Royan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580619120170701Multiple Sclerosis: Pathogenesis, Symptoms, Diagnoses and Cell-Based Therapy11025040810.22074/cellj.2017.4867ENNazem GhasemiDepartment of Anatomical Sciences, School of Medicine, Isfahan University of Medical
Sciences, Isfahan, IranShahnaz RazaviDepartment of Anatomical Sciences, School of Medicine, Isfahan University of Medical
Sciences, Isfahan, IranElham NikzadJesus Son of Mary Hospital, Isfahan University of Medical Sciences, Isfahan, IranJournal Article19700101Multiple sclerosis (MS) is a chronic inflammatory disease characterized by central nervous system (CNS) lesions that can lead to severe physical or cognitive disability as well as neurological defects. Although the etiology and pathogenesis of MS remains unclear, the present documents illustrate that the cause of MS is multifactorial and include genetic predisposition together with environmental factors such as exposure to infectious agents, vitamin deficiencies, and smoking. These agents are able to trigger a cascade of events in the immune system which lead to neuronal cell death accompanied by nerve demyelination and neuronal dysfunction. Conventional therapies for MS are based on the use of anti-inflammatory and immunomodulatory drugs, but these treatments are not able to stop the destruction of nerve tissue. Thus, other strategies such as stem cell transplantation have been proposed for the treatment of MS. Overall, it is important that neurologists be aware of current information regarding the pathogenesis, etiology, diagnostic criteria, and treatment of MS. Thus, this issue has been discussed according to recent available information.https://www.celljournal.org/article_250408_2714d92b0ef731c8553546912cae575f.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580619120170701A Review on Various Uses of N-Acetyl Cysteine1117250409ENVida MokhtariDepartment of Molecular Cytogenetics, Research and Clinical Center for Infertility, University of Medical Sciences,
Yazd, Iran;Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for ReproduParvaneh AfsharianDepartment of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine,
ACECR, Tehran, IranMaryam ShahhoseiniDepartment of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine,
ACECR, Tehran, IranSeyed Mehdi KalantarDepartment of Molecular Cytogenetics, Research and Clinical Center for Infertility, University of Medical Sciences,
Yazd, IranAshraf MoiniDepartment of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for
Reproductive Biomedicine, ACECR, Tehran, Iran;4Department of Obstetrics and Gynecology, Roointan-Arash HoJournal Article19700101N-acetyl cysteine (NAC), as a nutritional supplement, is a greatly applied antioxidant in vivo and in vitro. NAC is a precursor of L-cysteine that results in glutathione elevation biosynthesis. It acts directly as a scavenger of free radicals, especially oxygen radicals. NAC is a powerful antioxidant. It is also recommended as a potential treatment option for different disorders resulted from generation of free oxygen radicals. Additionally, it is a protected and endured mucolytic drug that mellows tenacious mucous discharges. It has been used for treatment of various diseases in a direct action or in a combination with some other medications. This paper presents a review on various applications of NAC in treatment of several diseases.https://www.celljournal.org/article_250409_64530927884ae10a446707369c67957e.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580619120170701Expression of Folliculogenesis-Related Genes in Vitrified Human Ovarian Tissue after Two Weeks In Vitro Culture1826250410ENZahra Shams MofaraheDepartment of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of
Medical Sciences, Tehran, IranMojdeh SalehniaDepartment of Anatomical Sciences, Faculty of Medical Sciences, Tarbiat Modares University,
Tehran, Iran0000-0001-7861-2232Marefat Ghaffari NovinDepartment of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of
Medical Sciences, Tehran, IranNassim GhorbanmehrDepartment of Biotechnology, Faculty of Biological Sciences, Alzahra University, Tehran, IranMohammad Gholami Fesharaki4Department of Biostatistics, Faculty of Medicine, Tarbiat Modares University, Tehran, IranJournal Article19700101<b>Objective</b><br/>This study was designed to evaluate the effects of vitrification and in vitro culture of human ovarian tissue on the expression of oocytic and follicular cell-related genes. <br><b>Materials and Methods</b><br> In this experimental study, ovarian tissue samples were obtained from eight transsexual women. Samples were cut into small fragments and were then assigned to vitrified and non-vitrified groups. In each group, some tissue fragments were divided into un-cultured and cultured (in α-MEM medium for 2 weeks) subgroups. The normality of follicles was assessed by morphological observation under a light microscope using hematoxylin and eosin (H&E) staining. Expression levels of factor in the germ line alpha (FIGLA), KIT ligand (KL), growth differentiation factor 9 (GDF-9) and follicle stimulating hormone receptor (FSHR) genes were quantified in both groups