Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622920190901The protective effects of silymarin on ischemia-reperfusion injuries: A mechanistic review9689761354910.22038/ijbms.2019.34284.8147ENVahid Akbari-korhkheyliStudent Research Committee, Mazandaran University of Medical Sciences, Sari, Iran0000-0002-6233-9726Kazem Abbaszadeh-GoudarziCellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, IranMohaddeseh Nejati-LaskokalayehStudent Research Committee, Mazandaran University of Medical Sciences, Sari, IranSetareh ZarpouStudent Research Committee, Mazandaran University of Medical Sciences, Sari, IranAbbas Khonakdar-tarsiDepartment of Biochemistry-Biophysics and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran0000-0002-8630-1722Journal Article20180818Ischemia-reperfusion injuries (IRI) occur in different clinical conditions such as stroke, trauma, organ transplantation, and so on. Ischemia damages mainly arise from oxygen depletion in tissues. The lack of oxygen as the last acceptor of electron in the respiratory chain causes a decrease in ATP production and eventually leads to disruption of membrane transport, acidosis, cellular edema and membrane distortion of organelles, and cells. Reperfusion can intensify ischemic injuries by the infiltration of inflammatory cells and also oxygen and calcium overloading. Since the tissue antioxidant contents decreased due to increased generation of reactive oxygen species (ROS) during IRI, the application of antioxidants is considered an appropriate strategy to ameliorate IRI. Silymarin constitutes about 70–80% of silybum marianum dry extract and is known as a strong free radical scavenger with anti-inflammatory properties. In several studies, silibinin as a major component of Silymarin could provide protective effects in various tissue IRI by different mechanisms such as scavenging free radicals, decreasing inflammatory cytokines, inhibiting cellular death, and increasing the expression of antioxidant enzymes. To clarify functional mechanisms, the present article evaluates studies about silymarin effects in different tissues IRI.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622920190901Molecular targets of pomegranate (Punica granatum) in preventing cancer metastasis9779881355010.22038/ijbms.2019.34653.8217ENNaghmeh AhmadiankiaCancer Prevention Research Center, Shahroud University of Medical Sciences, Shahroud, Iran0000-0001-8309-4935Journal Article20180904Metastasis is the primary cause of mortality and morbidity among cancer patients and accounts for about 90% of cancer deaths. The most common types of treatment for cancer metastasis are chemotherapy and radiotherapy. However, such therapy has many serious side effects that could diminish the quality of life in patients. There is increased appreciation by the scientific community that natural compounds can be potential weapons in fighting against cancer. Interestingly, much evidence shows that pomegranate (Punica granatum) has great potential to inhibit tumor growth and metastasis. In this review, we discussed the molecular targets of pomegranate, specifically, those that are prerequisite for cancer metastasis. The search was performed in Google Scholar, Medline, Scopus, and PubMed using keywords such as metastasis, pomegranate, and signaling pathways. Some of the most important papers from the search results were included. Based on recent studies, some molecules, including those involved in cell-cell and cell-extracellular matrix adhesions, are affected by pomegranate. The other targets of pomegranate are modulators of cytoskeleton dynamics and regulators of cancer cell anoikis and chemotaxis. Furthermore, the antimetastatic effect of pomegranate may be attributed to molecular changes of the extracellular matrix. Pro-inflammatory and pro-angiogenic molecules are the other targets of pomegranate regarding cancer metastasis. A wide variety of molecules can be targeted by pomegranate to suppress tumor metastasis. A better understanding of the molecules regulated by pomegranate is needed to provide a rational basis for its clinical application.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622920190901A significant increase in expression of FOXP3 and IL-17 genes in patients with allergic rhinitis underwent accelerated rush immunotherapy9899961343710.22038/ijbms.2019.32979.7878ENAmirabbas SalmaniDepartment of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran0000-0003-2864-0248Mojgan MohammadiAllergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran0000-0001-6514-8880Reza FaridhosseiniAllergy Research Center, Mashhad University of Medical Sciences, Mashhad, IranJalil Tavakol AfshariImmunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran0000-0003-0146-502Ali FouladvandDepartment of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranSajad DehnaviDepartment of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran0000-0002-8442-0584Maryam KhoshkhuiAllergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran0000-0002-0363-6536Farahzad Jabbari AzadAllergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran0000-0003-0673-4809Journal Article20180626<em><strong>Objective(s):</strong></em> Allergic rhinitis (AR) is a common hypersensitivity disease worldwide. Immunotherapy has been performed as the best treatment for years. This study aimed to study the gene expression pattern of immune system cells following an accelerated rush immunotherapy protocol (ARIT) in patients with AR.