Appropriate Scaffold Selection for CNS Tissue Engineering 2 2 Cellular transplantation, due to the low regenerative capacity of the Central Nervous System (CNS), is one of the promising strategies in the treatment of neurodegenerative diseases. The design and application of scaffolds mimicking the CNS extracellular matrix features (biochemical, bioelectrical, and biomechanical), which affect the cellular fate, are important to achieve proper efficiency in cell survival, proliferation, and differentiation as well as integration with the surrounding tissue. Different studies on natural materials demonstrated that hydrogels made from natural materials mimic the extracellular matrix and supply microenvironment for cell adhesion and proliferation. The design and development of cellular microstructures suitable for neural tissue engineering purposes require a comprehensive knowledge of neuroscience, cell biology, nanotechnology, polymers, mechanobiology, and biochemistry. In this review, an attempt was made to investigate this multidisciplinary field and its multifactorial effects on the CNS microenvironment. Many strategies have been used to simulate extrinsic cues, which can improve cellular behavior toward neural lineage. In this study, parallel and align, soft and injectable, conductive, and bioprinting scaffolds were reviewed which have indicated some successes in the field. Among different systems, three-Dimensional (3D) bioprinting is a powerful, highly modifiable, and highly precise strategy, which has a high architectural similarity to tissue structure and is able to construct controllable tissue models. 3D bioprinting scaffolds induce cell attachment, proliferation, and differentiation and promote the diffusion of nutrients. This method provides exceptional versatility in cell positioning that is very suitable for the complex Extracellular Matrix (ECM) of the nervous system. 203 220 Akram Shafiee Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical SciencesNanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical SciencesNanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences IranIran Hanie Ahmadi Department of Polymer Engineering, Amirkabir University of Technology Department of Polymer Engineering, Amirkabir University of Technology Iran Behnaz Taheri Department of Stem Cell Biology, Stem Cell Technology Research Center Iran Simzar Hosseinzadeh Faculty of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences Faculty of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences Iran Yousef Fatahi Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences Iran Masoud Soleimani Department of Hematology and Blood Banking, Faculty of Medicine, Tarbiat Modaress University Department of Hematology and Blood Banking, Faculty of Medicine, Tarbiat Modaress University Iran Fatemeh Atyabi Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical SciencesNanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences (TUMS) Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical SciencesNanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences (TUMS) IranIran Rassoul Dinarvand Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences (TUMS) Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences (TUMS) Iran BioprintingCell differentiationExtracellular matrixNeurodegenerative diseasesTissue engineering 30426.pdf Kiaei M. New hopes and challenges for treatment of neurodegenerative disorders: Great opportunities for young neuroscientists. Basic Clin Neurosci 2013;4(1):3-4. ##Johnson GS. Commercial viability of CNS drugs: Balancing the risk/reward profile. Neurobiol Dis 2014; 61:21-24. ##Brunner D, Balcı F, Ludvig EA. Comparative psychology and the grand challenge of drug discovery in psychiatry and neurodegeneration. Behav Processes 2012;89(2):187-195.##Xiao L, Saiki C, Ide R. Stem cell therapy for central nerve system injuries: glial cells hold the key. Neural Regen Res 2014;9(13):1253-1260.##Li X, Katsanevakisa E, Liua X, Zhangab N, Wen X. Engineering neural stem cell fates with hydrogel design for central nervous system regeneration. Prog Polym Sci 2012;37(8):1105-1129.##Tam RY, Fuehrmann T, Mitrousis N, Shoichet MS. Regenerative therapies for central nervous system diseases: a biomaterials approach. Neuropsychopharmacology 2014;39(1):169-188.##Siddiqi F, Wolfe JH. Stem cell therapy for the central nervous system in lysosomal storage diseases. Hum Gene Ther 2016;27(10):749-757. ##Triolo F, Srivastava AK. Current Approaches to Tissue Engineering of the Nervous System. In: Roger De Filippo (Ed.). Encyclopedia of Tissue Engineering and Regenerative Medicine. Elsevier Ltd., Oxford. 2018.##Raynald, Shu B, Liu XB, Zhou JF, Huang H, Wang JY, et al. Polypyrrole/polylactic acid nanofibrous scaffold cotransplanted with bone marrow stromal cells promotes the functional recovery of spinal cord injury in rats. CNS Neurosci Ther 2019;25(9):951-964.##Zamproni LN, Grinet MAVM, Mundim MTVV, Reis MBC, Galindo LT, Marcian FR, et al. Rotary jet-spun porous microfibers as scaffolds for stem cells delivery to central nervous system injury. Nanomedicine 2019;15(1):98-107.##Yang L, Chueng STD, Li Y, Patel M, Rathnam C, Dey G, et al. A biodegradable hybrid inorganic nanoscaffold for advanced stem cell therapy. Nat Commun 2018;9(1):1-14.##Brodmann, K., Brodmann's: Localisation in the cerebral cortex. 2007: Springer Science & Business Media.##Wickens, A., Introduction to biopsychology. 2009: Pearson Education.##Shaham S. Glia-neuron interactions in nervous system function and development. Curr Top Dev Biol 2005;69:39-66.##von Bartheld CS, Bahney J, Herculano‐Houzel S. The search for true numbers of neurons and glial cells in the human brain: A review of 150 years of cell counting. J Comp Neurol 2016;524(18):3865-3895. ##Azevedo FA, Carvalho LRB, Grinberg LT, Farfel JM, Ferretti REL, Leite REP, et al. Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled‐up primate brain. J Comp Neurol 2009;513(5):532-541. ##Araque A, Navarrete M. Glial cells in neuronal network function. Philos Trans R Soc Lond B Biol Sci 2010;365(1551):2375-2381.##Sapir L, Tzlil S. Talking over the extracellular matrix: How do cells communicate mechanically? Semin Cell Dev Biol 2017;71:99-105. ##Lovinger DM. Communication networks in the brain: neurons, receptors, neurotransmitters, and alcohol. Alcohol Res Health 2008;31(3):196-214.##Bath KG, Mandairon N, Jing D, Rajagopal R, Kapoor R, Chen ZY, et al. Variant brain-derived neurotrophic factor (Val66Met) alters adult olfactory bulb neurogenesis and spontaneous olfactory discrimination. J Neurosci 2008;28(10):2383-2393.##Young KM, Merson TD, Sotthibundhu A, Coulson EJ, Bartlett PF. p75 neurotrophin receptor expression defines a population of BDNF-responsive neurogenic precursor cells. J Neurosci 2007;27(19):5146-5155.##Zhao M, Dan Li, Shimazu K, Zhou YX, Lu B, Deng CX. Fibroblast growth factor receptor-1 is required for long-term potentiation, memory consolidation, and neurogenesis. Biol Psychiatry 2007;62(5):381-390.##Yanpallewar SU, Fernandes K, Marathe SV, Vadodaria KC, Jhaveri D, Rommelfanger K,et al. α2-adrenoceptor blockade accelerates the neurogenic, neurotrophic, and behavioral effects of chronic antidepressant treatment. J Neurosci 2010;30(3):1096-1109.##Duan W, Peng Q, Masuda N, Ford E, Tryggestad E, Ladenheim B, et al. Sertraline slows disease progression and increases neurogenesis in N171-82Q mouse model of Huntington's disease. Neurobiol Dis 2008;30(3):312-322.##Davis EA, Zhou W, Dailey MJ. Evidence for a direct effect of the autonomic nervous system on intestinal epithelial stem cell proliferation. Physiol Rep 2018;6(12):e13745. ##Landgraf D, Barth M, Layer PG, Sperling LE. Acetylcholine as a possible signaling molecule in embryonic stem cells: studies on survival, proliferation and death. Chem Biol Interact 2010;187(1-3):115-119. ##Tang JM, Yuan J, Li Q, Wang JN, Kong X, Zheng F, et al., Acetylcholine induces mesenchymal stem cell migration via Ca2+/PKC/ERK1/2 signal pathway. J Cell Biochem 2012;113(8):2704-2713.##Laifenfeld D, Klein E, Ben‐Shachar D. Norepinephrine alters the expression of genes involved in neuronal sprouting and differentiation: relevance for major depression and antidepressant mechanisms. J Neurochem 2002;83(5):1054-1064.##Molina‐Hernández A, Velasco I. Histamine induces neural stem cell proliferation and neuronal differentiation by activation of distinct histamine receptors. J Neurochem 2008;106(2):706-717.##Carozzi V, Marmiroli P, Cavaletti G. Focus on the role of glutamate in the pathology of the peripheral nervous system. CNS Neurol Disord Drug Targets 2008;7(4):348-360.