by real-time reverse transcriptase polymerase chain reaction (RT-PCR) at the beginning and the end of culture. <br><b>Results</b><br> The percentage of normal follicles was similar between non-cultured vitrified and non-vitrified groups (P > 0.05), however, cultured tissues had significantly fewer normal follicles than non-cultured tissues in both vitrified and non-vitrified groups (P < 0.05). In both cultured groups the rate of primary and secondary follicles was significantly higher than non-cultured tissues (P < 0.05). The expression of all examined genes was not significantly altered in both non-cultured groups. Whiles, in comparison with cultured tissues non-cultured tissues, the expression of FIGLA gene was significantly decreased, KL gene was not changed, GDF-9 and FSHR genes was significantly increased (P < 0.05). <br><b>Conclusion</b><br> Human ovarian vitrification following in vitro culture has no impairing effects on follicle normality and development and expression of related-genes. However, in vitro culture condition has deleterious effects on normality of follicles.https://www.celljournal.org/article_250410_cddd058ffa485cf922a1932576ddde3f.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580619120170701The Prevalence of Y Chromosome Microdeletions in Iranian Infertile Men with Azoospermia and Severe Oligospermia2733250411ENFahimeh AsadiDepartment of Molecular and Cellular Sciences, Faculty of Advanced Sciences and Technology, Pharmaceutical
Sciences Branch, Islamic Azad University, Tehran, IranMohammad Ali Sadighi GilaniDepartment of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine,
ACECR, Tehran, IranAzadeh GhaheriDepartment of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute
for Reproductive Biomedicine, ACECR, Tehran, IranJavad Roodgar Saffari4Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine,
ACECR, Tehran, IranMohammadreza Zamanian4Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine,
ACECR, Tehran, IranJournal Article19700101<b>Objective</b><br/>Microdeletions of the Y chromosome long arm are the most common molecular genetic causes of severe infertility in men. They affect three regions including azoospermia factors (AZFa, AZFb and AZFc), which contain various genes involved in spermatogenesis. The aim of the present study was to reveal the patterns of Y chromosome microdeletions in Iranian infertile men referred to Royan Institute with azoospermia/ severe oligospermia. <br><b>Materials and Methods</b><br> Through a cross-sectional study, 1885 infertile men referred to Royan Institute with azoospermia/severe oligospermia were examined for Y chromosome microdeletions from March 2012 to March 2014. We determined microdeletions of the Y chromosome in the AZFa, AZFb and AZFc regions using multiplex Polymerase chain reaction and six different Sequence-Tagged Site (STS) markers. <br><b>Results</b><br> Among the 1885 infertile men, we determined 99 cases of Y chromosome microdeletions (5.2%). Among 99 cases, AZFc microdeletions were found in 70 cases (70.7%); AZFb microdeletions in 5 cases (5%); and AZFa microdeletions in only 3 cases (3%). AZFbc microdeletions were detected in 18 cases (18.1%) and AZFabc microdeletions in 3 cases (3%). <br><b>Conclusion</b><br> Based on these data, our results are in agreement with similar studies from other regions of the world as well as two other recent studies from Iran which have mostly reported a frequency of less than 10% for Y chromosome microdeletions.https://www.celljournal.org/article_250411_3d9994a607a0ec6124990251a4c06c7b.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580619120170701Effects of Electromagnetic Stimulation on Gene Expression of Mesenchymal Stem Cells and Repair of Bone Lesions3444250412ENMaryam JazayeriNational Cell Bank of Iran, Pasteur Institute of Iran, Tehran, IranMohammad Ali ShokrgozarNational Cell Bank of Iran, Pasteur Institute of Iran, Tehran, IranNooshin HaghighipourNational Cell Bank of Iran, Pasteur Institute of Iran, Tehran, IranBahram BolouriDepartment of Biophysics and Medical Physics, Iran University of Medical Sciences, Tehran, IranFereshteh MirahmadiNational Cell Bank of Iran, Pasteur Institute of Iran, Tehran, IranMehdi FarokhiNational Cell Bank of Iran, Pasteur Institute of Iran, Tehran, IranJournal Article19700101<b>Objective</b><br/>Most people experience bone damage and bone disorders during their lifetimes. The use of autografts is a suitable way for injury recovery and healing. Mesenchymal stem cells (MSCs) are key players in tissue engineering and regenerative medicine. Their proliferation potential and multipotent differentiation ability enable MSCs to be considered as appropriate cells for therapy and clinical applications. Differentiation of stem cells depends on their microenvironment and biophysical stimulations. The aim of this study is to analyze the effects of an electromagnetic field on osteogenic differentiation of stem cells. <br><b>Materials and Methods</b><br> In this experimental animal study, we assessed the effects of the essential parameters of a pulsatile electromagnetic field on osteogenic differentiation. The main purpose was to identify an optimum