Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623720200701The worldwide frequency of MYO15A gene mutations in patients with autosomal recessive non-syndromic hearing loss: A meta‐analysis8418481565510.22038/ijbms.2020.35977.8563ENMahsa FarjamiDepartment of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranStudent Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran0000-0002-2280-9746Reza AsadiDepartment of Education Development Center, Mashhad University of Medical Sciences, Mashhad, IranFahimeh Afzal JavanStudent Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran0000-0001-7413-6945Malihe AlimardaniDepartment of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranStudent Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranSaeed EslamiPharmaceutical Research Center, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Medical Informatics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranSima Mansoori DerakhshanDepartment of Medical Genetics, Tabriz University of Medical Sciences, Tabriz, IranIbn Sina Medical Genetic Diagnostic Laboratory, Tabriz University of Medical Sciences, Tabriz, IranNeurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, IranAtieh EslahiDepartment of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranStudent Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran0000-0003-2992-7769Majid MojaradDepartment of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranMedical Genetics Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran0000-0001-8742-2844Journal Article20181106MYO15A is the third most crucial gene in hereditary sensorineural hearing loss after GJB2 and SLC26A4. In the present study, we reviewed the prevalence of MYO15A mutations in patients with autosomal recessive non-syndromic hearing loss (ARNSHL). In this meta-analysis, we conducted a search of PubMed, Web of Science, Excerpta Medica Database, and Scopus, and identified the articles up to September 2019 without any time limit. Two investigators independently selected the relevant papers and extracted the required information. A total of 44 case-control and case series studies were considered, and 4176 patients and 3706 healthy individuals, as the control group, were included. The pooled frequency of MYO15A mutations between patients suffering from ARNSHL was calculated as 6.2% (95% CI: 4.9-7.8, P-value<0.001). There was heterogeneity between our studies (P-value<0.001, I2=58.1%); therefore, the random-effects model was utilized for analysis. Given the results, in many countries, the MYO15A gene had a significant contribution to hearing loss. Moreover, in several regions, specific dominant mutations in this gene have been reported. Therefore, the ethnic background should be considered to investigate the mutations of the MYO15A gene.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623720200701Thymoquinone: From Nigella sativa to a protective pharmacological compound in managing opioid dependence and amphetamine type stimulant issues8498521557010.22038/ijbms.2020.41678.9841ENLiyana Hazwani Mohd AdnanFaculty of Medicine, University Sultan Zainal Abidin, City Campus, 20400 Kuala Terengganu, Malaysiahttps://orcid.org/00Nor Hidayah Abu BakarFaculty of Medicine, University Sultan Zainal Abidin, City Campus, 20400 Kuala Terengganu, MalaysiaNordin SimbakFaculty of Medicine, University Sultan Zainal Abidin, City Campus, 20400 Kuala Terengganu, MalaysiaNasir MohamadFaculty of Medicine, University Sultan Zainal Abidin, City Campus, 20400 Kuala Terengganu, MalaysiaRusli IsmailFaculty of Medicine, University Sultan Zainal Abidin, City Campus, 20400 Kuala Terengganu, MalaysiaNor Zidah AhmadFaculty of Medicine, University Sultan Zainal Abidin, City Campus, 20400 Kuala Terengganu, MalaysiaNor Suliana MustafaFaculty of Medicine, University Sultan Zainal Abidin, City Campus, 20400 Kuala Terengganu, Malaysia0000-0003-1011-2893Nurul Farah Aina Md FauziFaculty of Medicine, University Sultan Zainal Abidin, City Campus, 20400 Kuala Terengganu, MalaysiaJournal Article20190708Opioids, amphetamines, and other types of substances have been widely abused around the world. Opioid dependence and tolerance are two distinct phenomena that have been associated with substance abuse issues. The management of its adverse consequences is becoming more challenging. More and more people are treated in Methadone Maintenance Therapy (MMT) program yet the issues are still unresolved. Researchers are continuing to study the best formulation in treating opioid dependent people starting with modern and alternative drug therapies. Since 2008 , thymoquinone (TQ) has been extensively studied by researchers around the world and has emerged to be a new potential drug candidate in managing substance abuse issues. Thus, the aim of this article is to review the effects that TQ may have on opioid dependent subjects and other abused substances such as amphetamine may have been studied. All of the articles from 2008 until 2019 involving the effects of TQ on substance abuse from Google Scholar®, Scopus®, and Pubmed® databases have been searched and reviewed. The keywords used were thymoquinone, opioid dependence, amphetamine, and Nigella sativa. The research results also have been discussed in this article. Based on the research conducted, TQ was effective in reducing the adverse health consequences associated with substance abuse such as withdrawal symptoms, tolerance, and cell damages. It is concluded that TQ could be a potential drug that can be complemented with the currently available drugs in substance abuse therapies.