancies  in carcinogenesis and stem cell researches. Methods: 17 various human cancer, pluripotent and normal cells were cultured and their RNAs were extracted. Related cDNAs were synthesized and the expression pattern of OCT4 variants was investigated by RT-PCR assay. PCR products were cloned into pTZ57R/T vector and their authenticity was confirmed by DNA sequencing. Results: Expression pattern of OCT4 variants (OCT4A, OCT4B and OCT4B1) was analyzed by RT-PCR assay and the authenticity of PCR products was confirmed by DNA sequencing. A novel spliced variant of OCT4 was discovered and named as OCT4B3. This variant was very similar to OCT4B2 transcript except that 207-nt of exon 1b is lost. Moreover, the expression pattern of OCT4B3 variant was investigated in 17 human cell types, where its expression was only found in astrocytoma and bladder cancer cell types 1321N1 and 5637, respectively. Conclusion: OCT4 variants are differentially expressed in various human cancer cell lines. Moreover, a novel variant of OCT4, OCT4B3, was detected in two human cancer cell lines of bladder carcinoma (5637) and brain astrocytoma (1321N1) for the first time. 142 145 Ensieh M. Poursani Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University Iran Majid Mehravar Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University Iran Bahram Mohammad Soltani Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University Iran Seyed Javad Mowla Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University Iran James E. Trosko Food Safety Toxicology Center, Department of Pediatrics and Human Development, Michigan State University Food Safety Toxicology Center, Department of Pediatrics and Human Development, Michigan State University USA Alternative splicingCell lineGeneStem cells 282.pdf Schöler HR, Ruppert S, Suzuki N, Chowdhury K, Gruss P. New type of POU domain in germ line-specific protein Oct-4. Nature 1990;344(6265):435-439.##Nichols J, Zevnik B, Anastassiadis K, Niwa H, Klewe-Nebenius D, Chambers I, Schöler H, Smith A. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell 1998;95(3):379-391.##Wang X, Dai J. Concise review: isoforms of OCT4 contribute to the confusing diversity in stem cell biology. Stem Cells 2010;28(5):885-893.##Atlasi Y, Mowla SJ, Ziaee SA, Gokhale PJ, Andrews PW. OCT4 spliced variants are differentially expressed in human pluripotent and nonpluripotent cells. Stem Cells 2008;26(12):3068-3074.##Poursani EM, Mohammad Soltani B, Mowla SJ. Differential expression of OCT4 pseudogenes in pluripotent and tumor cell lines. Cell J 2016;18(1):28-36.##Black DL. Protein diversity from alternative splicing: a challenge for bioinformatics and post-genome biology. Cell 2000;103(3):367-370.##Kriventseva EV, Koch I, Apweiler R, Vingron M, Bork P, Gelfand MS, et al. Increase of functional diversity by alternative splicing. Trends Genet 2003;19(3):124-128.##Resch A, Xing Y, Modrek B, Gorlick M, Riley R, Lee C. Assessing the impact of alternative splicing on domain interactions in the human proteome. J Proteome Res 2004;3(1):76-83.##Wang ET, Sandberg R, Luo S, Khrebtukova I, Zhang L, Mayr C, et al. Alternative isoform regulation in human tissue transcriptomes. Nature 2008;456(7221):470-476.##Castle JC, Zhang C, Shah JK, Kulkarni AV, Kalsotra A, Cooper TA, et al. Expression of 24,426 human alternative splicing events and predicted cis regulation in 48 tissues and cell lines. Nat Genet 2008;40(12):1416-1425.##Wang Z, Burge CB. Splicing regulation: from a parts list of regulatory elements to an integrated splicing code. RNA 2008;14(5):802-813.##Sugnet CW, Srinivasan K, Clark TA, O'Brien G, Cline MS, Wang H, et al. Unusual intron conservation near tissue-regulated exons found by splicing microarrays. PLoS Comput Biol 2006;2(1):e4.