Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866191120161101Ecstasy (MDMA) and its effects on kidneys and their treatment: a review11511158781310.22038/ijbms.2016.7813ENFeyza BoraDepartment of Nephrology, Yenimahalle Training and Research Hospital, Yıldırım Beyazıt University, Ankara, TurkeyFatih YılmazDepartment of Nephrology, State Hospital, Zonguldak, TurkeyTaner BoraDepartment of Chemistry, Ankara Police Forensic Laboratory, Gölbaşı, Ankara, TurkeyJournal Article20161108Ecstasy (MDMA; 3,4-methylenedioxymethylamphetamine) is an illicit drug that has been increasingly abused by young people. Its effects include euphoria, enhanced sociability and heightened mental awareness. These come about via the increase of serotonin in both the central nervous system and the sympathetic nervous system. Despite the drug’s prevalent abuse, serious or adverse effects are rare. Due to personal pharmacokinetics, effects from the same dosage vary according to the individual. Fatal instances may include acute hyponatremia, hyperthermia (>42 <strong>°</strong>C), disseminated intravascular coagulation (DIC) resulting from hyperthermia affecting the kidneys, and non-traumatic rhabdomyolysis. However, it is seldom the case that hyponatremia and hyperthermia co-exist. Hyponatremia is thought to be caused by HMMA – a metabolite of MDMA. Hyponatremia is caused by the inappropriate secretion of arginine vasopressin (AVP) and the excessive intake of hypotonic liquid accompanied by increased hyperthermia. Symptomatic, even deadly hyponatremia is seen more frequently in females, with the effects of oestrogen on arginine vasopressin believed to be the cause. Onset in such cases is acute, and treatment should be given to symptomatic patients as quickly as possible, with 3% saline administered when necessary. Reasons for acute kidney injury may include rhabdomyolysis, malign hypertension, and necrotizing vasculitis.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866191120161101Effect of creatine supplementation on cognitive performance and apoptosis in a rat model of amyloid-beta-induced Alzheimer's disease11591165781410.22038/ijbms.2016.7814ENMalek Alimohammadi-KamalabadiDepartment of Cellular- Molecular Nutrition, School of Nutrition Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, IranMohammadreza EshraghianDepartment of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, IranMohammad-Reza ZarindastDepartment of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, IranAbbas AliaghaeiAnatomy and Cell Biology Department, School of Medicine, Shahid Beheshti University of Medical SciencesHamideh PishvaDepartment of Cellular- Molecular Nutrition, School of Nutrition Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, IranJournal Article20161108<strong><em>Objective(s)</em></strong>: Neuroprotective effect of creatine (Cr) against β-amyloid (Aβ) is reported in an <em>in vitro</em> study. This study investigated the effect of Cr supplementation on β-amyloid toxicity <em>in vivo</em>.
<strong><em>Materials and Methods: </em></strong>Thirty two, male Wistar rats were divided into 4 groups. During ten weeks of study, control group went through no surgical or dietary intervention. At the 4th week of study Sham group had a hippocampal normal saline injection, while Aβ and AβCr groups had an β-amyloid injection in the hippocampus. AβCr group were fed by Cr diet during the study. After 10 weeks, Morris water maze (MWM) test was administered to measure learning ability and memory retrieval. Animals were sacrificed for TUNEL anti apoptotic assay and staining of amyloid plaques by Thioflavin-T.
<strong><em>Results:</em></strong> There was a significant retention deficit among AβCr and Aβ group while the escape latency and the distance traveled to the platform were significantly higher in AβCr group compared to Aβ group. AβCr group had same percent of TUNEL positive neurons compared to Aβ group.
<strong><em>Conclusion:</em></strong> Cr supplementation before and after β-amyloid injection into the CA1 area of hippocampus deteriorates the learning and memory impairment of rats and it does not protect neuronal apoptosis caused by β-amyloid.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866191120161101Favorable effects of progesterone on skin random flap survival in rats11661170781510.22038/ijbms.2016.7815ENLin DingshengDepartment of Orthopaedics, Southern Medical University, Guangdong No.2 Province people’s Hospital, Guangdong, ChinaDepartment of Hand Surgeries, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaLiu ZengbingDepartment of Orthopaedics, Southern Medical University, Guangdong No.2 Province people’s Hospital, Guangdong, ChinaDepartment of Hand Surgeries, The No.4 People's Hospital of Hengshui, Hengshui, ChinaHuang DongDepartment of Orthopaedics, Southern Medical University, Guangdong No.2 Province people’s Hospital, Guangdong, ChinaJournal Article20161108<strong><em>Objective(s)</em></strong>: The aim of this study is to determine the effects of progesterone treatment on the survival of random skin flaps.
