Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866201220171201Mechanisms of spinal cord injury regeneration in zebrafish: a systematic review12871296962010.22038/ijbms.2017.9620ENZeynab NoorimotlaghMedical Student, Iran University of Medical Sciences, Sina Trauma and Surgery Research Center, Tehran, IranMahla BabaieMedical Student, Iran University of Medical Sciences, Sina Trauma and Surgery Research Center, Tehran, IranMahdi SafdarianIran University of Medical Sciences, Sina Trauma and Surgery Research Center, Tehran, IranTahereh GhadiriTabriz University of Medical Sciences, Tabriz, IranVafa Rahimi-MovagharSina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, 11365-3876, Iran0000-0001-7347-8767Journal Article20171112<strong><em>Objective(s)</em></strong>:To determine the molecular and cellular mechanisms of spinal cord regeneration in zebrafish.<br /> <strong><em>Materials and Methods:</em> </strong>Medical databases of PubMed and Scopus were searched with following key words: Zebrafish; spinal cord injuries; regeneration; recovery of function. The map of mechanisms was performed using Xmind software.<br /> <strong><em>Results: </em></strong>Wnt/ß-catenin signaling, L1.1, L1.2, Major vault protein (MVP), contactin-2 and High mobility group box1 (HMGB1) had positive promoting effects on axonal re-growth while Ptena had an inhibitory effect. Neurogenesis is stimulated by Wnt/ß-catenin signaling as well as HMGB1, but inhibited by Notch signaling. Glial cells proliferate in response to fibroblast growth factor (fgf) signaling and Lysophosphatidic acid (LPA). Furthermore, fgf signaling pathway causes glia bridge formation in favor of axonal regeneration. LPA and HMGB1 in acute phase stimulate inflammatory responses around injury and suppress regeneration. LPA also induces microglia activation and neuronal death in addition to glia cell proliferation, but prevents neurite sprouting.<br /> <strong><em>Conclusion:</em></strong> This study provides a comprehensive review of the known molecules and mechanisms in the current literature involved in the spinal cord injury (SCI) regeneration in zebrafish, in a time course manner. A better understanding of the whole determining mechanisms for the SCI regeneration should be considered as a main goal for future studies.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866201220171201Protective effect of metformin on toxicity of butyric acid and arsenic in isolated liver mitochondria and langerhans islets in male mice: an in vitro study12971305956710.22038/ijbms.2017.9567ENAkram AhangarpourHealth Research Institute, Diabetes Research Center, Department of Physiology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran0000-0002-4323-1672Leila ZeidooniDepartment of Toxicology, School of Pharmacy, Student Research Committee of Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranMohsen RezaeiDepartment of pharmacology, School of Pharmacy, Tarbiat Modares University, Tehran, IranSoheila AlboghobeishDepartment of pharmacology, School of Pharmacy, Student Research Committee of Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran0000-0002-6681-5793Azin SamimiDepartment of Toxicology, School of Pharmacy, Student Research Committee of Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranAli Akbar OroojanDepartment of Physiology, Student Research Committee of Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran0000-0001-5249-3239Journal Article20171101<strong><em>Objective(s)</em></strong>: Arsenic, a toxic metal in drinking water and butyric acid (BA) is a free fatty acid found in many foods. These two can induce oxidative stress in some tissues. The present study investigated the protective effect of metformin against toxicity induced by Arsenic (As) and BA in isolated mice liver mitochondria and pancreatic islets.<br /> <strong><em>Materials and Methods: </em></strong>In this study, liver mitochondria were isolated by adopting different centrifugation methods and pancreatic islets isolated by a collagenase method. Mitochondria were incubated by BA (75 μM), As (100 μM) and metformin (0, 0.5, 1, 3, 10 mM) and the islets also incubated by BA (1000 μM), As (100 μM) and metformin (0, 1, 3, 10 mM) for 1 hr. At the end of study, mitochondrial viability (MTT), mitochondrial membrane potential (MMP), reactive oxygen species (ROS), malondial- dehyde (MDA), glutathione (GSH) and islets insulin secretion were measured employing specific relevant methods.<br /> <strong><em>Results:</em></strong> As and BA significantly increased ROS, MDA and ΔΨm levels and decreased GSH level, succinate dehydrogenase activity and insulin secretion. On the other hand, pretreatment with metformin, returned mitochondrial complex ІІ activity, reduced ROS, MDA and ΔΨm levels and increased GSH level and insulin secretion of pancreatic islets.