##Takeda J, Seino S, Bell GI. Human Oct3 gene family: cDNA sequences, alternative splicing, gene organization, chromosomal location, and expression at low levels in adult tissues. Nucleic Acids Res 1992;20(17):4613-4620.##Lee J, Kim HK, Rho JY, Han YM, Kim J. The human OCT-4 isoforms differ in their ability to confer self-re-newal. J Biol Chem 2006;281(44):33554-33565.##Cauffman G, Liebaers I, Van Steirteghem A, Van de Velde H. POU5F1 isoforms show different expression patterns in human embryonic stem cells and preimplant-ation embryos. Stem Cells 2006;24(12):2685-2691.##Wang X, Zhao Y, Xiao Z, Chen B, Wei Z, Wang B, et al. Alternative translation of OCT4 by an internal ribosome entry site and its novel function in stress response. Stem Cells 2009;27(6):1265-1275.##Gao Y, Wei J, Han J, Wang X, Su G, Zhao Y, et al. The novel function of OCT4B isoform-265 in genotoxic stress. Stem Cells 2012;30(4):665-672.##Farashahi Yazd E, Rafiee MR, Soleimani M, Tavallaei M, Salmani MK, Mowla SJ. OCT4B1, a novel spliced variant of OCT4, generates a stable truncated protein with a potential role in stress response. Cancer Lett 2011;309(2):170-175.##

A Novel Variant in the PAH Gene Causing Phenylketonuria in an Iranian Pedigree 2 2 Background: Phenylalanine hydroxylase (PAH) gene is the well-known causative gene for classic Phenylketonuria (PKU) (OMIM#261600) disease, with more than 500 reported mutations. Through this study, a novel mutation in the PAH gene in an Iranian pedigree with phenylketonuria was introduced. Methods: A consanguineous family with a 10-year old affected girl was referred for genetic analysis. Mutation screening of all exons and exon-intron boundaries was performed by Sanger sequencing, and mini haplotype analysis was carried out by genotyping of Short Tandem Repeat (STR) and Variable Number Tandem Repeat (VNTR) alleles. Results: Mutation analysis revealed a novel homozygous insertion of a single adenine nucleotide at position 335 in exon 3 of the PAH gene. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, the change is interpreted as a pathogenic mutation which produces a premature termination signal (TAA) at codon 113 according to in silico assessments. The mini haplotype analysis showed that this mutation was linked to STR (15) –VNTR (3). Conclusion: In this study, a novel mutation was reported in a patient who had PKU symptoms without any previously reported mutations in the PAH gene (NM_000277.1: p.Asp112Glufs*2) that can be responsible for the classical PKU phenotype in the Iranian population. Detection of novel mutations indicates notable allelic heterogeneity of the PAH locus among this population. 146 149 Elaheh Alavinejad 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 Seyede Zahra Sajedi Immunology Research Center, Tabriz University of Medical SciencesDepartment of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences Immunology Research Center, Tabriz University of Medical SciencesDepartment of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences IranIran Masoumeh Razipour 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 Mona Entezam 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 Neda Mohajer 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 Aria Setoodeh Department of Pediatrics, Faculty of Medicine, Tehran University of Medical Sciences Department of Pediatrics, Faculty of Medicine, Tehran University of Medical Sciences Iran Saeid Talebi 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 Mohammad Keramatipour 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 MutationPhenylalanine hydroxylasePhenylketonuriasPopulation 283.pdf Scriver CR, Hurtubise M, Konecki D, Phommarinh M, Prevost L, Erlandsen H, et al. PAHdb 2003: what a locus-specific knowledgebase can do. Hum Mutat 2003;21(4):333-344##Zekanowski C, Jurkowska M, Bal J. Association between minihaplotypes and mutations at the PAH locus in Polish hyperphenylalaninemic patients. Hum Hered 2001;51(1-2):117-120.