<br /><em><strong>Materials and Methods:</strong></em> Fifteen patients with AR (15–55 years old) resident in Mashhad, Iran, with positive prick test to regional aeroallergens (weed mix, grass mix, tree mix, and Salsola) enrolled in this study. All patients were treated for three months with 3-day ARIT protocol between July 2015 and August 2016. Clinical symptoms and quality of life were recorded by two questioners. The expression levels of FOXP3, TGF-β, IL-10, IL-17, IL-4, and IFN-γ genes in patient’s peripheral blood mononuclear cells were evaluated by SYBR Green real-time RT-PCR technique.<br /><em><strong>Results:</strong></em> The severity of disease and quality of life showed significant improvement following ARIT (P-value<0.05). Gene expression of IFN-γ and IL-10 was increased whereas TGF-β and IL-4 down-regulated, following ARIT, but these changes were not significant. However, gene expression of FOXP3 and IL-17 was significantly increased after intervention when compared with the baseline (P-value< 0.002).<br /><em><strong>Conclusion:</strong></em> Significant up-regulation of FOXP3 and IL-17 genes, additionally, a significant improvement in the clinical signs following ARIT might be related to increases in HLA-DR- and FOXP3+ Treg population at the initiation phase of ARIT. Employing the flow cytometry technique to study the phenotype of these cells is suggested for future studies.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622920190901An investigation on some toxic effects of pyriproxyfen in adult male mice99710031343310.22038/ijbms.2019.33825.8051ENAmna ShahidDepartment of Zoology, Government College University, Katchery Road, Lahore, Pakistan0000-0002-9472-0580Syeda Durr-e- ShahwarZaidiDepartment of Zoology, Government College University, Katchery Road, Lahore, PakistanHaroon AkbarDepartment of Parasitology, University of Veterinary and Animal Sciences, Lahore, PakistanSania SaeedDepartment of Zoology, Government College University, Katchery Road, Lahore, PakistanJournal Article20180731<em><strong>Objective(s):</strong></em> Pyriproxyfen as an insect growth regulator is widely used globally for pest management. There are reports on adverse effects of insecticides such as organ toxicity, endocrine disruptions, and teratogenicity in animals and humans. We aimed to investigate reproductive toxicity of pyriproxyfen in adult male mice.<br /><em><strong>Materials and Methods:</strong></em> 48 male Swiss albino mice were divided into eight groups and received the different 1200, 600, 320, 200, 100, 40, 20, 0 mg/kg/day doses orally, and body weights were accessed for 28 consecutive days. In the end, mice were sacrificed, testes were dissected and weighed. Probable testicular tissue alterations were examined by histopathological studies. In addition, the diameter of seminiferous tubules and Leydig cells distribution were assessed in all experimental and control groups.<br /><em><strong>Results:</strong></em> Pyriproxyfen treatment caused significant (P<0.05) reduction in body and organ weights in mice. However, the shrinkage and displacement of seminiferous tubules, reduced lumen diameter, and vacuolization occurred in seminiferous tubules in higher doses exposed animals in comparison to controls. The relative testis weights, mean diameter of seminiferous tubules, and Leydig cells distribution remained unchanged at low doses. <br /><em><strong>Conclusion:</strong></em> These findings reveal that pyriproxyfen caused reduction in body weight gain as well as damage to the testicular architecture in mice and thus may potentially interfere with spermatogenesis. Findings in an outbred strain of mice can be extrapolated fairly reliably to the human model. The chemical can thus be further exploited to study its effects on impairment of fertility and as an endocrine disruptor.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622920190901Effects of probiotic Lactobacillus paracasei TD3 on moderation of cholesterol biosynthesis pathway in rats100410091343810.22038/ijbms.2019.33933.8073ENAbolfazl DehkohnehDepartment of Biotechnology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran0000-0002-7721-3819Parvaneh JafariMicrobiology Department, Faculty of science, Islamic Azad University, Arak Branch, Arak, Iran0000-0003-2771-9309Hossein FahimiDepartment of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran0000-0002-1744-8675Journal Article20180805<em><strong>Objective(s):</strong></em> Prevalence of high-fat food consumption, such as fast foods is one of the major causes of hypercholesterolemia, which can lead to cardiovascular diseases. 