<strong><em>Materials and Methods: </em></strong>McFarlane flaps were established and 40 male rats were randomly assigned to the progesterone-treated as the test group or normal saline-treated as the control group. Progesterone or normal saline (10 mg/kg) was administered intraperitoneally once daily. On postoperative day 2, malondialdehyde (MDA) and superoxide dismutase (SOD) were detected using test kits. Flap survival rates were evaluated with transparent graph paper under direct visualization, the levels of inflammation were examined by haematoxylin and eosin (H&E) staining, and the expression of vascular endothelial growth factor (VEGF) was immunohistochemically evaluated on day 7.
<strong><em>Results:</em></strong> Compared to that in the control group, the mean survival area was significantly larger in the progesterone group. SOD activity was increased significantly, but the MDA levels in the test group were decreased. H&E-stained slices revealed that inflammation was inhibited in the test group. VEGF expression markedly increased in the progesterone group.
<strong><em>Conclusion:</em></strong> This study showed that progesterone administered intraperitoneally significantly improved random skin flap survival in rats.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866191120161101The hedgehog/Gli-1 signaling pathways is involved in the inhibitory effect of resveratrol on human colorectal cancer HCT116 cells11711176781610.22038/ijbms.2016.7816ENZhou DuDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, ChinaFeng ZhouDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, ChinaZengrong JiaDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, ChinaBeishi ZhengDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, ChinaShaoliang HanDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, ChinaJun ChengDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, ChinaGuanbao ZhuDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, ChinaPing HuangOffice of Development and Planning, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, ChinaJournal Article20161108<strong><em>Objective(s)</em></strong>: The study aimed to investigate the effects of resveratrol on colorectal cancer HCT116 cells, including cell viability, apoptosis, and migration, and the partial mechanisms focused on hedgehog/gli-1 signaling pathways.<br /> <strong><em>Materials and Methods: </em></strong>We chose the appropriate time and concentration of recombinant human Sonic hedgehog (Shh) stimulation by cell viability. The proportion of cell apoptosis was detected by flow cytometry; HCT116 cell migration was measured by scratch test; the expression of Ptch, Smo, and Gli-1 was measured by Western blot analysis.<br /> <strong><em>Results:</em></strong> Shh signaling increased HCT116 cell viability and migration, inhibited cell apoptosis, and upregulated the expression of Ptch, Smo, and Gli-1. Resveratrol obviously inhibited HCT116 cell viability and migration, promoted cell apoptosis, and suppressed the protein of Ptch, Smo, and Gli-1. Furthermore, the effects of resveratrol and Shh on human colorectal cancer HCT116 cells were in a dose- and time-dependent manner.<br /> <strong><em>Conclusion:</em></strong> The inhibitory effect of resveratrol on HCT116 cells may be mediated by hedgehog/gli-1 signaling pathways.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866191120161101Involvement of microRNA-133 and -29 in cardiac disturbances in diabetic ovariectomized rats11771185781710.22038/ijbms.2016.7817ENParisa HabibiDepartment of Physiology, Tabriz University of Medical Sciences, Tabriz, Iran0000 0001 7508 071XAlireza AlihemmatiDepartment of Histology & Embryology, Tabriz University of Medical Sciences, Tabriz, IranMohammadreza NasirzadehDepartment of Physiology, Tabriz Branch, Islamic Azad University, Tabriz, IranHadi YousefiDepartment of Physiology, Tabriz University of Medical Sciences, Tabriz, IranMohammadrasoul HabibiTabriz University of Medical Sciences, Tabriz, IranNasser AhmadiaslDrug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, IranJournal Article20161108<strong><em>Objective(s)</em></strong>: Menopause and diabetes obviously increase the risk of cardiovascular disease in women. The aims of the present study were to evaluate the effects of ovariectomy in type 2 diabetes on the histology and expression of miRNA-29, miRNA-133, IGF-1 and Bcl-2 genes and Bcl-2 protein and caspase 3 activity in the hearts of female rats.
