Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623620200601Nigella sativa: Valuable perspective in the management of chronic diseases6997131549410.22038/ijbms.2020.37734.8978ENRaluca Maria PopIuliu Hatieganu University of Medicine and Pharmacy, Department of Pharmacology, Toxicology and Clinical Pharmacology, Cluj Napoca, Romania0000-0003-1899-5977Adrian Pavel TrifaIuliu Hatieganu University of Medicine and Pharmacy, Department of Genetics, Cluj Napoca, RomaniaAda PopoloUniversity of Salerno, Department of Pharmacy, Fisciano, Salerno, ItalyVeronica Sanda ChedeaResearch Station for Viticulture and Enology Blaj, Blaj, RomaniaClaudia MilitaruIuliu Hatieganu University of Medicine and Pharmacy, Department of Pharmacology, Toxicology and Clinical Pharmacology, Cluj Napoca, RomaniaIoana Corina BocsanIuliu Hatieganu University of Medicine and Pharmacy, Department of Pharmacology, Toxicology and Clinical Pharmacology, Cluj Napoca, Romania0000-0002-3279-5384Anca Dana BuzoianuIuliu Hatieganu University of Medicine and Pharmacy, Department of Pharmacology, Toxicology and Clinical Pharmacology, Cluj Napoca, RomaniaJournal Article20190117<em><strong>Objective(s):</strong></em> Over the past 20 years, increasing interest in the use of medicinal plants as alternative or adjuvant treatments of several chronic diseases was observed. Accordingly, Nigella sativa or black cumin, a medicinal plant rich in bioactive compounds, has been used worldwide for food purposes or in traditional medicines. This paper aims to reveal N. sativa potential as adjunct treatment in cardiovascular diseases, diabetes, and hematological malignancies, due to their increasing prevalence and difficult management in everyday life.<br /><em><strong>Materials and Methods:</strong></em> Databases like PubMed, Web of Science, Science Direct, Scopus, and Google Scholar were used to search the literature data. Keywords like anti-inflammatory effect, anti-oxidant effect, antihypertensive effects, hypolipidemic effects and hematological malignancies were used in combination with N. sativa.<br /><em><strong>Results:</strong></em> Because of its numerous pharmacological actions, but especially for its anti-oxidant and anti-inflammatory properties, in vivo and in vitro studies demonstrated N. sativa positive effect against diabetes, hypertension, and hypercholesterolemia, all of them associated to cardiovascular diseases progression. Also, it was proved to have marked anti-proliferative, cytotoxic, pro-apoptotic, and anti-metastatic effects, in both solid cancers and hematological malignancies.<br /><em><strong>Conclusion:</strong></em> N. sativa used as complementary treatment to classical medications can improve the management of several chronic diseasesMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623620200601Ameliorative effects of histidine on oxidative stress, tumor necrosis factor alpha (TNF-α), and renal histological alterations in streptozotocin/nicotinamide-induced type 2 diabetic rats7147231548110.22038/ijbms.2020.38553.9148ENMaryam NasriDepartment of Biochemistry and Genetics, Lorestan University of Medical Sciences, Khorramabad, IranGrowth and Development Research Center, Tehran University of Medical Science, Tehran, Iran0000-0002-6857-6132Sina MahdavifardDepartment of Clinical Biochemistry, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran0000-0001-9878-2984Esmaeel BabaeenezhadDepartment of Clinical Biochemistry, School of Medicine, Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, IranGlavizh AdibhesamiDepartment of Biochemistry and Genetics, Lorestan University of Medical Sciences, Khorramabad, Iran0000-0003-1794-6006Negar NouryazdanDepartment of Clinical Biochemistry, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran0000-0002-5166-8647Saeid VeiskaramiAgricultural and Natural Resources Research and Education Center, Department of Animal Science, Lorestan, IranSobhan Rahimi MonfaredDepartment of Biochemistry and Genetics, Lorestan University of Medical Sciences, Khorramabad, Iran0000-0001-8743-6664Mehdi BirjandiNutritional Health Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran0000-0002-0737-8044Hassan AhmadvandDepartment of Clinical Biochemistry, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, IranRazi Herbal Medicines Research Center, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran0000-0002-9406-3592Journal Article20190219<em><strong>Objective(s):</strong></em> The present study sought to evaluate the beneficial effects of histidine (His) on oxidative stress, tumor necrosis factor alpha (TNF-α), renal histological alterations and anti-oxidant enzymes gene expressions in type 2 diabetic rats.<br /><em><strong>Materials and Methods:</strong></em> Streptozotocin/nicotinamide (STZ/NA) induced diabetic rats were used as an animal model of type 2 diabetes. One group of rats received daily His (1000 mg/l) in drinking water for 8 weeks, whereas other groups (control and untreated diabetic groups) received only water. Different parameters such as glucose, insulin, insulin resistance, lipid profile, cardiac risk ratios, renal functional markers, and oxidative stress were determined in all groups. Moreover, renal histological alterations, mRNA expressions of anti-oxidant enzymes, and TNF-α were evaluated in the rats.<br /><em><strong>Results:</strong></em> His exhibited a protective effect on glucose, insulin, insulin resistance, lipid profile, cardiac risk ratios, renal functional markers, oxidative stress, and TNF-α. Furthermore, His restored the renal histological alterations and normalized the augmented mRNA expressions of renal anti-oxidant enzymes (glutathione peroxidase (GPX) and Cu-Zn superoxide dismutase (Cu-Zn SOD)) and TNF-α.<br /><em><strong>Conclusion:</strong></em> His could ameliorate diabetes complications related to oxidative stress, inflammation, dyslipidemia, hyperglycemia, insulin resistance, and nephropathy. Hence, the use of this amino acid is recommended for diabetic patients in order to reduce diabetes complications.