##Furukawa H, Singh SK, Mancusso R, Gouaux E. Subunit arrangement and function in NMDA receptors. Nature 2005;438(7065):185-192. ##Follmar K, Decroos FC, Prichard HL, Wang HT, Erdmann D, Olbrich KC. Effects of glutamine, glucose, and oxygen concentration on the metabolism and proliferation of rabbit adipose-derived stem cells. Tissue Eng 2006;12(12):3525-3533. ##Ota N, Shi T, Sweedler JV. D-Aspartate acts as a signaling molecule in nervous and neuroendocrine systems. Amino Acids 2012;43(5):1873-1886. ##O'Keeffe GC, Tyers P, Aarsland D, Dalley JW, Barker RA, Caldwell MA. Dopamine-induced proliferation of adult neural precursor cells in the mammalian subventricular zone is mediated through EGF. Proc Natl Acad Sci U S A 2009;106(21):8754-8759. ##Förstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J 2012;33(7):829-837.##Estrada C, Murillo-Carretero MM. Nitric oxide and adult neurogenesis in health and disease. Neuroscientist 2005;11(4):294-307. ##Kuriyama K, Ohkuma S. Role of nitric oxide in central synaptic transmission: effects on neurotransmitter release. Jpn J Pharmacol 1995;69(1):1-8. ##Bortolozzi A, Díaz-Mataix L, Cecilia Scorza M, Celada P, Artigas F. The activation of 5‐HT2A receptors in prefrontal cortex enhances dopaminergic activity. J Neurochem 2005;95(6):1597-1607. ##Lv J, Liu F. The role of serotonin beyond the central nervous system during embryogenesis. Front Cell NeuroscI 2017;11:74.##Kemp PJ, Rushton DJ, Yarova PL, Schnell C, Geater C, Hancock JM, et al. Improving and accelerating the differentiation and functional maturation of human stem cell‐derived neurons: role of extracellular calcium and GABA. J Physiol 2016;594(22):6583-6594. ##Salazar P, Velasco-Velázquez MA, Velasco I. GABA effects during neuronal differentiation of stem cells. Neurochem Res 2008;33(8):1546-1557. ##Avila A, Nguyen L, Rigo JM. Glycine receptors and brain development. Front Cell Neurosci 2013;7:184. ##Abdelhamid Bekri A, Liao M, Drapeau P. Glycine regulates neural stem cell proliferation during development via Lnx1-dependent Notch signaling. Front Mol Neurosci 2019;12:44. ##McConell TH, Hull KL. Human Form, Human Function: Essentials of Anatomy & Physiology. Lippincott Williams & Wilkins: 2011. 778 p.##Pereda AE. Electrical synapses and their functional interactions with chemical synapses. Nat Rev Neurosci 2014;15(4):250-263.##Horst W. Biochemical and physiological processes in brain function and drug actions. In: Preskorn SH, Feighner JP, Stanga CY, Ross R, (eds). Antidepressants: Past, Present and Future. Berlin, Heidelberg; Springer: 2004. p. 3-33.##Söhl G, Maxeiner S, Willecke K. Expression and functions of neuronal gap junctions. Nat Rev Neurosci 2005;6(3):191-200. ##Yang C, Zhang X, Guo Y , Meng F, Sachs F, Guo J. Mechanical dynamics in live cells and fluorescence-based force/tension sensors. Biochim Biophys Acta 2015;1853(8):1889-1904. ##Tyler WJ. The mechanobiology of brain function. Nat Rev Neurosci 2012;13(12):867-78. ##Donoghue PS, Lamond R, Boomkamp SD, Sun T, Gadegaard N, Riehle MO, Barnett SC. The development of a ɛ-polycaprolactone scaffold for central nervous system repair. Tissue Engineering Part A 2012;19(3-4):497-507.##Desai NS. Homeostatic plasticity in the CNS: synaptic and intrinsic forms. J Physiol Paris 2003;97(4-6):391-402. ##Gordon‐Weeks PR, Fournier AE. Neuronal cytoskeleton in synaptic plasticity and regeneration. J Neurochem 2014;129(2):206-212.##Franze K, Janmey PA, Guck J. Mechanics in neuronal development and repair. Annu Rev Biomed Eng 2013;15:227-251. ##Pham JT, Xue L, del Campo A, Salierno M. Guiding cell migration with microscale stiffness patterns and undulated surfaces. Acta Biomater 2016;38:106-115.##Holtzmann K, Gautier HOB, Christ AF, Guck J, Káradóttir RT, Franze K. Brain tissue stiffness is a sensitive marker for acidosis. J Neurosci Methods 2016;271:50-54.##Hormuzdi SG, Filippov MA, Mitropoulou G, Monyer H, Bruzzone R. Electrical synapses: a dynamic signaling system that shapes the activity of neuronal networks. Biochim Biophys Acta 2004;1662(1-2):113-137. ##Weickenmeier J, de Rooij R, Budday S , Steinmann P , Ovaert TC, Kuhl E. Brain stiffness increases with myelin content. Acta Biomater 2016;42:265-272.##Campos-Cantón I, Rangel-Lopez A, Martel-Gallegose G, Zarazua S, Vertiz-Hernandez A. An experimental electronic model for a neuronal cell. Eur J Phys 2014;35(3):035007.##Oakland RJ, Hall RM, Wilcox RK, Barton DC. The biomechanical response of spinal cord tissue to uniaxial loading. Proc Inst Mech Eng H 2006;220(4):489-492. ##Al-Habib A, Albakr A , Al Towim A, Alkubeyyer M, Abu Jamea A, Albadr F, et al. In vivo assessment of spinal cord elasticity using shear wave ultrasound in dogs. J Neurosurg Spine 2018;29(4):461-469. ##Medberry CJ. Central Nervous System Extracellular Matrix as a Therapeutic Bioscaffold for Central Nervous System Injury. 2014, University of Pittsburgh. Doctoral Dissertation. (Unpublished) http://d-scholarship.pitt.edu/20084/##Barnes JM, Przybyla L, Weaver VM. Tissue mechanics regulate brain development, homeostasis and disease. J Cell Sci 2017;130(1):71-82. ##Ohno N, Zhou H, Terada N, Ohno S. Extracellular space in central nervous system. In: Ohno S, Ohno N, Terada N, editors. In vivo cryotechnique in biomedical research and application for bioimaging of living animal organs. Japan: Springer; 2016. p. 175-178.##Barros CS, Franco SJ, Müller U. Extracellular matrix: functions in the nervous system. Cold Spring Harbor Perspect Biol 2011;3(1):a005108.##Brown NH. Extracellular matrix in development: insights from mechanisms conserved between invertebrates and vertebrates. Cold Spring Harbor Perspect Biol 2011;3(12):a005082. ##Sheppard AM, Hamilton SK, Pearlman AL. Changes in the distribution of extracellular matrix components accompany early morphogenetic events of mammalian cortical development. J Neurosci 1991;11(12):3928-3942.##Franco SJ, Müller U. Extracellular matrix functions during neuronal migration and lamination in the mammalian central nervous system. Dev Neurobiol 2011;71(11):889-900. ##Kjær M, Fabricius K, Sigaard RK, Pakkenberg B. Neocortical development in brain of young children—A stereological study. Cereb Cortex 2016;27(12):5477-5484. ##Carulli D, Kwok JC, Pizzorusso T. Perineuronal nets and CNS plasticity and repair. Neural Plasti 2016;2016:4327082. ##Frade JM, Ovejero-Benito MC. Neuronal cell cycle: the neuron itself and its circumstances. Cell Cycle 2015;14(5):712-720. ##Sorg BA, Berretta S, Blacktop JM, Fawcett JW , Kitagawa H, Kwok JCF, et al. Casting a wide net: role of perineuronal nets in neural plasticity. J Neuroscience 2016;36(45):11459-11468. ##Reichardt L, Prokop A. Introduction: the role of extracellular matrix in nervous system development and maintenance. Dev Neurobiol 2011;71(11):883-888.##Milošević NJ, Judaš M, Aronica E, Kostovic I. Neural ECM in laminar organization and connectivity development in healthy and diseased human brain. Prog Brain Res 2014;214:159-178. ##Ahmed M, Constant CF. Extracellular matrix regulation of stem cell behavior. Curr Stem Cell Rep 2016;2(3):197-206. ##Gattazzo F, Urciuolo A, Bonaldo P. Extracellular matrix: a dynamic microenvironment for stem cell niche. Biochim Biophys Acta Gen Subj 2014;1840(8):2506-2519.##Rozario T, DeSimone DW. The extracellular matrix in development and morphogenesis: a dynamic view. Developmental Biol 2010;341(1):126-140. ##Haggerty AE, Marlow MM, Oudega M. Extracellular matrix components as therapeutics for spinal cord injury. Neurosci Lett 2017;652:50-55.##Burnside E, Bradbury E.Manipulating the extracellular matrix and its role in brain and spinal cord plasticity and repair. Neuropathol Appl Neurobiol 2014;40(1):26-59. ##Miyata S, Komatsu Y, Yoshimura Y, Taya C, Kitagawa H. Persistent cortical plasticity by upregulation of chondroitin 6-sulfation. Nat Neurosci 2012;15(3):414. ##Reichardt LF, Tomaselli KJ. Extracellular matrix molecules and their receptors: functions in neural development. Annu Rev Neurosci 1991;14(1):531-570. ##Chen S, Lewallen M, Xie T. Adhesion in the stem cell niche: biological roles and regulation. Development 2013;140(2):255-265.##Togashi H, Sakisaka T, Takai Y. Cell adhesion molecules in the central nervous system. Cell Adh Migr 2009;3(1):29-35. ##Bukalo O, Dityatev A. Synaptic cell adhesion molecules. Adv Exp Med Biol 2012;970:97-128. ##Jang S, Lee H, Kim E. Synaptic adhesion molecules and excitatory synaptic transmission. Curr Opin Neurobiol 2017;45:45-50. ##Cui H, Freeman C, Jacobson GA, Small DH. Proteoglycans in the central nervous system: role in development, neural repair, and Alzheimer's disease. IUBMB life 2013;65(2):108-120. ##Lu P, Tuszynski MH. Growth factors and combinatorial therapies for CNS regeneration. Exp Neurol 2008;209(2):313-320.##Sanford SD, Gatlin JC, Hökfelt T, Pfenninger KH. Growth cone responses to growth and chemotropic factors. Eur J Neurosci 2008;28(2):268-278. ##Adams JC, Tucker RP. The thrombospondin type 1 repeat (TSR) superfamily: diverse proteins with related roles in neuronal development. Dev Dyn 2000;218(2):280-299. ##Tucker RP. The thrombospondin type 1 repeat superfamily. Int J Biochem Cell Biol 2004;36(6):969-974. ##He J, Wang XM, Spector M, Cyi FZ. Scaffolds for central nervous system tissue engineering. Front Mater Sci 2012;6(1):1-25.