<br /> <strong><em>Conclusion:</em></strong> As and BA in combination or in isolation induce oxidative stress in liver mitochondria and decrease insulin secretion of pancreatic islets. Metformin has a protective effect probably caused by its antioxidant feature. The findings suggest the potential role of metformin in mitochondria therapy and insulin secretion in many diseases.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866201220171201Curcumin enhances liver SIRT3 expression in the rat model of cirrhosis13061311960910.22038/ijbms.2017.9609ENSara ChenariDepartment of Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, IranFatemeh SafariDepartment of Physiology, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, IranAli MoradiDepartment of Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran0000-0003-3866-0867Journal Article20171108<strong><em>Objective(s)</em></strong>: Bill duct ligation (BDL) is a representative model of biliary cholestasis in animals. Curcumin has a protective effect on the liver; however, its underlying mechanisms are not completely known. This study explored the hepatoprotective activity of curcumin on hepatic damage via measuring the expression of sirtuin3 (SIRT3), AMP-activated protein kinase (AMPK), carnitine palmitoyltransferase 1A (CPT-1A), isocitrate dehydrogenase2 (IDH2) and manganese superoxide dismutase (MnSOD) as well as the level of serum lipid profile in the BDL fibrotic rat model.<br /> <strong><em>Materials and Methods: </em></strong>The study consisted of four groups (n=8 for each of Wistar rats): sham group, sham+curcumin (sham+Cur) group (received curcumin 100 mg/kg/day), BDL+Cur group, and BDL group. Transcription levels of SIRT3, AMPK, CPT-1A, IDH2, MnSOD and protein expression level of SIRT3 were measured by real-time PCR and Western blotting, respectively.<br /> <strong><em>Results:</em></strong> It was identified that SIRT3, AMPK, CPT-1A, IDH2 and MnSOD expression significantly decreased in BDL rats compared to sham rats; however, in the curcumin treatment of BDL rats, the expression of these factors increased significantly compared to BDL (<em>P-</em>value <0.05). It was, moreover, observed that treatment of BDL rats with curcumin reduced liver injury as verified by a reduction in the levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) and increase in high-density lipoprotein (HDL)(<em>P-</em>value <0.05).<br /> <strong><em>Conclusion:</em></strong> Curcumin reduced liver damage and oxidative stress in the liver tissue of BDL rats through up-regulation of SIRT3, AMPK, CPT-1A, IDH2 and MnSOD as well as changing the level of serum lipid profile.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866201220171201Genistein preserves the lungs of ovariectomized diabetic rats: addition to apoptotic and inflammatory markers in the lung13121317959910.22038/ijbms.2017.9599ENFaeze DaghighTuberculosis and Lung Research Center, Tabriz University of Medical Sciences, Tabriz, IranAlireza AlihemmatiDepartment of Histology & Embryology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, IranPouran KarimiNeurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, IranParisa HabibiDepartment of Physiology, Hamadan University of Medical Sciences, Hamadan, IranNaser AhmadiaslTuberculosis and Lung Research Center, Tabriz University of Medical Sciences, Tabriz, IranJournal Article20171107<strong><em>Objective(s)</em></strong>: The role of isoflavones in pulmonary structure and function during menopause is not well studied. Moreover, the important role of estrogen in the physiological function of respiratory system has been revealed. Genistein, as an isoflavone, mimics estrogenic in diabetic and ovariectomized rats. Here, we hypothesized that genistein would reverse changes in the protein expression levels related to estrogen deficiency in the lung of ovariectomized diabetic rats.<br /> <strong><em>Materials and Methods: </em></strong>Wistar female rats were assigned to four experimental groups (n=10 in each group): sham, rats underwent laparotomy without removing the ovaries; OVX, rats that underwent ovariectomy; OVX.D, rats underwent bilateral ovariectomy and were fed a high-fat diet (HFD); OVX.D.G, ovariectomized diabetic rats with genistein administration (1 mg/kg /day). After ovariectomy, rats continued to feed HFD for a 4-week period. After 4 weeks of HFD feeding, a single dose of 30 mg/kg of streptozotocin was administered in the diabetic group. Genistein was administered for eight weeks. At the end of the experiment, lung tissue was removed and Western blotting technique and hematoxylin-eosin staining were used for evaluation of the lung.