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623620200601Prenatal stress increased γ2 GABAA receptor subunit gene expression in hippocampus and potentiated pentylenetetrazol-induced seizure in rats7247291520810.22038/ijbms.2020.39519.9371ENMorteza BagheriCellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran0000-0002-4739-8517Ehsan SabooryZanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran0000-0003-4777-4751Mehrdad NejatbakhshDepartment of Physiology, School of Medicine, Urmia University of Medical Sciences, Urmia, IranShiva Roshan-MilaniDepartment of Physiology, School of Medicine, Urmia University of Medical Sciences, Urmia, IranNeurophysiology Research Center, Urmia University of Medical Sciences, Urmia, Iran0000-0003-1078-9386Leila DerafshpourDepartment of Physiology, School of Medicine, Urmia University of Medical Sciences, Urmia, IranNeurophysiology Research Center, Urmia University of Medical Sciences, Urmia, IranHojjat SayyadiDepartment of Biostatistics , School of Medicine, Urmia University of Medical Sciences, Urmia, IranYousef RasmiCellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran0000-0003-1506-1909Journal Article20190410<em><strong>Objective(s):</strong></em> Stress during pregnancy is able to bring extensive effects on neurobehavioral development in offspring. The GABAergic system plays a pivotal role in neuronal excitability, which can be affected by prenatal stress (PS). This study aimed to evaluate impact of the PS on γ2 subunit of gamma-aminobutyric acid A (GABAA) receptor gene expression in the hippocampus and seizure induced by pentylenetetrazol (PTZ) in developing rats.<br /><em><strong>Materials and Methods:</strong> </em>In this experimental study, female Wistar rats were exposed to restraint stress during gestation and their offspring were studied on postnatal days 14 and 21 (P14 and P21, respectively) for epileptic behaviors and γ2 GABAA receptor subunit gene expression. Quantitative real-time PCR was used for evaluating the γ2 GABAA receptor subunit gene expression in rat pups. Meanwhile, PTZ was injected into the pups, and seizure behaviors were recorded for 60 min. <br /><em><strong>Results:</strong></em> The results showed that γ2 subunit mRNA expression significantly increased in the hippocampus of the stressed pups. The expression level of γ2 subunit was higher on P21 compared to that on P14 in both groups. Number of seizures with tonic–clonic features increased in pups of stressed group compared to the control group. Prenatal stress significantly caused an increase in the total score of seizure on P21.<br /><em><strong>Conclusion:</strong></em> The effect of PS on seizure susceptibility is age-specific; the increased γ2 subunit level in the hippocampus might be, at least in part, the underlying mechanism for PS-induced augmentation of seizures in immature rats.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623620200601Clavulanic acid improves ethanol withdrawal symptoms in rats7307361547810.22038/ijbms.2020.39129.9287ENEhsan MohebiStudent Research Committee, Sabzevar University of Medical Sciences, Sabzevar, Iran0000-0001-6830-6311Mehdi MolaviDepartment of Internal Medicine, Sabzevar University of Medical Sciences, Mashhad, I.R. IranMohammad MohammadzadehCellular and Molecular Research Center, Department of Physiology and Pharmacology, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, IranDepartment of physiology and pharmacology, Mashhad University of Medical Sciences, Mashhad, I.R. Iran0000-0002-5250-6092Hossein HosseinzadehDepartment of Pharmacodynamics and Toxicology, Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, I.R. Iran0000-0002-3483-851XBahareh AminCellular and Molecular Research Center, Department of Physiology and Pharmacology, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran0000-0002-9121-7453Journal Article20190317<em><strong>Objective(s):</strong></em> Ethanol withdrawal following chronic use, is an important challenge clinically. In this study, the effect of clavulanic acid was evaluated on the symptoms of ethanol withdrawal in rats.<br /> <em><strong>Materials and Methods:</strong></em> Alcohol dependence was induced by the gavage of ethanol (10% v/v, 2 g/kg), twice daily for 10 days. Clavulanic acid (10, 20, 40, and 80 mg/kg) was administered concurrently with ethanol (sub-acute study), or a single dose after ethanol withdrawal (acute study). Six hours after the last dose of ethanol, anxiety was assessed by the elevated plus-maze (EPM). Seizure-like behavior was evaluated by a sub-convulsive dose of pentylenetetrazol (PTZ, 25 mg/kg/IP). Locomotor activity and motor coordination were measured by the open field and rotarod tests, respectively. Lipid peroxidation marker and antioxidant content were assessed through measuring malondialdehyde (MDA) and glutathione (GSH), respectively.<br /><em><strong>Results:</strong></em> The number of entries and time spent on the open arms of EPM decreased during the withdrawal state. Motor coordination and locomotor activity were significantly decreased. In the sub-acute study, clavulanic acid 80 mg/kg increased time spent and the number of entries to the open arms of EPM, in withdrawn animals. Both motor incoordination and locomotor activity reduction were normalized by clavulanic acid (10, 20, 40 and 80 mg/kg). Withdrawal-induced PTZ kindling seizure was also suppressed by all of the doses. MDA increased, while GSH decreased after withdrawal. Clavulanic acid attenuated such changes.<br /><em><strong>Conclusion:</strong></em> Clavulanic acid could prevent the development of alcohol withdrawal-induced anxiety and seizure. Alcohol withdrawal causes oxidative stress which can be prevented by clavulanic acid.