##Mammadov B, Sever M, Guler MO, Tekinay AB. Neural differentiation on synthetic scaffold materials. Biomater Sci 2013;1(11):1119-1137.##Carone TW, Hasenwinkel JM. Mechanical and morphological characterization of homogeneous and bilayered poly (2‐hydroxyethyl methacrylate) scaffolds for use in CNS nerve regeneration. J Biomed Mater Res B Appl Biomater 2006;78(2):274-282.##Manes TA, Rose MJ. Rigid scaffolds for the design of molecular catalysts and biomimetic active sites: A case study of anthracene-based ligands for modeling mono-iron hydrogenase (Hmd). Coord Chem Rev 2017;353:295-308.##Murphy AR, Laslett A, O'Brien CM, Cameron NR. Scaffolds for 3D in vitro culture of neural lineage cells. Acta Biomater 2017;54:1-20. ##Mammadov B, Sever M, Guler MO, Tekinay AB. Neural differentiation on synthetic scaffold materials. Biomater Sci 2013;1:1119-1137. ##Shoffstall AJ, Taylor DM, Lavik EB. Engineering therapies in the CNS: What works and what can be translated. Neurosci Lett 2012;519(2):147-154. ##Knowlton S, Anand S, Shah T, Tasoglu S. Bioprinting for neural tissue engineering. Trends Neurosci 2018;41(1):31-46.##Esmaeili E, Soleimani M, Ghiass MA, Hatamie S, Vakilian S, Soufi Zomorrod M, et al. Magnetoelectric nanocomposite scaffold for high yield differentiation of mesenchymal stem cells to neural‐like cells. J Cell Physiol 2019;234(8):13617-13628.##Xia B, Huang L, Zhu L, Liu Z, Ma T, Zhu S, et al. Manipulation of schwann cell migration across the astrocyte boundary by polysialyltransferase-loaded superparamagnetic nanoparticles under magnetic field. Int J Nanomedicine 2016;11:6727-6741. ##Dubey N, Letourneau P, Tranquillo R. Guided neurite elongation and Schwann cell invasion into magnetically aligned collagen in simulated peripheral nerve regeneration. Exp Neurol 1999;158(2):338-350. ##Antman-Passig M, Shefi O. Remote magnetic orientation of 3D collagen hydrogels for directed neuronal regeneration. Nano Lett 2016;16(4):2567-2573.##Yang EZ, Zhang EZ, Xu JG , Chen S, Wang H, Cao LL, et al. Multichannel polymer scaffold seeded with activated Schwann cells and bone mesenchymal stem cells improves axonal regeneration and functional recovery after rat spinal cord injury. Acta Pharmacol Sin 2017;38(5):623-637. ##Zhang X, Aoyama T, Yasuda T, Oike M, Ito A, Tajino J, et al. Effect of microfabricated microgroove-surface devices on the morphology of mesenchymal stem cells. Biomed Microdevices 2015;17(6): 116.##Xi Y, Pozzo LD. Electric field directed formation of aligned conjugated polymer fibers. Soft Matter 2017;13(21):3894-3908.##Weightman A, Jenkins S, Pickard M, Chari D, Yang Y. Alignment of multiple glial cell populations in 3D nanofiber scaffolds: toward the development of multicellular implantable scaffolds for repair of neural injury. Nanomedicine 2014;10(2):291-295.##Shi X, Zhou W, Ma D, Ma Q, Bridges D, Ma Y, et al. Electrospinning of nanofibers and their applications for energy devices. J Nanomater 2015;16(1):122.##Kenry Lim CT. Nanofiber technology: current status and emerging developments. Prog Polym Sci 2017;70:1-17.##De Mulder EL, Buma P, Hannink G. Anisotropic porous biodegradable scaffolds for musculoskeletal tissue engineering. Materials 2009;2(4):1674-1696. ##Zhang Z, Rouabhia M, Wang Z, Roberge C, Shi G, Roche P, et al. Electrically conductive biodegradable polymer composite for nerve regeneration: electricity‐stimulated neurite outgrowth and axon regeneration. Artif Organs 2007;31(1):13-22. ##Ghasemi-Mobarakeh L, Prabhakaran MP, Morshed M, Nasr-Esfahani MH, Ramakrishna S. Electrical stimulation of nerve cells using conductive nanofibrous scaffolds for nerve tissue engineering. Tissue Engineering Part A 2009;15(11):3605-3619. ##Guo B, Ma PX. Conducting polymers for tissue engineering. Biomacromolecules 2018;19(6):1764-1782. ##Baranes K, Shevach M, Shefi O, Dvir T. Gold nanoparticle-decorated scaffolds promote neuronal differentiation and maturation. Nano Lett 2015;16(5):2916-2920.##Zhou Z, Liu X, Wu W, Park S, Miller Ii AL, Terzic A, et al. Effective nerve cell modulation by electrical stimulation of carbon nanotube embedded conductive polymeric scaffolds. Biomater Sci 2018;6(9):2375-2385. ##Gu BK, Kim MS, Kang CM, Kim JL, Park SJ, Kim CH. Fabrication of conductive polymer-based nanofiber scaffolds for tissue engineering applications. J Nanosci Nanotechnol 2014;14(10):7621-7626. ##Ghasemi‐Mobarakeh L, Prabhakaran MP, Morshed M, Nasr-Esfahani MH, Baharvand H, Kiani S, et al. Application of conductive polymers, scaffolds and electrical stimulation for nerve tissue engineering. J Tissue Eng Regen Med 2011;5(4):e17-e35. ##Harris AR, Wallace GG. Organic electrodes and communications with excitable cells. Adv Mater Interfaces 2018;28(12):1700587.##Kaur G, Adhikari R, Cass P, Bown M, Gunatillake P. Electrically conductive polymers and composites for biomedical applications. RSC Adv 2015;5(47):37553-37567.##Wu Y, Wang L, Hu T, Ma PX, Guo B. Conductive micropatterned polyurethane films as tissue engineering scaffolds for Schwann cells and PC12 cells. J Colloid Interface Sci 2018;518:252-262. ##Xie J, MacEwan MR, Willerth SM, Li X, Moran DW, Sakiyama-Elbert SE, et al. Conductive core–sheath nanofibers and their potential application in neural tissue engineering. Adv Funct Mater 2009;19(14):2312-2318. ##Yow SZ, Lim TH, Yim EKF, Lim Ct, Leong KM. A 3D electroactive polypyrrole-collagen fibrous scaffold for tissue engineering. Polymers 2011;3(1):527-544.##Ferraz N, Strømme M, Fellström B, Pradhan S, Nyholm L, Mihranyan A. In vitro and in vivo toxicity of rinsed and aged nanocellulose–polypyrrole composites. J Biomed Mate Res Part A 2012;100(8):2128-2138. ##Liu X, Kim JC, Lee Miller A, Waletzki BE, Lu L. Electrically conductive nanocomposite hydrogels embedded with functionalized carbon nanotubes for spinal cord injury. New J Chem 2018;42(21):17671-17681.##Kabiri M, Soleimani M, Shabani I, Futrega K, Ghaemi N, Hanaee Ahvaz H, et al. Neural differentiation of mouse embryonic stem cells on conductive nanofiber scaffolds. Biotechnol Lett 2012;34(7):1357-1365.##Kuzmenko V, Kalogeropoulosc T, Thunbergac J, Johannessonc S, Häggc D, Enoksson P, et al. Enhanced growth of neural networks on conductive cellulose-derived nanofibrous scaffolds. Mater Sci Engineering: C 2016;58:14-23.##Chen YS, Hsiue GH. Directing neural differentiation of mesenchymal stem cells by carboxylated multiwalled carbon nanotubes. Biomaterial 2013;34:4936-4944.##Sridharan I, Kim T, Strakova Z, Wang R. Matrix-specified differentiation of human decidua parietalis placental stem cells. Biochem Biophy Res Commun 2013;437:489-495. ##Bhatnagar R, Li S. Biomimetic scaffolds for tissue engineering. Conf Proc IEEE Eng Med Biol Soc 2004;2004:5021-5023. ##Nisbet DR, Crompton KE, Horne MK, Finkelstein DI, Forsythe JS. Neural tissue engineering of the CNS using hydrogels. J Biomed Mater Res B Appl Biomater 2008;87(1):251-263. ##Zhu J, Marchant RE. Design properties of hydrogel tissue-engineering scaffolds. Expert Rev Med Devices 2011;8(5):607-626. ##Li J, Mooney DJ. Designing hydrogels for controlled drug delivery. Nature Reviews Materials 2016; 1(12):16071.##Mosahebi A, Fuller P, Wiberg M, Terenghi G. Effect of allogeneic Schwann cell transplantation on peripheral nerve regeneration. Exp Neurol 2002;173(2):213-223. ##Suzuki Y, Kitaura M, Wu S, Kataoka K, Suzuki K, Endo K, et al., Electrophysiological and horseradish peroxidase-tracing studies of nerve regeneration through alginate-filled gap in adult rat spinal cord. Neurosci Lett 2002;318(3):121-124.##Tian W, Hou SP, Ma J, Zhang CL, Xu QY, Lee IS, et al. Hyaluronic acid–poly-D-lysine-based three-dimensional hydrogel for traumatic brain injury. Tissue Eng 2005;11(3-4):513-525. ##Yuan Y, Zhang P, Yang Y, Wang X, Gu X. The interaction of schwann cells with chitosan membranes and fibers in vitro. Biomaterials 2004;25(18):4273-4278.##Tsai EC, Dalton PD, Shoichet MS, Tator CH. Synthetic hydrogel guidance channels facilitate regeneration of adult rat brainstem motor axons after complete spinal cord transection. J Neurotrauma 2004;21(6):789-804.##Urbanski MM, Kingsbury L, Moussouros D, Kassim I, Mehjabeen S, Paknejadet N, et al. Myelinating glia differentiation is regulated by extracellular matrix elasticity. Sci Rep 2016;6:33751.##Koffler J, Zhu W, Qu X, Platoshyn O, Dulin JN, Brocket J, et al. Biomimetic 3D-printed scaffolds for spinal cord injury repair. Nat Med 2019;25(2):263-269. ##Kothapalli CR, Kamm RD. 3D matrix microenvironment for targeted differentiation of embryonic stem cells into neural and glial lineages. Biomaterials 2013;34(25):5995-6007. ##Ning L, Xu Y, Chen X, Schreyer DJ. Influence of mechanical properties of alginate-based substrates on the performance of Schwann cells in culture. J Biomater Sci Polym Ed 2016;27(9):898-915. ##Mori H, Hara M. Clusters of neural stem/progenitor cells cultured on a soft poly (vinyl alcohol) hydrogel crosslinked by gamma irradiation. J Biosci Bioeng 2016;121(5):584-590. ##Chang B, Ahuja N , Ma C, Liu X. Injectable scaffolds: Preparation and application in dental and craniofacial regeneration. Mater Sci Eng R Rep 2017;111:1-26. ##Johnson CD, Ganguly D, Zuidema JM, Cardinal TJ, Ziemba AM, Kearnset KR, et al. Injectable, magnetically orienting electrospun fiber conduits for neuron guidance. ACS Appl Mater Interfaces 2019;11(1):356-372.