فهرست مطالب

Basic Medical Sciences - Volume:20 Issue: 9, Sep 2017

Iranian Journal of Basic Medical Sciences
Volume:20 Issue: 9, Sep 2017

  • تاریخ انتشار: 1396/06/19
  • تعداد عناوین: 15
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  • Mahshid Naghashpour, Sima Jafarirad, Reza Amani *, Alireza Sarkaki, Ahmad Saedisomeolia Pages 958-966
    Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Riboflavin plays an important role in myelin formation, and its deficiency is implicated as a risk factor for multiple sclerosis. Here, we systematically reviewed the literature concerning the health benefits of riboflavin on MS. The literature recorded within four main databases, including relevant clinical trials, experimental, and case-control studies from 1976 to 2017 were considered. Both human and animal studies were included for review, with no restrictions on age, gender, or ethnicity. Experimental studies demonstrated that riboflavin deficiency triggers neurologic abnormalities related to peripheral neuropathies such as demyelinating neuropathy. Moreover, randomized controlled trials (RCT) and case-control studies in which MS patients received riboflavin supplementation or had higher dietary riboflavin intake showed improvements in neurological motor disability. Riboflavin is a cofactor of xanthine oxidase and its deficiency exacerbates low uric acid caused by high copper levels, leading to myelin degeneration. The vitamin additionally plays a significant role in the normal functioning of glutathione reductase (GR) as an antioxidant enzyme, and conditions of riboflavin deficiency lead to oxidative damage. Riboflavin promotes the gene and protein levels of brain-derived neurotrophic factor (BDNF) in the CNS of an animal model of MS, suggesting that BDNF mediates the beneficial effect of riboflavin on neurological motor disability. Research to date generally supports the role of riboflavin in MS outcomes. However, further observational and interventional studies on human populations are warranted to validate the effects of riboflavin.
    Keywords: Brain-derived neurotrophic factor, Demyelinating disease, Multiple sclerosis, Riboflavin, Riboflavin deficiency
  • Kehinde Adebayo Babatunde, Ali Najafi, Pouya Salehipour, Mohammad Hossein Modarressi, Maryam Beigom Mobasheri * Pages 967-974
    Cancer testis antigens (CTAs), a large family of tumor-associated and immunogenic antigens expressed in human tumors of various histological origins, are highly restricted to the testis and trophoblast. CTAs have been identified as potent targets for tumor-specific immunotherapeutic advances and have immensely lead to the development of different clinical trials of CTA-based vaccine therapy because of their resilient in vivo immunogenicity and tumor-restricted expression pattern. Bladder cancer, non-small cell lung carcinoma, and melanoma are grouped as high CT gene expressors. Prostate and breast cancer as moderate, and colon and renal cancers are considered as low CT gene expressors. Large percentages of these identified CT genes are expressed during spermatogenesis but their function is still vaguely unknown. Researchers have taken a keen interest in CT genes as pertaining to their role in tumor growth and spermatogenesis. Testis has many similarities with cancerous tissues like cell division, immigration, and immortalization. The aim is to give a concise in-depth review on the role of some specific CT genes in spermatogenesis.
    Keywords: Cancer testis genes, Carcinogenesis, Spermatogenesis, Sperm biology, Sperm genes functions, Testis genes
  • Parvin Asadi, Ghadamali Khodarahmi *, Ali Jahanian-Najafabadi, Lotfollah Saghaie, Farshid Hassanzadeh Pages 975-989
    Objective(s)
    Hybridization of bioactive natural and synthetic compounds is one of the most promising novel approaches for the design of hit and lead compounds with new molecular structures. In this investigation, a series of novel hybrid structures bearing quinazolinone, benzofuran and imidazolium moieties were designed and synthesized.
    Materials And Methods
    Novel hybrid compounds were prepared and their structures were characterized by spectral and analytical data. In order to evaluate the biological activities, the synthesized hybrid compounds were studied for in vitro antibacterial activity against three Gram positive bacteria (Staphylococcus aureu, Bacillus subtilis, Listeria monocitogenes) and three Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Salmonella entritidis) and also, Candida albicans as one yeast-like fungi strain. Cytotoxic activities of the synthesized compounds were also evaluated by the MTT assay in the human breast cancer cell line (MCF-7) and finally docking studies of cytotoxic derivatives were performed on aromatase enzyme.