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and cytochrome P450 7A1 (CYP7A1) are two key genes in cholesterol metabolism. Use of probiotics in the diet is a promising approach for modulation of serum lipid. To confirm the modulation of serum lipids by probiotics, in this study, we have examined the efficacy of Lactobacillus paracasei TD3 in improving blood cholesterol levels. <br /><em><strong>Materials and Methods:</strong></em> 21 male Wistar rats were divided into three groups randomly (n=7). G1: negative control with normal diet, G2: positive control with high-fat diet, G3T: test group with high-fat diet plus supplementation with L. paracasei TD3 (1010 CFU). In the 21st day, the rats were anesthetized using chloroform and then sacrificed. Blood samples were collected to analyze lipid panel parameters and hepatic enzymes by the auto-analyzer system. Adipose tissue samples were analyzed using real-time PCR for HMGCR and CYP7A1 genes expression.<br /><em><strong>Results:</strong></em> Consumption of L. paracasei TD3 could reduce serum cholesterol levels significantly (P<0.05); whereas, there was no significant difference between experimental groups for triglycerides, LDL, and HDL levels. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) enzymes were significantly decreased in the probiotic group. Furthermore, expression of HMGCR and CYP7A1 genes was dramatically declined in the probiotic group. There was no significant change in either uric acid or urea between the control and treated groups.<br /><em><strong>Conclusion:</strong></em> Introduction of L. paracasei TD3 in rat’s diet can modulate serum cholesterol levels.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622920190901Early oleate deficiency leads to severe defects in fetal rat liver development101010151353310.22038/ijbms.2019.35084.8345ENFatemeh MohammadzadehLiver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran0000-0002-3804-782XAlireza AlihemmatiDepartment of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran0000-0002-2929-006XAbbas Pirpour TazehkandDepartment of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, IranMasoud DarabiLiver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran0000-0001-6380-272XAmir MehdizadehEndocrine Research Center, Tabriz University of Medical Sciences, Tabriz, IranComprehensive Health Lab, Tabriz University of Medical Sciences, Tabriz, Iran0000-0002-3029-4172Journal Article20180924<em><strong>Objective(s):</strong></em> Oleate can be produced through de novo synthesis, which contributes to biological processes and signaling pathways. However, the role of this non-essential fatty acid in hepatic development remains unclear. The current study aimed to evaluate the influence of early oleate deficiency induced by the inhibitor of de novo oleate synthesis MF-438 on fetal rat liver development.<br /><em><strong>Materials and Methods:</strong></em> Female Wistar rats with an average weight of 200±20 g were subjected to this study. After mating, pregnant rats were divided into three groups and gavaged with the vehicle, MF 438 or MF-438 plus oleate from day 3 of pregnancy for five days. Obtained fetuses were sacrificed and the liver tissues were retrieved. Hepatic morphological index, biochemical markers, and gene expression of hepatic development markers were analyzed using Hematoxylin-Eosine, spectrometry, and real-time PCR techniques, respectively.<br /><em><strong>Results:</strong></em> Relatively, deficient morphological indices and hepatic maturation markers were observed in fetus livers of the inhibitor-treated group. In comparison to the other two groups, total hepatic protein and glycogen content were increased with treatment of MF-438 plus oleate. Hepatocyte nuclear factor 1α, alpha fetoprotein, albumin, and cytochrome P450 gene expression were also significantly increased in the group treated with both MF-438 and oleate.<br /><em><strong>Conclusion:</strong></em> Our data indicate that oleate availability during early embryo development is linked with fetal rat liver development.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622920190901Kidney therapeutic potential of peptides derived from the bromelain hydrolysis of green peas protein101610251354810.22038/ijbms.2019.33945.8075ENMeilinah HidayatFaculty of Medicine, Universitas Kristen Maranatha, Bandung Indonesiahttps://orcid.org/00Sijani PrahastutiFaculty of Medicine, Universitas Kristen Maranatha, Bandung IndonesiaDestiya RiyaniFaculty of Medicine, Universitas Kristen Maranatha, Bandung IndonesiaAndreanus SoemardjiSchool of Pharmacy, Institute Teknologi Bandung IndonesiaNova SuliskaSchool of Pharmacy, Institute Teknologi Bandung Indonesia0000-0003-0410-319XAfrilia GarmanaSchool of Pharmacy, Institute Teknologi Bandung IndonesiaBobby AssiddiqAlphasains Centre, Serpong IndonesiaKhomaini HassanFaculty of Medicine, Universitas Jenderal Achmad Yani, Bandung Indonesia0000-0002-7395-4206Journal Article20180806<em><strong>Objective(s):</strong></em> Kidney disease is a global health problem that needs a solution to its therapy. In the previous study, we found that protein hydrolysate of green peas origin of Indonesia hydrolysed by bromelain (PHGPB) showed improve kidney function in cisplatin-induced nephropathy rats. In this study, we investigated the effect of PHGPB to obtain effective dose that exerts a therapeutic effect on chronic kidney disease (CKD) based on reducing urea and creatinine levels and to elucidate its mechanism of action. <br /><em><strong>Materials and Methods:</strong></em> Two sets of experiments were conducted: (1) characteristics and proteomic profile of PHGPB, (2) in vivo test of PHGPB in gentamycin-induced Wistar rats, including urea and creatinine measurements, activities of antioxidant and kidney-related peptides (ANP, COX-1, and renin).