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623720200701Evaluation of CD133 and CD56/NCAM expression in Wilms tumor and their association with prognostic factors8538571559510.22038/ijbms.2020.41468.9804ENAmir Hossein JafarianDepartment of Pathology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran0000-0003-4004-262xNona Zaboli NejadDepartment of Pathology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranNema Mohamadian RoshanDepartment of Pathology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranSara HashemiDepartment of Pathology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranMasoumeh GharibDepartment of Pathology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran0000-0003-2501-2684Journal Article20190629<em><strong>Objective(s):</strong></em> To validate certain markers for cancer stem cell populations and their clinical importance in Wilms tumor (WT)<br /><em><strong>Materials and Methods:</strong></em> Immunohistochemical study for CD133 and CD56/NCAM was performed on forty-six cases of WT that were diagnosed between 1999 and 2015, and the association of these markers with survival and prognostic factors was analyzed. <br /><em><strong>Results:</strong></em> Thirty-four (73.9%) of WTs were positive for CD133 and thirty-nine (84.8%) were positive for CD56/NCAM. A significant positive correlation between CD133 and CD56/NCAM expression and the National Wilms Tumor Stage (NWTS) and death was found. Moreover, overall survival time was significantly correlated with CD133 and CD56/NCAM H-score, NWTS stage, and death. <br /><em><strong>Conclusion:</strong></em> It seems that CD133 and CD56/NCAM expressions can be used as strong prognostic parameters for the survival of patients with WT and can be used to predict WT patients’ stage. Moreover, their targeted therapies can abolish cancer stem cells in children with recurrent tumors.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623720200701Involvement of the 5-HT1A receptor of the cuneiform nucleus in the regulation of cardiovascular responses during normal and hemorrhagic conditions8588641550410.22038/ijbms.2020.40453.9579ENReza MohebbatiDepartment of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran0000-0002-1645-7094Mahmoud HosseiniDivision of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, IranMajid KhazaeiDepartment of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran0000-0002-3150-5883Abolfazl KhajaviradDepartment of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran0000-0001-7046-1134Mohammad Naser ShafeiNeurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran0000-0001-5148-9895Journal Article20190519<em><strong>Objective(s):</strong></em> The 5-hydroxytryptamine1A (5-HT1A) receptor is one of the serotonin receptors in the brain, which regulates cardiovascular responses, especially in hemorrhage. Presence of this receptor in the cuneiform nucleus (CnF) has been shown. The present study evaluates the cardiovascular effect of this receptor of the CnF in normal and hypotensive hemorrhagic rats.<br /><em><strong>Materials and Methods:</strong></em> Agonist (8-OH-DPAT) and antagonist (WAY-100635) of 5-HT1A microinjected into the CnF in basal and hemorrhagic conditions and cardiovascular responses were evaluated. Hemorrhage induced by blood withdrawal from the femoral artery and 2 min after that drugs microinjected. Time course and peak changes (∆) of the mean arterial pressure (MAP), systolic blood pressure (SBP) and heart rate (∆HR) were obtained and compared to the control and hemorrhage groups.<br /><em><strong>Results:</strong></em> In basal condition, 8-OH-DPAT significantly decreased ∆SBP, ∆MAP and ∆HR compared to the control (P<0.05-P<0.01), while way-100635 did not have a significant effect. Hypotension and tachycardia induced by hemorrhage ameliorated by agonist (P<0.05-P<0.01), while antagonist deteriorated hypotension (P<0.05) but attenuated tachycardia (P<0.01).<br /><strong><em>Conclusion:</em></strong> This study shows that 5-HT1A receptor of the CnF involves in regulation of the cardiovascular responses. However, this effect in basal and hemorrhage conditions is different.