<br /> <strong><em>Results:</em></strong> Treatment with genistein significantly decreased inflammatory and apoptotic biomarkers in the ovariectomized diabetic rats compared to non-treated animals (<em>P</em><0.05). Also, genistein exerted a protective effect in the lung architecture.<br /> <strong><em>Conclusion:</em></strong> Genistein partly reversed ovariectomy-induced changes in apoptotic and inflammatory biomarkers in the lung. Our data suggest that genistein treatment as a natural replacement therapy may prevent the estrogen deficiency effects in the lung of diabetic menopausal women.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866201220171201Antimalarial and cytotoxic activities of roots and fruits fractions of Astrodaucus persicus extract13181323955410.22038/ijbms.2017.9554ENSaied GoodarziMedicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IranMehdi NateghpourDepartment of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, IranParina AsgharianDepartment of Pharmacognosy, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran0000000191108209Abbas HadjiakhoondiMedicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IranNarguess YassaMedicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IranSaeed TavakoliDepartment of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IranJalal MirzaeiDepartment of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IranLeila FarivarDepartment of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, IranAfsaneh Motevalli HaghiDepartment of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, IranZahra TofighiMedicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran0000-0001-8909-6595Journal Article20171031<strong><em>Objective(s)</em></strong>:<em>Astrodaucus persicus </em>(Apiaceae) is one of the two species of this genus which grows in different parts of Iran. Roots of this plant were rich in benzodioxoles and used as food additive or salad in Iran and near countries. The aim of present study was evaluation of antimalarial and cytotoxic effects of different fractions of <em>A. persicus</em> fruits and roots extracts.<br /> <strong><em>Materials and Methods:</em></strong> Ripe fruits and roots of A<em>. persicus</em>were extracted and fractionated by hexane, chloroform, ethyl acetate and methanol, separately. Antimalarial activities of fractions were performed based on <em>Plasmodium berghei</em> suppressive test in mice model and percentage of parasitemia and suppression were determined for each sample. Cytotoxicity of fruits and roots fractions were investigated against human breast adenocarcinoma (MCF-7), colorectal carcinoma (SW480) and normal (L929) cell lines by MTT assay and IC<sub>50</sub> of them were measured.<br /> <strong><em>Results:</em></strong> Hexane fraction of roots extract (RHE) and ethyl acetate fraction of fruits extract (FEA) of <em>A. persicus</em> demonstrated highest parasite inhibition (73.3 and 72.3%, respectively at 500 mg/kg/day) which were significantly different from negative control group (<em>P</em><0.05). In addition, RHE showed potent anticancer activities against MCF-7 (IC<sub>50</sub> of 0.01 µg/ml), SW480 (IC<sub>50</sub> of 0.36 µg/ml) and L929 (IC<sub>50</sub> of 0.70 µg/ml) cell lines.<br /> <strong><em>Conclusion:</em></strong> According to the results, RHE and FEA fractions of <em>A. persicus</em> could be introduced as excellent choice for antimalarial drug discovery. In addition, cytotoxic activity of RHE was noticeable.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866201220171201Neuroprotection of a sesamin derivative, 1, 2-bis [(3-methoxy- phenyl) methyl] ethane-1, 2-dicaroxylic acid (MMEDA) against ischemic and hypoxic neuronal injury13241330954310.22038/ijbms.2017.9543ENChang-Tsen HungDepartment of Health and Leisure Management, Yuanpei University of Medical Technology, Hsinchu, TaiwanLi-Dian ChenDepartment of Convalescence Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou ChinaChien-Wei HouDepartment of Biotechnology and Pharmaceutical Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan0000-0001-9300-506XJournal Article20171026<strong><em>Objective(s)</em></strong>: Stroke may cause severe neuronal damage. The sesamin have been demonstrated to possess neuroprotection by its antioxidant and anti-inflammatory properties. One sesamin derivative was artificially composited, 1, 2-bis [(3-methoxyphenyl) methyl] ethane-1, 2-dicaroxylic acid (MMEDA) had been developed to study its antioxidative activity and neuroprotection.<br /> <strong><em>Materials and Methods: </em></strong>The infaction of Sprague Dawley (SD) rats and hypoxia models of BV-2 microglia or PC12 cells were investigated for <em>in vivo</em> and <em>in vitro</em> test respectively. Lipid peroxidation and reactive oxygen species (ROS), prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) and related signaling pathways from hypoxic cells were analyzed by ELISA or Western blot assay, respectively.