<br /><em><strong>Results:</strong></em> PHGPB showed three bands under 10 kDa using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and contained 10 identified proteins using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Significant differences in urea and creatinine levels were found between all PHGPB treatments and positive controls (P<0.01). The lowest levels of urea and creatinine that were validated by high super oxide dismutase (SOD) activity and atrial natriuretic peptide (ANP) level were obtained in the 200 mg/day PHGPB treatment. However, the mean renin level was high and cyclooxygenase-1 (COX-1) level did not exceed positive and negative control levels. <br /><em><strong>Conclusion:</strong></em> PHGPB at dose 200 mg/kgBW shows a potential CKD therapeutic effect that is dose-dependent. Higher PHGPB dose corresponds to better effect on kidney function by increasing antioxidant activity and ANP levels in gentamycin-induced Wistar rats.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622920190901Brevinin-2R-linked polyethylenimine as a promising hybrid nano-gene-delivery vector102610351355310.22038/ijbms.2019.37125.8842ENFatemeh ZohrabDepartment of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran0000000181214171Ahmad AsoodehDepartment of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, IranAmin JaliliDepartment of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran0000-0002-8140-2735Majid DarroudiNuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran0000-0002-2624-7242Reza Kazemi OskueeTargeted Drug Delivery Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran0000-0001-9166-2939Journal Article20181224<em><strong>Objective(s):</strong></em> Polyethylenimine (PEI) is one of the most widely used polymers in gene delivery. The aim of this study was to modify PEI by replacing some of its primary amines with Brevinin 2R (BR-2R) peptide in order to increase the efficiency of gene delivery.<br /><em><strong>Materials and Methods:</strong></em> Polyethylenimine was modified by BR-2R peptide by two different approaches; A) conjugation methods including (І) using succinimidyl 3-(2-pyridyldithio) propionate (SPDP), (П) EDC/NHS protocol and (ПІ) EDC/NHS+6-bromohexanoic acid protocol, and B) physical interaction method. The modified polymers were characterized for their ability of plasmid condensation, number of primary amines, size and zeta potential. The transfection efficiency and cytotoxicity were evaluated on HEK293, L929, WEHI164 and Neuro2A cell lines by green fluorescent protein (GFP)-based plasmid (pGFP) reporter gene and viability assays, respectively. Apoptosis induction ability was also evaluated via PI/Annexin V assay. <br /><em><strong>Results:</strong></em> Polyplex had size and zeta potential between 200-270 nm and +21.5- +28.4 mV, respectively. All vectors were able to condense plasmid DNA in C/P=4 (carrier-plasmid ratio). Transfection results on the Neuro2A cell line showed that the vector containing the BR-2R peptide, which was synthesized using EDC-NHS protocol had the best transfection efficiency. <br /><em><strong>Conclusion:</strong></em> Our results showed that conjugation of Brevinin 2R as cell penetrating peptide to polyethyleneimine could enhance the transfection ability of the polymer.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622920190901Effect of vitamin D on apoptotic marker, reactive oxygen species and human sperm parameters during the process of cryopreservation103610431353010.22038/ijbms.2019.36258.8634ENMahin Taheri MoghadamCellular and Molecular Research center, Ahvaz Jundishapur University of Medical Sciences0000-0002-7409-4519Yousef Asadi FardStudent Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran0000-0003-4536-7167Ghasem SakiCellular and Molecular Research center, Ahvaz Jundishapur University of Medical Sciences0000-0002-3738-703XRoshan NikbakhtFertility, Infertility and Perinatology center, Imam Khomeini Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranJournal Article20181115<em><strong>Objective(s):</strong> </em>Sperm cryopreservation plays an undeniable role in assisted reproductive technology. However, this process significantly reduces the motility, viability, morphology and nuclear integrity of sperm. Reasons of these changes were oxidative stress and apoptosis. The aim of this study was to evaluate the influence of vitamin D on the survival and integrity of fertile sperm after cryopreservation.<br /> <em><strong>Materials and Methods:</strong></em> Semen sample of 18 males with normal parameters was used. After swimming up, each sample was divided into two parts. 