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623720200701Trastuzumab increases pulmonary vein arrhythmogenesis through modulating pulmonary vein electrical and conduction properties via phosphatidylinositol 3-kinase signaling8658701556810.22038/ijbms.2020.44651.10432ENJun-Hei ChangDepartment of Medical, Tri-Service General Hospital Songshan Branch, National Defense Medical Center, Taipei, TaiwanDepartment of Biomedical Engineering, National Defense Medical Center, Taipei, Taiwan0000-0002-1325-6887Chen-Chuan ChengDepartment of Cardiology, Chi-Mei Medical Center, Tainan, TaiwanYen-Yu LuDivision of Cardiology, Department of Internal Medicine, Sijhih Cathay General Hospital, New Taipei City, TaiwanSchool of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei City, TaiwanYao-Chang ChenDepartment of Biomedical Engineering, National Defense Medical Center, Taipei, TaiwanShih-Ann ChenHeart Rhythm Center and Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, TaiwanYi-Jen ChenCardiovascular Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, TaiwanGraduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan0000-0001-7224-4491Journal Article20191127<em><strong>Objective(s):</strong></em> Drug-induced atrial fibrillation (AF) is considered an adverse effect of chemotherapeutic drugs. AF is a crucial risk factor for stroke, heart failure, myocardial infarction, and mortality. Pulmonary veins (PVs) are considered triggers inducing AF, and the sinoatrial node (SAN) may modulate PV activity and participate in AF genesis. AF was associated with early discontinuation of trastuzumab in patients with breast cancer. However, whether trastuzumab directly modulates the electrophysiological characteristics of PV and SAN remains unclear. <br /><em><strong>Materials and Methods:</strong></em> ECG and conventional microelectrode system were used to record rabbit heart rhythm in vivo and electrical activities in vitro from isolated SAN, PV, and SAN-PV preparations. <br /><em><strong>Results:</strong></em> Trastuzumab reduced the beating rate in isolated PV and SAN preparations at 1, 10, and 30 μM (particularly in isolated SAN preparations) and induced burst firings in isolated PV preparations at 10 μΜ. In addition, trastuzumab (10 μM) induced SAN-PV conduction block and burst firings, which were blocked by wortmannin (a PI3K inhibitor, 100 nM). Similarly, ECG recordings showed that acute intravenous administration of trastuzumab (10 mg/kg) reduced rabbit heart rates. <br /><em><strong>Conclusion:</strong></em> Trastuzumab increased PV arrhythmogenesis through interfering with PI3K signaling, which may contribute to the genesis of AF.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623720200701Effects of 8-hydroxyquinoline-coated graphene oxide on cell death and apoptosis in MCF-7 and MCF-10 breast cell lines8718781557210.22038/ijbms.2020.41277.9751ENFiroozeh KheiltashDepartment of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran0000-0002-4343-7216Kazem ParivarDepartment of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran0000-0002-2836-9710Nasim Hayati RoodbariDepartment of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran0000-0002-5942-5770Behnam SadeghiCancer Immunotherapy and Regenerative Medicine, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, IranAlireza BadieiSchool of Chemistry, College of Science, University of Tehran, Tehran, IranJournal Article20190621<em><strong>Objective(s):</strong></em> Breast cancer is a devastating disease related to women. The anticancer properties of 8-hydroxyquinoline (8HQ) and the increasing use of graphene oxide (GO), as a drug delivery system with anti-cancerous properties, led us to investigate the toxicity and apoptosis-induction capability of 8HQ-coated GO on breast cancer cells compared with normal breast cells.<br /><em><strong>Materials and Methods:</strong></em> Breast cancer (MCF-7) and normal breast (MCF-10) cell lines were treated with several doses of 8-HQ-coated GO for 12, 24, and 48 hr. The toxicity of the nanocomposite was measured using MTT assay and the effect of the nanocomposite on cell apoptosis was determined by examining the expression of P53, P21, Bax, and BCL2 genes, as well as Annexin-V /PI apoptosis assay.<br /><em><strong>Results:</strong></em> There were significantly increased cell deaths in nanocomposite-treated MCF-7 breast cancer cells, compared with treated normal breast cells. Significantly increased expression of P53, P21, and Bax genes and reduced expression of BCL2 gene were found in the treated breast cancer cell line compared with the normal cell line. Annexin-V/PI assay also illustrated significant induction of apoptosis in MCF-7 following nanocomposite treatment.<br /><em><strong>Conclusion:</strong></em> Overall, 8HQ-coated GO has toxicity for breast cancer cell lines and one of the mechanisms through which this nanocomposite can induce cell death is the induction of apoptosis. With complementary in vitro and in vivo studies, this nanocomposite can be suggested as a nano-drug with anti-cancer properties.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623720200701Comparison of the effects of intramyocardial and intravenous injections of human mesenchymal stem cells on cardiac regeneration after heart failure8798851549310.22038/ijbms.2020.40886.9660ENBehnaz MokhtariPhysiology Research Center, Iran University of Medical Sciences, Tehran, IranDepartment of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran0000-0002-3355-9869Nahid AboutalebPhysiology Research Center, Iran University of Medical Sciences, Tehran, IranDepartment of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran0000-0002-7514-5939Donya NazariniaPhysiology Research Center, Iran University of Medical Sciences, Tehran, IranDepartment of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, IranMahin NikougoftarBlood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, IranSeyed Mohammad Taghi Razavi TousiMedical Biotechnology Research Center, Guilan University of Medical Sciences, Rasht, IranMohammad MolazemDepartment of Veterinary Diagnostic Imaging, Faculty of Veterinary Medicine, University of Tehran, Tehran, IranMohammad-Reza AzadiPhysiology Research Center, Iran University of Medical Sciences, Tehran, IranJournal Article20190603<em><strong>Objective(s):</strong></em> Existing studies have demonstrated that intravenous and intramyocardial-administrated mesenchymal stem cells (MSCs) lead to tissue repair after cardiac disorders. We compared the efficiency of both administration methods.