electromagnetic field for osteogenesis induction. After isolating MSCs from male Wistar rats, passage-3 (P3) cells were exposed to an electromagnetic field that had an intensity of 0.2 millitesla (mT) and frequency of 15 Hz for 10 days. Flow cytometry analysis confirmed the mesenchymal identity of the isolated cells. Pulsatile electromagnetic field-stimulated cells were examined by immunocytochemistry and real-time polymerase chain reaction (PCR). <br><b>Results</b><br> Electromagnetic field stimulation alone motivated the expression of osteogenic genes. This stimulation was more effective when combined with osteogenic differentiation medium 6 hours per day for 10 days. For the in vivo study, an incision was made in the cranium of each animal, after which we implanted a collagen scaffold seeded with stimulated cells into the animals. Histological analysis revealed bone formation after 10 weeks of implantation. <br><b>Conclusion</b><br> We have shown that the combined use of chemical factors and an electromagnetic field was more effective for inducing osteogenesis. These elements have synergistic effects and are beneficial for bone tissue engineering applications.https://www.celljournal.org/article_250412_66a76fd11c3d14098a19ff6f2361f786.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580619120170701Effects of A 4-Week Aerobic Exercise on Lipid Profile and Expression of LXRα in Rat Liver4549250413ENFatemeh KazeminasabDepartment of Exercise Physiology, Faculty of Sport Sciences, University of Isfahan, Isfahan, IranMohammad MarandiDepartment of Exercise Physiology, Faculty of Sport Sciences, University of Isfahan, Isfahan, IranKamran GhaediDepartment of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran0000-0002-9790-5644Fahimeh EsfarjaniDepartment of Exercise Physiology, Faculty of Sport Sciences, University of Isfahan, Isfahan, IranJamal MoshtaghianDepartment of Biology, Faculty of Sciences, University of Isfahan, Isfahan, IranJournal Article19700101<b>Objective</b><br/>Liver X receptors (LXRs) are ligand-activated transcription factors of the nuclear hormonal receptor superfamily which modulate the expression of genes involved in cholesterol homeostasis. Hence, further unraveling of the molecular function of this gene may be helpful in preventing cardiovascular diseases. <br><b>Materials and Methods</b><br> This experimental intervention study included twelve adult Wistar male rats (12-14 weeks old, 200-220 g) which were divided into the control (n=6) and training (n=6) groups. The training group received exercise on a motor-driven treadmill at 28 meters/minute (0% grade) for 60 minutes a day, 5 days a week for 4 weeks. Rats were sacrificed 24 hours after the last session of exercise. A portion of the liver was excised, immediately washed in ice-cold saline and frozen in liquid nitrogen for extraction of total RNA. Plasma was collected for high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and triglycerides (TG) measurements. All variables were compared by independent t test. <br><b>Results</b><br> A significant increase in LXRα transcript level was observed in trained rats (P < 0.01). Plasma HDL-C concentration was also significantly higher (P < 0.01) in trained rats. There was a significant decrease in the concentrations of LDL-C (P < 0.01) and TC (P < 0.02), and the ratios of TC/HDL-C (P < 0.001) and LDL/HDL-C (P < 0.002) in trained rats. However, the TG concentration was unchanged (P > 0.05). <br><b>Conclusion</b><br> We found that endurance training induces significant elevation in LXRα gene expression and plasma HDL-C concentration resulting in depletion of the cellular cholesterol. Therefore, it seems that a contributor to the positive effects of exercise in cardiovascular disease prevention is through the expression of LXRα, which is a key step in reverse cholesterol transport.https://www.celljournal.org/article_250413_e25e2da7c52b7784abfa2319a8b6031c.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580619120170701Lovastatin Reduces Stemness via Epigenetic Reprograming of BMP2 and GATA2 in Human Endometrium and Endometriosis5064250414ENMahdieh TaghizadehMehrdad Noruzinia0000-0002-1325-3758Journal Article19700101<b>Objective</b><br/>The stem cell theory in the endometriosis provides an advanced avenue of targeting these cells as a novel therapy to eliminate endometriosis. In this regard, studies showed that lovastatin alters the cells from a stem-like state to more differentiated condition and reduces stemness. The aim of this study was to investigate whether lovastatin treatment could influence expression and methylation patterns of genes regulating differentiation of endometrial mesenchymal stem cells (eMSCs) such as BMP2, GATA2 and RUNX2 as well as eMSCs markers. <br><b>Materials and Methods</b><br> In this experimental investigation, MSCs were isolated from endometrial and endometriotic tissues and treated with lovastatin and decitabin. To investigate the osteogenic and adipogenic differentiation of eMSCs treated with the different concentration of lovastatin and decitabin, BMP2, RUNX2 and GATA2 expressions were measured by real-time polymerase chain reaction (PCR). To determine