##Wang TW, Chang KC, Chen LH, Liao SY, Yeh CW, Chuang YJ. Effects of an injectable functionalized self-assembling nanopeptide hydrogel on angiogenesis and neurogenesis for regeneration of the central nervous system. Nanoscale 2017;9(42):16281-16292. ##Wang Y, Tan H, Hui X. Biomaterial scaffolds in regenerative therapy of the central nervous system. BioMed Res Int 2018. 2018.##Hoffman AS. Hydrogels for biomedical applications. Ann N Y Acad Sci 2012;944:62-73. ##Chung HJ, Park TG. Self-assembled and nanostructured hydrogels for drug delivery and tissue engineering. Nano Today 2009;4(5):429-437.##Zhao T, Sellers DL, Cheng Y, Horner PJ, Pun SH. Tunable, injectable hydrogels based on peptide-cross-Linked, cyclized polymer nanoparticles for neural progenitor cell delivery. Biomacromolecules 2017;18(9):2723-2731. ##Broguiere N, Isenmann L, Zenobi-Wong M. Novel enzymatically cross-linked hyaluronan hydrogels support the formation of 3D neuronal networks. Biomaterials 2016;99:47-55. ##Mekhail M, Cui QL, Almazan G, Antel J. Chitosan sponge containing brain derived neurotrophic factor (BDNF) to enhance human oligodendrocyte progenitor cells'(OPC) differentiation. MRS Online Proceedings Library Archive, 2014;1621:127-132##Domingues HS, Portugal CC,Socodato R,Relvas JB. Oligodendrocyte, astrocyte, and microglia crosstalk in myelin development, damage, and repair. Front Cell Dev Biol 2016;4:71. ##Wegner M. Neural crest diversification and specification: transcriptional control of Schwann Cell differentiation. In: Lemke G, (eds). Developmental Neurobiology. London: Elsevier Ltd; 2009.p.153-158.##Caprile T, Montecinos H. Analyzing the role of extracellular matrix during nervous system development to advance new regenerative strategies. Neural Regen Res 2017;12(4):566-567. ##Bishop ES, Mostafa S, Pakvasa M, Luu HH, Lee MJ, Wolf JM, et al. 3-D bioprinting technologies in tissue engineering and regenerative medicine: Current and future trends. Gen Dis 2017;4(4):185-195. ##Zhu W, O'Brien C, O'Brien JR, Zhang LG. 3D nano/microfabrication techniques and nanobiomaterials for neural tissue regeneration. Nanomedicine 2014;9(6):859-875.##Knowlton S, Cho Y, Li XJ, Khademhosseini A, Tasoglu S. Utilizing stem cells for three-dimensional neural tissue engineering. Biomater Sci 2016;4(5):768-784.##Melissinaki V, Gill AA, Ortega I, Vamvakaki M, Ranella A, Haycok JW, et al., Direct laser writing of 3D scaffolds for neural tissue engineering applications. Biofabrication 2011;3(4):045005. ##Zhang YS, Yue K, Aleman J, Mollazadeh Moghaddam K, Bakht SM, Yang J, et al. 3D bioprinting for tissue and organ fabrication. Ann Biomed Eng 2017;45(1):148-163.##Joung D, Truong V, Neitzke CC, Guo S, Walsh PJ, Monatet JR, al. 3D Printed stem‐cell derived neural progenitors generate spinal cord scaffolds. Adv Funct Mater 2018;28(39):1801850.##

Antibiofilm Activity of Kefir Probiotic Lactobacilli Against Uropathogenic Escherichia coli (UPEC) 2 2 Background: Inhibition of biofilm formation is essential for the prevention and treatment of urinary tract infection. This study was aimed to identify the probiotic potential of Lactobacillus strains isolated from kefir and evaluate their antimicrobial and antibiofilm activities against Uropathogenic Escherichia coli (UPEC).  Methods: Twelve Lactobacillus strains were evaluated. Antimicrobial and antibiofilm activities of Cell Free Supernatant (CFS) of the Lactobacillus strains against UPEC isolates were evaluated by agar well diffusion method and crystal violet assay, respectively. Probiotic potential of selected isolates was assessed by analyzing their tolerance to acidic pH and bile salts, auto-aggregation ability, co-aggregation with Escherichia coli (E. coli) and hemolytic activity. The isolates were identified by phenotypic and 16S rRNA gene sequencing. Results:  The CFS of all lactobacilli strains was able to inhibit UPEC isolates even after neutralization. Four out of 12 isolates inhibited the biofilm formation by UPEC in the range 62-75%. The viability under acidic condition varied among the isolates ranging from 6-89.8%. All the isolates could tolerate the 0.3% bile and eight isolates showed the adaptation time of less than 1 hr. All the strains exhibited co-aggregation with E. coli. Auto-aggregation was highly correlated with co-aggregation of all lactobacilli strains with E. coli (r=0.889, p<0.001). The isolates with satisfactory probiotic potential and higher ability of biofilm inhibition and antibacterial activity belonged to the species Lactobacillus rhamnosus and Lactobacillus paracasei. Conclusion: All four selected probiotic strains exhibited antimicrobial and antibiofilm activities, which suggest potential applications for controlling or preventing infections caused by UPEC. 221 229 Maryam Ghane Laleh Babaeekhou Department of Biology, Islamshahr Branch, Islamic Azad University Department of Biology, Islamshahr Branch, Islamic Azad University Iran Seyedeh Sepideh Ketabi Department of Biology, Islamshahr Branch, Islamic Azad University Department of Biology, Islamshahr Branch, Islamic Azad University Iran KefirLactobacillus paracaseiLactobacillus rhamnosusProbioticsUrinary tract infectionUropathogenic E. coli 30427.pdf Toval F, Köhler CD, Vogel U, Wagenlehner F, Mellmann A, Fruth A, et al. Characterization of Escherichia coli isolates from hospital inpatients or outpatients with urinary tract infection. J Clin Microbiol 2014;52(2):407-418.##Eberly A, Floyd K, Beebout C, Colling S, Fitzgerald M, Stratton C, et al. Biofilm formation by uropathogenic Escherichia coli is favored under oxygen conditions that mimic the bladder environment. Int J Mol Sci 2017;18(10):2077.##Zuccotti GV, Meneghin F, Raimondi C, Dilillo D, Agostoni C, Riva E, et al. Probiotics in clinical practice: an overview. J Int Med Res 2008;36(Suppl 1):1A-53A.##Quigley EMM. Prebiotics and probiotics in digestive health. Clin Gastroenterol Hepatol 2019;17(2):333-344. ##Leite AMdO, Miguel MAL, Peixoto RS, Rosado AS, Silva JT, Paschoalin VMF. Microbiological, technological and therapeutic properties of kefir: a natural probiotic beverage. Braz J Microbiol 2013;44(2):341-349.##Nielsen B, Gürakan GC, Ünlü G. Kefir: a multifaceted fermented dairy product. Probiotics Antimicrob Proteins 2014;6(3-4):123-135.##Chifiriuc MC, Cioaca AB, Lazar V. In vitro assay of the antimicrobial activity of kephir against bacterial and fungal strains. Anaerobe 2011;17(6):433-435.##Leite AM, Miguel M, Peixoto R, Ruas-Madiedo P, Paschoalin V, Mayo B, et al. Probiotic potential of selected lactic acid bacteria strains isolated from Brazilian kefir grains. J Dairy Sci 2015;98(6):3622-3632. ##Zheng Y, Lu Y, Wang J, Yang L, Pan C, Huang Y. Probiotic properties of Lactobacillus strains isolated from Tibetan kefir grains. PloS One 2013;8(7):e69868.##Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D. Manual of clinical microbiology. systems for detection and identification of bacteria and yeasts. 10th ed. Vol. 1. ASM Press;2011;18-19.##Patel J, Cockerill III F, Eliopoulos G, Jenkins S, Lewis J, Limbago B, et al. M100 Performance standards for antimicrobial susceptibility testing. United State: Clinical and Laboratory Standards Institute. 2017:240.##González L, Sandoval H, Sacristán N, Castro J, Fresno J, Tornadijo M. Identification of lactic acid bacteria isolated from Genestoso cheese throughout ripening and study of their antimicrobial activity. Food Control. 2007;18(6):716-722.##Stepanović S, Vuković D, Hola V, Bonaventura GD, Djukić S, Ćirković I, et al. Quantification of biofilm in microtiter plates: overview of testing conditions and practical recommendations for assessment of biofilm production by staphylococci. APMIS 2007;115(8):891-899.##Kaur S, Sharma P, Kalia N, Singh J, Kaur S. Anti-biofilm properties of the fecal probiotic Lactobacilli against Vibrio spp. Front Cell Infect Microbiol 2018;8:120. ##Argyri AA, Zoumpopoulou G, Karatzas KAG, Tsakalidou E, Nychas GJE, Panagou EZ, et al. Selection of potential probiotic lactic acid bacteria from fermented olives by in vitro tests. Food Microbiol 2013;33(2):282-291. ##Guo Z, Wang J, Yan L, Chen W, Liu XM, Zhang HP. In vitro comparison of probiotic properties of Lactobacillus casei Zhang, a potential new probiotic, with selected probiotic strains. LWT-Food Science and Technology 2009;42(10):1640-1646.##Collado MC, Meriluoto J, Salminen S. Adhesion and aggregation properties of probiotic and pathogen strains. European Food Research and Technology 2008;226(5):1065-1073.