<br /> <strong><em>Results:</em></strong> MMEDA showed a protective effect when given 90 min after the focal cerebral ischemia. The neuroprotection of MMEDA was further confirmed by attenuating ROS and PGE<sub>2</sub> release from hypoxic BV-2 or PC12 cells. MMEDA significantly reduced hypoxia-induced JNK and caspase-3 (survival and apoptotic pathways) in PC12 cells.<br /> <strong><em>Conclusion:</em></strong> The neuroprotective effect of MMEDA on ischemia/hypoxia models was involved with its antioxidative activity and anti-inflammatory effects. These results suggest that MMEDA exert effective neuroprotection against ischemia/hypoxia injury.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866201220171201Effect of fetal and adult bovine serum on pyocyanin production in Pseudomonas aeruginosa isolated from clinical and soil samples13311338962110.22038/ijbms.2017.9621ENAylin MoayediDepartment of Microbiology, Tehran North Branch, Islamic Azad University, Tehran, IranJamileh NowrooziDepartment of Microbiology, Tehran North Branch, Islamic Azad University, Tehran, Iran0000-0003-4735-9208Abbas Akhavan SepahyDepartment of Microbiology, Tehran North Branch, Islamic Azad University, Tehran, IranJournal Article20171113<strong><em>Objective(s)</em></strong>: Pyocyanin is a blue-greenish redox-active pigment, produced by <em>Pseudomonas aeruginosa</em>, with a wide range of biological and biotechnological applications. Pyocyanin biosynthesis is regulated by the quorum-sensing (QS) system in which the expression of QS genes and QS-controlled virulence genes may be affected by serum as a complex medium. In the current study, effects of adult bovine serum (ABS) and fetal bovine serum (FBS) on the production of pyocyanin were examined in order to develop it.<br /> <strong><em>Materials and Methods: </em></strong>The presence of pyocyanin-producing specific genes and proteins in clinical and soil isolates of <em>P. aeruginosa </em>was confirmed using PCR and SDS-PAGE. Isolates were inoculated to media containing different concentrations of complement-active/-inactivated ABS or FBS and pyocyanin concentration was measured by spectrophotometry. Extracted pigment was characterized by using UV-Visible spectrophotometry. Titration of ABS antibodies against studied isolates was performed by the tube agglutination test.<br /> <strong><em>Results:</em></strong> Adding ABS to <em>P. aeruginosa</em> culture medium decreased pyocyanin production compared to the control, while its production increased in FBS-containing media (113.21±2.581 vs. 55.26±0.827 μg.ml<sup>-1</sup> and 126.80±2.036 vs. 30.56±0.382 μg.ml<sup>-1</sup> of C<sub>11</sub> and E<sub>8</sub> pyocyanin concentration in the presence of 10% FBS vs. control, respectively).<br /> <strong><em>Conclusion:</em></strong> In this study, due to the presence of inhibitors such as complement proteins and antibodies in ABS samples, the use of FBS devoid of antibodies was effective to increase pyocyanin production in studied isolates.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866201220171201The role of sirolimus in proteinuria in diabetic nephropathy rats13391344961810.22038/ijbms.2017.9618ENJinJun WangDepartment of Transplantation, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, ChinaZiQiang XuDepartment of Transplantation, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, ChinaBiCheng ChenDepartment of Transplantation, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, ChinaShaoLing ZhengDepartment of Transplantation, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, ChinaPeng XiaDepartment of Transplantation, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China0000-0001-8667-1558Yong CaiDepartment of Transplantation, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, ChinaJournal Article20171112<strong><em>Objective(s)</em></strong>: The aim of this study was to observe the impact of sirolimus on proteinuria in streptozotocin (STZ) induced diabetic rats.<br /> <strong><em>Materials and Methods: </em></strong>Rats were given a single injection of STZ to induce diabetic rat model. Rats’ 24 hr urine was collected to test, urinary and the kidney tissues were harvested at the 8<sup>th</sup> and 20<sup>th</sup> weeks, respectively. Podocyte morphological changes were examined by electron microscopy and the ZO-1, podocin expressions in kidneys were detected by immunohistochemistry; the protein levels of Raptor and pS6 were measured by Western blot assay.