20 µmol vitamin D was added to one part as experimental group and the other part was left untreated as control group. The samples in all groups were frozen for 14 days. Post-thawing, the groups were evaluated for sperm motility, and viability using eosin staining, morphology using the Diff-Quick staining and apoptosis by TUNEL, Annexin-V and caspase-3 activity assay. By using nitrobluetetraxolium test and thiobarbituric acid, the reactive oxygen species (ROS) and lipid peroxidation of sperms were measured, respectively.<br /><em><strong>Results:</strong></em> In comparison with control groups, motile and viable sperm concentration was substantially higher in treated groups (P-value<0.05); however, morphological analysis did not show any remarkable changes. Also, ROS and lipid peroxidation values were dramatically reduced by vitamin D (P-value<0.05). TUNEL and Annexin assay for apoptosis were considerably lower in treated groups (P-value<0.05), but caspase activity assay revealed no significant difference between groups.<br /> <em><strong>Conclusion:</strong></em> The results have shown that the addition of vitamin D to a freezing medium leads to higher quality and function of human sperm.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622920190901Metabolomics analysis of the saliva in patients with chronic hepatitis B using nuclear magnetic resonance: a pilot study104410491324410.22038/ijbms.2019.36669.8733ENKambiz GilanyReproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, IranIntegrative Oncology Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran0000-0003-2916-7245Ashraf MohamadkhaniDigestive Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, IranSaeed ChashmniamDepartment of Chemistry, Sharif University of Technology, Tehran, IranParisa ShahnazariReproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, IranMehdi AminiReproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, IranBabak ArjmandCell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, IranReza MalekzadehDigestive Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran0000-0003-1043-3814Bibi Fatemeh Nobakht Motlagh GhoochaniNoncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, IranDepartment of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran0000-0002-2500-0002Journal Article20181203<em><strong>Objective(s):</strong></em> Hepatitis B virus infection causes chronic disease such as cirrhosis and hepatocellular carcinoma. The metabolomics investigations have been demonstrated to be related to pathophysiologic mechanisms in many disorders such as hepatitis B infection. The aim of this study was to investigate the saliva metabolic profile of patients with chronic hepatitis B infection and to identify underlying mechanisms as well as potential biomarkers associated with the disease. <br /><em><strong>Materials and Methods:</strong></em> Saliva from 16 healthy subjects and 20 patients with chronic hepatitis B virus were analyzed by nuclear magnetic resonance (NMR). Then, multivariate statistical analysis was performed to identify discriminative metabolites between two groups. <br /><em><strong>Results:</strong></em> A set of metabolites were detected, including propionic acid, putrescine, acetic acid, succinic acid, tyrosine, lactic acid, butyric acid, pyruvic acid, 4-pyridoxic acid and 4-hydroxybenzoic acid, which in combination with one another could accurately distinguish patients from healthy controls. Our results clearly demonstrated altered metabolites are involved in nine metabolic pathways.<br /> <em><strong>Conclusion:</strong></em> Metabolomics has the potential to be considered as a novel clinical tool for hepatitis B diagnosis while contributing to a comprehensive understanding of disease mechanisms.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622920190901Inhibiting miR-155 protects against myocardial ischemia/reperfusion injury via targeted regulation of HIF-1α in rats105010581353210.22038/ijbms.2019.34853.8270ENJian-Guo ChenDepartment of Pediatric Surgery, Jingzhou Central Hospital, the Second Clinical Medical College, Yangtze University, Jingzhou 434020, Hubei, China0000-0003-4486-919XXiao-Ming XuDepartment of Orthopedic surgery, Jingzhou Central Hospital, the Second Clinical Medical College, Yangtze University, Jingzhou 434020, Hubei, ChinaHui JiDepartment of Pediatric Surgery, Jingzhou Central Hospital, the Second Clinical Medical College, Yangtze University, Jingzhou 434020, Hubei, ChinaBo SunDepartment of Clinical Laboratory, Jining Medical College Affiliated Hospital, Jining Medical College, Jining 272000, Shandong, China0000-0002-0684-1869Journal Article20180913<em><strong>Objective(s):</strong></em> The aim of this study was to identify the role of miR-155 in the myocardial ischemia/reperfusion (I/R) injury through targeting hypoxia-inducible factor 1-alpha (HIF-1α). <br /><em><strong>Materials and Methods:</strong></em> We constructed rat models with myocardial I/R injury and H9C2 cell models with hypoxia/reoxygenation (H/R) damage. Anti-miR-155 and HIF-1α short hairpin RNA (shRNA) were used to treat rats and H9C2 cells to measure infarct area (IA) by TTC staining, determine creatine kinase (CK) and lactate dehydrogenase (LDH) activities by automatic biochemical analyzer, cardiac troponin T (cTnT) and cardiac troponin I (cTnI) levels by ELISA, and detect apoptosis-related proteins by Western blotting. TUNEL staining and flowcytometry were employed to evaluate the apoptosis, JC-1 staining to detect mitochondrial membrane potential (MMP), and MTT assay to determine H9C2 cell viability.