<strong><em>Materials and Methods: </em></strong>Forty Female Wistar rats were divided into four groups: control, sham, ovariectomized (OVX), and ovariectomized with type 2 diabetes (OVX.D). After the 8-week experiment, the histological evaluation of the heart tissue was performed using H&E staining and PAS analysis, and cardiac expression of miRNA-29, miRNA-133, IGF-1, and Bcl-2 were evaluated using real-time PCR, and Bcl-2 protein and caspase 3 activity were evaluated using Western blot and ELISA.
<strong><em>Results:</em></strong> Ovariectomy significantly decreased miRNA-29, miRNA-133, IGF-1, and BCL-2 expression and Bcl-2 protein and increased caspase 3 activity in the heart compared to sham animals group (<em>P</em><0.05). Type 2 diabetes in ovariectomized rats markedly decreased expression of miRNA-29, miRNA-133, IGF-1, BCL-2 genes, and Bcl-2 protein, and increased caspase 3 activity and reduced collagen and fibroblast tissue and glycogen granule deposition in relation to OVX group (<em>P</em><0.05).
<strong><em>Conclusion:</em></strong> Our findings suggest that type 2 diabetes and menopause synergically could enhance the cardiac fibrosis through dysregulation of miRNA-29, miRNA-133, IGF-1, and Bcl-2 genes expression and Bcl-2 protein and upregulation of caspase 3 activity.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866191120161101Sertoli cell condition medium can induce germ like cells from bone marrow derived mesenchymal stem cells11861192781810.22038/ijbms.2016.7818ENMahdieh Hajian MonfaredDepartment of Anatomical Sciences, School of Medicine, Tehran University of Medical Science, Tehran, IranBagher MinaeeDepartment of Anatomical Sciences, School of Medicine, Tehran University of Medical Science, Tehran, IranTayebeh RastegarDepartment of Anatomical Sciences, School of Medicine, Tehran University of Medical Science, Tehran, IranEbrahim KhrazinejadDepartment of Anatomical Sciences, School of Medicine, Tehran University of Medical Science, Tehran, IranMohammad BarbarestaniDepartment of Anatomical Sciences, School of Medicine, Tehran University of Medical Science, Tehran, IranJournal Article20161108<strong><em>Objective(s)</em></strong>: Although many researchers have confirmed induction of germ cells from bone marrow mesenchymal stem cells (BMMSCs), there are no reports that confirm spontaneous differentiation of germ cells from BMMSCs. In this study, we have evaluated the effect of adult Sertoli cell condition medium (SCCM) as a mutative factor in the induction of germ cells from BMMSCs.
<strong><em>Materials and Methods: </em></strong>BMMSCs were collected from the bone marrow of 6-8-week old NMRI mice and their mesenchymal entities were proven using superficial markers (expression of CD44 and CD73 and non-expresion of CD45 and CD11b) by fow cytometry. Their multi-potential entities were proved with differentiation to osteogenic and adipogenic cells for 21 days. Also isolated Sertoli cells were enriched using lectin coated plates and Sertoli cell condition medium (SCCM) was collected. Sertoli cells were identified by immunocytochemistry and Vimentin marker. The cells were then differentiated into germ cells with SCCM for 2 weeks. Finally induced cells were evaluated by RT-PCR and immunocytochemistry.
<strong><em>Results:</em></strong> Differentiation of mesenchymal stem cells to osteoblast and adipocyte showed their multi-potential property. Expression of CD44 and CD73 and non-expression of CD45 and CD11b confirmed mesenchyme cells. Immunocytochemistry and RT-PCR results showed expression of germ cells specific marker (Mvh).
<strong><em>Conclusion:</em></strong> This study confirmed the effect of SCCM as a motivational factor that can used for differentiation of germ cells from BMMSCs.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866191120161101Synergistic effect of Thymbra spicata L. extracts with antibiotics against multidrug- resistant Staphylococcus aureus and Klebsiella pneumoniae strains11931200781910.22038/ijbms.2016.7819ENMohammad F HarounFaculty of Pharmacy, Al Andalus University for Medical Sciences, SyriaRawaa S Al-KayaliFaculty of Pharmacy, Aleppo University, SyriaPublic Health Department, Center for Strategic Studies and Research, Aleppo University, SyriaJournal Article20161108<strong><em>Objective(s)</em></strong>: To evaluate the <em>i</em><em>n vitro</em> interaction between different extracts of <em>Thymbra spicata </em>L. and certain antimicrobial drugs of different mechanisms, including ampicillin, cefotaxime, amikacin and ciprofloxacin. This study was performed against multidrug-resistant strains of <em>Staphylococcus aureus</em> and <em>Klebsiella</em> <em>pneumoniae.</em>
<strong><em>Materials and Methods: </em></strong>Evaluation of antibacterial activity and synergy interaction between plant extracts and antimicrobial agents was carried out using checkerboard microdilution.