    Results
    The results of antimicrobial activity showed that compound 14e, with two halogen atoms on quinazolinone and benzofuran was the most active against all the tested strains of microorganisms with the MIC value 16-128 µg/ml. Some of the tested compounds showed good cytotoxicity on MCF-7, and compound 14c with IC50=0.59 micromolar (μM) was found to be the most cytotoxic compound among the studied hybrid derivatives. The docking analysis showed acceptable binding interactions for these compounds.
    Conclusion
    Based on the obtained results, the hybrid derivatives of quinazolinone, benzofuran and imidazolium could be regarded as efficient candidates for further molecular developments of anticancer and antimicrobial agents.
    Keywords: Antibacterial, Benzofuran, Cytotoxic, Imidazolium salt, QM, MM Docking, Quinazolinone
  • Wu Lu, He Ke, Ding Qianshan, Wang Zhen, Xiang Guoan, Yu Honggang * Pages 990-995
    Objective(s)
    Apatinib recently has been used to treat patients with gastric cancer, but the function of apatinib in colon cancer remains unclear. This study was conducted to investigate the impacts of apatinib on the biological function and its potential mechanism of colon cancer cells in vitro.
    Materials And Methods
    The effect of apatinib in colon cancer cells were detected by assessing cell viability, migration and invasion capabilities. Apoptosis cells and the cell cycle distribution of colon cancer cells were analyzed by flow cytometry. The potential mechanism was investigated via autophagy related proteins and pathways in vitro.
    Results
    The proliferation, migration and invasion of colon cancer cells were inhibited when they were treated with different concentration of apatinib (20, 40 μM). When HCT116 and SW480 cells were treated with apatinib at the concentration of 20 μM, the apoptosis percentage were 3.7% and 5.8% respectively. As the drug concentration increased to 40μΜ, the the apoptosis percentage increased to 11.9% and 13.5%. Meanwhile, cell cycle was also altered. Furthermore, apatinib inhibited the expression of AKT-mTOR signaling pathway and increased the expression of LC3-Ⅱ.
    Conclusion
    Apatinib can significantly inhibit the malignant phenotype of colon cancer cells, and it was involved in regulation of autophagy.
    Keywords: Apatinib, Apoptosis, Autophagy, Colon cancer, Migration, mTOR
  • Masoud Naseri, Abbas Parham, Ali Moghimi Pages 996-1001
    Objective(s)
    Development of the nervous system in human and most animals is continued after the birth. Critical role of this period in generation and specialization of the neuronal circuits is confirmed in numerous studies. Any pharmacological intervention in this period may result in structural, functional or behavioral abnormalities. In this study, sodium thiopental a GABA mimetic drug was administrated to newborn rats and their GAD65 and GAD67 expression in hippocampus was evaluated before and after puberty.
    Materials And Methods
    Newborn male Wistar rats were received sodium thiopental (35 mg/kg) daily for 11 days (from 4 to 14 days after birth). Expression of GAD65 and GAD67 in their hippocampus was compared with control groups in 15 and 45 days after birth with RT-qPCR method.
    Results
    Significant down regulation of GAD65 and GAD67 gene expression was observed in treated rats compared with control group in 45 days after birth animals. But no significant difference was shown between experimental and control groups 15 days after birth animals.
    Conclusion
    The effect of sodium thiopental on GAD65 and GAD67 expression only at adult rats showed a latent period of influence which can be attributed to dosage or intension of sodium thiopental neurotoxicity. Significant down regulation of GAD65 and GAD67 showed unwanted effect of sodium thiopental as GABA mimetic drug in critical period of development.