##García-Cayuela T, Korany AM, Bustos I, de Cadiñanos LPG, Requena T, Peláez C, et al. Adhesion abilities of dairy Lactobacillus plantarum strains showing an aggregation phenotype. Food Res Int 2014;57:44-50.##De Vos P, Garrity GM. Bergey's manual of systematic bacteriology: New York: Springer; 2009.1450 p.##Bjarnsholt T, Ciofu O, Molin S, Givskov M, Høiby N. Applying insights from biofilm biology to drug development-can a new approach be developed? Nat Rev Drug Discov 2013;12(10):791-808.##Boll EJ, Struve C, Boisen N, Olesen B, Stahlhut SG, Krogfelt KA. Role of enteroaggregative Escherichia coli virulence factors in uropathogenesis. Infect Immun 2013;81(4):1164-1171. ##Salminen S, Von Wright A. Lactic acid bacteria: microbiological and functional aspects: CRC Press; 2004. 656 p.##Rao KP, Chennappa G, Suraj U, Nagaraja H, Raj AC, Sreenivasa M. Probiotic potential of Lactobacillus strains isolated from sorghum-based traditional fermented food. Probiotics Antimicrob Proteins 2015;7(2):146-156. ##Yeganeh M, Hosseini H, Mehrabian S, Torbati ES, Zamir SM. Antibiofilm effects of Lactobacilli against ciprofloxacin-resistant uropathogenic Escherichia coli strains in pasteurized milk. Applied Food Biotechnology 2017;4(4):241-250.##Sharma D, Saharan BS. Functional characterization of biomedical potential of biosurfactant produced by Lactobacillus helveticus. Biotechnol Rep (Amst) 2016;11:27-35.##Tokatlı M, Gülgör G, Bağder Elmacı S, Arslankoz İşleyen N, Özçelik F. In vitro properties of potential probiotic indigenous lactic acid bacteria originating from traditional pickles. BioMed Res Int 2015;2015.##Ahmadova A, Todorov SD, Choiset Y, Rabesona H, Zadi TM, Kuliyev A, et al. Evaluation of antimicrobial activity, probiotic properties and safety of wild strain Enterococcus faecium AQ71 isolated from Azerbaijani Motal cheese. Food Control 2013;30(2):631-641.##Floros G, Hatzikamari M, Litopoulou-Tzanetaki E, Tzanetakis N. Probiotic and technological properties of facultatively heterofermentative lactobacilli from Greek traditional cheeses. Food Biotechnol 2012;26(1):85-105.##Iñiguez-Palomares C, Pérez-Morales R, Acedo-Félix E. Evaluation of probiotic properties in Lactobacillus isolated from small intestine of piglets. Rev Latinoam Microbiol 2007;49(3-4):46-54.##Bautista-Gallego J, Arroyo-López F, Rantsiou K, Jiménez-Díaz R, Garrido-Fernández A, Cocolin L. Screening of lactic acid bacteria isolated from fermented table olives with probiotic potential. Food Res Int 2013;50(1):135-142.##Ramos CL, Thorsen L, Schwan RF, Jespersen L. Strain-specific probiotics properties of Lactobacillus fermentum, Lactobacillus plantarum and Lactobacillus brevis isolates from Brazilian food products. Food Microbiol 2013;36(1):22-29. ##Sorroche FG, Spesia MB, Zorreguieta Á, Giordano W. A positive correlation between bacterial autoaggregation and biofilm formation in native Sinorhizobium meliloti isolates from Argentina. Appl Environ Microbiol 2012;78(12):4092-4101.##Tareb R, Bernardeau M, Gueguen M, Vernoux JP. In vitro characterization of aggregation and adhesion properties of viable and heat-killed forms of two probiotic Lactobacillus strains and interaction with foodborne zoonotic bacteria, especially Campylobacter jejuni. J Med Microbiol 2013;62(4):637-649. ##Huang CH, Li SW, Huang L, Watanabe K. Identification and classification for the Lactobacillus casei group. Front Microbiol 2018;9:1974.##

Removal of Cefixime from Water Using Rice Starch by Response Surface Methodology 2 2 Background: Remaining pharmaceutical compounds cause environmental pollution. Therefore, refining these compounds has become a major challenge. In this study, the function of eliminating Cefixime (CFX) using rice starch was evaluated under controlled conditions. Methods: Response Surface Methodology (RSM) was used to design, analyze, and optimize experiments, and the interaction between four variables including pH (3-9), rice starch dose (0–300 mg/L), CFX initial concentration (0–16 mg/L) and time (20–120 min) was investigated on CFX removal. Results: The optimum pH, starch dose, initial concentration and time were 4.5, 225 mg/L, 7.9 mg/L and 95 min, respectively. The maximum efficiency of CFX removal was 70.22%. According to RSM, this study follows a quadratic model (R2=0.954). Conclusion: Rice starch has been successful in removing CFX from the aqueous solution. Therefore, it is recommended to utilize this process to remove CFX from aqueous solutions. 230 235 Fatemeh Sadat Tabatabaei Department of Environmental Health Engineering, Faculty of Health, Qom University of Medical Sciences Department of Environmental Health Engineering, Faculty of Health, Qom University of Medical Sciences Iran Mahdi Asadi-Ghalhari Rahim Aali Department of Environmental Health Engineering, Faculty of Health, Qom University of Medical Sciences Department of Environmental Health Engineering, Faculty of Health, Qom University of Medical Sciences Iran Fatemeh Mohammadi Department of Environmental Health Engineering, Faculty of Health, Qom University of Medical Sciences Department of Environmental Health Engineering, Faculty of Health, Qom University of Medical Sciences Iran Roqiyeh Mostafaloo Department of Environmental Health Engineering, Faculty of Health, Qom University of Medical Sciences Department of Environmental Health Engineering, Faculty of Health, Qom University of Medical Sciences Iran Rezvaneh Esmaeili Department of Environmental Health Engineering, Faculty of Health, Qom University of Medical Sciences Department of Environmental Health Engineering, Faculty of Health, Qom University of Medical Sciences Iran Zohreh Davarparast Department of Environmental Health Engineering, Faculty of Health, Qom University of Medical Sciences Department of Environmental Health Engineering, Faculty of Health, Qom University of Medical Sciences Iran Zahra Safari Department of Environmental Health Engineering, Faculty of Health, Qom University of Medical Sciences Department of Environmental Health Engineering, Faculty of Health, Qom University of Medical Sciences Iran CefiximeResponse surface methodology (RSM)Rice starch 30434.pdf Homem V, Santos L. Degradation and removal methods of antibiotics from aqueous matrices- a review. J Environ Manage 2011;92(10):2304-2347.##Aydin S, Aydin ME, Beduk F, Ulvi A. Removal of antibiotics from aqueous solution by using magnetic Fe3O4/red mud-nanoparticles. Sci Total Environ 2019;670:539-546. ##Shaniba C, Akbar M, Ramseena K, Raveendran P, Narayanan BN, Ramakrishnan RM. Sunlight-assisted oxidative degradation of cefixim antibiotic from aqueous medium using TiO2/nitrogen doped holey graphene nanocomposite as a high performance photocatalyst. J Environmental Chemical Engineering 2018;8(1):102204.##Pham TD, Bui TT, Truong TTT, Hoang TH, Le TS, Duong VD, et al. Adsorption characteristics of beta-lactam cefixime onto nanosilica fabricated from rice HUSK with surface modification by polyelectrolyte. J Mol Liq 2020;298:111981.##Kümmerer K, Alexy R, Hüttig J, Schöll A. standardized tests fail to assess the effects of antibiotics on environmental bacteria. Water Res 2004;38(8):2111-2116. ##Mostafaloo R, Mahmoudian MH, Asadi-Ghalhari M. BiFeO3/Magnetic Nanocomposites for the Photocatalytic Degradation of Ceﬁxime From Aqueous Solutions under Visible Light. J Photochem Photobiol A Chem 2019;382:111926.##Belghadr I, Shams Khorramabadi G, Godini H, Almasian M. The removal of the cefixime antibiotic from aqueous solution using an advanced oxidation process (UV/H2O2). Desalination Water Treat 2015;55(4):1068-1075.##Khan MN, Qayum A, Rehman UU, Gulab H, Idrees M. Spectrophotometric method for Quantitative determination of cefixim in bulk and pharmaceutical preparation (using ferron complex). J Appl Spectrosc 2015;82(4):705-711.##Goossens H, Ferech M, Coenen S, Stephens P. Comparison of diseases in the United States and 27 European countries.outpattient systemic antibacterial use in 2004. Clinical Infectious Diseases 2007;44(8):1091-1095.##Kandhro AA LA, Mahesar SA, Saleem R, Nelofar A, Khan ST, et al. Application of attenuated total reflectance Fourier transform infrared spectroscopy for determination of cefixime in oral pharmaceutical formulations. Spectrochim Acta A Mol Biomol Spectrosc 2013;115:51-56.##Esmaeili Bidhendi M, Poursorkh Z, Sereshti H, Rashidi Nodeh H, Rezania S, Afzal Kamboh M. Nano-size biomass derived from pomegranate peel for enhanced removal of cefixime antibiotic from aqueous media: kinetic, equilibrium and thermodynamic study. Int J Environ Res Public Health .2020;17(12):4223. ##Iram M, Guo C, Guan Y, Ishfaq A, Liu H. Adsorption and magnetic removal oh neutral red dye from aqueous solution using Fe3O4 hollow nanospheres. J Hazard Mater 2010;181(1-3):1039-1050. ##Montanher S, Oliveira E, Rollemberg M. Removal of metal ions from aqueous solutions by sorption onto rice bran. J Hazard Mater 2005;117(2-3):207-211.