<strong><em>Results:</em></strong> Different interactions (synergistic, additive and indifference) were observed between plant crude extracts and used antibiotics depending on the strain. The fractional inhibitory concentration (FIC) index ranged from 0.02 to 1.5 for <em>S. aureus</em> and 0.25 to 2 for <em>K. pneumoniae</em> strains. The best synergistic capacity appeared with cefotaxime against <em>S. aureus</em> strains, where the activity of cefotaxime was increased from 8- to 128-fold.
<strong><em>Conclusion:</em></strong> These results may indicate that <em>T. spicata</em> extracts potentiates the antimicrobial action of antibiotics, suggesting a possible utilization of this herb in combination therapy against emerging multidrug-resistance <em>S. aureus</em> and <em>K. pneumoniae</em><em>.</em>Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866191120161101Preparation and characterization of a novel nanobody against T-cell immunoglobulin and mucin-3 (TIM-3)12011208782010.22038/ijbms.2016.7820ENVida HomayouniImmunology Department, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, IranMazdak Ganjalikhani-hakemiImmunology Department, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran0000-0002-4764-7616Abbas RezaeiImmunology Department, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, IranHossein KhanahmadGenetic Department, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran0000-0002-5573-3557Mahdi BehdaniBiotechnology Research Center, Biotechnology Department, Venom & Bio-therapeutics Molecules Lab, Pasteur Institute of Iran, Tehran, Iran0000-0002-4839-5123Fatemeh Kazemi LomedashtBiotechnology Research Center, Biotechnology Department, Venom & Bio-therapeutics Molecules Lab, Pasteur Institute of Iran, Tehran, IranJournal Article20161108<strong><em>Objective(s):</em></strong> As T-cell immunoglobulin and mucin domain 3 (TIM-3) is an immune regulatory molecule; its blocking or stimulating could alter the pattern of immune response towards a desired condition. Based on the unique features of nanobodies, we aimed to construct an anti-TIM-3 nanobody as an appropriate tool for manipulating immune responses for future therapeutic purposes.<br /> <strong><em>Materials and Methods:</em></strong>We immunized a camel with TIM-3 antigen and then, synthesized a VHH pha<strong>ge</strong>mid library from its B cell’s transcriptome using nested PCR. Library selection against TIM-3antigen was performed in three rounds of panning. Using phage-ELISA, the most reactive colonies were selected for sub-cloning in soluble protein expression vectors. The Nanobody was purified and confirmed with a nickel-nitrilotriacetic acid (Ni-NTA) column, SDS-PAGE and Western blotting. A flowcytometric analysis was performed to analyze the binding and biologic activities of theTIM-3 specific nanobody with TIM-3 expressing HL-60 and HEK cell lines.<br /> <strong><em>Results:</em></strong>Specific 15kD band representing for nanobody was observed on the gel and confirmed with Western blotting. The nanobody showed significant specific immune-reactivity against TIM-3 with a relatively high binding affinity. The nanobody significantly suppressed the proliferation of TIM-3 expressing HL-60 cell line.<br /> <strong><em>Conclusion: </em></strong>Finally, we successfully prepared a functional anti-humanTIM-3 specific nanobody with a high affinity and an anti-proliferative activity on an AML cell line <em>in vitro</em>.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866191120161101Movento influences development of granulosa cells and ovarian follicles and FoxO1 and Vnn1 gene expression in BALB/c mice12091215782110.22038/ijbms.2016.7821ENSakineh Kaboli KafshgiriDepartment of Biology, Science and Research Branch, Islamic Azad University, Tehran, IranKazem ParivarDepartment of Biology, Science and Research Branch, Islamic Azad University, Tehran, IranJavad BahararaDepartment of Biology, Research Center for Applied Biology, Mashhad Branch, Islamic Azad University, Mashhad, IranMohammad Amin KerachianMedical Genetics Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranNasim Hayati RoodbariDepartment of Biology, Science and Research Branch, Islamic Azad University, Tehran, IranJournal Article20161108<strong><em>Objective(s)</em></strong>: Pesticides has wide range of infertility in female reproductive. This study was done to evaluate the effect of movento pesticide on development of granulosa cells and ovarian follicles and FoxO1 and Vnn1 gene expression in BALB/c mice.