    Keywords: Gamma aminobutyric acid, Glutamate decarboxylase 1, Glutamate decarboxylase 2, Real-time polymerase chain reaction, Thiopental
  • Dunling Xia, Hong Zhang * Pages 1002-1008
    Objective(s)
    The aim of this study was to investigate the effects of mild hypothermia on expression of NF-E2-related factor 2 (Nrf2) and heme-oxygenase-1 (HO-1) of rat cerebral cortex and hippocampus after cardiopulmonary resuscitation and further investigate the possible mechanism of action.
    Material and
    Methods
    To copy an asphyxia heart arrest model, Sprague Dawley rats were randomly divided into normothermia group, mild hypothermia group before restoration of spontaneous circulation (ROSC), and mild hypothermia group after ROSC. Body temperature in normothermia group was maintained at 37.5-39℃, while in mild hypothermia group maintained at 32-34 °C by surface cooling with the ice pack. Each group then divided into three subgroups: 15 min, 30 min, and 60 min. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect the expression of Nrf2 and HO-1 mRNA in cerebral cortex and hippocampus. Hematoxylin-eosin (H&E) staining was performed to observe histological changes. Immunohistochemistry was performed to detect the expression of Nrf2 and HO-1 protein expression.
    Results
    The expression of Nrf2 and HO-1 in cerebral cortex and hippocampus after cardiopulmonary resuscitation (CPR) was significantly increased and mild hypothermia up regulated this level. HE staining showed that mild hypothermia significantly improved neuronal injury.
    Conclusion
    Mild hypothermia has neuroprotective effects on cerebral ischemia/reperfusion injury after cardiac arrest. The possible mechanism is that Nrf2-ARE pathway in cerebral cortex and hippocampus after CPR is activated.
    Keywords: Heart arrest, Heme-oxygenase-1, Mild hypothermia, Neuroprotection, NF-E2-related factor 2, Nrf2
  • Hadi Yousefi, Pouran Karimi, Alireza Alihemmati, Mohmmad Reza Alipour, Parisa Habibi, Nasser Ahmadiasl * Pages 1009-1015
    Objective(s)
    Genistein, as a phytoestrogen found in legumes, has several biological activities in general and anti-diabetic activity particularly. In this study, we investigated the effect of genistein on proteins involved in β-cell proliferation, survival and apoptosis to further reveal its anti-diabetic potential in the ovariectomized diabetic rat.
    Materials And Methods
    We used three-month-old female Wistar rats that either underwent ovariectomy (OVX) or received a sham surgery (Sham). In a subsequent series of experiments, OVX rats received high-fat diet and low dose STZ to induce diabetes (OVX.D) and genistein treatment (OVX.D.G). Western blot analysis was used for the assessment of phosphorylation of ERK1/2 and AKT and expression of Bcl-2 and caspase-3 in pancreas tissue. Hematoxylin-Eosin (H&E) staining was used for histopathological assessment.
    Results
    Genistein induced AKT and ERK1/2 phosphorylation protein expression of Bcl-2 in the pancreas. In addition, genistein suppressed protein level of caspase-3. Administration of genistein significantly improved hyperglycemia in ovariectomized diabetic rat, concomitant with improved islet β-cell morphology and mass.
    Conclusion
    These findings suggest that the beneficial antidiabetic effect of genistein partially mediated by directly modulating pancreatic β-cell function via activation of the AKT, ERK1/2, and Bcl-2, as cell survival and anti-apoptotic factors, and decreasing of proapoptotic caspase-3.
    Keywords: AKT-ERK, Bcl-2, Caspase-3, Diabetes, Genistein, Ovariectomy
  • Xiaoyan Xu, De Wu, Shu Hou, Jing Zhu, Jing Li, Jiulai Tang * Pages 1016-1020
    Objective(s)
    To evaluate whether prenatal exposure to TAK242 affects childhood autism in the offspring in animal models of autism spectrum disorder (ASD).
    Materials And Methods
    The pregnant rats were pseudo-randomly divided into three groups, the ASD model group, the TAK242 treatment group, and the control group. The ASD model was constructed by injecting IP with LPS. The blood samples from 1-month-old offspring were collected for cytokine evaluation and the social interaction test was used in the offspring of ASD rats. Rats were killed and the hippocampus, cerebral cortex, and cerebellum were used for the immunohistochemical study.