<br /><em><strong>Materials and Methods:</strong></em> A rat model of isoproterenol-induced heart failure (ISO-HF) was established to compare the effects of intravenous and intramyocardial-administrated MSCs on cardiac fibrosis and function. The animals were randomly assigned into six groups: i) control or normal, ii) ISO-HF (HF) iii) ISO-HF rats treated with intramyocardial administration of culture medium (HF+IM/CM), iv) ISO-HF rats treated with intravenous administration of culture medium ( HF+IV/CM), v) ISO-HF rats treated with intravenous administration of MSCs (HF+IV/MSCs), vi) ISO-HF rats treated with intramyocardial administration of MSCs ( HF+IM/MSCs). Cultured MSCs and culture medium were administrated at 4 weeks after final injection of ISO. Heart function, identification of MSCs, osteogenic differentiation, adipogenic differentiation, cardiac fibrosis and tissue damage were evaluated by echocardiography, flow-cytometery, von Kossa, oil red O, Masson’s trichrome and H & E staining, respectively. <br /><em><strong>Results:</strong></em> Both intravenous and intramyocardial MSCs therapy significantly improved heart function and reduced cardiac fibrosis and tissue damage (P<0.05), whereas the cultured medium had no beneficial effects. <br /><em><strong>Conclusion:</strong></em> In sum, our results confirm the validity of both administration methods in recovery of HF, but more future research is required.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623720200701Anti-cancer properties of Escherichia coli Nissle 1917 against HT-29 colon cancer cells through regulation of Bax/Bcl-xL and AKT/PTEN signaling pathways8868931552010.22038/ijbms.2020.43016.10115ENSiamak AlizadehDepartment of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, IranResearch Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran0000-0003-4308-8252Abolghasem EsmaeiliDepartment of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran0000-0002-8844-4591Yadollah OmidiResearch Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran0000-0003-0067-2475Journal Article20190907<strong><em>Objective(s):</em></strong> Chemotherapies used to treat colon cancer might often fail due to the emergence of chemoresistance and side effects. Escherichia coli Nissle 1917 (EcN) is a beneficial probiotic, whose molecular mechanisms in the prevention of colon cancer are yet to be fully understood. The present study assessed the anti-cancer effects of EcN treatments in human colorectal cancer, HT-29 cell line, with the analysis of related mechanisms. <br /><em><strong>Materials and Methods:</strong> </em>The co-culture conditioned-media (CM) of EcN with adenocarcinoma HT-29 cells and heat-inactivated bacteria (HIB) were applied for the treatment of the HT-29 cells. To study the inhibition potential of CM and HIB on cancer cells, various cellular/molecular analyses were implemented, including DAPI-staining and DNA ladder assays, flow cytometry and Real-time quantitative PCR (qPCR), as well as Western blotting analyses.<br /><em><strong>Results:</strong> </em>Our results indicated that EcN could elicit apoptotic impacts on the colon cancer HT-29 cells by up-regulating PTEN and Bax and down-regulating AKT1 and Bcl-xL genes. <br /><em><strong>Conclusion:</strong></em> Based on our findings, EcN is proposed as a useful supplemental probiotic treatment against colon cancer.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623720200701Electroacupuncture reduces chronic fibromyalgia pain through attenuation of transient receptor potential vanilloid 1 signaling pathway in mouse brains8949001556910.22038/ijbms.2020.39708.9408ENChia-Ming YenCollege of Chinese Medicine, Graduate Institute of Acupuncture Science, China Medical University, Taichung 40402, TaiwanDepartment of Anesthesiology, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation0000-0002-9774-8634Ching-Liang HsiehCollege of Chinese Medicine, Graduate Institute of Integrated Medicine, China Medical University, Taichung 40402, TaiwanYi-Wen LinCollege of Chinese Medicine, Graduate Institute of Acupuncture Science, China Medical University, Taichung 40402, TaiwanChinese Medicine Research Center, China Medical University, Taichung 40402, Taiwan0000-0001-7204-8837Journal Article20190418<em><strong>Objective(s):</strong></em> Fibromyalgia pain is a mysterious clinical pain syndrome, characterized by inflammation in the brain, whose molecular mechanisms are still unknown. Females are more commonly affected by fibromyalgia, exhibiting symptoms such as widespread mechanical pain, immune dysfunction, sleep disturbances, and poor quality of life. Electroacupuncture (EA) has been used to relieve several types of pain, including fibromyalgia pain.