<strong><em>Materials and Methods: </em></strong>In this study 40 healthy BALB/c mice 5-6 weeks age were used. Animals were randomly allocated into four groups. Control (without any intervention), three experimental groups received 25, 50 and 100 mg/kg movento dissolved in PBS by gavage for 21 days. Animals scarified after three weeks. For determining the effects of movento on granulosa cells in culture, treatments were conducted to movento (125, 250, 500 μg/ml) for 24 hr. We surveyed the expression of the FoxO1 and Vnn1 in granulosa cells <em>in vitro</em>, and its relation to cell death by flowcytometer and DAPI. Levels of FoxO1 and Vnn1 were analyzed by real-time PCR.
<strong><em>Results:</em></strong> Exposure to movento significantly decreased ovarian weight and the number of primary, secondary and antral follicles. Further, treatment with different concentration of movento induced apoptosis on granulosa cells. Gene expression analysis showed the transcriptional expression of FoxO1 and vnn1 in granulosa cells. Level of Vnn1 mRNA in granulosa cells was decreased in granulosa cells and expression of FoxO1 significantly increased in treated groups in compare to controls (<em>P</em>-value <0.05).
<strong><em>Conclusion:</em></strong> Exposure to movento significantly reduced the number of follicles and increased apoptosis of granulosa cells leading disruption of the reproductive system. Also movento reduced expression of Vnn1 and increased FoxO1 genes in a dose dependent manner.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866191120161101The preventive and therapeutic roles of phytoestrogen α-Zearalanol on osteoporetic rats due to ovariectomization12161221782210.22038/ijbms.2016.7822ENShaochun LiSchool of Basic Medical Sciences, Hebei University, Baoding 071002, ChinaXiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, ChinaWeiwei ZhangSchool of Basic Medical Sciences, Hebei University, Baoding 071002, ChinaFei DuanSchool of Basic Medical Sciences, Hebei University, Baoding 071002, ChinaWeihua LiuSchool of Basic Medical Sciences, Hebei University, Baoding 071002, ChinaXiaofang SunSchool of Basic Medical Sciences, Hebei University, Baoding 071002, ChinaXuefeng PanSchool of Basic Medical Sciences, Hebei University, Baoding 071002, ChinaSchool of Life Science, Beijing Institute of Technology, Beijing 10081, ChinaJournal Article20161108<strong><em>Objective(s):</em></strong> The aim of this study was to observe the influence of phytoestrogen α-Zearalanol on ovariectomy-induced postmenopausal osteoporosis in rats.
<strong><em>Materials and Methods</em></strong><em>:</em>40 SD female rats were randomly divided into four groups: Sham group, OVX group (ovariectomized and fed estrogen), α-Zearalanol group (ovariectomized and fed α-Zearalanol) and untreated group (ovariectomized). Three weeks later after surgery, α-Zearalanol and estradiol valerate were administered by oral gavage for 12 weeks to the α-Zearalanol group and the OVX group, respectively. In contrast, the sham and untreated controls were treated with distilled water in a daily basis. After the treatments, uterus histomorphometry, bone mechanical strength, bone histomorphometry, bone mineral density (BMD) of femur, and serum biochemical indicators, such as serum E<sub>2</sub>, CT and PTH, as well as the levels of TNF and IL-1 were examined.
<strong><em>Results</em>:</strong> The BMD was overall declined rigorously in the OVX rats, and that could be mitigated through feeding on either estrogen or α-Zearalanol. Estrogen or α-Zearalanol was found to decrease the levels of serum ALP and BGP in OVX rats, while, α-Zearalanol was found to increase the levels of serum E<sub>2</sub> and CT, the thickness of the endometrium, and decrease the levels of PTH, TNF and IL-1 in serum in OVX rats. Feeding the OVX rats on α-Zearalanol improved the bone histomorphometric parameters impaired due to estrogen deficiency and enhanced the bone mechanical properties in the ovariectomized rats.