involvement of DNA methylation in BMP2 and GATA2 gene regulations of eMSCs, we used quantitative Methylation Specific PCR (qMSP) for evaluation of the BMP2 promoter status and differentially methylated region of GATA2 exon 4. <br><b>Results</b><br> In the present study, treatment with lovastatin increased expression of BMP2 and RUNX2 and induced BMP2 promoter demethylation. We also demonstrated that lovastatin treatment down-regulated GATA2 expression via inducing methylation. In addition, the results indicated that CD146 cell marker was decreased to 53% in response to lovastatin treatment compared to untreated group. <br><b>Conclusion</b><br> These findings indicated that lovastatin treatment could increase the differentiation of eMSCs toward osteogenic and adiogenic lineages, while it decreased expression of eMSCs markers and subsequently reduced the stemness.https://www.celljournal.org/article_250414_16ba1d30baafef5c52fee71d32f57683.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580619120170701Micro-Environmental Signature of The Interactions between Druggable Target Protein, Dipeptidyl Peptidase-IV, and Anti-Diabetic Drugs6583250415ENChiranjib ChakrabortyInstitute for Skeletal Aging and Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital,
Chuncheon, Korea;Department of Bio-Informatics, School of Computer and Information Sciences, Galgotias University,Bidyut MallickDepartments of Physics, Galgotias College of Engineering and Technology, Greater Noida, IndiaAshish Ranjan SharmaInstitute for Skeletal Aging and Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital,
Chuncheon, KoreaGarima SharmaInstitute for Skeletal Aging and Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital,
Chuncheon, KoreaSupriya JaggaInstitute for Skeletal Aging and Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital,
Chuncheon, KoreaC George Priya Doss4Department of Integrative Biology, VIT University, Vellore Tamil Nadu, IndiaJu-Suk NamInstitute for Skeletal Aging and Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital,
Chuncheon, KoreaJournal Article19700101<b>Objective</b><br/>Druggability of a target protein depends on the interacting micro-environment between the target protein and drugs. Therefore, a precise knowledge of the interacting micro-environment between the target protein and drugs is requisite for drug discovery process. To understand such micro-environment, we performed in silico interaction analysis between a human target protein, Dipeptidyl Peptidase-IV (DPP-4), and three anti-diabetic drugs (saxagliptin, linagliptin and vildagliptin). <br><b>Materials and Methods</b><br> During the theoretical and bioinformatics analysis of micro-environmental properties, we performed drug-likeness study, protein active site predictions, docking analysis and residual interactions with the protein-drug interface. Micro-environmental landscape properties were evaluated through various parameters such as binding energy, intermolecular energy, electrostatic energy, van der Waals’+H-bond+desolvo energy (EVHD) and ligand efficiency (LE) using different in silico methods. For this study, we have used several servers and software, such as Molsoft prediction server, CASTp server, AutoDock software and LIGPLOT server. <br><b>Results</b><br> Through micro-environmental study, highest log P value was observed for linagliptin (1.07). Lowest binding energy was also observed for linagliptin with DPP-4 in the binding plot. We also identified the number of H-bonds and residues involved in the hydrophobic interactions between the DPP-4 and the anti-diabetic drugs. During interaction, two H-bonds and nine residues, two H-bonds and eleven residues as well as four H-bonds and nine residues were found between the saxagliptin, linagliptin as well as vildagliptin cases and DPP-4, respectively. <br><b>Conclusion</b><br> Our in silico data obtained for drug-target interactions and micro-environmental signature demonstrates linagliptin as the most stable interacting drug among the tested anti-diabetic medicines.https://www.celljournal.org/article_250415_3ab6b1038fd1fd3c58e21e52b79d041e.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580619120170701Lavandula Reduces Heart Injury via Attenuating Tumor Necrosis Factor-Alpha and Oxidative Stress in A Rat Model of Infarct-Like Myocardial Injury8493250416ENJafar SadeghzadehResearch Center and Department of Physiology, Faculty of Medicine, Semnan University of Medical Sciences,
Semnan, IranAbedin VakiliResearch Center and Department of Physiology, Faculty of Medicine, Semnan University of Medical Sciences,
Semnan, IranAhmad Reza BandegiDepartment of Biochemistry, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, IranHamid Reza SameniResearch Center of Nervous System Stem Cells, Department of Anatomy, Faculty of Medicine, Semnan University of
Medical Sciences, Semnan, IranMahdi Zahedi KhorasaniResearch Center and Department of Physiology, Faculty of Medicine, Semnan University of Medical Sciences,