<br /><em><strong>Materials and Methods:</strong></em> In the present study, we used dual injections of acidic saline into the gastrocnemius muscle to initiate a neural activation that resulted in fibromyalgia pain in mice. We used the Von Frey test to measure mechanical hyperalgesia and Western blot to measure protein levels. <br /><em><strong>Results:</strong></em> Results indicated that mechanical hyperalgesia can be induced in mice for 4 weeks, suggesting the induction of chronic fibromyalgia (CFM). Furthermore, continuous EA treatment reliably attenuated the mechanical hyperalgesia, but not in the sham control group. Results also suggested that the mechanical hyperalgesia can be prevented in mice with TRPV1 gene deletion. Mice with CFM showed increased expressions of TRPV1, Nav1.7, and Nav1.8 in the dorsal root ganglion (DRG) and the spinal cord (SC). The expression of TRPV1-associated molecules such as pPKA, pERK, and pCREB was also increased in the thalamus and somatosensory cortex (SSC) of the mice. All the aforementioned mechanisms were reversed by EA treatment and TRPV1 gene deletion. <br /><em><strong>Conclusion:</strong></em> Altogether, our results implied significant mechanisms of CFM and EA-analgesia that involve the regulation of the TRPV1 signaling pathway. These findings may be relevant to the evaluation and treatment of CFM.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623720200701Point-of-care detection of Escherichia coli O157:H7 in water using AuNPs-based aptasensor9019081559710.22038/ijbms.2020.44016.10322ENVahid SoheiliDepartment of Pharmacology and Toxicology, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran000000025047797XSeyed Mohammad TaghdisiTargeted Drug Delivery Research Center, Pharmaceutical Technology Institute, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran0000-0001-9836-2189Khalil AbnousPharmaceutical Research Center, Pharmaceutical Technology Institute, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran0000-0001-6314-0164Mohsen EbrahimiDepartment of Pharmacology and Toxicology, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran0000-0001-6862-6972Journal Article20191026<em><strong>Objective(s):</strong></em> Access to safe drinking and irrigation water has always been one of the major human concerns worldwide. Thus, rapid, sensitive, and inexpensive approaches for pathogenic bacteria detection, such as Escherichia coli O157:H7 (EHEC) that can induce important infectious diseases, are highly on demand. <br /><em><strong>Materials and Methods:</strong></em> In this study, a sensitive aptamer-based AuNPs bioassay was developed that demonstrated its potential to detect EHEC. In the presence of the target bacterium, the specific adsorbed aptamer, leaves AuNPs surface and interacts with EHEC. The bare nanoparticles aggregate in the presence of NaCl and the color shifts from red to purple and blue depending on the bacterial concentration. <br /><em><strong>Results:</strong></em> The proposed aptasensor exhibited a good linear response over a wide concentration range of 876 to 107 CFU/ml and was closely correlated with the line equation of “y=0.0094x+0.0006” (R2= 0.9861). It also showed a low detection limit (LOD) of 263 CFU/ml (Signal/Noise=3). No response was recorded in the presence of other tested bacterial strains including Listeria monocytogenes and Salmonella typhi, indicating the high selectivity of the aptasensor. <br /><em><strong>Conclusion:</strong></em> This biosensor may be used as a smart device to screen water reservoirs and prevents the outbreak of EHEC-related life-threatening contagious diseases.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623720200701A new DNA vaccine expressing HspX-PPE44-EsxV fusion antigens of Mycobacterium tuberculosis induced strong immune responses9099141557110.22038/ijbms.2020.38521.9171ENBagher MoradiEsfarayen Faculty of Medical Sciences, Esfarayen, Iran0000-0002-3875-2510Mojtaba SankianImmunology Research Center, Mashhad University of Medical Sciences, Mashhad, IranYousef AminiInfectious Diseases and Tropical Medicine Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, IranAida GholoobiMedical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran0000-0001-6399-1612Zahra MeshkatAntimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran0000-0002-4032-7599Journal Article20190224<em><strong>Objective(s):</strong></em> Infection with tuberculosis (TB) is regarded as a major health issue. Due to the emergence of antibiotic resistance during TB treatment, prevention via vaccination is one of the most effective ways of controlling the infection. DNA vaccines are developed at a greater pace due to their ability in generating a long-lasting immune response, higher safety compared to the live vaccines, and relatively lower cost of production. In the present study, we evaluated a new DNA vaccine encoding the fusion HspX-PPE44-EsxV antigens, separately, and in combination with Bacillus Calmette–Guérin (BCG) administration, in a prime-boost method in mice.