<strong><em>Conclusion:</em></strong> α-Zearalanol treated rats reduced the resorption of bone, and showed a preventive and therapeutic effect of α-Zearalanol on postmenopausal osteoporosis.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866191120161101Minocycline attenuates cirrhotic cardiomyopathy and portal hypertension in a rat model: Possible involvement of nitric oxide pathway12221230782310.22038/ijbms.2016.7823ENSeyyedeh Elaheh MousaviDepartment of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, IranDepartment of Toxicology–Pharmacology, Faculty of Pharmacy, Pharmaceutical Science Branch, Islamic Azad University (IAUPS), Tehran, IranSeyed Mahdi RezayatDepartment of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, IranDepartment of Toxicology–Pharmacology, Faculty of Pharmacy, Pharmaceutical Science Branch, Islamic Azad University (IAUPS), Tehran, IranMaliheh NobakhtDepartment of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, IranSeyed Soheil Saeedi SaraviDepartment of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, IranDepartment of Toxicology-Pharmacology, Faculty of Pharmacy, Guilan University of Medical Sciences, Rasht, IranIraj YazdaniExperimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, IranDepartment of Pharmacology, School of Medicine, International Campous, Tehran University of Medical Sciences, Tehran, IranAmir RashidianDepartment of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, IranExperimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, IranAhmad Reza DehpourDepartment of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, IranExperimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, IranJournal Article20161108<strong><em>Objective(s)</em></strong><strong>: </strong>An increase in nitric oxide (NO) production has been reported in cirrhotic cardiomyopathy and, portal hypertension. Since minocycline has been shown to inhibit NO overproduction, we aimed to examine its role in a rat model of CCl<sub>4</sub>-induced cirrhotic cardiovascular complications.
<strong><em>Materials and Methods: </em></strong>Portal pressure and inotropic responsiveness of isolated papillary muscles to isoproterenol were measured in cirrhotic rats, following minocycline (50 mg/kg/day for 8 weeks) treatment. Moreover, isolated papillary muscles were incubated with nonselective and selective nitric oxide synthase (NOS) inhibitors, N (ω)-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine (AG) respectively, in an organ bath. Ventricular expression and localization of inducible NOS (iNOS), tumor necrosis factor-alpha (TNF-α) and serum nitrite concentration were evaluated.
<strong><em>Results:</em></strong> We found a decreased portal hypertension in minocycline-treated cirrhotic rats. Cirrhosis decreased contractility in response to isoproterenol stimulation, which was significantly attenuated by minocycline. Incubation with either L-NAME or AG reversed the impaired contractility in cirrhotic rats. Furthermore, minocycline decreased iNOS expression and localization in cardiomyocytes. A drop in serum nitrite and cardiac TNF-α level were also observed in cirrhotic rat that were treated by minocycline.
<strong><em>Conclusion:</em></strong> The results suggest that minocycline may improve impaired cardiac contractility and hyperdynamic state in cirrhotic rats, and this effect could be mediated by NO-dependent mechanism.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866191120161101Antifungal activity of Zataria multiflora essential oil-loaded solid lipid nanoparticles in-vitro condition12311237782410.22038/ijbms.2016.7824ENMahboobeh NasseriDepartment of Horticulture Science, Faculty of Agriculture, Ferdowsi University of Mashhad, Iran0000-0002-3180-5341Shiva GolmohammadzadehNanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IranHossein ArouieeDepartment of Horticulture Science, Faculty of Agriculture, Ferdowsi University of Mashhad, IranMahmoud Reza JaafariBiotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran0000-0003-3908-6828Hossein NeamatiDepartment of Horticulture Science, Faculty of Agriculture, Ferdowsi University of Mashhad, IranJournal Article20161108<strong><em>Objective(s):</em></strong> The aim of the present study was to prepare, characterize, and evaluate solid lipid nanoparticles (SLNs) containing <em>Zataria multiflora</em> essential oil (ZEO).