<br /> <strong><em>Results:</em></strong> In the early stage of diabetic nephropathy (DN), sirolimus reduced the proteinuria significantly (<em>P</em><0.05); but in the advanced stage of DN, sirolimus worsened proteinuria (<em>P</em><0.05). Electron microscopy test suggested that sirolimus could reduce the injury of podocyte at the early DN, but increased the injury at the late DN podocyte. Immunohistochemistry results indicated that sirolimus increased the expressions of podocin and ZO-1 at the early DN (<em>P</em><0.05), but reduced the expressions of ZO-1 and podocin (<em>P</em><0.05) at the advanced DN. In the different periods of DN, the expression levels of Raptor and pS6 in sirolimus-treated groups were significantly lower than in the DN control groups (<em>P</em><0.05).<br /> <strong><em>Conclusion: </em></strong>Sirolimus can reduce proteinuria and alleviate the early DN podocyte injury in diabetic rat model by inhibiting the activity of mTORC1; but in the advanced stage of DN, sirolimus can increase podocyte injury and urine protein level.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866201220171201The effects of activated-omental extract on nuclear and cytoplasmic in vitro maturation of rat oocytes13451353962210.22038/ijbms.2017.9622ENFakhroddin MesbahDepartment of Anatomical Sciences, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IranAris Donic PrachaDepartment of Anatomical Sciences, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IranTahereh Talaei-KhozaniDepartment of Anatomical Sciences, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran0000-0002-8425-8871Soghra BahmanpourDepartment of Anatomical Sciences, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IranJournal Article20171113<strong><em>Objective:</em></strong> The role of growth factors, including vascular endothelial growth factor of activated omentum on mitosis is clearly known, though not on all the aspects of <em>in vitro</em> oocyte maturation. This study was designed to assess the effect of activated-omental extract (AOE) on <em>in vitro</em> maturation (IVM) of rat cumulus-oocyte complexes (COCs).<br /> <strong><em>Materials and Methods:</em></strong> In this experimental study, the COCs were incubated in Ham’s F-10 supplemented with either 20% AOE, 20% fetal bovine serum (FBS) or serum-free media. Post-culture COCs were studied according to the cumulus cells (CCs) expansion, nuclear maturation and cytoplasmic maturation. Cumuli expansion was evaluated by inverted microscope without staining; nuclear maturation was assessed by aceto-orcein staining (light microscope) and cytoplasmic maturation was also observed by TEM.<br /> <strong><em>Results:</em></strong> Expansion of CCs and nuclear maturation of the oocytes in <em>in vitro</em> for 24 hr was significantly higher in AOE- and FBS-supplemented groups (<em>P</em>=0.000 and 0.013) and (<em>P</em>=0.004 and 0.014), respectively, compared to serum-free group. At ultra-structural level, after 24 hr, both FBS and AOE-supplemented media showed uniformly wide perivitelline space (PVS). After 12 hr, the cortical granules were found in the oocytes cultured in FBS and AOE-supplemented media. Within 24 hr, both granules and mitochondria were large without any detectable topographic tendency across the ooplasm. In AOE and FBS- supplemented oocytes, the number and size of microvilli were more than those in serum-free one.<br /> <strong><em>Conclusion:</em></strong> Although AOE supplementation induced a higher rate of the CCs expansion, and <em>resuming meiosis</em>, it was not as potent as FBS to provide cytoplasmic maturation of rat oocytes.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866201220171201The effects of specific expression of apoptin under the control of PSES and PSA promoter on cell death and apoptosis of LNCaP cells13541359959810.22038/ijbms.2017.9598ENVida MohammadiDepartment of Medical Biotechnology, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, IranDiagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, IranAbbas Behzad BehbahaniDepartment of Medical Biotechnology, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, IranDiagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, IranGholam Reza RafieeDepartment of Medical Biotechnology, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, IranDiagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, IranSeyed Younes HosseiniDepartment of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran0000-0002-5881-6796Marzieh Alizadeh ZareiDepartment of Medical Biotechnology, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, IranMohammad Ali OkhovatDepartment of Medical Biotechnology, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, IranDiagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, IranMohammad Ali TakhshidDepartment of Medical Biotechnology, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, IranDiagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran0000-0003-0246-3765Journal Article20171107<strong><em>Objective(s)</em></strong>: Apoptotic effect of apoptin has been demonstrated in numerous studies. However, its tumor specificity has been questioned by some reports. The aim of this study was to confine the expression of apoptin in the prostate tumor cells by inducing its gene expression under the control of a chimeric enhancer composing of prostate-specific membrane antigen (PSMA) and prostate-specific antigen (PSA) regulatory elements (PSES). Furthermore, we investigated the effects of apoptin expression on LNCaP prostate carcinoma cell survival and apoptosis using MTT assay and annexinV/7-AAD flow cytometry assay.