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623620200601Construction and assessment of the immunogenicity and bactericidal activity of fusion protein porin A from Neisseria meningitidis serogroups A and B admixed with OMV adjuvant as a novel vaccine candidate7377431549710.22038/ijbms.2020.40470.9581ENParviz AfroughDepartment of Mycobacteriology & Pulmonary Research, Pasteur Institute of Iran, Tehran, IranMicrobiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran0000-0002-6513-7142Mohammad Reza Asadi KaramDepartment of Molecular Biology, Pasteur Institute of Iran, Tehran, IranFarzam VaziriDepartment of Mycobacteriology & Pulmonary Research, Pasteur Institute of Iran, Tehran, IranMicrobiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran0000-0001-7788-2548Ava BehrouziDepartment of Mycobacteriology & Pulmonary Research, Pasteur Institute of Iran, Tehran, IranMicrobiology Research Center (MRC), Pasteur Institute of Iran, Tehran, IranSeyed Davar SiadatDepartment of Mycobacteriology & Pulmonary Research, Pasteur Institute of Iran, Tehran, IranMicrobiology Research Center (MRC), Pasteur Institute of Iran, Tehran, IranEndocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran0000-0002-6892-5603Journal Article20190519<em><strong>Objective(s):</strong></em> The porins A and B and also outer membrane vesicles (OMVs) of Neisseria meningitidis are used for vaccine purposes. In the present study, we aimed to design a new vaccine candidate based on a fusion of PorA of serogroups A and B of N. meningitidis admixed with OMV and evaluate it in an animal model.<br /><em><strong>Materials and Methods:</strong></em> After bioinformatic studies, a fusion protein composed of porin A from both serogroups A and B of N. meningitidis was constructed, expressed, and purified by nickel resins. Extraction of OMV of N. meningitidis was performed using a chemical method. The mice were vaccinated subcutaneously in different groups with mixtures of PorA proteins, OMV, and Freund’s adjuvants. Then, the immune responses were measured using the ELISA method. Finally, serum bactericidal activity (SBA) procedure was applied to assay the activity of the immune responses in mice. <br /><em><strong>Results:</strong></em> Mice received the PorA protein plus Freund’s adjuvant. Mice vaccinated with PorA fusion of serogroups A+B plus Freund’s adjuvant produced more IgG, IgG1, and IgG2a than combinations admixed with OMV. Furthermore, the vaccinated mice tended to direct the IgG responses toward IgG1. Sera of the mice that received PorA+Freund’s and those that received PorA+OMV produced higher bactericidal activity than the controls. <br /><em><strong>Conclusion:</strong></em> Fusion protein porin A could be a valuable target for developing vaccines against N. meningitidis. Although, Freund’s adjuvant induced the strongest IgG responses, given that Freund’s adjuvant has no human use, and OMV is a human adjuvant, OMV could be considered in vaccine design against N. meningitidis.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623620200601Soluble uric acid induces inflammation via TLR4/NLRP3 pathway in intestinal epithelial cells7447501551110.22038/ijbms.2020.44948.10482ENChunling MaMedical Research Center, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, 266000, P. R. ChinaDepartment of obstctrics, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, 266000, P. R. China0003-1250-329XXiaoming YangMedical Research Center, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, 266000, P. R. ChinaQiulan LvMedical Research Center, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, 266000, P. R. ChinaShandong Institute of Orthopaedics and Traumatology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, 266000, P. R. China0001-9383-1193Zhimei YanMedical Research Center, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, 266000, P. R. ChinaZeqing ChenMedical Research Center, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, 266000, P. R. ChinaDaxing XuMedical Research Center, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, 266000, P. R. ChinaXiu LiuMedical Research Center, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, 266000, P. R. ChinaWan YangMedical Research Center, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, 266000, P. R. ChinaShichao XingMedical Research Center, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, 266000, P. R. ChinaSchool of Cardiovascular Medicine and Science, King’s College London, BHF Centre, London, SE5 9NU, United Kingdom0000-0001-7704-2813Journal Article20191211<em><strong>Objective(s):</strong> </em>Hyperuricemia is a risk for cardiovascular and metabolic diseases, but the mechanism is ambiguous. Increased intestinal permeability is correlated with metabolic syndrome risk factors. Intestinal epithelial cells play a pivotal role in maintaining intestinal permeability. Uric acid is directly eliminated into intestinal lumen, however, the mechanism and effect of uric acid on intestinal epithelial cells is poorly explored. Here we carried out an analysis to identify the effect and mechanism of uric acid on intestinal epithelial cells.<br /><em><strong>Materials and Methods:</strong></em> IEC-6 was exposed to different concentrations of uric acid to simulate the effect of uric acid on intestinal epithelial cells. Cell viability was determined by MTS assay. Protein content and mRNA were assessed using Western blotting and Q-PCR, respectively. Intracellular ROS was determined using flow-cytometry and fluorescence microscopy. Mitochondrial membrane potential was detected by immunofluorescence using a mitochondrial membrane potential assay kit with JC-1. Small interfering RNA transfection was used to suppress the expression of TLR4.<br /><em><strong>Results:</strong></em> We found soluble uric acid alone increased the release of ROS, depolarized the mitochondrial membrane potential, up-regulated TSPO, increased the expression of TLR4 and NLRP3, and then activated NLRP3 inflammasome and NF-κB signaling, which further resulted in lower expression of tight junction protein and exerted adverse effects on intestinal epithelial cells. Furthermore, the elevated IL-1β could be restored by silencing of TLR4, indicating soluble uric acid induces inflammation via the TLR4/NLRP3 pathway.<br /><em><strong>Conclusion:</strong></em> Soluble uric acid exerted detrimental effect on intestinal epithelial cells through the TLR4/NLRP3 pathway.