##Wang L, Xie B, Shi J, Xue S, Deng Q, Wei Y, et al. Physicochemical properties and structure of starches from Chinese rice cultivars. Food Hydrocolloids 2010;24(2-3):208-216.##Dehghani S, Jonidi Jafari A, Farzadkia M, Gholami M. Sulfonamide antibiotic reduction in aquatic environment by application of fenton oxidation process. Iranian J Environ Health Sci Eng 2013;10(1):29. ##Kobya M, Demirbas E, Gebologlu U, Oncel M, Yildirim Y. Optimization of arsenic removal from drinking water by electrocoagulation batch process using response surface methodology. Desalination Water Treat 2013;51(34-36):6676-6687.##Mostafaloo R, Asadi Ghalhari M. Modeling and optimization of the electrochemical process for cefixime removal from water. Analytical Bioanalytical Electrochemistry 2020;12(1):36-47.##Karimi R, Yousefi F, Ghaedi M, Dashtian K. Back propagation artificial neural network and central composite design modeling of operational parameter impact for sunset yellow and azur (II) adsorption onto MWCNT and MWCNT-Pd-NPs: Isotherm and kinetic study. Chemometr Intell Lab Syst 2016;159:127-137.##Anacona J, Estacio J. Synthesis and antibacterial activity of cefixime metal complexes. Transition Metal Chemistry 2006;31(2):227-231.##Dehghani S JjA, Farzadkia M, Gholami M. [Investigation of the efficiency of Fenton’s advanced oxidation process in sulfadiazine antibiotic removal from aqueous solutions]. Arak Med Univ J 2012;15(66):19-290. Persian.##Yoosefian M, Ahmadzadeh S, Aghasi M, Dolatabadi M. Optimization of electrocoagulation process for efficient removal of ciprofloxacin antibiotic using iron electrode; kinetic and isotherm studies of adsorption. J Mol Liq 2016;225:544-553.##Ouaissa YA, Chabani M, Amrane A, Bensmaili A. Removal of tetracycline by electrocoagulation: Kinetic and isotherm modeling through adsorption. J Environ Chem Eng 2014;2(1):177-184.##Maghsoudi M, Ghaedi M, Zinali A, Ghaedi A, Habibi M. Artificial neural network (ANN) method for modeling of sunset yellow dye adsorption using zinc oxide nanorods loaded on activated carbon: Kinetic and isotherm study. Spectrochim Acta A Mol Biomol Spectrosc 2015;134:1-9.##Fakhri A , Adami S. Adsorption and thermodynamic study of Cephalosporins antibiotics from aqueous solution onto MgO nanoparticles. J Taiwan Inst Chem Eng 2014;45(3):1001-1006.##Elmolla ES, Chaudhuri M. Photocatalytic degradation of amoxicillin, ampicillin and cloxacillin antibiotics in aqueous solution using UV/TiO2 and UV/H2O2/TiO2 photocatalysis. Desalination 2010;252(1-3):46-52.##Roy P, Dey U, Chattoraj S, Mukhopadhyay D, Mondal NK. Modeling of the adsorptive removal of arsenic (III) using plant biomass: a bioremedial approach. Appl Water Sci 2017;7(3):1307-1321.##Ghaedi M. Comparison of cadmium hydroxide nanowires and silver nanoparticles loaded on activated carbon as new adsorbents for efficient removal of Sunset yellow: Kinetics and equilibrium study. Spectrochim Acta A Mol Biomol Spectrosc 2012;94:346-351. ##Homem V, Alves A, Santos L. Amoxicillin degradation at ppb levels by Fenton's oxidation using design of experiments. Sci Total Environ 2010;408(24):6272-6280. ##Mostafaloo R, Yari AR, Mohammadi MJ, Khaniabadi YO, Asadi-Ghalhari M. Optimization of the electrocoagulation process on the effectiveness of removal of Cefixime antibiotic from aqueous solutions. Desalin Water Treat 2019;144:138-144.##

Screening PAX9, MSX1 and WNT10A Mutations in 4 Iranian Families with Non-Syndromic Tooth Agenesis 2 2 Background: Tooth agenesis is one of the most common developmental anomalies in human and the main reasons for its occurrence are still unknown. Mutations of several genes such as PAX9, MSX1, AXIN2, KDF1 and WNT10A have been reported which are associated with non-syndromic tooth agenesis. However, PAX9, MSX1 and WNT10A are commonly reported in the literature. Hence, the aim of this study was to investigate the mutations of these genes in 4 Iranian families with non-syndromic tooth agenesis. Methods: DNA extractions from peripheral blood cells of patients with non-syndromic tooth agenesis from 4 unrelated Iranian families were performed by salting out method, and the candidate genes were amplified then followed by Sanger sequencing method. Results: One missense variant (rs4904210) and 4 Single Nucleotide Polymorphisms (SNPs) (rs2236007, rs12883298, rs12882923 and rs12883049) were found in PAX9 gene. Five variants (rs149370601, rs8670, rs186861426 and rs774949973) including a missense variant (rs36059701) were detected in MSX1 gene and no variants were found in WNT10A gene. Conclusion: All variants were analyzed based on bioinformatics websites and Iranian gene databases, and as a result, it was revealed that variants of PAX9, MSX1 and WNT10A may not play a role in non-syndromic tooth agenesis among Iranian cases. 236 240 Shiva Safari Iran Asghar Ebadifar Department of Orthodontic, Faculty of Dentistry, Shahid Behehsti University of Medical Sciences Department of Orthodontic, Faculty of Dentistry, Shahid Behehsti University of Medical Sciences Iran Hossien Najmabadi Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran Iran Koorosh Kamali Department of Public Health, Faculty of Public Health, Zanjan University of Medical Sciences Department of Public Health, Faculty of Public Health, Zanjan University of Medical Sciences Iran Seyedeh Sedigheh Abedini Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran Iran IranMSX1MutationPAX9Tooth agenesisWNT10A 30435.pdf Nieminen P. Genetic basis of tooth agenesis. J Exp Zool B Mol Dev Evol 2009;312B(4):320-342. ##Polder BJ, Van’t Hof MA, Van der Linden FP, Kuijpers‐Jagtman AM. A meta‐analysis of the prevalence of dental agenesis of permanent teeth. Community Dent Oral Epidemiol 2004;32(3):217-226. ##Sheikhi M, Sadeghi MA, Ghorbanizadeh S. Prevalence of congenitally missing permanent teeth in Iran. Dental ResJ 2012;9(Suppl 1):105-111. ##Vieira A. Oral clefts and syndromic forms of tooth agenesis as models for genetics of isolated tooth agenesis. J Dent Res 2003;82(3):162-165. ##Tatematsu T, Kimura M, Nakashima M, Machida J, Yamaguchi S, Shibata A, et al. An aberrant splice acceptor site due to a novel intronic nucleotide substitution in MSX1 gene is the cause of congenital tooth agenesis in a Japanese family. PloS One 2015;10(6):e0128227. ##Haddaji Mastouri M, De Coster P, Zaghabani A, Jammali F, Raouahi N, Ben Salem A, et al. Genetic study of non‐syndromic tooth agenesis through the screening of paired box 9, msh homeobox 1, axin 2, and Wnt family member 10A genes: a case‐series. Eur J Oral Sci 2018;126(1):24-32. ##Abid M, Simpson M, Barbosa I, Seppala M, Irving M, Sharpe P, et al. WNT 10A mutation results in severe tooth agenesis in a family of three sisters. Orthod Craniofac Res 2018;21(3):153-159.##van den Boogaard M-J, Créton M, Bronkhorst Y, van der Hout A, Hennekam E, Lindhout D, et al. Mutations in WNT10A are present in more than half of isolated hypodontia cases. J Med Genet 2012;49(5):327-331. ##Han D, Gong Y, Wu H, Zhang X, Yan M, Wang X, et al. Novel EDA mutation resulting in X-linked non-syndromic hypodontia and the pattern of EDA-associated isolated tooth agenesis. Eur J Med Genet 2008;51(6):536-546. ##Zeng B, Lu H, Xiao X, Yu X, Li S, Zhu L, et al. KDF1 is a novel candidate gene of non-syndromic tooth agenesis. Arch Oral Biol 2019;97:131-136. ##Zhang T, Zhao X, Hou F, Sun Y, Wu J, Ma T, et al. A novel PAX9 mutation found in a Chinese patient with hypodontia via whole exome sequencing. Oral Dis 2019;25(1):234-241. ##Wong SW, Han D, Zhang H, Liu Y, Zhang X, Miao M, et al. Nine novel PAX9 mutations and a distinct tooth agenesis genotype-phenotype. J Dent Res 2018;97(2):155-162. ##Kapadia H, Mues G, D'souza R. Genes affecting tooth morphogenesis. Orthod Craniofac Res 2007;10(3):105-113. ##Zhang W, Qu H, Zhang Y. PAX-9 polymorphism may be a risk factor for hypodontia: a meta-analysis. Genet Mol Res 2014;13(4):9997-10006. ##Mastouri MH, De Coster P, Zaghabani A, Trabelsi S, May Y, Saad A, et al. Characterization of a novel mutation in PAX9 gene in a family with non-syndromic dental agenesis. Arch Oral Biol 2016;71:110-116. ##Nieminen P, Arte S, Tanner D, Paulin L, Alaluusua S, Thesleff I, et al. Identification of a nonsense mutation in the PAX9 gene in molar oligodontia. Eur J Hum Genet 2001;9(10):743-746.##van den Boogaard M-JH, Dorland M, Beemer FA, van Amstel HKP. MSX1 mutation is associated with orofacial clefting and tooth agenesis in humans. Nat Genet 2000;24(4):342-343. ##Liang J, Qin C, Yue H, He H, Bian Z. A novel initiation codon mutation of PAX9 in a family with oligodontia. Arch Oral Biol 2016;61:144-148. ##Vainio S, Karavanova I, Jowett A, Thesleff I. Identification of BMP-4 as a signal mediating secondary induction between epithelial and mesenchymal tissues during early tooth development. Cell 1993;75(1):45-58. ##Bohring A, Stamm T, Spaich C, Haase C, Spree K, Hehr U, et al. WNT10A mutations are a frequent cause of a broad spectrum of ectodermal dysplasias with sex-biased manifestation pattern in heterozygotes. Am J Hum Genet 2009;85(1):97-105. ##Kantaputra P, Sripathomsawat W. WNT10A and isolated hypodontia. Am J Med Genet A 2011;155(5):1119-1122. ##Chhabra N, Goswami M, Chhabra A. Genetic basis of dental agenesis-molecular genetics patterning clinical dentistry. Med Oral Patol Oral Cir Bucal 2014;19(2):e112-e119. ##Bonczek O, Balcar V, Šerý O. PAX9 gene mutations and tooth agenesis: a review. Clin Genet 2017;92(5):467-476. ##Wang J, Jian F, Chen J, Wang H, Lin Y, Yang Z, et al. Sequence analysis of PAX9, MSX1 and AXIN2 genes in a Chinese oligodontia family. Arch Oral Biol 2011;56(10):1027-1034.