Semnan, IranMohsen Darabian4Department of Cardiology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, IranJournal Article19700101<b>Objective</b><br/>Lavender is used in herbal medicine for different therapeutic purposes. Nonetheless, potential therapeutic effects of this plant in ischemic heart disease and its possible mechanisms remain to be investigated. <br><b>Materials and Methods</b><br> In this experimental study, lavender oil at doses of 200, 400 or 800 mg/kg was administered through gastric gavage for 14 days before infarct-like myocardial injury (MI). The carotid artery and left ventricle were cannulated to record arterial blood pressure (BP) and cardiac function. At the end of experiment, the heart was removed and histopathological alteration, oxidative stress biomarkers as well as tumor necrosis factor-alpha (TNF-α) level were evaluated. <br><b>Results</b><br> Induction of M.I caused cardiac dysfunction, increased levels of lipid peroxidation, TNF-α and troponin I in heart tissue (P < 0.001). Pretreatment with lavender oil at doses of 200 and 400 mg/kg significantly reduced myocardial injury, troponin I and TNF-α. In addition, it improved cardiac function and antioxidant enzyme activity (P < 0.01). <br><b>Conclusion</b><br> Our finding showed that lavender oil has cardioprotective effect through inhibiting oxidative stress and inflammatory pathway in the rat model with infarct-like MI. We suggest that lavender oil may be helpful in prevention or attenuation of heart injury in patients with high risk of myocardial infarction and/or ischemic heart disease.https://www.celljournal.org/article_250416_7882724f7c0153aab4ea786c86167c7e.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580619120170701Comparative Study on The Preventive Effect of Saffron Carotenoids, Crocin and Crocetin, in NMU-Induced Breast Cancer in Rats94101253591ENMeysam SajjadiDepartment of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IranZahra BathaieDepartment of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IranJournal Article20220723<strong>Objective: </strong>Crocin (Cro) and crocetin (Crt) are two widely known saffron carotenoids, which exert anticancer effects by different mechanisms. Here, we investigated and compared the preventive effect of Cro and Crt at the initiation and promotion stages of breast cancer induction in an animal model.<br /><strong>Materials and Methods:</strong> In this experimental study, female Wistar albino rats were injected with three doses of N-methyl-N-nitrosourea (NMU). The preventive intervention was done at different times for the initiation and promotion stages. Thus, Cro/Crt was administered by gavage 20 days before, or one week after, the first NMU injection, for the<br />prevention at the initiation or promotion stages respectively. The treatment was repeated every three days, and continued up to the end of experiment. Tumor appearance was checked by palpation and some parameters were determined after sacrifice.<br /><strong>Results:</strong> Tumor volume, latency period, and tumor number were significantly decreased in the rat groups treated with both saffron carotenoids for prevention at both the initiation and promotion stages. Tumor incidence was 77% due to NMU injection, which was decreased to 45 and 33% (on average) after Cro and Crt administration, respectively. In addition, enkephaline degrading aminopeptidase (EDA) was decreased significantly in the ovaries of the animals, however, changes in the brain were not significant.<br /><strong>Conclusion:</strong> Crt/Cro showed a significant protective effect against the NMU-induced<br />breast cancer in rats. However, Crt was more effective than Cro and prevention at the<br />initiation stage was more effective than at the promotion stage. https://www.celljournal.org/article_253591_ee57a4dd2a82f1dc78085021422615c0.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580619120170701Coadministration of Dexamethasone and Melissa officinalis Has Neuroprotective Effects in Rat Animal Model with Spinal Cord Injury102116250417ENSeyed Ruhollah HosseiniNeuroscience Research Centre, Baqiyatallah University of Medical Sciences, Tehran, IranGholamreza KakaNeuroscience Research Centre, Baqiyatallah University of Medical Sciences, Tehran, IranMohammad Taghi JoghataeiDepartment of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, IranMehdi HooshmandiNeuroscience Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, IranSeyed Homayoon Sadraie4Department of Anatomy, School of Medicine, Baqiyatallah University of Medical Sciences, Tehran, IranKayvan YaghoobiNeuroscience Research Centre, Baqiyatallah University of Medical Sciences, Tehran, IranKorosh Mansoori5Department of Physical Medicine and Rehabilitation, Iran University of Medical Sciences, Tehran, IranAlireza MohammadiNeuroscience Research Centre, Baqiyatallah University of Medical Sciences, Tehran, IranJournal Article19700101<b>Objective</b><br/>Spinal cord injury (SCI) causes inflammation, deformity and cell loss. It has been shown that Melissa officinalis (MO), as herbal medicine, and dexamethasone (DEX) are useful in the prevention of various neurological diseases. The present study evaluated combinational effects of DEX and MO on spinal cord injury. <br><b>Materials and Methods</b><br> Thirty six adult male Wistar rats were used in this experimental