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623620200601Simvastatin combined with bone marrow mesenchymal stromal cells (BMSCs) improve burn wound healing by ameliorating angiogenesis through SDF-1α/CXCR4 pathway7517591550610.22038/ijbms.2020.39782.9465ENJavad Mohajer AnsariDepartment of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran0000-0002-5090-592XParisa RamhormoziDepartment of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran0000-0001-7366-4519Ronak ShabaniDepartment of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, IranHamidreza Pazoki-toroudiPhysiology research center and department of physiology, faculty of medicine, Iran University of Medical Sciences, Tehran, IranAbazar YariDepartment of Anatomy, faculty of medicine, Alborz University of Medical Sciences, Karaj, IranDietary Supplements and Probiotics Research Center, Alborz University of Medical Sciences, Karaj, IranMahmood BaratiDeparment of medical biotechnology, faculty of allied medicine, Iran University of Medical Sciences, Tehran, Iran0000-0002-9663-9313Mostafa DahmardeheiBurn research center, Iran University of Medical Sciences, Tehran, IranAzar BabakhaniDepartment of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran0000-0001-5787-2967Maliheh NobakhtDepartment of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, IranAnti-Microbial Resistance Research Center, Iran University of Medical Sciences, Tehran, Iran0000-0002-4281-5924Journal Article20190427<em><strong>Objective(s):</strong></em> Chemokines are wound mediators that promote angiogenesis during wound healing. We hypothesized that Simvastatin in combination with the bone marrow mesenchymal stromal cells (BMSCs) improve burn wound healing by ameliorating angiogenesis via SDF-1α/CXCR4 pathway.<br /><em><strong>Materials and Methods:</strong></em> Under general anesthesia, deep partial-thickness burns were created on the inter-scapular area of 48 male rats. Study groups were administrated with petroleum jelly (Simvastatin Vehicle), a single dose of intradermal BMSCs (1×106), topical Simvastatin (0.5 mg/kg) daily and combination of BMSCs and Simvastatin for 14 days. In this study, we used MTT assay, in vivo and in vitro wound closure, H&E and Trichorome staining, immunohistochemistry (IHC), real- time PCR, Western blot and tube formation assay.<br /><em><strong>Results:</strong></em> A significant improvement in wound closure percentage, epithelial thickness, collagen remodeling, and up-regulation of stromal cell-derived factor 1 alpha (SDF1α), C-X-C chemokine receptor type 4 (CXCR4), protein kinase B (AKT), and phosphatidylinositol 3- kinase (PI3K), as well as CD31 and vascular endothelial growth factor (VEGF) expression were observed after treatment with simvastatin, BMSCs and combination of them compared to the vehicle group. However, the co-treatment group revealed considerable superiority in examined factors. BMSCs treated with Simvastatin showed the highest viability in the concentration of 0.5 and 1 Nanomolar (nM). Increment in proliferation and capillary vessels formation of BMSCs was observed in the 0.5 nM and 1 nM concentrations of Simvastatin in vitro. <br /><em><strong>Conclusion:</strong></em> Treatment of deep partial-thickness of burns with co-treatment of BMSCs and Simvastatin resulted in improved burn wound healing through up-regulating of SDF-1α/CXCR4 pathway.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623620200601Mesobuthus eupeus venom induced injury in the colorectal carcinoma cell line (HT29) through altering the mitochondria membrane stability7607671547910.22038/ijbms.2020.40884.9659ENMassood ValizadeCell & Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranToxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran0000-0001-5860-5676Atefeh Raesi VananiToxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranDepartment of Toxicology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranMohsen RezaeiToxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranDepartment of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IranLayasadat KhorsandiCell & Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranDepartment of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran0000-0002-3391-3055Leila ZeidooniToxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranMasoud MahdaviniaToxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranDepartment of Toxicology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran0000-0001-9448-1500Journal Article20190603<em><strong>Objective(s):</strong></em> The purpose of this study was to investigate cytotoxicity and membrane toxicity effects induced by Mesobuthus eupeus venom (MEV) on the HT-29 cell line. <br /><em><strong>Materials and Methods:</strong></em> To determine the in vitro cytotoxicity via MTT assays, HT-29 (as cancer cell line) and Hek-293T (as normal cell) were treated through different concentrations of MEV, and cytotoxicity effects were then measured through assessment of mitochondrial membrane potential (ΔΨm), reactive oxygen species (ROS) generation, and apoptosis induction. The colony formation assay was performed to measure the antiproliferative effect of MEV on HT-29 cells. Nuclei alterations were also observed during apoptosis following DAPI staining. Besides, atomic force microscopy (AFM) was used to detect alterations in morphology and ultrastructure of the cells at a nanoscale level.<br /><em><strong>Results:</strong></em> According to MTT and clonogenic assays, MEV caused a significant decrease in cell viability and proliferation of HT-29 cells while it did not have any impact on normal cells and the IC50 value was found to be 10 µg/ml. Induction of apoptosis was also confirmed by flowcytometric analysis in HT-29 cells. Moreover, the results indicated that MEV had led to a suppression of proliferation and induction of apoptosis through increased ROS and depolarization of mitochondria. Furthermore, AFM imaging demonstrated apoptosis cell death after being treated with MEV in HT-29 cells. <br /><em><strong>Conclusion:</strong></em> This study showed that MEV had an antiproliferative effect on HT-29 cells by inducing apoptosis through the mitochondria signaling pathway. These findings suggested that MEV could be used as a promising natural remedy for cancer treatment.