<br /><em><strong>Materials and Methods:</strong></em> A novel DNA vaccine encoding HspX-PPE44-EsxV fusion antigen of Mycobacterium tuberculosis was constructed, and RT-PCR and Western blot analysis were performed to verify the expression of the antigen. Female BALB/c mice were divided into five groups (PBS, BCG, pcDNA3.1 (+) vector, pDNA/HspX-PPE44-EsxV vaccine, and the BCG-prime boost groups). In order to evaluate the immunogenicity of the recombinant vector, BALB/c mice were injected with 100 μg of pDNA at 2-week intervals. Then, cytokine assay was conducted using eBioscience ELISA kits (Ebioscience, AUT) according to manufacturers’ instructions to evaluate the concentrations of IL-4, IL-12, TGF-β, and IFN-γ.<br /><em><strong>Results:</strong></em> The concentrations of INF-γ, IL-12, and TGF-beta were significantly increased compared to the control groups (P<0.001). INF-γ and IL-12 production were increased significantly in pDNA/HspX-PPE44-EsxV+BCG group compared to pDNA/HspX-PPE44-EsxV group (P<0.001).<br /><em><strong>Conclusion:</strong></em> This study showed that the present DNA vaccine could induce a high level of specific cytokines in mice. It was also shown that using this DNA vaccine in a BCG prime-boost protocol can produce significant amounts of IFN-γ, IL-12, and TGF-β.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623720200701Genotypic and phenotypic characterization of enteroaggregative Escherichia coli (EAEC) isolates from diarrheic children: An unresolved diagnostic paradigm exists9159211549510.22038/ijbms.2020.42119.9959ENHaiffa HelalatDepartment of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran0000-0002-8970-2214Seyedeh Elham RezatofighiDepartment of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran0000-0003-1373-7346Mohammad Roayaei ArdakaniDepartment of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, IranLuis Fernando Dos SantosAdolfo Lutz Institute, Centere of Bacteriology, National Reference Laboratory for E. coli enteric infections and HUS. São Paulo, BrazilMahdi Askari BadoueiDepartment of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran0000-0001-5051-813XJournal Article20190726<em><strong>Objective(s):</strong></em> The enteroaggregative Escherichia coli (EAEC) has been one of the most intriguing emerging bacterial pathogens in children that occur both in developing countries and the industrial world. Although various phenotypic and genotypic based protocols have been suggested for diagnosis of EAEC, they are not conclusive or practical to be used in most clinical laboratories. <br /><em><strong>Materials and Methods:</strong></em> In this study, we analyzed and compared 36 typical EAEC strains (aggR-positive) by various genotypic and phenotypic methods.<br /><em><strong>Results:</strong></em> Briefly, pCVD432 was detected in all of isolates along with aggR, then it was followed by other virulence genes including app, astA, aggA, and pet genes in 32 (88.8%), 21 (58.3%), 9 (25%), and 2 (5.5%) isolates, respectively. Biofilm was formed by 34 (94.4%) isolates, while only 26 (72.2%) isolates showed an aggregative adherence pattern to HEp-2 cells. <br /><em><strong>Conclusion:</strong></em> The genetic and phenotypic features of EAEC were highly inconsistent, which may have considerable diagnostic implications. The variations in the virulence genes, phenotypic characteristics, and genetic profiles among the EAEC isolates again emphasized the genetic heterogeneity of this emerging pathotype. Biofilm formation may be an important phenotypic virulence property of this pathotype, especially in strains with the aggR-pCVD432-aap-astA profile.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623720200701Preparation and characterization of bear bile-loaded pH sensitive in-situ gel eye drops for ocular drug delivery9229291565110.22038/ijbms.2020.45386.10562ENXiaomin NiSchool of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China0000-0001-8667-8063Qin GuoSchool of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR ChinaYiqing ZouSchool of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR ChinaYang XuanSchool of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR ChinaImran Shair MohammadSchool of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China0000-0002-1351-0216Qing DingYunnan Dai Medicine Co., Ltd., Yunnan 678699, PR ChinaHaiyan HuSchool of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR ChinaJournal Article20191228<em><strong>Objective(s):</strong></em> In this study, a stable bear bile-loaded pH sensitive in-situ eye drop gel was prepared for sustain delivery and enhanced therapeutic application. <br /><em><strong>Materials and Methods:</strong></em> Bear bile-loaded in-situ ocular gels with different Carbopol/Hydroxypropyl methylcellulose (HPMC) ratios were prepared and their stability was tested in PBS at a series of pH at 40 °C. The morphology was observed by SEM examination and rheology was observed by Rheometer equipped with a 60-mm cone-plate at apex angle of 1°. Gel erosion and release kinetics of Tauroursodeoxycholic acid (TUDCA) was determined by HPLC. While, the in vivo dwelling time was obtained after administering the fluorescent-loaded gel in ocular disease-free New Zealand rabbits. Finally, biocompatibility and toxicity was observed by irritation test and H&E staining of eye-ball tissues, respectively. <br /><em><strong>Results:</strong></em> The bear bile-loaded in-situ ocular gel showed excellent stability at different pH (pH 5.0, 5.5, 6.0, 6.5, 7.0 and 8.0) up to 5 days, and bear bile extract significantly attenuated the gelling ability of the in-situ gel. The viscosity of in-situ gels formulation was decreased with increase in shear rate (0.01 to 100 s-1), and morphological examination of freeze-dried preparation showed three-dimensional reticular structure at physiological pH. The in-situ ocular gel exhibited promising sustained drug release up to 160 min in vitro, and showed prolonged retention time up to 3-folds in vivo. Finally, the biocompability data confirmed that the formulation did not induce any toxic effects and was completely compatible with eye tissues.