    Results
    As compared to the control, the levels of IFN-γ, IL-1β, IL-2, and IL-6 were significantly increased (P
    Conclusion
    Prenatal exposure to TAK242 affects serum cytokines levels and the social interaction time in rat offspring in animal models of ASD.
    Keywords: Autism spectrum disorder, Childhood autism in offspring, Serum cytokines, Social interaction time, TAK242, Wistar rat
  • Ehsan Saburi, Jalil Tavakolafshari, Yousef Mortazavi *, Alireza Biglari, Seyed Abbas Mirzaei, Samad Nadri Pages 1021-1028
    Objective(s)
    Extracellular matrix (ECM) is composed of many kinds of glycoproteins containing glycosaminoglycans (GAGs) moiety. The research was conducted based on the N-Acetylgalactosamine (GalNAc) degradation of ECM components by α-N-acetylgalactosaminidase (Nagalase) which facilitates migration and invasion of cancer cells. This study aims to investigate the effects of Naga-shRNA downregulation on migration and invasion of cancer cell lines.
    Materials And Methods
    In this study, MCF-7 cell line (human mammary carcinoma cell line) and A2780 (human ovarian carcinoma cell line) were used. The level of normalized Naga expression and Nagalase protein were evaluated by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay/western blotting, respectively. Migration and invasion were determined using transwell assays, and statistical analysis was carried out by ANOVA test.
    Results
    Response to transduction by shRNA compared to the control group, migrative and invasive properties of the transfected cells were significantly inhibited.
    Conclusion
    These results indicate that Nagalase may have an important role in migration and invasion of cancer cells and can be considered as a candidate for further studies.
    Keywords: Alpha-N-Acetylgalactosamini dase, Cancer, Extracellular matrix, Invasion, Migration, shRNA
  • Peng Yan, Liangjie Bai, Wei Lu, Yuzhong Gao, Yunlong Bi, Gang Lv * Pages 1029-1036
    Objective(s)
    AMP-activated protein kinase/sirtuin 1 (AMPK/SIRT1) signaling pathway has been proved to be involved in the regulation of autophagy in various models. The aim of this study was to evaluate the effect of AMPK/SIRT1 pathway on autophagy after spinal cord injury (SCI).
    Materials And Methods
    The SCI model was established in rats in vivo and the primary spinal cord neurons were subjected to mechanical injury (MI) in vitro. The apoptosis in spinal cord tissue and neurons was assessed by TUNEL staining and Hoechst 33342 staining, respectively. The autophagy-related proteins levels were detected by Western blot. The activation of AMPK/SIRT1 pathway was determined by Western blot and immunohistochemical staining.
    Results
    We found that the apoptosis of spinal cord tissue and cell damage of spinal cord neurons was obvious after the trauma. The ratio of LC3II/LC3I and level of p62 were first increased significantly and then decreased after the trauma in vivo and in vitro, indicating the defect in autophagy. The levels of p-AMPK and SIRT1 were increased obviously after the trauma in vivo and in vitro. Further activation of the AMPK/SIRT1 pathway by pretreatment with resveratrol, a confirmed activator of the AMPK/SIRT1 pathway, alleviated the cell damage and promoted the autophagy flux via downregulation of p62 in spinal cord neurons at 24 hr after MI.
    Conclusion
    Our results demonstrate that regulation of autophagy by AMPK/SIRT1 pathway can restrain spinal cord neurons damage, which may be a potential intervention of SCI.
    Keywords: AMPK-SIRT1 pathway, Autophagy flux, p62, Resveratrol, Spinal cord injury
  • Najmeh Ghatei, Ariane Sadr Nabavi, Mohammad Hossein Bahreyni Toosi *, Hosein Azimian, Mansour Homayoun, Reza Ghasemnezhad Targhi, Hossein Haghir Pages 1037-1041
    Objective(s)
    The increasing rate of over using cell phones has been considerable in youths and pregnant women. We examined the effect of mobile phones radiation on genes expression variation on cerebellum of BALB/c mice before and after of the birth.