study. The weight-drop contusion method was employed to induce spinal cord injury in rats. DEX and MO were administrated alone and together in different treatment groups. Intra-muscular injection of DEX (1 mg/kg) was started three hours after injury and continued once a day for seven days after injury. Intra-peritoneal (I.P) injection of MO (150 mg/ kg) was started one day after injury and continued once a day for 14 days. <br><b>Results</b><br> Our results showed motor and sensory functions were improved significantly in the group received a combination of DEX and MO, compared to spinal cord injury group. Mean cavity area was decreased and loss of lower motor neurons and astrogliosis in the ventral horn of spinal cord was significantly prevented in the group received combination of DEX and Melissa officinalis, compared to spinal cord injury group. Furthermore, the findings showed a significant augmentation of electromyography (EMG) recruitment index, increase of myelin diameter, and up-regulation of myelin basic protein in the treated group with combination of DEX and MO. <br><b>Conclusion</b><br> Results showed that combination of DEX and MO could be considered as a neuroprotective agent in spinal cord injury.https://www.celljournal.org/article_250417_799bea9157ad3404c3af33e4d3dba77f.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580619120170701Adipose-Derived Mesenchymal Stem Cells for Treatment of Airway Injuries in A Patient after Long-Term Exposure to Sulfur Mustard117126250418ENAmir Nejad-MoghaddamChemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, IranSoheila AjdariDepartment of Immunology, Pasteur Institute of Iran, Tehran, IranEisa TahmasbpourChemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, IranHassan GoodarziChemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, IranYunes PanahiChemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, IranMostafa GhaneiChemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, IranJournal Article19700101<b>Objective</b><br/>Sulfur mustard (SM) is a potent mutagenic agent that targets several organs, particularly lung tissue. Changes in morphological structure of the airway system are associated with chronic obstructive pulmonary deficiency following exposure to SM. Although numerous studies have demonstrated pathological effects of SM on respiratory organs, unfortunately there is no effective treatment to inhibit further respiratory injuries or induce repair in these patients. Due to the extensive progress and achievements in stem cell therapy, we have aimed to evaluate safety and potential efficacy of systemic mesenchymal stem cell (MSC) administration on a SM-exposed patient with chronic lung injuries. <br><b>Materials and Methods</b><br> In this clinical trial study, our patient received 100×106cells every 20 days for 4 injections over a 2-month period. After each injection we evaluated the safety, pulmonary function tests (PFT), chronic obstructive pulmonary disease (COPD) Assessment Test (CAT), St. George’s Respiratory Questionnaire (SGRQ), Borg Scale Dyspnea Assessment (BSDA), and 6 Minute Walk Test (6MWT). One-way ANOVA test was used in this study which was not significant (P > 0.05). <br><b>Results</b><br> There were no infusion toxicities or serious adverse events caused by MSC administration. Although there was no significant difference in PFTs, we found a significant improvement for 6MWT, as well as BSDA, SGRQ, and CAT scores after each injection. <br><b>Conclusion</b><br> Systemic MSC administration appears to be safe in SM-exposed patients with moderate to severe injuries and provides a basis for subsequent cell therapy investigations in other patients with this disorder (Registration Number: IRCT2015110524890N1).https://www.celljournal.org/article_250418_7b50e45bc40c8be0795cc5d5a87cb71d.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580619120170701Inhibitory Effect of Mesenchymal Stem Cell Co-Culture on Erythroid Differentiation of K562 Cells Compared to The Control Group127136250419ENMahshid SalehHematology Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, IranKarim ShamsasanjanHematology Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, IranAli Akbari MovassaghpourHematology Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, IranParvin AkbarzadehlalehDepartment of Pharmacutical Biotechnology, Tabriz University of Medical Sciences, Tabriz, IranZahra MolaeipourHematology Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, IranJournal Article19700101<b>Objective</b><br/>Bone marrow mesenchymal stem cells (BMMSCs) reside in the bone marrow and control the process of hematopoiesis. They are an excellent instrument for regenerative treatment and co-culture with hematopoietic stem cells (HSCs). <br><b>Materials and Methods</b><br> In this experimental study, K562 cell lines were either treated with butyric acid and co-cultured with MSCs, or cultivated in a conditioned medium from MSCs plus butyric acid for erythroid differentiation. We used the trypan blue dye exclusion assay to determine cell counts and viability in each group. For each group, we separately assessed erythroid differentiation of the K562 cell