##Pereira TV, Salzano FM, Mostowska A, Trzeciak WH, Ruiz-Linares A, Chies JA, et al. Natural selection and molecular evolution in primate PAX9 gene, a major determinant of tooth development. Proc Natl Acad Sci USA 2006;103(15):5676-5681. ##Kapadia H, Frazier-Bowers S, Ogawa T, D'souza RN. Molecular characterization of a novel PAX9 missense mutation causing posterior tooth agenesis. Eur J Hum Genet 2006;14(4):403-409. ##Hloušková A, Bonczek O, Izakovičová-Hollá L, Lochman J, Šoukalová J, Štembírek J, et al. Novel PAX9 gene polymorphisms and mutations and susceptibility to tooth agenesis in the Czech population. Neuro Endocrinol Lett 2015;36(5):452-457. ##Boeira Junior B, Echeverrigaray S. Novel missense mutation in PAX9 gene associated with familial tooth agenesis. J Oral Pathol Med 2013;42(1):99-105. ##Modesto A, Moreno L, Krahn K, King S, Lidral A. MSX1 and orofacial clefting with and without tooth agenesis. J Dent Res 2006;85(6):542-546.##Pawlowska E, Janik-Papis K, Wisniewska-Jarosinska M, Szczepanska J, Blasiak J. Mutations in the human homeobox MSX1 gene in the congenital lack of permanent teeth. Tohoku J Exp Med 2009;217(4):307-312. ##Paixão-Côrtes VR, Braga T, Salzano FM, Mundstock K, Mundstock CA, Bortolini MC. PAX9 and MSX1 transcription factor genes in non-syndromic dental agenesis. Arch Oral Biol 2011;56(4):337-344.##Junior BB, Echeverrigaray S. Polymorphism in the MSX1 gene in a family with upper lateral incisor agenesis. Arch Oral Biol 2012;57(10):1423-1428.##

Pharmacokinetic Effect of MDR Gene Polymorphism rs2032582 on the Therapeutic Response in Iraqi Patients with Acute Myeloid Leukemia 2 2 Background: The main problem in treatment of leukemia patients is the chemotherapy resistance which is a main concern in recent years. The cause of chemotherapy drug resistance is related to MDR gene which is located on chromosome 7 (7q21-31) and it is mainly connected with energy-dependent efflux (P-glycoprotein). This study was conducted to assess the correlation between MDR polymorphism and chemotherapy efficiency with Vincristine in a sample of Iraqi Acute Myeloid Leukemia (AML) patients. Methods: The blood sample of 200 AML patients and 200 controls were collected and the frequency of rs2032582 was calculated through sequencing and then the role of different genetic patterns was evaluated on cancer cells by MTT assay. Results: The results indicate that GG and TT genotypes (20 and 20.5% from total patients count) are more frequent in Iraqi AML patients than other genetic patterns in MDR gene and also the genotype TA is more sensitive to Vincristine chemotherapy than other genotypes. Conclusion: It seems that genetic pattern is the main factor in determination of chemotherapy of AML patients, and patients should not undergo chemotherapy with such drugs, especially Vincristine. 241 245 Rafid A Abdulkareem Institute of Genetic Engineering and Biotechnology for Post Graduate Studies, University of Baghdad Institute of Genetic Engineering and Biotechnology for Post Graduate Studies, University of Baghdad Iraq Tamadher Abbas Rafaa University of Anbar University of Anbar Iraq Hamsa Ahmed Jasim Institute of Genetic Engineering and Biotechnology for Post Graduate Studies, University of Baghdad Institute of Genetic Engineering and Biotechnology for Post Graduate Studies, University of Baghdad Iraq Ahmed Abdul Jabbar Suleiman Acute myeloid leukemiaGeneticMDR genePolymorphismVincristine 30436.pdf Liang XJ, Chen C, Zhao Y, Wang PC. Circumventing tumor resistance to chemotherapy by nanotechnology. Methods Mol Biol 2010;596:467-88.##Housman G, Byler S, Heerboth S, Lapinska K, Longacre M, Snyder N, et al. Drug Resistance in Cancer: An Overview. Cancers (Basel) 2014;6(3):1769-1792.##Bernardes N, Fialho A. Perturbing the dynamics and organization of cell membrane components: A new paradigm for cancer-targeted therapies. Int J Mol Sci 2018;19(12):3871.##Steinbichler TB, Dudás J, Skvortsov S, Ganswindt U, Riechelmann H, Skvortsova II. Therapy resistance mediated by exosomes. Mol Cancer 2019;18(1):58.##Alfarouk KO, Stock CM, Taylor S, Walsh M, Muddathir AK, Verduzco D, et al. Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp. Cancer Cell Int 2015;15(1):71.##Bodor M, Kelley EJ, Ho RJ. Characterization of the humanMDR1 gene. AAPS J 2005;7(1):E1-5. ##Robey RW, Pluchino KM, Hall MD, Fojo AT, Bates SE, Gottesman MM. Revisiting the role of ABC transporters in multidrug-resistant cancer. Nat Rev Cancer 2018;18(7):452-464. ##Fung KL, Gottesman MM. A synonymous polymorphism in a common MDR1 (ABCB1) haplotype shapes protein function. Biochim Biophys Acta - Proteins Proteomics 2009;1794(5):860-871.##Mijac D, Vukovic-Petrovic I, Mijac V, Perovic V, Milic N, Djuranovic S, et al. MDR1 gene polymorphisms are associated with ulcerative colitis in a cohort of Serbian patients with inflammatory bowel disease. PLoS One 2018;13(3):e0194536.##Zhao J, Ouyang A, Su X, Dou Y. MDR1 polymorphisms are associated with sensitivity to platinum-based chemotherapy in gastric cancer. Int J Clin Exp Pathol 2016;9(2):2235-2240.##Hemauer SJ, Nanovskaya TN, Abdel-Rahman SZ, Patrikeeva SL, Hankins GDV, Ahmed MS. Modulation of human placental P-glycoprotein expression and activity by MDR1 gene polymorphisms. Biochem Pharmacol 2010;79(6):921-925.##Samanian S, Mahjoubi F, Mahjoubi B, Mirzaee R, Azizi R. MDR1 gene polymorphisms: possible association with its expression and clinicopathology characteristics in colorectal cancer patients. Asian Pac J Cancer Prev 2011;12(11):3141-3145.##Zhu CY, Lv YP, Yan DF, Gao FL. Knockdown of MDR1 Increases the sensitivity to adriamycin in drug resistant gastric cancer cells. Asian Pacific J Cancer Prev [2013 Nov 30;14(11):6757-6760. ##Rocco A, Compare D, Liguori E, Cianflone A, Pirozzi G, Tirino V, et al. MDR1-P-glycoprotein behaves as an oncofetal protein that promotes cell survival in gastric cancer cells. Lab Investig 2012;92(10):1407-1418. ##Talaat RM, Y K El-Kelliny M, El-Akhras BA, Bakry RM, Riad KF, Guirgis AA. Association of C3435T, C1236T and C4125A polymorphisms of the MDR-1 gene in Egyptian children with acute lymphoblastic leukaemia. Asian Pac J Cancer Prev 2018;19(9):2535-2543.##Ankathil R. ABCB1 genetic variants in leukemias: current insights into treatment outcomes. Pharmgenomics Pers Med 2017;10:169-181. ##Gregers J, Gréen H, Christensen IJ, Dalhoff K, Schroeder H, Carlsen N, et al. Polymorphisms in the ABCB1 gene and effect on outcome and toxicity in childhood acute lymphoblastic leukemia. Pharmacogenomics J 2015;15(4):372-379. ##Kolesnikova M, Sen’kova A, Tairova S, Ovchinnikov V, Pospelova T, Zenkova M. Clinical and prognostic significance of cell sensitivity to chemotherapy detected in vitro on treatment response and survival of leukemia patients. J Pers Med 2019;9(2):24. ##Mrózek K, Harper DP, Aplan PD. Cytogenetics and molecular genetics of acute lymphoblastic leukemia. Hematol Oncol Clin North Am 2009;23(5):991-1010. ##Wang LH, Song YB, Zheng WL, Jiang L, Ma WL. The association between polymorphisms in the MDR1 gene and risk of cancer: a systematic review and pooled analysis of 52 case–control studies. Cancer Cell Int 2013;13(1):46. ##Bazrafshani MR, Poulton K V, Mahmoodi M. A linkage and association analysis study in the multidrug resistance gene 1 (mdr1) in renal patients. Int J Mol Epidemiol Genet 2012;3(4):314-320.##Sakaeda T. Review MDR1 genotype-related pharmacokinetics: fact or fiction? Drug Metab Pharmacokinet 2005;20(6):391-414. ##