##Kwok SC, Ledley FD, DiLella AG, Robson KJ, Woo SL. Nucleotide sequence of a full-length complementary DNA clone and amino acid sequence of human phenylalanine hydroxylase. Biochemistry 1985;24(3):556-561.##Scriver CR, Beaudet AL, Sly WS. The metabolic basis of inherited disease. 1st ed. New York: McGraw-Hill; 1989. 170 p.##Scriver CR. The PAH gene, phenylketonuria, and a paradigm shift. Hum Mutat 2007;28(9):831845.##Smith I, Beasley MG, Ades AE. Intelligence and quality of dietary treatment in phenylketonuria. Arch Dis Child 1990;65(5):472-478.##Claustres M, Horaitis O, Vanevski M, Cotton RG. Time for a unified system of mutation description and reporting: a review of locus-specific mutation databases. Genome Res 2002;12(5):680-688.##Goltsov AA, Eisensmith RC, Konecki DS, Lichter-Konecki U, Woo SL. Associations between mutations and a VNTR in the human phenylalanine hydroxylase gene. Am J Hum Genet 1992;51(3):627-636.##Goltsov AA, Eisensmith RC, Naughton ER, Jin L, Charkraborty R, Woo SL. A single polymorphic STR system in the human phenylalanine hydroxylase gene permits rapid prenatal diagnosis and carrier screening for phenylketonuria. Hum Mol Genet 1993;2(5):577-581.##Choi Y, Sims GE, Murphy S, Miller JR, Chan AP. Predicting the functional effect of amino acid substitutions and indels. PLoS One 2012;7(10):e46688.##Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. A method and server for predicting damaging missense mutations. Nat Methods 2010;7(4):248-249.##Schwarz JM, Rodelsperger C, Schuelke M, Seelow D. Mutation Taster evaluates disease-causing potential of sequence alterations. Nat Methods 2010;7(8):575-576.##van der Velde KJ, Kuiper J, Thompson BA, Plazzer JP, van Valkenhoef G, de Haan M, et al. Evaluation of CADD scores in curated mismatch repair gene variants yields a model for clinical validation and prioritization. Hum Mutat 2015;36(7):712-719.##Richards CS, Bale S, Bellissimo DB, Das S, Grody WW, Hegde MR, et al. ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007. Genet Med 2008;10(4):294-300.##Alibakhshi R, Moradi K, Mohebbi Z, Ghadiri K. Mutation analysis of PAH gene in patients with PKU in western Iran and its association with polymorphisms: identification of four novel mutations. Metab Brain Dis 2014;29(1):131-138.##Zschocke J, Haverkamp T, Møller LB. Clinical utility gene card for: Phenylketonuria. Eur J Hum Genet 2012;20(2).##Flatmark T, Stevens RC. Structural insight into the aromatic amino acid hydroxylases and their disease-related mutant forms. Chem Rev 1999;99(8):21372160.##Kobe B, Jennings IG, House CM, Michell BJ, Goodwill KE, Santarsiero BD, et al. Structural basis of autoregulation of phenylalanine hydroxylase. Nat Struct Mol Biol 1999;6(5):442-448.##Baker KE, Parker R. Nonsense-mediated mRNA decay: terminating erroneous gene expression. Curr Opin Cell Biol 2004;16(3):293-299.##Chang YF, Imam JS, Wilkinson MF. The nonsense-mediated decay RNA surveillance pathway. Annu Rev Biochem 2007;76:51-74.##

Polymorphisms in the Estrogen Receptor Beta Gene and the Risk of Unexplained Recurrent Spontaneous Abortion 2 2 Background: Recurrent Spontaneous Abortion (RSA) is caused by multiple genetic and non-genetic factors. Around 50% of the RSA cases have no known etiology and are considered as Unexplained RSA (URSA). Estrogens, via binding to their receptors, play an important role in female reproduction. This study aimed to investigate whether single nucleotide polymorphisms (SNPs; +1082G/A, +1730G/A and rs1256030C/T) in the estrogen receptor beta (ESR2) gene are associated with susceptibility to URSA in a population of Iranian women. Methods: In this case-control study, the study groups consisted of 240 subjects with a history of URSA and 102 fertile women as controls. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were measured on day 2-3 of menstrual cycle. Two functional SNPs, +1082G/A (a silent mutation in exon 5) and +1730G/A (3' untranslated region of the exon 8),and one intron,rs1256030C/T, in the ESR2 gene were genotyped, using polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) analysis. Results: Serum levels of LH were significantly increased in URSA women. No significant differences in distribution of +1082G/A, +1730G/A and rs1256030C/T between URSA and control groups were observed. Conclusion: Our findings suggest that the studied SNPs on ESR2 gene may not be associated with URSA. 150 154 Marzieh Mahdavipour Reproductive Immunology Research Center, Avicenna Research Institute, ACECR Reproductive Immunology Research Center, Avicenna Research Institute, ACECR Iran Saeed Zarei Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Iran Ramina Fatemi Reproductive Immunology Research Center, Avicenna Research Institute, ACECR Reproductive Immunology Research Center, Avicenna Research Institute, ACECR Iran Haleh Edalatkhah Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran Hamed Heidari-Vala Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran Mahmood Jeddi-Tehrani Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Iran Farah Idali Reproductive Immunology Research Center, Avicenna Research Institute, ACECR Reproductive Immunology Research Center, Avicenna Research Institute, ACECR Iran Estrogen receptorHabitual abortionPolymerase chain reactionRestriction fragment length polymorphismSingle-nucleotide polymorphism 284.pdf Baek KH. Aberrant gene expression associated with recurrent pregnancy loss. Mol Hum Reprod 2004;10(5):291-297.##Idali F, Zareii S, Mohammad-Zadeh A, Reihany-Sabet F, Akbarzadeh-Pasha Z, Khorram-Khorshid HR, et al. Plasminogen activator inhibitor 1 and methylenetetrahydrofolate reductase gene mutations in iranian women with polycystic ovary syndrome. Am J Reprod Immunol 2012;68(5):400-407.##Ogasawara M, Aoki K, Okada S, Suzumori K. Embryonic karyotype of abortuses in relation to the number of previous miscarriages. Fertil Steril 2000;73(2):300-304##Hanna CW, Bretherick KL, Liu CC, Stephenson MD, Robinson WP. Genetic variation within the hypo-thalamus-pituitary-ovarian axis in women with recurrent miscarriage. Hum Reprod 2010;25(10):2664-2671.##Albrecht ED, Aberdeen GW, Pepe GJ. The role of estrogen in the maintenance of primate pregnancy. Am J Obstet Gynecol 2000;182(2):432-438.##Tsai MJ, O'Malley BW. Molecular mechanisms of action of steroid/thyroid receptor superfamily members. Annu Rev Biochem 1994;63:451-486.##Nilsson S, Gustafsson JA. Estrogen receptor transcription and transactivation: Basic aspects of estrogen action. Breast Cancer Res 2000;2(5):360-366.##Hewitt SC, Korach KS. Oestrogen receptor knockout mice: roles for oestrogen receptors alpha and beta in reproductive tissues. Reproduction 2003;125(2):143-149.##Hosokawa K, Ottander U, Wahlberg P, Ny T, Cajander S, Olofsson IJ. Dominant expression and distribution of oestrogen receptor beta over oestrogen receptor alpha in the human corpus luteum. Mol Hum Reprod 2001;7(2):137-145.##Sundarrajan C, Liao WX, Roy AC, Ng SC. Association between estrogen receptor-beta gene polymorphisms and ovulatory dysfunctions in patients with menstrual disorders. J Clin Endocrinol Metab 2001;86(1):135-139.##Sheikhha MH, Kalantar SM, Aflatoonian A. The relationship between estrogen receptor alpha gene polymorphism and ovarian response to ovulation induction in women under IVF treatment. J Reprod Infertil 2007;7(4):315-323.##Zulli K, Bianco B, Mafra FA, Teles JS, Christofolini DM, Barbosa CP. Polymorphism of the estrogen receptor β gene is related to infertility and infertility-associated endometriosis. Arq Bras Endocrinol Metabol 2010;54(6):567-571.##Govindan S, Shaik NA, Vedicherla B, Kodati V, Rao KP, Hasan Q. Estrogen receptor-alpha gene (T/C) Pvu II polymorphism in endometriosis and uterine fibroids. Dis Markers 2009;26(4):149-154.