<br /><em><strong>Conclusion:</strong></em> pH sensitive in-situ ocular gel provides new research opportunities to efficiently treat eye diseases.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623720200701Carvacrol and Zataria multiflora influenced the PPARγ agonist effects on systemic inflammation and oxidative stress induced by inhaled paraquat in rat9309361559610.22038/ijbms.2020.45962.10648ENFatemeh AminDepartment of Physiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran0000-0003-0961-7667Arghavan MemarziaDepartment of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranHamid Reza KazeraniDepartment of Physiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran0000000311569254Mohammad Hossein BoskabadyDepartment of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranNeurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran0000-0001-5736-9755Journal Article20200119<em><strong>Objective(s):</strong></em> The effects of PPAR-γ agonist alone and in combination with carvacrol and Zataria multiflora on inhaled paraquat (PQ) induced-systemic inflammation and oxidative stress were examined.<br /> <em><strong>Materials and Methods:</strong></em> Control group exposed to normal saline aerosol, one group exposed to 54 mg/m3 PQ aerosol and four groups exposed to PQ aerosol and treated with 5 mg/kg/day pioglitazone, pioglitazone + 200 mg/kg/day Z. multiflora extract, pioglitazone + 20 mg/kg/day carvacrol, and 0.03 mg /kg/day dexamethasone for 16 days after the end of exposure to PQ were studied. Exposure to normal saline or PQ was performed every other days for 30 min (8 times). Different variables were measured after the end of treatment period.<br /><em><strong>Results:</strong></em> PQ exposure significantly increased serum levels of NO2, MDA and IL-6 but dexreased CAT and IFN-γ levels and IFN-γ/IL-6 ratio compared to control group (P<em><strong>Conclusion:</strong> </em>The effects of combination therapy of pioglitazone with Z. multiflora or carvacrol on inhaled paraquat (PQ) induced-oxidative stress and systemic inflammation were higher than the effects of pioglitazone alone. These results suggested that the effects of the extract and carvacrol may mediated through PPAR-γ receptors.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623720200701Developing oncolytic Herpes simplex virus type 1 through UL39 knockout by CRISPR-Cas99379441550310.22038/ijbms.2020.43864.10286ENSaeedeh EbrahimiInfectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iranhttps://orcid.org/0000-0003-3117-6669Manochehr MakvandiInfectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran0000-0002-7488-6479Samaneh AbbasiAbadan Faculty of Medical Science, Abadan, Iran0000-0002-5441-5119Keyhan AzadmaneshDepartment of Virology, Pasteur Institute of Iran, Tehran, IranAli TeimooriInfectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranDepartment of Virology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran0000-0003-0766-8591Journal Article20191017<em><strong>Objective(s):</strong></em> Oncolytic Herpes simplex virus type 1 (HSV-1) has emerged as a promising strategy for cancer therapy. However, development of novel oncolytic mutants has remained a major challenge owing to low efficiency of conventional genome editing methods. Recently, CRISPR-Cas9 has revolutionized genome editing.<br /><em><strong>Materials and Methods:</strong></em> In this study, we aimed to evaluate the capability of CRISPR-Cas9 to manipulate the UL39 gene to create oncolytic HSV-1. Herein, three sgRNAs were designed against the UL39 gene and transfected into HEK-293 cell line followed by infection with HSV-1 KOS.<br /><em><strong>Results:</strong></em> After three rounds of plaque purification, several HSV-1 mutants were identified by PCR analysis and sequencing. One of these mutations in which 55 nucleotides were deleted resulted in a frameshift mutation that in turn produced a truncated protein with only 167 amino acids from 1137 amino acids. Functional analysis in Vero and primary fibroblast cells revealed that viral replication was significantly lower and plaque size was smaller in the HSV-1 mutant compared with HSV-1 KOS. Moreover, the relative amount of viral genome present in the supernatants of infected cells (Vero and primary fibroblast cells) with HSV-1 mutant was significantly decreased compared with those of HSV-1 KOS.<br /><em><strong>Conclusion:</strong></em> Our data revealed that targeting UL39 with CRISPR-Cas9 could develop oncolytic HSV-1.