<br /> <strong><em>Materials and Methods:</em></strong> In this study, <em>Z. multiflora </em>essential oil-loaded solid lipid nanoparticles (ZE-SLNs) were prepared to improve its efficiency in controlling some fungal pathogens<em>.</em> SLNs containing <em>Z. multiflora </em>essential oil were prepared by high shear homogenization and ultra sound technique. ZEO-SLNs contained 0.03% ZEO in 5% of lipid phase (Glyceryl monostearate-GMS and Precirol<sup>®</sup> ATO 5).Tween 80 and Poloxamer 188 (2.5% w/v) were used as surfactant in the aqueous phase. The antifungal efficacy of ZE-SLNs and ZEO was compared under <em>in vitro</em> conditions.<br /> <strong><em>Results:</em></strong>The particle size of ZE-SLNs was around 255.5±3 nm with PDI of 0.369±0.05 and zeta potential was about -37.8±0.8 mV. Encapsulation efficacy of ZE-SLNs in crystalline form was 84±0.92%. The results showed that the ZEO and ZE-SLNs had 54 and 79% inhibition on the growth of fungal pathogens, respectively. The minimum inhibitory concentration (MIC) under <em>in vitro</em> conditions for the ZEO on the fungal pathogens of <em>Aspergillus ochraceus, Aspergillus niger, Aspergillus flavus, Alternaria solani, Rhizoctonia solani, </em>and<em> Rhizopus stolonifer</em> was 300, 200, 300, 200, 200 and 200 ppm, respectively, for ZE-SLNs, it was 200, 200, 200, 100, 50 and 50 ppm. The antifungal efficacy of ZE-SLNs was significantly more than ZEO.<br /> <strong><em>Conclusion:</em></strong> Our results showed that the SLNs were suitable carriers for <em>Z. multiflora</em> essential oil in controlling the fungal pathogens and merits further investigation.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866191120161101Gene therapy based on interleukin-12 loaded chitosan nanoparticles in a mouse model of fibrosarcoma12381244782510.22038/ijbms.2016.7825ENSaiedeh Razi SoofiyaniImmonuology Research Center, Tabriz University of Medical Sciences, Tabriz, IranSomayeh Hallaj-NezhadiFaculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, IranDrug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, IranFarzaneh LotfipourFaculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, IranDrug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, IranAkbar Mohammad HosseiniImmonuology Research Center, Tabriz University of Medical Sciences, Tabriz, IranBehzad BaradaranImmonuology Research Center, Tabriz University of Medical Sciences, Tabriz, IranJournal Article20161108<strong><em>Objective(s)</em></strong>: Interleukin-12 (IL-12) as a cytokine has been proved to have a critical role in stimulating the immune system and has been used as immunotherapeutic agents in cancer gene therapy. Chitosan as a polymer, with high ability of binding to nucleic acids is a good candidate for gene delivery since it is biodegradable, biocompatible and non-allergenic polysaccharide. The objective of the present study was to investigate the effects of cells transfected with IL-12 loaded chitosan nanoparticles on the regression of fibrosarcoma tumor cells (WEHI-164) <em>in vivo</em>.
<strong><em>Materials and Methods: </em></strong>WEHI-164 tumor cells were transfected with IL-12 loaded chitosan nanoparticles and then were injected subcutaneously to inoculate tumor in BALB/c mice. Tumor volumes were determined and subsequently extracted after mice sacrifice. The immunohistochemistry staining was performed for analysis of Ki-67 expression (a tumor proliferation marker) in tumor masses. The expression of IL-12 and IFN-γ were studied using real-time polymerase chain reaction and immunoblotting.
<strong><em>Results:</em></strong> The group treated with IL-12 loaded chitosan nanoparticles indicated decreasing of tumor mass volume (<em>P</em><0.001). The results of western blotting and real-time PCR showed that the IL-12 expression was increased in the group. Immunohistochemistry staining indicated that the Ki-67expression was reduced in the group treated with IL-12 loaded chitosan nanoparticles.