    Materials And Methods
    In this study, amobile phone jammer, which is an instrument to prevent receiving signals between cellular phonesand base transceiver stations (two frequencies 900 and 1800 MHz) for exposure was used and twelve pregnant mice (BALB/c) divided into two groups (n=6), first group irradiated in pregnancy period (19th day), the second group did not irradiate in pregnancy period. After childbirth, offspring wereclassified into four groups (n=4):Group1: control, Group 2: B1 (Irradiated after birth), Group 3: B2 (Irradiated in pregnancy period and after birth), Group 4: B3 (Irradiated in pregnancy period). When maturity was completed (8-10 weeks old), mice were dissected and cerebellum was isolated. The expression level of bax, bcl-2, p21 and p53 genes examined by real-time reverse transcription polymerase chain reaction (Real-Time RT- PCR).
    Results
    The data showed that mobile phone radio waves were ineffective on the expression level of bcl-2 and p53 genes) P>0.05(. Also gene expression level of bax decreased and gene expression level of p21 increased comparing to the control group (P
    Conclusion
    From the obtained data it could be concluded that the mobile phone radiations did not induce apoptosis in cells of the cerebellum and the injured cells canbe repaired by cell cycle arrest.
    Keywords: Apoptosis, Cerebellum, Gene expression, Mobile phone, Mice
  • Jimei Bu, Hengbing Zu * Pages 1044-1049
    Objective(s)
    In previous studies, researchers observed that doxepin could improve cognitive processes and has protective effectson the central nervous system. Thus, this study was designed to analyze the effects of doxepin on β-amyloid (Aβ)-induced memory impairment and neuronal toxicity in ratand to explore the underlying mechanism.
    Materials And Methods
    Rats were treated with Aβ1-42 and doxepin was injected to validate its effects on cognitive function. The Morris water maze test was performed to detect memory function. Aβ1-42-treated SH-SY5Y human neuroblastoma cell line was also used to detect the effects of doxepin and to explore the underlying mechanism. Western blotting analysis was used to detect the protein expression levels of PSD-95, synapsin 1, p-AKT and p-mTOR in rats.
    Results
    After treated with 1 mg/kg of doxepin, Aβ1-42-treated rats showed markedly lower escape latency and higher platform-finding strategy score. Low doses of doxepin significantly reversed the effects of Aβ1-42 on the protein expression levels of PSD-95, synapsin 1, p-AKT and p-mTOR in rats. In vitro experiment showed the consistent results. Besides, PI3K inhibitor (LY294002) treatment could markedly reversed the effects of doxepin on Aβ1-42-treated SH-SY5Y cells.
    Conclusion
    Our results demonstrated that doxepin could protect against the Aβ1-42-induced memory impairment in rats. The protective effect of doxepin was associated with the enhancement of PSD-95 and synapsin 1 expression via PI3K/AKT/mTOR signaling pathway.
    Keywords: Alzheimer's disease, Doxepin, Memory injury, PI3-K-AKT-mTOR- signaling, ?-amyloid1-42
  • Ali Razei, Rahim Sorouri, Seyed Latif Mousavi, Shahram Nazarian, Jafar Amani, Hosien Aghamollaei Pages 1050-1055
    Objective(s)
    Listeria monocytogens, Bacillus cereus and Campylobacter jejuni are three toxin producing bacteria over the world, especially in Iran, and it is essential to find a certain, rapid procedure to identify these microorganisms. In this research, these bacteria were simultaneously detected by multiplex PCR technique in foods.
    Materials And Methods
    The primary approval of bacterial strains was performed by biochemical tests. PCR primers were designed based on the nucleotide sequences of the NHEB/NHEC gene of B. cereus, the hly gene of L. monocytogenes and the C gene of C. jejuni. The specificity of Multiplex PCR method was determined using seven food poisoning bacteria including Salmonella typhi, Shigella dysentery, Yersinia pestis, Staphylococcus aureus, Clostridium perfringens, Clostridium botulinum and Vibrio cholerae. To confirm the reaction, DNA extraction was performed from 30 food samples (milk), and gene amplification was performed by PCR. The length of amplified fragments was 300 bp, 210 bp and 160 bpfor NHEB/NHEC, hly and C genes, respectively.