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623620200601The effect of different pulp-capping materials on proliferation, migration and cytokine secretion of human dental pulp stem cells7687751521410.22038/ijbms.2020.41511.9814ENSalma OmidiDepartment of Endodontics, Dental School, Mazandaran University of Medical Sciences, Sari, IranMehdi BagheriClinical Research Development Unit, Imam Hossein Hospital, Shahroud University of Medical Sciences, Shahroud, IranMozhgan FazliSchool of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran0000-0000-0000-0000Naghmeh AhmadiankiaSchool of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran0000-0001-8309-4935Journal Article20190701<em><strong>Objective(s):</strong></em> Biocompatibility of dental biomaterials plays a critical role in regeneration of dental stem cells. The aim of present study was to evaluate the effects of novel biomaterials of TheraCal-LC (TheraCal; Bisco), Angelus mineral trioxide aggregate (MTA; Angelus), calcium-enriched mixture (CEM; BioniqueDent), and Biodentine (Septodont) on viability of human dental pulp stem cells (hDPSCs). Moreover, the recruitment of dental pulp stem cells is a prerequisite for regeneration of damaged dentin. Therefore, in this study the effects of mentioned biomaterials on migration of hDPSCs and the secretion of some chemoattractive molecules by these cells were examined. <br /><em><strong>Materials and Methods:</strong></em> The cell viability of hDPSCs was assessed using MTT assay. Transwell migration assay was used to determine cell migration ability. The cytokine secretion was evaluated using enzyme-linked immunosorbent assay. <br /><em><strong>Results:</strong></em> The biomaterials of MTA, CEM, and Biodentine at different dilutions had no cytotoxic effects on hDPSCs at different time points; however, non-diluted extract of TheraCal showed toxic effects after 24, 48, and 72 hr. Meanwhile, the highest cell migration was observed in the presence of CEM and Biodentine (P<0.05). The secretion of MCP-1 and TGF-β1 were higher in hDPSCs treated with Biodentine compared to some other groups (P<0.05, P<0.01). Moreover, TheraCal decreased protein secretion of TNF-α (P<0.05), and IL-8 (P<0.01) in hDPSCs. <br /><em><strong>Conclusion:</strong></em> The biological compatibility associated with CEM and Biodentine indicates promising applications in the field of vital pulp therapy.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623620200601Probiotic treatment differentially affects the behavioral and electrophysiological aspects in ethanol exposed animals7767801492510.22038/ijbms.2020.41685.9846ENAmir Hosein Hadidi ZavarehDepartment of Biology, North Tehran Branch, Islamic Azad University, Tehran, Iran0000-0002-1571-4298Ramin Haji KhaniDepartment of Biology, North Tehran Branch, Islamic Azad University, Tehran, IranBahareh PakpourDepartment of Biology, Faculty of Sciences Central Tehran Branch, Islamic Azad University, Tehran, IranMasoud SoheiliPhysiology Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran0000-0003-2888-7312Mahmoud SalamiPhysiology Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran0000-0002-2635-1453Journal Article20190708<em><strong>Objective(s):</strong></em> Harmful effects of alcohol on brain function including cognitive phenomena are well known. Damage to gut microbiota is linked to neurological disorders. Evidence indicates that intestinal flora can be strengthened by probiotic bacteria. In this study, we evaluated the effect of probiotics administration on LTP induction in rats receiving ethanol.<br /><em><strong>Materials and Methods:</strong></em> To assess if probiotic treatment influences toxic effect of ethanol, vehicle (CON) and probiotic treated (CON+PRO) control rats, and chronic ethanol (CE) exposed and CE probiotic treated (CE+PRO) animals were entered into the experiments. Shuttle box test and in vivo electrophysiological recordings were accomplished to evaluate memory and hippocampal baseline filed excitatory postsynaptic potentials (fEPSPs) and long term potentiation (LTP), respectively. <br /><em><strong>Results:</strong> </em>Ethanol impaired memory in the CE rats. It also diminished the slope size of fEPSPs and prevented LTP induction. While the probiotic supplementation improved memory in the CE+PRO rats, it did not influence synaptic transmission in these animals. <br /><em><strong>Conclusion:</strong></em> Conclusively, behavioral but not electrophysiological aspect of cognition is sensitive to probiotic treatment in the ethanol exposed animals.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623620200601Synthesis of a novel PEGylated colon-specific azo-based 4- aminosalicylic acid prodrug7817871550510.22038/ijbms.2020.41152.9736ENFatemeh SadeghiTargeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran0000-0001-7075-7656Atie EidizadeTargeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, IranFarinaz SaremnejadDepartment of Food Science and Technology, Ferdowsi University of Mashhad, Mashhad, Iran0000-0003-3466-3147Farzin HadizadehBiotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran0000-0002-7680-8191Elham KhodaverdiTargeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IranAbbas AkhgariTargeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran0000-0001-9310-3428Journal Article20190617<em><strong>Objective(s):</strong></em> 4-aminosalicylic acid (4-ASA) is an isomer of mesalazine that has recently been shown to be effective against inflammatory bowel disease (IBD), and more specifically, ulcerative colitis. However, the majority of orally administered 4-ASA is readily and extensively absorbed from the stomach and small intestine, so only a small amount is transported to the colon. A mutual ester and azo prodrug of 4-ASA was synthesized with polyethylene glycol (PEG) and dimethylaniline, respectively , to overcome this issue. <br /><em><strong>Materials and Methods:</strong></em> The 4-ASA prodrug was synthesized via a two-step process and then characterized by 1H-NMR. The stability of the prodrug was evaluated in simulated gastric fluid (pH 1.2). Furthermore, the in vitro release profiles of the drug conjugate was evaluated at pH 1.2, as well as pH 6.8 in the absence or presence of rat cecal content. <br /><em><strong>Results:</strong></em> The prepared prodrug was stable at pH 1.2, indicating that it could be protected from the acidic environment of the stomach. Also, the results of drug release at pH 6.8 showed that the amount of 4-ASA released was 63% within 12 hr in the absence of rat cecal content, while in the presence of rat cecal content, 97% of 4-ASA was released from the prodrug in 6 hr. <br /><em><strong>Conclusion:</strong></em> Overall, the synthesized PEGylated azo-based 4-ASA prodrug could be a potential candidate for targeted drug delivery to the inflamed gut tissue in IBD.