<br /> <strong><em>Materials and Methods: </em></strong>Recombinant plasmids containing apoptin gene under the control of PSES/PSA promoter or Cytomegalovirus (CMV) promoter were constructed. Tumor cell lines including LNCaP cells and HeLa cells, and LX-2 cells (as a normal control) were transfected with the plasmids and the expression <strong>o</strong>f apoptin was evaluated by real time-PCR and western blot analyses. The effects of apoptin expression on cell survival and apoptosis were then investigated using MTT and annexinV/7-AAD flow cytometry assay, respectively.<br /> <strong><em>Results:</em></strong> Western blot and real time PCR analyses confirmed the specific expression of apoptin under the control of PSES/PSA regulatory element in the LNCaP cells, while CMV promoter caused apoptin expression in both tumor and normal cell lines. Apoptin expression significantly increased cell death and apoptosis in tumor cells when compared with the normal cells (<em>P</em><0.001).<br /> <strong><em>Conclusion:</em></strong> These results suggest that PSES/PSA regulatory element may be considered as an efficient approach for specific expression of apoptin gene in prostate tumor cells and treatment of prostate cancer.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866201220171201Vitamin E improved bone strength and bone minerals in male rats given alcohol13601367961010.22038/ijbms.2017.9610ENSyuhada ZakariaDepartment of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, MalaysiaSiti-Zulaikha Mat-HusainDepartment of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, MalaysiaKong Ying-HweyDepartment of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, MalaysiaKek Xin-KaiDepartment of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, MalaysiaAbdullah Mohd-BadawiDepartment of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, MalaysiaNurul-Amiza Abd-GhaniDepartment of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, MalaysiaMuhamad-Arizi AzizDepartment of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, MalaysiaMohamed NorazlinaDepartment of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, MalaysiaJournal Article20171109<strong><em>Objective(s)</em></strong>: Alcohol consumption induces oxidative stress on bone, which in turn increases the risk of osteoporosis. This study determined the effects of vitamin E on bone strength and bone mineral content in alcohol-induced osteoporotic rats.<br /> <strong><em>Materials and Methods: </em></strong>Three months old Sprague Dawley male rats were randomly divided into 5 groups: (I) control group; (II) alcohol (3 g/kg) + normal saline; (III) alcohol (3 g/kg) + olive oil; (IV) alcohol (3 g/kg) + alpha-tocopherol (60 mg/kg) and (V) alcohol (3 g/kg) + palm vitamin E (60 mg/kg). The treatment lasted for three months. Following sacrifice, the right tibia was subjected to bone biomechanical test while the lumbar (fourth and fifth lumbar) and left tibia bones were harvested for bone mineral measurement.<br /> <strong><em>Results:</em></strong> Alcohol caused reduction in bone biomechanical parameters (maximum force, ultimate stress, yield stress and Young’s modulus) and bone minerals (bone calcium and magnesium) compared to control group (<em>P</em><0.05). Palm vitamin E was able to improve bone biomechanical parameters by increasing the maximum force, ultimate stress and Young’s modulus (<em>P</em><0.05) while alpha-tocopherol was not able to. Both alpha-tocopherol and palm vitamin E were able to significantly increase tibia calcium and magnesium content while only alpha-tocopherol caused significant increase in lumbar calcium content (<em>P</em><0.05).<br /> <strong><em>Conclusion:</em></strong> Both palm vitamin E and alpha-tocopherol improved bone mineral content which was reduced by alcohol. However, only palm vitamin E was able to improve bone strength in alcohol treated rats.