<br /><em><strong>Results:</strong> </em>After I/R and H/R, significant elevations were observed in IA, apoptosis, CK, LDH, cTnT, cTnI, and miR-155 levels with reduced HIF-1α. Besides, H/R-induced H9C2 cells presented decreases in MMP and Bcl-2/Bax, but increases in cytosolic/mitochondrial ratio of cytochrome C (Cyt-C) and expressions of cleaved caspase-3 and cleaved caspase-9. However, both rats and H9C2 cells showed an opposite tendency concerning the above after anti-miR-155 treatment. Nevertheless, HIF-1α shRNA effectively reversed protective effects of anti-miR-155 on alleviating I/R- and H/R- induced injury.<br /><em><strong>Conclusion:</strong></em> Inhibiting miR-155 could reduce myocardial infarct size, suppress I/R-induced cardiomyocyte apoptosis, and maintain the MMP to alleviate I/R-induced injury via specific regulation of HIF-1α.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622920190901Behavioral and electrophysiological aspects of cognition in neonate rats lactated by morphine addicted mothers105910641343410.22038/ijbms.2019.36892.8789ENFatemeh AghighiPhysiology Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran0000-0003-0025-4142Mojgan MohammadifarPhysiology Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, IranHamidreza BanafshePhysiology Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, IranMahmoud SalamiPhysiology Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, IranSayyed Alireza TalaeiPhysiology Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran0000-0001-9781-7313Journal Article20181214<em><strong>Objective(s):</strong></em> In addition to genetic factors, environmental phenomena during postnatal age highly affect development and, in turn, function of the brain. The present work evaluates if morphine consumption during lactation period influences the spatial performances and synaptic plasticity in rats at neonatal period of age. <br /><em><strong>Materials and Methods:</strong> </em>Three groups of mothers were subcutaneously administered by 5 (M5), 10 (M10) or 20 (M20) mg/kg morphine every 12 hours during the lactation period. At 45 days old, their offspring were introduced to Morris water maze for assessment of spatial learning and memory. Basic field excitatory post-synaptic potentials (fEPSPs) were recorded in the CA1 area of hippocampus and, then, long term potentiation (LTP) was induced by tetanic stimulation. <br /><em><strong>Results:</strong></em> We found that the M10 and M20 rats spent more time and traveled longer distance to find the hidden platform of maze when compared to the control animals (P<em><strong>Conclusion:</strong></em> The present study provides behavioral and electrophysiological proofs for negative effect of morphine on the hippocampal-related function in the neonatally morphine-exposed rats.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622920190901The effects of supraphysiological levels of testosterone on neural networks upstream of gonadotropin-releasing hormone neurons106510721353110.22038/ijbms.2019.36127.8605ENMohammad Saied SalehiClinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, IranDepartment of Animal Physiology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran0000-0002-3535-1578Homayoun KhazaliDepartment of Animal Physiology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran0000-0002-9007-020XFariba MahmoudiFaculty of Basic Sciences, University of Mohaghegh Ardabili, Ardabil, Iran0000-0001-6092-1352Mahyar JanahmadiNeuroscience Research Center and Department of Physiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranJournal Article20181109<em><strong>Objective(s):</strong></em> Several pathological conditions are associated with hyper-production of testosterone; however, its impacts are not well understood. Hence, we evaluated the effects of supraphysiological levels of testosterone on gonadotropin-releasing hormone (GnRH) system in the hypothalamus of male rats. Also, we assessed the expression of two excitatory (kisspeptin and neurokinin-B) and two inhibitory (dynorphin and RFamide-related-peptide) neuropeptides upstream of GnRH neurons as possible routes to relay androgen information. <br /><em><strong>Materials and Methods:</strong></em> Gonadectomized (GDX) male rats received single injection of 100, 250 or 500 mg/kg testosterone undecanoate and three weeks later, posterior (PH) and anterior (AH) hypothalamus was dissected for evaluation of target genes using quantitative RT-PCR.