Innovation and Technology in Iran

en 28706604 Innovation and Technology in Iran 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 https://www.ajmb.org/En/Article.aspx?id=276 https://www.ajmb.org/PDF/En/FullText/276.pdf ShahinAkhondzadehPsychiatric Research Center, Roozbeh Hospital, South Kargar Street, Tehran, Iran739

en 28706605 Embryonic Stem Cell Conditioned Medium Supports In Vitro Maturation of Mouse Oocytes 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. Assisted reproductive technologies, Embryonic stem cells, Mice, Oocytes 114 119 https://www.ajmb.org/En/Article.aspx?id=277 https://www.ajmb.org/PDF/En/FullText/277.pdf SaberMirakiDepartment of Anatomy, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran1125AramMokarizadehDepartment of Immunology and Hematology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran1126OmidBanafshiCellular and Molecular Research Center, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran1181VahidehAssadollahiCellular and Molecular Research Center, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran1182MahdadAbdiDepartment of Anatomy, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran1127DaemRoshaniSocial Determinants of Health Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran1183FardinFathiCellular and Molecular Research Center, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran571

en 28706606 Biosynthesis of Silver Nanoparticles using Chlorella vulgaris and Evaluation of the Antibacterial Efficacy Against Staphylococcus aureus 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. Biosynthesis, Chlorella vulgaris, Nanoparticles, Silver 120 125 https://www.ajmb.org/En/Article.aspx?id=278 https://www.ajmb.org/PDF/En/FullText/278.pdf MohammadSoleimaniDepartment of Microbiology, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran133MaziarHabibi-PirkoohiDepartment of Microbiology, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran1129

en 28706607 Evaluation of Factors Affecting Size and Size Distribution of Chitosan-Electrosprayed Nanoparticles 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. Chitosan, Electrospray, Experimental design Nanoparticles, Particle size 126 132 https://www.ajmb.org/En/Article.aspx?id=279 https://www.ajmb.org/PDF/En/FullText/279.pdf MortezaAbyadehDepartment of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran1130Ali AkbarKarimi ZarchiDepartment of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran1131Mohammad AliFaramarziDepartment of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran931AmirAmaniDepartment of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran1132

en 28706608 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 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. Alzheimer disease, Gene expression, Herbal medicine 133 137 https://www.ajmb.org/En/Article.aspx?id=280 https://www.ajmb.org/PDF/En/FullText/280.pdf NiloofarBazazzadeganGenetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran930MarziehDehghan ShasaltanehLaboratory of Neuro-organic Chemistry, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran1007KioomarsSaliminejadReproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran393KooroshKamaliReproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran89MehdiBananGenetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran1152Hamid RezaKhorram KhorshidGenetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran42

en 28706609 Distribution of Class I Integron and smqnr Resistance Gene Among Stenotrophomonas maltophilia Isolated from Clinical Samples in Iran 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. Resistance, Stenotrophomonas maltophilia, Trimethoprim-sulfamethoxazole 138 141 https://www.ajmb.org/En/Article.aspx?id=281 https://www.ajmb.org/PDF/En/FullText/281.pdf MohammadaliMalekanMicrobiology Research Center, Pasteur Institute of Iran, Tehran, Iran1134BahmanTabaraieKousha Faravar Giti, Industrial Research Institute of Biotechnology, Tehran, Iran1135LadanAkhoundtabarDepartment of Microbiology, Azad University of Jahrom, Jahrom, Iran1136ParvizAfroughDepartment of Mycobacteriology and Pulmonary Research, Pasteur Institute, Tehran, Iran1137AvaBehrouziDepartment of Mycobacteriology and Pulmonary Research, Pasteur Institute, Tehran, Iran1138

en 28706610 A Novel Variant of OCT4 Entitled OCT4B3 is Expressed in Human Bladder Cancer and Astrocytoma Cell Lines 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. Alternative splicing, Cell line, Gene, Stem cells 142 145 https://www.ajmb.org/En/Article.aspx?id=282 https://www.ajmb.org/PDF/En/FullText/282.pdf Ensieh M.PoursaniDepartment of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran1139MajidMehravarDepartment of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran1140BahramMohammad SoltaniDepartment of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran1141Seyed JavadMowlaDepartment of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran248James E.TroskoFood Safety Toxicology Center, Department of Pediatrics and Human Development, Michigan State University, East Lansing, Michigan (MI), USA1142

en 28706611 A Novel Variant in the PAH Gene Causing Phenylketonuria in an Iranian Pedigree 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. Mutation, Phenylalanine hydroxylase, Phenylketonurias, Population 146 149 https://www.ajmb.org/En/Article.aspx?id=283 https://www.ajmb.org/PDF/En/FullText/283.pdf ElahehAlavinejadDepartment of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran1143Seyede ZahraSajediDepartment of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran1144MasoumehRazipourDepartment of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran1145MonaEntezamDepartment of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran1146NedaMohajerDepartment of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran1147AriaSetoodehDepartment of Pediatrics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran1148SaeidTalebiDepartment of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran735MohammadKeramatipourDepartment of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran18

en 28706612 Polymorphisms in the Estrogen Receptor Beta Gene and the Risk of Unexplained Recurrent Spontaneous Abortion 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. Estrogen receptor, Habitual abortion, Polymerase chain reaction, Restriction fragment length polymorphism, Single-nucleotide polymorphism 150 154 https://www.ajmb.org/En/Article.aspx?id=284 https://www.ajmb.org/PDF/En/FullText/284.pdf MarziehMahdavipourReproductive Immunology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran1149SaeedZareiMonoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran1150RaminaFatemiReproductive Immunology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran849HalehEdalatkhahReproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran1151HamedHeidari-ValaReproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran258MahmoodJeddi-TehraniMonoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran15FarahIdaliReproductive Immunology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran855

en 28706613 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 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. Adiponectin, Nonalcoholic fatty liver disease (NAFLD), Polymorphism 155 161 https://www.ajmb.org/En/Article.aspx?id=294 https://www.ajmb.org/PDF/En/FullText/294.pdf FatemehMohseniCellular and Molecular Research Center of Qazvin University of Medical Science, Qazvin, Iran1184SaharMoghbelinejadCellular and Molecular Research Center of Qazvin University of Medical Science, Qazvin, Iran1185RezaNajafipourCellular and Molecular Research Center of Qazvin University of Medical Science, Qazvin, Iran1186