line with Giemsa stain under light microscopy, expression of specific markers of erythroid cells by flowcytometry, and erythroidspecific gene expressions by real-time polymerase chain reaction (RT-PCR). <br><b>Results</b><br> There was enhandced erythroid differentiation of K562 cells with butyric acid compared to the K562 cell line co-cultured with MSCs and butyric acid. Erythroid differentiation of the K562 cell line cultivated in conditioned medium with butyric acid was higher than the K562 cell line co-cultured with MSCs and butyric acid, but less than K562 cell line treated with butyric acid only. <br><b>Conclusion</b><br> Our results showed that MSCs significantly suppressed erythropoiesis. Therefore, MSCs would not be a suitable optimal treatment strategy for patients with erythroid leukemia.https://www.celljournal.org/article_250419_2d741a6e2876ad77195458469fe24a08.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580619120170701Adipose Derived Stem Cells Exert Immunomodulatory Effects on Natural Killer Cells in Breast Cancer137145250420ENBehdokht BahramiShiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran;Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IranAhmad HosseiniShiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IranAbdol-Rasoul TaleiBreast Diseases Research Center (BDRC), Shiraz University of Medical Sciences, Shiraz, IranAbbas GhaderiShiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran;Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IranMahboobeh RazmkhahShiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IranJournal Article19700101<b>Objective</b><br/>Adipose derived stem cells (ASCs), as one of the important stromal cells in the tumor microenvironment, are determined with immunomodulatory effects. The principle aim of this study was to evaluate the immunosuppressive effects of ASCs on natural killer (NK) cells. <br><b>Materials and Methods</b><br> In this experimental study, we assessed the expressions of indolamine 2, 3-dioxygenase (IDO1), IDO2 and human leukocyte antigen-G5 (HLA-G5) in ASCs isolated from breast cancer patients with different stages as well as normal individuals, using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Immunomodulatory effects of ASCs on the expression of CD16, CD56, CD69, NKG2D, NKp30, NKG2A and NKp44 was also assessed in peripheral blood lymphocytes (PBLs) by flow-cytometry. <br><b>Results</b><br> Our result showed that IDO1, IDO2 and HLA-G5 had higher mRNA expressions in ASCs isolated from breast cancer patients than those from normal individuals (P > 0.05). mRNA expression of these molecules were higher in ASCs isolated from breast cancer patients with stage III tumors than those with stage II. The indirect culture of ASCs isolated from breast cancer patients and normal individuals with activated PBLs significantly reduced NKG2D+ and CD69+ NK cells (P < 0.05). <br><b>Conclusion</b><br> Results of the present study suggest more evidences for the immunosuppression of ASCs on NK cells, providing conditions in favor of tumor immune evasion.https://www.celljournal.org/article_250420_49b449144120ab93148c5e7eefc86a94.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580619120170701Sodium Nitroprusside Changed The Metabolism of Mesenchymal Stem Cells to An Anaerobic State while Viability and Proliferation Remained Intact146158250421ENSadiyeh PariMohammad Hussein Abnosi0000-0002-1485-8847Reza PakyariJournal Article19700101<b>Objective</b><br/>We used sodium nitroprusside (SNP), a nitric oxide (NO) releasing molecule, to understand its effect on viability and proliferation of rat bone marrow mesenchymal stem cells (BM-MSCs). <br><b>Materials and Methods</b><br> This experimental study evaluated the viability and morphology of MSCs in the presence of SNP (100 to 2000 µM) at 1, 5, and 15 hours. We chose the 100, 1000, and 2000 µM concentrations of SNP for one hour exposure for further analyses. Cell proliferation was investigated by the colony forming assay and population doubling number (PDN). Na+, K+, and Ca2+ levels as well as activities of lactate dehydrogenase (LDH), alkaline phosphatase (ALP), aspartate transaminase (AST), and alanine transaminase (ALT) were measured. <br><b>Results</b><br> The viability of MSCs dose-dependently reduced from 750 µM at one hour and 250 µM at 5 and 15 hours. The 100 µM caused no change in viability, however we observed a reduction in the cytoplasmic area at 5 and 15 hours. This change was not observed at one hour. The one hour treatment with 100 µM of SNP reduced the mean colony numbers but not the diameter when the cells were incubated for 7 and 14 days. In addition, one hour treatment with 100 µM of SNP significantly reduced ALT, AST, and ALP activities whereas the activity of LDH increased when incubated for 24 hours. The same treatment caused an increase in Ca2+ and reduction in Na+ content. The 1000 and 2000 µM concentrations reduced all the factors except Ca2+ and LDH which increased. <br><b>Conclusion</b><br> The high dose of SNP, even for a short time, was toxic. The low dose was safe with respect to viability and proliferation, especially over a short time. However elevated LDH activity might increase anaerobic metabolism.https://www.celljournal.org/article_250421_67741d433d17ee8e53a34c9f54fc1161.