##Christofolini DM, Vilarino FL, Mafra FA, Andre GM, Bianco B, Barbosa CP. Combination of polymorphisms in luteinizing hormone β, estrogen receptor β and progesterone receptor and susceptibility to infertility and endometriosis. Eur J Obstet Gynecol Reprod Biol 2011;158(2):260-264.##Rousseau F, Réhel R, Rouillard P, DeGranpré P, Khandjian EW. High throughput and economical mutation detection and RFLP analysis using a minimethod for DNA preparation from whole blood and acrylamide gel electrophoresis. 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Major Components of Metabolic Parameters and Nutritional Intakes in Different Genotypes of Adiponectin +276 G>T Gene Polymorphism in Non-Diabetes and Non-Alcoholic Iranian Fatty Liver Patients 2 2 Background: Genetic and environmental factors are both involved in the etiology of Non-Alcoholic Fatty Liver Disease (NAFLD). Among the genetic factors, certain polymorphisms of adiponectin gene are associated with NAFLD. In the current study, we investigated the association between metabolic parameters with different genotypes of adiponectin +276 G>T polymorphism among the Iranian NAFLD patients, and the effect of nutritional intake with development of NAFLD. Methods: In this study, 75 patients with NAFLD and 76 healthy individuals were enrolled. Dietary intakes were assessed using a semi- quantitative Food-Frequency Questionnaire (FFQ). Body Mass Index (BMI) and Waist to Hip Ratio (WHR) were calculated. Biochemical assays including FSG (Fasting Serum Glucose), liver enzymes, lipid profiles, Malondialdehyde, insulin resistance and Total Antioxidant Capacity (TAC) were measured after 12 hr fasting. Gene polymorphism study was done by using of sequencing method. Results: Although, T allele frequency was more prevalent in patients with NAFLD than control, adiponectin +276 G>T polymorphism was not associated with risk of NAFLD. Among the metabolic parameters, TAC in TT genotype was significantly lower 1.44(0.69 to 2.81) p>0.05, AST in GT, GG genotypes, and ALT in all three genotypes were higher in NAFLD patients in compared to healthy subjects (p<0.05). Patients with GT genotype have significantly lower fat consumption and vitamin E intake as compared to control group with the same genotype (p<0.05). Conclusion: In this study, we showed the association of different genotypes of +276 G>T polymorphism in adiponectin gene with some metabolic parameters. 155 161 Fatemeh Mohseni Cellular and Molecular Research Center of Qazvin University of Medical Science Cellular and Molecular Research Center of Qazvin University of Medical Science Iran Sahar Moghbelinejad Cellular and Molecular Research Center of Qazvin University of Medical Science Cellular and Molecular Research Center of Qazvin University of Medical Science Iran Reza Najafipour Cellular and Molecular Research Center of Qazvin University of Medical Science Cellular and Molecular Research Center of Qazvin University of Medical Science Iran AdiponectinNonalcoholic fatty liver disease (NAFLD)Polymorphism 294.pdf Weiß J, Rau M, Geier A. Non-alcoholic fatty liver disease: epidemiology, clinical course, investigation, and treatment. Dtsch Arztebl Int 2014;111(26):447-452.##Hashemi M, Hanafi Bojd H, Eskandari Nasab E, Bahari A, Hashemzehi NA, Shafieipour S, et al. Association of adiponectin rs1501299 and rs266729 gene polymorphisms with nonalcoholic fatty liver disease. Hepat Mon 2013;13(5):e9527.##Lankarani KB, Ghaffarpasand F, Mahmoodi M, Lotfi M, Zamiri N, Heydari ST, et al. Non alcoholic fatty liver disease in southern Iran: a population based study. Hepat Mon 2013;13(5):e9248.##Wong VW, Wong GL, Tsang SW, Hui AY, Chan AW, Choi PC, et al. Genetic polymorphisms of adiponectin and tumor necrosis factor‐alpha and nonalcoholic fatty liver disease in Chinese people. J Gastroenterol Hepatol 2008;23(6):914-921.