<br /><em><strong>Results:</strong></em> We found that GnRH mRNA in the PH was high in GDX rats and 500 mg/kg testosterone reduced GnRH level expression. Finding revealed extremely high level of Kiss1 mRNA in the PH of GDX rats. However, in GDX rats treated with different levels of testosterone, Kiss1 expression was not significantly different than control. We also found that testosterone replacement increased the Kiss1 mRNA level in the AH. Moreover, neurokinin-B mRNA level in PH of GDX rats was similar to control. However, excess testosterone levels were effective in significantly inducing the down-regulation of neurokinin-B expression. The basal level of dynorphin mRNA was increased following testosterone treatments in the AH, where we found no significant difference in the level of RFamide-related-peptide mRNA between the experimental groups. <br /><em><strong>Conclusion:</strong></em> Excess levels of testosterone could act differently from its physiological concentration to regulate hypothalamic androgen sensitive neurons to control GnRH cell.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622920190901Anti-MRSA activity of a bioactive compound produced by a marine Streptomyces and its optimization using statistical experimental design107310841354710.22038/ijbms.2019.33880.8058ENHamed NorouziDepartment of Biology, University of Isfahan, Isfahan, Iran0000-0003-2652-5502Mohamad Rabbani KhorasganiDepartment of Biology, University of Isfahan, Isfahan, IranAbolghasem DaneshBiotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran0000-0002-1122-6641Journal Article20180802<em><strong>Objective(s):</strong></em> To address the alarming problem of methicillin-resistant Staphylococcus aureus (MRSA), herein, a marine Streptomyces capable of producing an anti-MRSA compound has been studied.<br /><em><strong>Materials and Methods:</strong> </em>Strain MN41 was morphologically and physiologically characterized and then, molecularly identified using 16SrRNA analysis. To produce the bioactive compound in large scale, a kind of submerged liquid fermentation was adopted. The antibacterial agent was purified using a silica gel column followed by a semi-preparative HPLC and the isolated metabolite was identified using mass spectrometry, Nuclear magnetic resonance (NMR) and Fourier-transform infrared (FTIR). Finally, the production process was subjected to a two steps optimization using Plackett-Burman design (PBD) and Response Surface Method (RSM), respectively. In addition, the antitumor activity of the active agent was studied.<br /><em><strong>Results:</strong></em> The purified compound with a molecular weight of 421.2 was identified as a natural pyrrole-derivative. The optimization revealed a significant effect for starch, pH, calcium carbonate and peptone on the production of this anti-MRSA compound and resulted in a 218% increase in the production yield. <br /><em><strong>Conclusion:</strong></em> The isolated pyrrole-derivative showed a remarkable activity against MRSA and also showed some promising anti-tumor activity.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622920190901Electroacupuncture attenuates chronic fibromyalgia pain through the phosphorylated phosphoinositide 3-kinase signaling pathway in the mouse brain108510901343510.22038/ijbms.2019.35887.8547ENChao-Tsung ChenCenter for General Education, Chung Yuan Christian University, Taoyuan 32023, Taiwan0000-0002-7011-0614Jaung-Geng LinCollege of Chinese Medicine, School of Chinese Medicine, China Medical University, Taichung 40402, TaiwanChun-Ping HuangCollege of Chinese Medicine, Graduate Institute of Acupuncture Science, China Medical University, Taichung 40402, TaiwanYi-Wen LinCollege of Chinese Medicine, Graduate Institute of Acupuncture Science, China Medical University, Taichung 40402, Taiwan0000-0001-7204-8837Journal Article20181030<em><strong>Objective(s):</strong></em> Fibromyalgia (FM) is a central nervous system disorder characterized by widespread mechanical hyperalgesia due to unknown mechanisms. Several inflammatory mediators, such as interleukin-1 (IL-1), IL-6, IL-8, and tumor necrosis factor, are increased in the serum of FM patients. Although medications including pregabalin, duloxetine, and milnacipran are used to treat FM, the results are unsatisfying. In the present study we assessed whether electroacupuncture (EA) can reduce chronic FM pain and then proposed an underlying mechanism for this effect. <br /><em><strong>Materials and Methods:</strong></em> Chronic FM pain was induced in mice by dual acid saline injection lasting up to 4 weeks. <br /><em><strong>Results:</strong></em> Chronic FM pain was treated by EA manipulation, but not in the sham operated group. Phosphorylated phosphatidylinositol 3-kinase (pPI3K), protein kinase B, mechanistic target of rapamycin, and nuclear factor kappa-light-chain-enhancer of activated B cells were unaltered in the mouse dorsal root ganglion (DRG) and spinal cord (SC) after inducing FM and administering EA treatment. The pPI3K-associated nociceptive signaling pathway was increased in the thalamus of FM mice, but reversed by EA. Similar results were observed in the mouse somatosensory cortex.<br /> <em><strong>Conclusion:</strong></em> These data suggest that EA has a significant effect on a signaling pathway in brain areas of FM mice. These findings suggest the value of EA for clinical practice.