    Results
    The detection limits of the PCR method were 5, 4 and 3 pg for L. monocytogenes, B. cereus and C. jejuni, respectively. Specifisity test showed that this reaction is spesific to these 3 bacteria.
    Conclusion
    In this study, we introduced a new multiplex PCR method for simultsnus detection of L. monocytogens, B. cereus and C. jejuni. These results can be used for detection of other toxin producing bacteria in food.
    Keywords: Bacillus cereus, Campylobacter jejuni, Hly, Listeria Monocytogenes, Multiplex PCR, NHEB-NHEC
  • Liu Chao, Pengyuan Zheng*, Liu Xia, Yu Yong, Gaofeng Lu, Fuai Tang, Zhiguo Zhao Pages 1056-1062
    Objective(s)
    Inflammatory bowel disease (IBD) results from dysregulation of intestinal mucosal immunity. It is an incurable disease that affects millions of people worldwide. Developing new strategies for the treatment of colitis has been a major challenge. Here, we report the effect of calycosin, a plant-derived flavonoid, in successfully managing colitis in murine model.
    Material and
    Methods
    In vivo model of colitis was induced using 2.5% (w/v) dextran sodium sulfate (DSS, 36,000 to 50,000 Mw). Body weight and disease activity index (DAI) were evaluated every day. Hematoxylin-Eosin (H&E) staining was used to estimate the effect of calycosin on DSS-induced colon damage. The levels of proinflammatory genes and mRNA expression were determined using real-time PCR, whereas the proinflammatory cytokines were assessed with ELISA. The content of other parameters including myeloperoxidase (MPO), glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA) were also evaluated. Western blot assay was further used to determine the effect of calycosin on both NF-κB and mitogen activated protein kinases (MAPK) pathways.
    Results
    The results showed that calycosin prevented weight loss and shortening of the colon length, maintained an intact mucosa, increased GSH and SOD activities, and decreased MDA levels. The drug also significantly inhibited proinflammatory cytokine mRNA expression and decreased MPO activity. Additionally, it remarkably inhibited NF-κB pathway and c-Jun N-terminal kinase (JNK) phosphorylation with no effect on p38 and extracellular signal-regulated kinase (ERK1/2) phosphorylation levels in colon tissue.
    Conclusion
    These findings revealed that calycosin successfully ameliorated the effect of DSS-induced colitis in mice, which could be associated with NF-κB and JNK pathway modulations.
    Keywords: Colitis, Calycosin, Free radical, Inflammatory cell, NF-κB, Signaling pathway
  • Saeid Abbasi-Maleki *, Zahra Mousavi Pages 1063-1073
    Objective(s)
    Studies indicate that major deficiency in the levels of monoaminergic transmitters is a reason for severe depression. On the other hand, it is shown that Carthamus tinctorius L. (CT) may improve neuropsychological injuries by regulation of the monoamine transporter action. Hence, the present study was undertaken to evaluate the involvement of monoaminergic systems in antidepressant-like effect of CT extract in the tail suspension test (TST) in mice.
    Materials And Methods
    The mice were intraperitoneally (IP) treated with CT extract (100–400 mg/kg) 1hr before the TST. To investigate the involvement of monoaminergic systems in antidepressant-like effect, the mice were treated with receptor antagonists 15 min before CT extract treatment (400 mg/kg, IP) and 1hr before the TST.
    Results
    Findings showed that CT extract (100–400 mg/kg, IP), dose-dependently induced antidepressant-like effect (P
    Conclusion
    Our findings firstly showed that components (especially N-Hexadecanoic acid) of CT extract induce antidepressant-like effects by interaction with dopaminergic (D1 and D2) and serotonergic (5HT1A, 5-HT2A receptors) systems. These findings validate the folk use of CT extract for the management of depression.
    Keywords: Antidepressant-like effect, Carthamus tinctorius L, Mice, Monoaminergic system, Tail suspension test