##Gaggini M, Morelli M, Buzzigoli E, DeFronzo RA, Bugianesi E, Gastaldelli A. Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease. 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Curr Opin Clin Nutr Metab Care 2008;11(4):477-482.##Hashemi kani A, Alavian SM, Esmaillzadeh A, Adibi P, Azadbakht L. Dietary quality indices and biochemical parameters among patients with non alcoholic fatty liver disease (NAFLD). Hepat Mon 2013;13(7):e10943.##Kalafati IP, Borsa D, Dedoussis GVZ. The genetics of nonalcoholic fatty liver disease: role of diet as a modifying factor. Curr Nutr Rep 2014;3(3):223-232.##Barrera F, George J. Non-alcoholic fatty liver disease: more than just ectopic fat accumulation. Drug Discov Today Dis Mech 2013;10(1-2):e47-e54.##Pagano C, Soardo G, Esposito W, Fallo F, Basan L, Donnini D, et al. Plasma adiponectin is decreased in nonalcoholic fatty liver disease. Eur J Endocrinol 2005;152(1):113-118.##Medina-Bravo P, Meza-Santibáñez R, Rosas-Fernández P, Galván-Duarte R, Saucedo-García R, Velázquez-López L, et al. Decrease in serum adiponectin levels associated with visceral fat accumulation independent of pubertal stage in children and adolescents. Arch Med Res 2011;42(2):115-121.##Leu HB, Chung CM, Lin SJ, Jong YS, Pan WH, Chen JW. Adiponectin gene polymorphism is selectively associated with the concomitant presence of metabolic syndrome and essential hypertension. PLoS One 2011;6(5):e19999.##Wong VW, Hui AY, Tsang SW, Chan JL, Tse AM, Chan KF, et al. Metabolic and adipokine profile of Chinese patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2006;4(9):1154-1161.##Melistas L, Mantzoros CS, Kontogianni M, Antonopoulou S, Ordovas JM, Yiannakouris N. Association of the +45T>G and +276G>T polymorphisms in the adiponectin gene with insulin resistance in nondiabetic Greek women. Eur J Endocrinol 2009;161(6):845-852.##Mohseni F, Rashvand Z, Najafipour R, Hadizadeh S, Moghbelinejad S. Evaluating -238 G>A polymorphism association in TNF-α gene with metabolic parameters and nutritional intakes among the Iranian NAFLD patients. Biochem Genet 2016;54(4):685-695.##Friedewald WT, Levy RI, Fredrickson DS. 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Influence of polygenetic polymorphisms on the susceptibility to non-alcoholic fatty liver disease of Chinese people. J Gastroenterol Hepatol 2010;25(4):772-777.##Utzschneider KM, Kahn SE. Review: The role of insulin resistance in nonalcoholic fatty liver disease. J Clin Endocrinol Metab 2006;91(12):4753-4761.##Musso G, Gambino R, De Michieli F, Cassader M, Rizzetto M, Durazzo M, et al. Dietary habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis. Hepatology 2003;37(4):909-916.##Wang ZL, Xia B, Shrestha U, Jiang L, Ma CW, Chen Q., et al. Correlation between adiponectin polymorphisms and non-alcoholic fatty liver disease with or without metabolic syndrome in Chinese population. J Endocrinol Invest 2008;31(12):1086-1091.##Erhardt A, Stahl W, Sies H, Lirussi F, Donner A, Häussinger D. Plasma levels of vitamin E and carotenoids are decreased in patients with nonalcoholic steatohepatitis (NASH). Eur J Med Res 2011;16(2):76-78.##Oliveira CP, Stefano JT. Genetic polymorphisms and oxidative stress in non-alcoholic steatohepatitis (NASH): a mini review. Clin Res Hepatol Gastroenterol 2015;39 Suppl 1:S35-40.##Schwarz JM, Linfoot P, Dare D, Aghajanian K. Hepatic de novo lipogenesis in normoinsulinemic and hyperinsulinemic subjects consuming high-fat, low-carbohydrate and low-fat, high-carbohydrate isoenergetic diets. Am J Clin Nutr 2003;77(1):43-50.##Solga S, Alkhuraishe AR, Clark JM, Torbenson M, Greenwald A, Diehl AM, et al. Dietary composition and nonalcoholic fatty liver disease. Dig Dis Sci 2004;49(10):1578-1583.##Loktionov A. Common gene polymorphisms and nutrition: emerging links with pathogenesis of multifactorial chronic diseases (review). J Nutr Biochem 2003;14(8):426-451.##