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623620200601Chitosan-based nano-scaffolds as antileishmanial wound dressing in BALB/c mice treatment: Characterization and design of tissue regeneration7887991548210.22038/ijbms.2020.41361.9770ENSeyyed Javad Seyyed TabaeiDepartment of Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran0000-0002-9061-5089Mohsen RahimiDepartment of Parasitology and Mycology, School of Medicine, Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran0000-0002-2537-651xMohsen AkbaribazmAnatomical Sciences, Fertility and Infertility Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran0000-0001-9162-8706Seyed Ali ZiaiDepartment of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran0000-0002-1102-8119Minoo SadriDepartment of Biochemistry and Biophysics, Education and Research Center of Science and Biotechnology, Malek Ashtar University of Technology, Tehran, Iran0000-0001-8540-7464Seyed Reza ShahrokhiDoctor of Veterinary Medicine (D.V.M.), Rasht, Iran0000-0002-8426-9482Mitra Sadat RezaeiVirology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, IranPathology Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran0000-0001-8228-8623Journal Article20190625<em><strong>Objective(s):</strong></em> Rapid healing of cutaneous leishmaniasis as one of the most important parasitic diseases leads to the decrease of scars and prevention of a great threat to the looks of the affected people. Today, the use of nano-scaffolds is rapidly increasing in tissue engineering and regenerative medicine with structures similar to the target tissue. Chitosan (CS) is a bioactive polymer with antimicrobial and accelerating features of healing wounds, which is commonly used in biomedicine. This study aimed to investigate the effects of CS/polyethylene oxide (PEO)/berberine (BBR) nanofibers on the experimental ulcers of Leishmania major in BALB/c mice.<br /><em><strong>Materials and Methods:</strong></em> CS/PEO/BBR nanofibers were prepared by the electrospinning method, and their morphology was examined by SEM, TEM, and AFM. Then, water absorption, stability, biocompatibility, porosity, and drug release from nano-scaffolds were explored. Afterward, 28 BALB/c mice infected with the parasite were randomly divided into control and experimental groups, and their wounds were dressed with the produced nano-scaffolds. Finally, the effect of nanobandage on the animals was investigated by macroscopic, histopathologic, and in vivo imaging examinations.<br /><em><strong>Results:</strong></em> The prepared nanofibers were completely uniform, cylindrical, bead-free, and biocompatible with an average diameter of 94±12 nm and had appropriate drug release. In addition, the reduced skin ulcer diameter (P=0.000), parasite burden (P=0.003), changes in the epidermis (P=0.023), and dermis (P=0.032) indicated significantly strong effectiveness of the produced nano-scaffolds against leishmania ulcers. <br /><em><strong>Conclusion:</strong></em> Studies showed that CS/PEO/BBR nanofibers have a positive effect on the rapid healing of leishmania ulcers. Future studies should focus on other chronic ulcers treatment.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623620200601Polymorphisms within methotrexate pathway genes: Relationship between plasma methotrexate levels, toxicity experienced and outcome in pediatric acute lymphoblastic leukemia8008091548010.22038/ijbms.2020.41754.9858ENMohammad Ali EsmailiDepartment of Hematology, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran0000-0001-6851-7872Ahmad KazemiDepartment of Hematology, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, IranMohammad FaranoushPediatric Growth and Development Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, IranMahak Hematology Oncology Research Center (MAHAK-HORC), Mahak Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran0000-0002-2775-2347Hakan MellstedtDepartment of Oncology-Pathology, Immune and Gene Therapy Lab, Cancer Center Karolinska (CCK), Karolinska University Hospital Solna and Karolinska Institute, Stockholm 17176, SwedenFarhad ZakerCellular and Molecular Research Center, School of Allied Medicine, Iran University of Medical Sciences, Tehran, IranMajid SafaCellular and Molecular Research Center, Department of Hematology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, IranNarjes MehrvarCancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran0000-0001-5984-2913Mohammad Reza RezvanyDepartment of Hematology, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, IranPediatric Growth and Development Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, IranDepartment of Oncology-Pathology, Immune and Gene Therapy Lab, Cancer Center Karolinska (CCK), Karolinska University Hospital Solna and Karolinska Institute, Stockholm 17176, Sweden0000 0003 0323 7671Journal Article20190710<em><strong>Objective(s):</strong></em> The current study aimed to investigate the relationship of genetic polymorphism and plasma methotrexate (MTX) levels, toxicity experience and event free survival (EFS) in pediatric acute lymphoblastic leukemia (ALL). <br /><em><strong>Materials and Methods:</strong></em> The study included 74 ALL patients. Polymerase chain reaction and genotyping of methylene tetrahydrofolate reductase (MTHFR) rs1801133, MTHFR rs1801131, ATP-binding cassette superfamily B1 (ABCB1) rs1045642, ATP-binding cassette superfamily G2 (ABCG2) rs2231142 and solute carrier 19A1 (SLC19A1) rs1051266 genetic variations were performed. The plasma MTX levels were investigated at 48 hr after the first dose of MTX infusion.<br /><strong><em>Results:</em></strong> MTHFR rs1801133 TT genotype, ABCBa1 rs1045642 CT genotype and ABCG2 rs2231142 CA genotype revealed a statistically significant association with the MTX plasma levels (P<0.01, P<0.05, P<0.05, respectively). The MTHFR rs1801133 TT genotype had a statistically significant association with hematopoietic toxicity (P<0.01) and interventions (P<0.05). The MTHFR rs1801131 AC genotype was related to the decreased hepatic toxicity (P<0.05). The SLC19A1 rs 1051266 GA genotype was related to the increased hepatic toxicity (P<0.05). Only the ABCB1 rs1045642 CT and TT genotypes had a statistically significant correlation with EFS (P<0.05, P<0.05, respectively). <br /><em><strong>Conclusion:</strong></em> Our findings showed that genetic polymorphism could be associated with plasma MTX levels, toxicity experienced and EFS in Iranian pediatric ALL. Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623620200601The effects of synthetic orally administrated insulin nanoparticles in comparison to injectable insulin on the renal function markers of type 1- diabetic rats8108181521610.22038/ijbms.2020.42292.9985ENNejat KeiripourResearch Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran0000-0003-0684-7125Behnam AlipoorDepartment of Laboratory Sciences, Faculty of Paramedicine, Yasuj University of Medical Sciences, Yasuj, IranAkram RanjbarToxicology and Pharmacology Department, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, IranYasin PourfarjamDepartment of Chemistry, University of Cincinnati, Cincinnati, OH, United States of AmericaFarzaneh Kazemi NajafabadiToxicology and Pharmacology Department, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, IranNarges DehkhodaieToxicology and Pharmacology Department, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, IranMasumeh FarhadiannezhadStudent Research Committee, Abadan School of Medical Sciences, Abadan, IranHassan GhasemiDepartment of Clinical Biochemistry, Abadan Faculty of Medical Sciences, Abadan, Iran0000-0002-2568-4168Journal Article20190801<em><strong>Objective(s):</strong></em> Injectable insulin is the most widely used therapy in patients with type 1 diabetes which has several disadvantages. The present study was aimed to evaluate the efficacy of injectable insulin on diabetes mellitus-related complications in comparison to orally encapsulated insulin nanoparticles.<br /><em><strong>Materials and Methods:</strong></em> This study involved 42 Wistar rats separated into 5 groups, including control (C), diabetic control (D), diabetic receiving regular insulin (INS), diabetic receiving encapsulated insulin nanoparticle (INP), and diabetic receiving chitosan for two months. Biochemical parameters in serum and urine were measured using spectrophotometric or ELISA methods. mRNA levels of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were evaluated using quantitative PCR. <br /><em><strong>Results:</strong></em> There were no significant differences between the two forms of insulin in controlling the glycemic condition (P-value>0.05), but oral INP was more effective in correcting diabetic dyslipidemia in comparison to injectable insulin (P-value<0.05). Urine volume and creatinine excretion were significantly modulated by insulin and oral INP in diabetic groups (P-value<0.05), although the effects of INP on the modulation of execration of urea, acid uric, and albumin was more dramatic. Oral INP caused a significant decrease in urine concentration of KIM-1 and NGAL as well as expression of KIM-1 in renal tissue (P-value<0.05).<br /><em><strong>Conclusion:</strong></em> Our results suggested that oral INP is more effective than injectable insulin in modulation of urine and serum diabetic-related parameters.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623620200601Triiodothyronine potentiates angiogenesis-related factor expression through PI3K/AKT signaling pathway in human osteoarthritic osteoblasts8198251551210.22038/ijbms.2020.43634.10252ENLi LeiDepartment of Orthopaedics,the First Affiliated Hospital of University of Science and Technology of China, #17 Lujiang Road, Hefei, Anhui, ChinaDepartment of Orthopaedics, the First Affiliated Hospital of Anhui Medical University, #269 Jixi Road, Hefei, Anhui, ChinaPang YiqunDepartment of Radiology, the First Affiliated Hospital of University of Science and Technology of China, #17 Lujiang Road, Hefei, Anhui, ChinaLinlin ZhangDepartment of Orthopaedics,The First Affiliated Hospital of University of Science and Technology of China, #17 Lujiang Road, Hefei, Anhui, ChinaMeng LiDepartment of Orthopaedics,The First Affiliated Hospital of University of Science and Technology of China, #17 Lujiang Road, Hefei, Anhui, ChinaZhu ChenDepartment of Orthopaedics,The First Affiliated Hospital of University of Science and Technology of China, #17 Lujiang Road, Hefei, Anhui, ChinaShiyuan FangDepartment of Orthopaedics,The First Affiliated Hospital of University of Science and Technology of China, #17 Lujiang Road, Hefei, Anhui, ChinaYin ZongshengDepartment of Orthopaedics, the First Affiliated Hospital of Anhui Medical University, #269 Jixi Road, Hefei, Anhui, China0000-0003-3353-9363Journal Article20191007<em><strong>Objective(s):</strong> </em>Previous study has indicated that triiodothyronine (T3) facilitated cartilage degeneration in osteoarthritis (OA). This study aimed to investigate the effects of T3 on angiogenesis-related factor expression in human osteoblasts of OA subchondral bone.<br /><em><strong>Materials and Methods:</strong> </em>The subchondral bone specimens were obtained from OA patients and healthy participants. The expressions of VEGF, HIF-1α, AKT, and phosphorylated AKT was detected by immunohistochemistry, Western blotting, and RT-qPCR in OA. Angiogenesis-related factor expression in OA osteoblasts was measured by treating different concentrations of T3. The hypoxia model and PX-478 (HIF-1α inhibitor) were employed to confirm the regulative role of HIF-1α for VEGF expression. The level of VEGF secretion was examined in osteoblasts supernatant using ELISA. <br /><em><strong>Results:</strong> </em>Immunohistochemistry showed strong staining of VEGF and HIF-1α in OA subchondral bone. The expression of VEGF, HIF-1α, and p-AKT in OA osteoblasts was higher than that of normal osteoblasts at protein and mRNA levels. The physiological concentration of T3 (10-7 M) in OA osteoblasts up-regulated the expression of VEGF, HIF-1α, and p-AKT after 24 hr and 48 hr culture, while a higher dose of T3 displayed the adverse effects. Additionally, VEGF and p-AKT expression was down-regulated when PX-478 inhibited HIF-1α protein. <br /><em><strong>Conclusion:</strong></em> Our results suggested that local T3 could effectively increase angiogenesis-related factor expression by PI3K/AKT signaling pathway, and HIF-1α regulated the VEGF expression in OA osteoblasts.