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866201220171201The effects of CCK-8S on spatial memory and long-term potentiation at CA1 during induction of stress in rats13681376961910.22038/ijbms.2017.9619ENMalihe SadeghiDepartment of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, IranParham ReisiDepartment of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, IranMaryam RadahmadiDepartment of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran0000-0002-1383-9572Journal Article20171112<strong><em>Objective(s)</em></strong>: Cholecystokinin (CCK) has been proposed as a mediator in stress. However, it is still not fully documented what are its effects. We aimed to evaluate the effects of systemic administration of CCK exactly before induction of stress on spatial memory and synaptic plasticity at CA1 in rats.<br /> <strong><em>Materials and Methods: </em></strong>Male Wistar rats were divided into 4 groups: the control, the control-CCK, the stress and the stress-CCK. Restraint stress was induced 6 hr per day, for 24 days. Cholecystokinin sulfated octapeptide (CCK-8S) was injected (1.6 µg/kg, IP) before each session of stress induction. Spatial memory was evaluated by Morris water maze test. Long term potentiation (LTP) in Schaffer collateral-CA1 synapses was assessed (by 100 Hz tetanization) in order to investigate synaptic plasticity.<br /> <strong><em>Results:</em></strong> Stress impaired spatial memory significantly (<em>P</em><0.01). CCK in the control rats improved memory (<em>P</em><0.05), and prevented the impairments in the stress group. With respect to the control group, both fEPSP amplitude and slope were significantly (<em>P</em><0.05) decreased in the stress group. However, there were no differences between responses of the control–CCK and Stress–CCK groups compared to the control group.<br /> <strong><em>Conclusion:</em></strong> The present results suggest that high levels of CCK-8S during induction of stress can modulate the destructive effects of stress on hippocampal synaptic plasticity and memory. Therefore, the mediatory effects of CCK in stress are likely as compensatory responses.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866201220171201Cytotoxic and apoptotic effects of root extract and tanshinones isolated from Perovskia abrotanoides Kar13771384956810.22038/ijbms.2017.9568ENArehzoo ZakerDepartment of Biology, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, IranJavad AsiliDepartment of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IranParvaneh AbrishamchiDepartment of Biology, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, IranZahra Tayarani-NajaranMedical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IranSeyed Hadi MousaviMedical Toxicology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, IranPharmacological Research Center of Medicinal Plants, School of Medicine, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Pharmacology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, IranJournal Article20171101<strong><em>Objective(s)</em></strong>:<em>Perovskia abrotanoides </em>Kar., from family Lamiaceae, is a little known medicinal plant growing in various regions of Iran. In the present study, cryptotanshinone (CT), tanshinone 2A (Tan2A), and hydroxycryptotanshinone (HCT) were isolated and purified from the roots of <em>P. abrotanoides</em>. In addition, cytotoxic and apoptotic effects of total root extract (TE) and three purified tanshinones were investigated in human cervical carcinoma (HeLa) and human breast cancer (MCF-7) cell lines. <br /> <strong><em>Materials and Methods:</em></strong> Alamar Blue<sup>®</sup> assay was used to determine cell viability. Cell apoptotic rate was detected using propidium iodide staining of DNA fragmentation by flow cytometry (sub-G1 peak). The PARP cleavage, as the sign of apoptosis, was investigated by Western blotting.<br /> <strong><em>Results:</em></strong> The results revealed that CT, Tan2A, HCT, and TE exhibited significant cytotoxicity in cancer cell lines. All of these compounds caused apoptosis in treated cells and induced sub-G1 peak in the related flow cytometry histograms. HCT was found to have the highest anti-proliferative activity on cancer cells. Western blotting analysis showed cleavage of PARP protein in MCF-7 cells treated with purified tanshinones and TE after 48 hr contact with cells.<br /> <strong><em>Conclusion:</em></strong> The findings suggest that root extract of <em>P. abrotanoides</em> and purified tanshinones especially Tan2A and HCT have cytotoxic and apoptotic effects against cancer cell lines. So, they may serve as potential cytotoxic agents for future investigations.