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622920190901Attenuation by l-thyroxine of oxidant-induced gut epithelial damage109110961355410.22038/ijbms.2019.37169.8852ENZahra ShahediDepartment of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IranMasoumeh VarediDepartment of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran0000-0003-3691-5053Zohreh BagheriDepartment of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IranAfagh MoatariDepartment of Microbiology & virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IranHengameh SharafpourDepartment of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IranJournal Article20181227<strong><em>Objective(s):</em></strong> Severe injuries are often associated with tissue hypothyroidism, elevated damaging mediators in circulation, and broken gut epithelial barrier. However, the relationships between the hypothyroid state and gut epithelial damage are largely unknown. Therefore, in this study, we investigated the effects of L-thyroxine (T4) on in vitro models of intact and compromised gut epithelium. <br /><em><strong>Materials and Methods:</strong></em> Gut epithelium equivalent was generated by cultivation of IEC-18 rat intestinal epithelial cells into transwell inserts. Confluent cultures were then compromised by scratching or H2O2 and traumatized rat sera (TUR sera) treatments. Macromolecules permeation and transepithelial electrical resistance (TEER) were evaluated by conventional methods. Morphology and scratch wound closure were assessed microscopically. Cell viability/proliferation was assessed by MTT assay. <br /><em><strong>Results:</strong></em> Both H2O2 and TUR sera induced marked yet different types of epithelial disintegration. While H2O2 significantly increased and decreased probe permeation and TEER, respectively, TUR sera was ineffective. Cultures treated with normal rat sera (sham sera) exhibited morphology, probe permeation, and TEER comparable to those of control cultures. Presence of T4 attenuated the H2O2-induced but not TUR sera-induced damages. T4 treatment accelerated, albeit marginally, wound closure but had virtually no effects on cell viability/proliferation. <strong> </strong><br /><em><strong>Conclusion:</strong></em> These data suggest that different mechanisms are involved in oxidant- and trauma-induced gut epithelial barrier breakdown. Besides, they show that T4 markedly attenuates oxidant-induced gut epithelial damage. Accordingly, one may also conclude that tissue hypothyroidism does not contribute to trauma-induced gut barrier breakdown.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622920190901Protective effects of Vitex agnus-castus in ovariectomy mice following permanent middle cerebral artery occlusion109711011353410.22038/ijbms.2019.31692.7625ENRaheleh AlimohamadiStudent Research Committee, Rafsanjan University of Medical Sciences, Rafsanjan, Iran0000-0002-6592-1287Iman FatemiResearch Center for Tropical and Infectious Diseases, Kerman University of Medical Sciences, Kerman, Iran0000-0002-9666-9651Soudabeh NaderiStudent Research Committee, Rafsanjan University of Medical Sciences, Rafsanjan, IranElham HakimizadehPhysiology-Pharmacology Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, IranDepartment of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran0000-0002-2811-7716Mohammad-Reza RahmaniPhysiology-Pharmacology Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, IranDepartment of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, IranMohammad AllahtavakoliPhysiology-Pharmacology Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, IranDepartment of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran0000-0001-6612-9729Journal Article20180507<strong><em>Objective(s):</em></strong> Previous studies have indicated that phytoestrogens induce estrogenic as well as anti-inflammatory effects, and they are found in high abundance in the extracts of some herbs such as Vitex Agnus Castus (VAC). Therefore, we investigated the effect of VAC extract on ovariectomized mice after the induction of permanent middle cerebral artery occlusion (PMCAO) model. <br /><em><strong>Materials and Methods:</strong></em> In this study, 50 mice ranging from 25 to 35 g were divided into five experimental groups as follows: Control, VAC, Estrogen, Tamoxifen, and Tamoxifen-VAC. Animals were ovariectomized, and after 30 days of treatment, they were given PMCAO induction. Behavioral assessment (adhesive removal and wire hanging tests) was evaluated 24 hr, 48 hr, and one week after induction of stroke. The infarct volume, as well as serum levels of matrix metalloproteinase-9 (MMP-9) and interleukin-10 (IL-10), were measured one week after stroke.<br /><em><strong>Results:</strong></em> One week after stroke, in both VAC and estrogen groups, the infarct size reduced in comparison with the control group. Estrogen and VAC extract improved adhesive removal and wire hanging test, increased the level of IL-10, and decreased the level of MMP-9 compared with the control group. In addition, co-administration of tamoxifen and VCA extract had no significant effect on measured indices compared with control and tamoxifen groups. <br /><em><strong>Conclusion:</strong> </em>Based on our findings, VAC extract has neuroprotective properties and can reduce stroke injuries in PMCAO-induced ovariectomized mice via anti-inflammatory and estrogenic properties.