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580619120170701Percutaneous Autologous Bone Marrow-Derived Mesenchymal Stromal Cell Implantation Is Safe for Reconstruction of Human Lower Limb Long Bone Atrophic Nonunion159165250422ENMohsen EmadedinNarges LabibzadehRoghayeh FazeliFatemeh MohseniSeyedeh Esmat HosseiniReza MoghadasaliSoura MardpourVajiheh AzimianAlireza GoodarziMaede Ghorbani LiastaniAli Mirazimi BafghiMohamadreza Baghaban EslaminejadNasser Aghdami0000-0002-0562-9567Journal Article19700101<b>Objective</b><br/>Nonunion is defined as a minimum of a 9-month period of time since an injury with no visibly progressive signs of healing for 3 months. Recent studies show that application of mesenchymal stromal cells (MSCs) in the laboratory setting is effective for bone regeneration. Animal studies have shown that MSCs can be used to treat nonunions. For the first time in an Iranian population, the present study investigated the safety of MSC implantation to treat human lower limb long bone nonunion. <br><b>Materials and Methods</b><br> It is a prospective clinical trial for evaluating the safety of using autologus bone marrow derived mesenchymal stromal cells for treating nonunion. Orthopedic surgeons evaluated 12 patients with lower limb long bone nonunion for participation in this study. From these, 5 complied with the eligibility criteria and received MSCs. Under fluoroscopic guidance, patients received a one-time implantation of 20-50×106 MSCs into the nonunion site. All patients were followed by anterior-posterior and lateral X-rays from the affected limb, in addition to hematological, biochemical, and serological laboratory tests obtained before and 1, 3, 6, and 12 months after the implantation. Possible adverse effects that included local or systemic, serious or non-serious, and related or unrelated effects were recorded during this time period. <br><b>Results</b><br> From a safety perspective, all patients tolerated the MSCs implantation during the 12 months of the trial. Three patients had evidence of bony union based on the after implantation Xrays. <br><b>Conclusion</b><br> The results have suggested that implantation of bone marrow-derived MSCs is a safe treatment for nonunion. A double-blind, controlled clinical trial is required to assess the efficacy of this treatment (Registration Number: NCT01206179).https://www.celljournal.org/article_250422_43474497abe063afb49bf96accfd32bd.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580619120170701Di-(2-ethylhexyl) Phthalate-Induced Hippocampus-Derived Neural Stem Cells Proliferation166172250423ENAlireza AbdanipourDepartment of Anatomy, School of Medicine, Zanjan University of Medical Sciences, Zanjan, IranAli Noori-ZadehDepartment of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IranSeyed Alireza Mesbah-NaminDepartment of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IranSalar BakhtiyariStudent Research Committee Center, Ilam University of Medical Sciences, Ilam, IranReza NejatbakhshDepartment of Anatomy, School of Medicine, Zanjan University of Medical Sciences, Zanjan, IranIraj Jafari AnarkooliDepartment of Anatomy, School of Medicine, Zanjan University of Medical Sciences, Zanjan, IranJournal Article19700101The brain and spinal cord have a limited capacity for self-repair under damaged conditions. One of the best options to overcome these limitations involves the use of phytochemicals as potential therapeutic agents. In this study, we have aimed to investigate the effects of di-(2-ethylhexyl) phthalate (DEHP) on hippocampus-derived neural stem cells (NSCs) proliferation to search phytochemical candidates for possible treatment of neurological diseases using endogenous capacity. In this experimental study, neonatal rat hippocampus-derived NSCs were cultured and treated with various concentrations of DEHP (0, 100, 200, 400 and 600 µM) and Cirsium vulgare (C. vulgare) hydroethanolic extract (0, 200, 400, 600, 800 and 1000 µg/ml) for 48 hours under in vitro conditions. Cell proliferation rates and quantitative Sox2 gene expression were evaluated using MTT assay and real-time reverse transcription polymerase chain reaction (RT-PCR). We observed the highest average growth rate in the 400 µM DEHP and 800 µg/ml C. vulgare extract treated groups. Sox2 expression in the DEHP-treated NSCs significantly increased compared to the control group. Gas chromatography/mass spectrometry (GC/ MS) results demonstrated that the active ingredients that naturally occurred in the C. vulgare hydroethanolic extract were 2-ethyl-1-hexanamine, n-heptacosane, 1-cyclopentanecarboxylic acid, 1-heptadecanamine, 2,6-octadien-1-ol,2,6,10,14,18,22-tetracosahexaene, and DEHP. DEHP profoundly stimulated NSCs proliferation through Sox2 gene overexpression. These results provide and opportunity for further use of the C. vulgure phytochemicals for prevention and/or treatment of neurological diseases via phytochemical mediated-proliferation of endogenous adult NSCs.https://www.celljournal.org/article_250423_3f88f1fe2d384b9db02a312edbfd0ef0.pdf