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866201220171201Sodium hydrosulfide upregulates mRNA and protein expression of TGF-α in gastric mucosa in experimental model of stimulated gastric acid secretion in rats13851389959710.22038/ijbms.2017.9597ENGhaidafeh AkbariPhysiology Research Center (PRC), Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranResearch Center for Infectious Diseases of Digestive System [Alimentary Tract Research Center], Physiology Research Center (PRC), Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranSeyyed Ali MardResearch Center for Infectious Diseases of Digestive System [Alimentary Tract Research Center], Physiology Research Center (PRC), Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranSeyed Esmaeil KhoshnamPhysiology Research Center (PRC), Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranIraj AhmadiPhysiology Research Center (PRC), Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranJournal Article20171107<strong><em>Objective(s)</em></strong>: Transforming growth factor alpha (TGF-α) has been shown to modulate the gastric acid secretion. Therefore, the aim of the present study was to investigate the effect of sodium hydrosulfide (NaHS) on TGF-α expression in gastric mucosa in rats.<br /> <strong><em>Materials and Methods: </em></strong>Eighteen rats were randomly divided into 3 groups (6 per group). To determine the effect of NaHS on gene and protein expression of TGF-α in gastric mucosa in response to gastric acid, the acid output induced by gastric distension. At the end of experiment, rats were euthanized by anesthetics, and gastric effluents, in addition to mucosa were collected to measure the pH of gastric effluents and to quantify protein and gene expression of TGF-α.<br /> <strong><em>Results:</em></strong> The stimulated gastric acid upregulated expression levels of TGF-α in gastric mucosa. These levels were higher in animals pretreated with NaHS.<br /> <strong><em>Conclusion:</em></strong> TGF-α upregulatory effect of sodium hydrosulfate implied that TGF-α is involved in the acid inhibitory effect of NaHS.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866201220171201Anti-hyperglycemic and antioxidant potential of Croton bonplandianus. Bail fractions in correlation with polyphenol content13901397962310.22038/ijbms.2017.9623ENUma Dharshini Karuppiah VijayamuthuramalingamDepartment of Biomedical Sciences, Sri Ramachandra University, Porur, Chennai, IndiaRajeswari RajaramDepartment of Biomedical Sciences, Sri Ramachandra University, Porur, Chennai, IndiaKalaivani Madhavaram KuppusamyDepartment of Biomedical Sciences, Sri Ramachandra University, Porur, Chennai, IndiaBhavana JonnalagaddaDepartment of Biomedical Sciences, Sri Ramachandra University, Porur, Chennai, IndiaSumathy ArokiasamyDepartment of Biomedical Sciences, Sri Ramachandra University, Porur, Chennai, India0000-0002-6569-5806Journal Article20171113<strong><em>Objective(s)</em></strong>:Diabetes mellitus, a carbohydrate metabolic disorder, occurs due to absolute or relative deficiency of insulin. Current treatment strategies involve either preventing or delaying the intestinal absorption of glucose to lower the levels of postprandial hyperglycemia (PPHG). Herbal remedies have been since ancient times for treating diabetes mellitus. Therefore, identifying novel phytocompounds with α-amylase and α-glucosidase inhibitory activity that would reduce the glucose absorption as well as the rise in postprandial blood glucose level is vital. Consequently, the present study was aimed to investigate the anti-hyperglycemic activity of <em>Croton bonplandianus</em>against these pancreatic enzymes.<br /> <strong><em>Materials and Methods: </em></strong>The methanol extract of <em>C. bonplandianus</em>leaf was prepared and further fractionation was performed with n-hexane, ethyl acetate and chloroform. The antioxidant activity and anti-hyperglycemic activity of the extracts and its fractions were determined. Further, GC-MS analysis was performed for the leaf extract.<br /> <strong><em>Results:</em></strong>The chloroform fraction (ChF) was found to contain highest quantity of polyphenols (114.28 µg/ml of GAE), flavonoids (95.68 µg/ml of quercetin) and tannins (63.80 µg/ml of GAE) and also possessed effective inhibitory activity against α amylase (IC<sub>50</sub>95.78 µg/ml) and α glucosidase (IC<sub>50</sub> 126.81 µg/ml). The antioxidant activity of ChFwas also higher when compared to other fractions. Further, GC-MS analysis of ChF showed the presence of various components that may be responsible for the above mentioned activities.<strong> </strong><br /> <strong><em>Conclusion:</em></strong>The study findings suggest that the components present in the leaves of <em>C. bonplandianus</em>, may provide a potential therapeutic source in developing treatment forhyperglycemia. Further bioassay guided fractionation procedure is required to identify the active constituents.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866201220171201Contributors (Peer Reviewers)13981400962410.22038/ijbms.2017.9624ENJournal Article20171113