Effective Anti-SARS-CoV-2 RNA Dependent RNA Polymerase Drugs Based on Docking Methods : The Case of Milbemycin, Ivermectin, and Baloxavir Marboxil 2 2 Background: Severe Acute Respiratory Syndrome-coronavirus 2 (SARS-CoV-2) is a new virus with a global pandemic. Yet, no vaccine or efficient treatments are found against the disease. The viral RNA dependent RNA Polymerase (RdRP) is a suitable target for developing antiviral agents. SARS-CoV-2 RdRP was employed to test its binding activity with some drugs. Methods: Using some docking methods, RdRP was targeted by Milbemycins (MMs), Ivermectin (IMT), Baloxavir Marboxil (BM), and Tadalafil (TF), a phosphodiesterase type 5 inhibitor. Results: MM-A3 5-oxime (MMA35O), MM-A3 (MMA3), MM-A4 5-oxime (MMA45O), IMT, BM, and TF showed the highest binding affinity to RdRp. Conclusion: The drugs used in the present computational investigation are effective against the SARS-CoV-2 RdRP with high affinity values especially, milbemycins, ivermectin, and Baloxavir marboxil, which could further be studied in laboratory and clinical trials for saving millions of lives around the world. 246 250 Ali Hassan Daghir Janabi BaloxavirCOVID-19IvermectinTadalafil 30438.pdf Tchesnokov EP, Feng JY, Porter DP, Götte M. Mechanism of inhibition of ebola virus RNA-dependent RNA polymerase by remdesivir. Viruses2019;11(4):326.##Warren TK, Jordan R, Lo MK, Ray AS, Mackman RL, Soloveva V, et al. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature 2016;531(7594):381-385.##Agostini ML, Andres EL, Sims AC, Graham RL, Sheahan TP, Lu X, et al. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. MBio 2018;9(2):e00221-18.##Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A, et al. Compassionate use of remdesivir for patients with severe Covid-19. N Engl J Med 2020;382(24):2327-2336.##Furuta Y, Komeno T, Nakamura T. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc Jpn Acad Ser B Phys Biol Sci 2017;93(7):449-463.##Sleeman K, Mishin VP, Deyde VM, Furuta Y, Klimov AI, Gubareva L V. In vitro antiviral activity of favipiravir (T-705) against drug-resistant influenza and 2009 A(H1N1) viruses. Antimicrob Agents Chemother 2010;54(6):2517-2524.##Gao Y, Yan L, Huang Y, Liu F, Zhao Y, Cao L, et al. Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science 2020;368(6492):779-782.##The PyMOL Molecular Graphics System. No Title [Internet]. Schrödinger, LLC.; 2020. Available from: https://pymol.org##Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res 2020;178:104787. ##Heo YA. Baloxavir: First global approval. Drugs 2018;78(6):693-697. ##Guo J, Liang H, Toro R, Wu Y. Effects of tadalafil and sildenafil on HIV infection in vitro. J Hum Virol Retrovirology 2015;2(1):00030. ##Dallakyan S, Olson AJ. Small-molecule library screening by docking with PyRx. Methods Mol Biol 2015;1263:243-250.##O’Hanlon R, Shaw ML. Baloxavir marboxil: the new influenza drug on the market. Curr Opin Virol 2019;35:14-18.##Coward RM, Carson CC. Tadalafil in the treatment of erectile dysfunction. Ther Clin Risk Manag 2008;4(6):1315-1330.##Henrie AM, Nawarskas JJ, Anderson JR. Clinical utility of tadalafil in the treatment of pulmonary arterial hypertension: An evidence-based review. Core Evid 2015;10:99-108.##

Application of Electrospray in Preparing Solid Lipid Nanoparticles and Optimization of Nanoparticles Using Artificial Neural Networks 2 2 Background: Electrospray (Electrohydrodynamic atomization) has been introduced as a novel approach to prepare nanoparticles. This work aimed to prepare SLNs through electrospray and evaluate factors affecting particle size of prepared Solid Lipid Nanoparticles (SLNs). Methods: SLNs were prepared by electrospray method. To study the factors affecting particle size of SLNs, Artificial Neural Networks (ANNs) were employed. Four input variables, namely, Tween 80 concentration, lipid concentration, flow rate, and polymer to lipid ratio were analyzed through ANNs and particle size was the output. Results: The analyzed model presented concentration of Tween 80 (surfactant) and lipid as effective parameters on particle size. By increasing surfactant and decreasing lipid concentration, minimum size could be obtained, while flow rate and polymer to lipid ratio appeared not to be effective. Conclusion: Concentration of surfactant/lipid plays the most important role in determining the size. 251 254 Elaheh Shanaghi Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical SciencesDepartment of Biotechnology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical SciencesDepartment of Biotechnology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University IranIran Mahdi Aghajani 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 Fariba Esmaeli 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 Hoda Jahandar Pharmaceutical Sciences Research Center, Tehran Medical Sciences, Islamic Azad University Pharmaceutical Sciences Research Center, Tehran Medical Sciences, Islamic Azad University Iran Amir Amani Medical Biomaterials Research Center (MBRC), Tehran University of Medical Sciences Medical Biomaterials Research Center (MBRC), Tehran University of Medical Sciences Iran NanoparticlesNeural networksParticle size Polymers 30439.pdf Müller RH, Radtke M, Wissing SA. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv Drug Deliv Rev 2002;54(Suppl 1):S131-S155. ##Muller RH, Keck CM. Challenges and solutions for the delivery of biotech drugs--a review of drug nanocrystal technology and lipid nanoparticles. J Biotechnol 2004;113(1-3):151-170.##Wu Y, Fei Z, Lee LJ, Wyslouzil BE. Coaxial electrohydrodynamic spraying of plasmid DNA/polyethylenimine (PEI) polyplexes for enhanced nonviral gene delivery. Biotechnol Bioeng 2010;105(4):834-841.##Trotta M, Cavalli R, Trotta C, Bussano R, Costa L. Electrospray technique for solid lipid-based particle production. Drug Dev Ind Pharm 2010;36(4):431-438.##Eltayeb M, Bakhshi PK, Stride E, Edirisinghe M. Preparation of solid lipid nanoparticles containing active compound by electrohydrodynamic spraying. Food Research International 2013;53(1):88-95.##Amani A, York P, Chrystyn H, Clark BJ, Do DQ. Determination of factors controlling the particle size in nanoemulsions using Artificial Neural Networks. Eur J Pharm Sci 2008;35(1-2):42-51.##Morad MR, Rajabi A, Razavi M, Sereshkeh SP. A very stable high throughput Taylor cone-jet in electrohydrodynamics. Scientific Reports 2016;6:38509.##Khani S, Abbasi S, Keyhanfar F, Amani A. Use of artificial neural networks for analysis of the factors affecting particle size in mebudipine nanoemulsion. J Biomol Struct Dyn 2019;37(12):3162-3167.##Kim Y, Lee Chung B, Ma M, Mulder WJ, Fayad ZA, Farokhzad OC, et al. Mass production and size control of lipid–polymer hybrid nanoparticles through controlled microvortices. Nano Lett 2012;12(7):3587-3591.##Jaworek A, Sobczyk AT. Electrospraying route to nanotechnology: An overview. J Electrostatics 2008;66(3-4):197-219.##

Nanoformulation-Based Antiviral Combination Therapy for Treatment of COVID-19 2 2 No Abstract 255 256 Hoda Keshmiri Neghab Department of Photo Healing and Regeneration, Medical Laser Research Center, Yara Institute, ACECRInstitute of Biochemistry and Biophysics, University of Tehran Institute of Biochemistry and Biophysics, University of Tehran IranIran Seyedeh Sara Azadeh Department of Biology, Science and Research branch, Islamic Azad University Department of Biology, Science and Research branch, Islamic Azad University Iran Mohammad Hasan Soheilifar Department of Medical Laser, Medical Laser Research Center, Yara Institute, ACECR Iran Fariba Dashtestani Editorial 30440.pdf Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395(10223):497-506. ##Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, et al. A new coronavirus associated with human respiratory disease in China. Nature 2020;579(7798):265-269.##Habibzadeh P, Stoneman EK. The novel coronavirus: A bird’s eye view. Int J Occup Environ Med 2020;11(2):65-71.##Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive CareMed 2020;46(4):586-590.##Huang L, Sexton DJ, Skogerson K, Devlin M, Smith R, Sanyal I, et al. Novel peptides inhibitors of angiotensin converting enzyme 2. J Biol Chem 2003;278(18):15532-15540.##Koren G, King S, Knowles S, Phillips E. Ribavirin in the treatment of SARS: A new trick for an old drug? CMAJ. 2003;168(10):1289-1292. ##Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury. Nat Med 2005;11(8):875-879. ##Gao Y, Kraft JC, Yu D, Ho RJ. Recent developments of nanotherapeutics for targeted and long-acting, combination HIV chemotherapy. Eur J Pharm Biopharm 2019;138:75-91. ##Zarei-Ghobadi M, Mozhgani SH, Dashtestani F, Yadegari A, Hakimian F, Norouzi M, et al. A genosensor for detection of HTLV-I based on photoluminescence quenching of fluorescent carbon dots in presence of iron magnetic nanoparticle-capped Au. Scientific Reports 2018;8(1):1-8.##Zhu B, Liu GL, Ling F, Wang GX. Carbon nanotube-based nanocarrier loaded with ribavirin against grass carp reovirus. Antiviral Res 2015;118:29-38. ##Cojocaru FD, Botezat D, Gardikiotis I, Uritu CM, Dodi G, Trandafir L, et al. Nanomaterials designed for antiviral drug delivery transport across biological barriers. Pharmaceutics 2020;12(2):171.##Ventola CL. Progress in nanomedicine: approved and investigational nanodrugs. PT 2017;42(12):742-755.##Pedersen KB, Sriramula S, Chhabra KH, Xia H, Lazartigues E. Species-specific inhibitor sensitivity of angiotensin-converting enzyme 2 (ACE2) and its implication for ACE2 activity assays. Am J Physiol Regul Integr Comp Physiol 2011;301(5):R1293-1299. ##Locatelli E, Comes Franchini M. Biodegradable PLGA-b-PEG polymeric nanoparticles: synthesis, properties, and nanomedical applications as drug delivery system. J Nanopart Res 2012;14(12):1316.##