<strong><em>Conclusion:</em></strong> IL-12 gene therapy using chitosan nanoparticles has therapeutic effects on the regression of tumor masses in fibrosarcoma mouse model.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866191120161101Ginkgetin induces apoptosis in 786-O cell line via suppression of JAK2-STAT3 pathway12451250782610.22038/ijbms.2016.7826ENYu RenLaboratory of kidney Carcinoma, Ningbo Urology and Nephrology Hospital, Urology and Nephrology Institute of Ningbo University, Ningbo 315000, Zhejiang Province, P.R. ChinaShuang-shuang HuangLaboratory of kidney Carcinoma, Ningbo Urology and Nephrology Hospital, Urology and Nephrology Institute of Ningbo University, Ningbo 315000, Zhejiang Province, P.R. ChinaXue WangLaboratory of kidney Carcinoma, Ningbo Urology and Nephrology Hospital, Urology and Nephrology Institute of Ningbo University, Ningbo 315000, Zhejiang Province, P.R. ChinaZhong-guan LouLaboratory of kidney Carcinoma, Ningbo Urology and Nephrology Hospital, Urology and Nephrology Institute of Ningbo University, Ningbo 315000, Zhejiang Province, P.R. ChinaXu-ping YaoLaboratory of kidney Carcinoma, Ningbo Urology and Nephrology Hospital, Urology and Nephrology Institute of Ningbo University, Ningbo 315000, Zhejiang Province, P.R. ChinaGuo-bin WengLaboratory of kidney Carcinoma, Ningbo Urology and Nephrology Hospital, Urology and Nephrology Institute of Ningbo University, Ningbo 315000, Zhejiang Province, P.R. ChinaJournal Article20161108<strong><em>Objective(s)</em></strong>: Renal cell carcinoma (RCC) is insensitive to conventional chemotherapy. Ginkgetin effectively treats several carcinoma cells. However, little is known about effects of Ginkgetin on RCC. In the present study, using 786-O cells, we evaluate whether Ginkgetin exerts anticancer effects against RCC.
<strong><em>Materials and Methods: </em></strong>786-O cells suspended in the medium containing Ginkgetin were cultured for 24 hr to 72 hr, and then MTT assay was used to study cytotoxic effect of Ginkgetin. Apoptosis in 786-O was measured by an FITC Annexin apoptosis detection kit. Protein expression was detected by Western blotting. 786-O cells with active Janus kinase 2 (JAK2)-Signal transducer and activator of transcription 3 (STAT3) were prepared by stimulant of interleukin-6 (IL-6), whereas 786-O cells with deactivated STAT3 were produced by small interfering RNA (siRNA) STAT3.
<strong><em>Results:</em></strong> Ginkgetin suppressed the growth of 786-O in dose and time-dependent manners with IC<sub>50</sub> values of 7.23 μM. Ginkgetin induced apoptosis of 786-O cells and increased the levels of caspase-8, caspase-9, and caspase-3. Additionally, Ginkgetin treated 786-O cells showed decreased levels of JAK2 and phosphorylated-STAT3 whether or not IL-6 was pretreated. Interestingly, pretreatment of siRNA STAT3 exerted inhibitory effects on the growth of 786-O cells, and the observation could be further reinforced after the Ginkgetin treatment.
<strong><em>Conclusion:</em></strong> Our results indicate Ginkgetin possesses obvious inhibitory effects on the proliferation of 786-O, and this effect is probably due to its inhibition of JAK2/STAT3 pathway. Our findings imply Ginkgetin is a potential therapeutic medicine for RCC.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866191120161101Protective effects of nimodipine and lithium against aluminum-induced cell death and oxidative stress in PC12 cells12511257782710.22038/ijbms.2016.7827ENJamileh SaberzadehDiagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, IranMehdi OmraniFaculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, IranMohammad Ali TakhshidDiagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran0000-0003-0246-3765Journal Article20161108<strong><em>Objective(s)</em></strong>: The role of aluminum (Al) in the pathogenesis of neurodegenerative diseases has been implicated in several studies. However, the exact mechanisms of cytotoxic effects of Al have not been elucidated yet. The aim of this study was to investigate the effect of L-type calcium channel antagonist, nimodipine (NM), and lithium chloride (LiCl) on Al-induced toxicity in PC12 cells.<br /> <strong><em>Materials and Methods: </em></strong>PC12 cells were treated with Al-maltolate (Almal) in the presence and absence of different concentrations of NM (50-150 μm) and/or LiCl (0.5-1.0 mm) for 48 hr. Cell viability, apoptosis, and catalase (CAT) activity, a marker of oxidative stress, were then measured using MTT, flow cytometry and enzyme assay, respectively.<br /> <strong><em>Results:</em></strong> The results showed that Almal, dose dependently induced cell death, apoptosis and CAT activity in the PC12 cells. NM significantly increased cell viability and decreased apoptosis and CAT activity of Almal-treated cells in a dose dependent mode. LiCl reduced CAT activity and increased cell viability in Almal-treated cells, without significant effect on apoptosis (<em>P</em>=0.74).<br /> <strong><em>Conclusion:</em></strong> These findings suggest that NM and Li may have benefits in the prevention of Al-induced cytotoxicity through decreasing oxidative stress.