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623720200701Human Wharton’s jelly mesenchymal stem cells-derived secretome could inhibit breast cancer growth in vitro and in vivo9459531549610.22038/ijbms.2020.42477.10020ENMansoureh MirabdollahiApplied Physiology Research Center, Cardiovascular Research Institute, Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran0000-0002-6378-7555Hojjat Sadeghi-aliabadiMedicinal Chemistry Department, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran0000-0002-7260-0625Shaghayegh Haghjooy JavanmardApplied Physiology Research Center, Cardiovascular Research Institute, Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran0000-0002-3853-5006Journal Article20190808<em><strong>Objective(s):</strong></em> Controversial results have been reported regarding the anti-tumor properties of extracellular vesicles derived from mesenchymal stem cells (MSCs). The present study was conducted to evaluate whether secretome derived from Human Wharton’s jelly mesenchymal stem cells (hWJMSCs) may stimulate or inhibit breast cancer growth in vitro and in vivo.<br /><em><strong>Materials and Methods:</strong></em> MTT assays was performed to determine anti-tumor effects of hWJMSCs-secretome on both MCF-7 and 4T1 tumor cells in vitro. Afterward, 4T1 breast tumors were established in different groups of Balb/C mice (12 mice/group). The tumor sizes were monitored in different treatment groups and at day 30 post-tumor inoculation (PTI), blood samples were obtained and 6 mice of each group were sacrificed for hematological and histopathological assays. The rest of the mice in each group (n=6) were left alive up to day 120 PTI to determine survival rate. <br /><em><strong>Results:</strong></em> We found that hWJMSCs-secretome can inhibit growth of MCF-7 and 4T1 tumor cell lines in vitro. Moreover, intratumoral administration of hWJMSCs-secretome resulted in significant tumor growth inhibition and improvement of hematological indices in vivo and prolonged survival rate of tumor bearing mice. <br /><em><strong>Conclusion:</strong></em> According to our findings, hWJMSCs-secretome could be considered a potent anti-tumor agent, however, further investigation should be done on other cancer models.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386623720200701Curcumin promotes osteogenic differentiation of periodontal ligament stem cells through the PI3K/AKT/Nrf2 signaling pathway9549601565210.22038/ijbms.2020.44070.10351ENYixuan XiongSchool of Stomatology, Shandong University, Jinan, ChinaShandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, China0000-0003-3794-8009Bin ZhaoSchool of Stomatology, Shandong University, Jinan, ChinaShandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, ChinaWenjing ZhangSchool of Stomatology, Shandong University, Jinan, ChinaShandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, ChinaLinglu JiaSchool of Stomatology, Shandong University, Jinan, ChinaShandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, ChinaYunpeng ZhangSchool of Stomatology, Shandong University, Jinan, ChinaShandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, ChinaDepartment of Oral Implantology, the Affiliated Stomatology Hospital of Kunming Medical University, Kunming, ChinaXin XuSchool of Stomatology, Shandong University, Jinan, ChinaShandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, Chinaxinxu@sdu.edu.cnJournal Article20191103<em><strong>Objective(s):</strong></em> The aim of this study was to investigate the effect of curcumin on the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) and its underlying potential mechanism.<br /><em><strong>Materials and Methods:</strong></em> The tissue explant adherence method was used to isolate hPDLSCs. Flowcytometry, Alizarin Red staining and Oil Red O staining were applied to confirm the stemness of the stem cells. CCK8 assays were used to evaluate the effect of curcumin at different concentrations on cytotoxicity, and alkaline phosphate (ALP) activity assays, ALP staining and Alizarin Red staining were used to measure the osteogenic differentiation ability. In addition, hPDLSCs were treated with LY294002 (a phosphatidylinositol-3-kinase [PI3K] inhibitor) and erythroid transcription factor NF-E2 siRNA (siNrf2), respectively in the presence of curcumin. Western blotting was applied to evaluate the protein kinase B (AKT) phosphorylation levels and the Nrf2 levels. Besides, western blotting, RT-qPCR, ALP activity assays, ALP staining and Alizarin Red staining were used to detect the potential effects of curcumin on osteogenic differentiation.<br /><em><strong>Results:</strong></em> Curcumin at an appropriate concentration had no cytotoxicity and could promote osteogenic differentiation of the hPDLSCs. The results of western blotting and RT-qPCR revealed that the protein and mRNA levels of ALP, COL1 and RUNX2 were increased by curcumin, while the PI3K/AKT/Nrf2 signaling pathway was activated. In addition, LY294002 was added to inhibit the PI3K/AKT signaling pathway, or siNrf2 was used to block the Nrf2 pathway; then, the stimulatory effects of curcumin on osteogenic differentiation were reversed.<br /><em><strong>Conclusion:</strong></em> Curcumin could promote the osteogenesis of hPDLSCs, and the effect is related to the PI3K/AKT/Nrf2 signaling pathway.