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623620200601A novel formulation of Mtb72F DNA vaccine for immunization against tuberculosis8268321550910.22038/ijbms.2020.41806.9881ENRazieh DalirfardoueiResearch Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, IranDepartment of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran0000-0001-5162-476XMohsen TafaghodiNanotechnology Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran0000-0002-8286-0973Zahra MeshkatAntimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran0000-0002-4032-7599Adel NajafiLaboratory Division, Fatemieh Hospital, Hamadan University of Medical Sciences, Hamadan, IranAida GholoobiMedical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran0000-0001-6399-1612Maryam NabaviniaDepartment of Pharmacognosy, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Shahid Sadoughi University of Medical
Sciences, Yazd, IranSamineh SajedifarMashhad University of Medical Sciences, Mashhad, IranMojtaba MeshkatMashhad Branch, Isalmic Azad University, Mashhad, Iran0000-0003-0507-3295Ali BadieeNanotechnology Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran0000-0003-1595-2218Mohammad RamezaniNanotechnology Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran0000-0001-5888-6703Abdolreza VarastehImmunobiochemistry Lab, Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, IranMahboobeh NaderinasabAntimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran0000-0002-9799-1706Journal Article20190713<em><strong>Objective(s):</strong></em> Mycobacterium tuberculosis (M. tuberculosis), an intracellular pathogen, causes 1.5 million deaths globally. Bacilli Calmette-Guérin (BCG) is commonly administered to protect people against M. tuberculosis infection; however, there are some obstacles with this first-generation vaccine. DNA vaccines, the third generation vaccines, can induce cellular immune responses for tuberculosis (TB) protection. In this study, optimized DNA vaccine (pcDNA3.1-Mtb72F) entrapped in poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) was used to achieve higher immunogenicity. <br /><em><strong>Materials and Methods:</strong></em> Plasmid Mtb72F was formulated in PLGA NPs using double emulsion method in the presence of TB10.4 and/or CpG as an adjuvant. Female BALB/c mice were immunized either with NP-encapsulated Mtb72F or naked Mtb72F with or without each adjuvant, using the BCG-prime DNA boost regimen. <br /><em><strong>Results:</strong></em> These NPs were approximately 250 nm in diameter and the nucleic acid and protein encapsulation efficiency were 80% and 25%, respectively. The NPs smaller than 200 nm are able to promote cellular rather than humoral responses. The immunization with the formulation consisting of Mtb72F DNA vaccine and TB10.4 entrapped in PLGA NPs showed significant immunogenicity and induced predominantly interferon-ɣ (IFN-ɣ) production and higher INF-ɣ/interleukin-4 (IL-4) ratio in the cultured spleen cells supernatant. <br /><em><strong>Conclusion:</strong></em> PLGA NPs loaded with Mtb72F DNA-based vaccine with TB10.4 could be considered as a promising candidate for vaccination against TB. These results represent an excellent initial step toward development of novel vaccine for TB protection.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623620200601Wi-Fi (2.4 GHz) affects anti-oxidant capacity, DNA repair genes expression and apoptosis in pregnant mouse placenta8338401551010.22038/ijbms.2020.40184.9512ENHomeira VafaeiMaternal Fetal Medicine Research Center, Shiraz University of Medical Sciences, Shiraz, Iran0000-0002-9399-7836Ghazal KavariMaternal Fetal Medicine Research Center, Shiraz University of Medical Sciences, Shiraz, IranHamid Reza IzadiShiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, IranZahra Zare DorahiStem Cell Technology Research Center, Shiraz University of Medical Sciences, Shiraz, IranMehdi DianatpourStem Cell Technology Research Center, Shiraz University of Medical Sciences, Shiraz, IranDepartment of Human Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran0000-0003-1217-9477Afrooz DaneshparvarStem Cell Technology Research Center, Shiraz University of Medical Sciences, Shiraz, IranIman JamhiriStem Cell Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran0000-0002-4772-8678Journal Article20190506<em><strong>Objective(s):</strong></em> The placenta provides nutrients and oxygen to embryo and removes waste products from embryo’s blood. As far as we know, the effects of exposure to Wi-Fi (2.4 GHz) signals on placenta have not been evaluated. Hence, we examined the effect of prenatal exposure to Wi-Fi signals on anti-oxidant capacity, expressions of CDKNA1, and GADD45a as well as apoptosis in placenta and pregnancy outcome. <br /><em><strong>Materials and Methods:</strong> </em>Pregnant mice were exposed to Wi-Fi signal (2.4 GHz) for 2 and 4 hr. Placenta tissues were examined to measure the MDA and SOD levels. To measure SOD, CDKNA1, GADD45a, Bax, and Bcl-2 expressions were compared by real-time PCR analysis. TUNEL assay was used to assess apoptosis in placenta tissues. The results were analyzed by one-way analysis of variance (ANOVA) using Prism version 6.0 software. <br /><em><strong>Results:</strong></em> MDA and SOD levels had significantly increased in exposed Wi-Fi signal groups (P-value< 0.05). Also, quantitative PCR experiment showed that SOD mRNA expression significantly increased in Wi-Fi signal groups. The data showed that CDKN1A and GADD45a genes were increased in Wi-Fi groups (P-value<0.05). The quantitative PCR and the TUNEL assay showed that apoptosis increased in Wi-Fi groups (P-value<0.05). <br /><em><strong>Conclusion:</strong></em> Our results provide evidence that Wi-Fi signals increase lipid peroxidation, SOD activity (oxidative stres), apoptosis and CDKN1A and GADD45a overexpression in mice placenta tissue. However, further experimental studies are warranted to investigate other genes and aspects of pregnancy to determine the role of Wi-Fi radiation on fertility and pregnancy.