فهرست مطالب

Basic Medical Sciences - Volume:20 Issue: 2, Feb 2017

Iranian Journal of Basic Medical Sciences
Volume:20 Issue: 2, Feb 2017

  • تاریخ انتشار: 1395/11/27
  • تعداد عناوین: 16
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  • Maryam Esfahani, Nooshin Shabab, Massoud Saidijam* Pages 107-109
    Atherosclerosis has serious role in coronary arteries disease,so it is important to establish effective strategies for prevention or even treatment of atherosclerosis. Adiponectin, as one of the most abundant adipokines, has insulin sensitivity, anti-inflammatory and anti-atherogenic properties. Disturbed adiponectin actions through its receptor, (AdipoR1 and AdipoR2) may be involved in atherosclerosis development. Some adiponectin effects are mediated by AMPK and PPAR-α signaling. AdipoRon is an orally active synthetic molecule which can bind to AdipoR1, Adipo R2 and activate them. AdipoRon can activate AdipoR1-AMPK- PGC-1α pathway and AdipoR2-PPAR-α pathway. Some studies indicated insulin sensitivity, anti-apoptotic and anti-oxidative effect of AdipoRon. We hypothesize that AdipoRon has anti atherosclerotic effect and may suppress atherosclerosis processes. With confirmation the benefit role of AdipoRon on atherosclerosis, it may be used in patients at risk of atherosclerotic development.
    Keywords: Adiponectin, Adiponectin receptors, AdipoRon, Atherosclerosis, Cardiovascular disease
  • Hasan Badie Bostan, Soghra Mehri, Hossein Hosseinzadeh* Pages 110-121
    Saffron (Crocus sativus L.) has been considered as a medicinal plant since ancient times and also widely used as food additive for its color, taste and odor. The pharmacological properties of saffron and its main constituents, crocin and safranal have been evaluated using different in vivo and in vitro models. Additionally, other lines of studies have found toxicological effects of saffron. However, a comprehensive review that covers all aspects of its toxicity has not been published yet. The current study provides classified information about the toxic effects of saffron and its constituents in various exposure conditions including acute, sub-acute, sub-chronic and chronic studies. Therapeutic doses of saffron exhibits no significant toxicity in both clinical and experimental investigations.
    Keywords: Crocetin, Crocin, Saffron, Safranal, Toxicity
  • Ali Asghar Baghani, Saman Soleimanpour, Hadi Farsiani, Arman Mosavat, Masoud Yousefi, Zahra Meshkat, Seyed Abdolrahim Rezaee, Saeid Amel Jamehdar, Mohammad Reza Akbari Eydgahi, Hamid Sadeghian, Kiarash Ghazvini * Pages 122-130
    Objective(s)
    Despite treatment with antibiotics and vaccination with BCG, tuberculosis (TB) is still considered as one of the most important public health problems in the world. Therefore, designing and producing a more effective vaccine against TB seems urgently. In this study, immunogenicity of a fusion protein which consisting or comprising CFP-10 from Mycobacterium tuberculosis and the Fc-domain of mouse IgG2a was evaluated as a novel subunit vaccine candidate against TB.
    Materials And Methods
    The genetic constructs were cloned in pPICZαA expression vector and recombinant vectors (pPICZαA-CFP-10: Fcγ2a and pPICZαA-CFP-10:His) were transformed into Pichia pastoris. To evaluate the expression of recombinant proteins, SDS-PAGE and immunoblotting were used. The immunogenicity of recombinant proteins, with and without BCG were assessed in BALB/c mice and specific cytokines against recombinant proteins (IFN-γ, IL-12, IL-4, IL-17 and TGF-β) were evaluated.
    Results
    The levels of IFN-γ and IL-12 in mice that received recombinant proteins was higher than the control groups (BCG and PBS). Thus, both recombinant proteins (CFP-10:Fcγ2a and CFP-10:His) could excite good response in Th1-cells. The Fc-tagged protein had a stronger Th1 response with low levels of IL-4, as compared to CFP-10:His. However, the highest level of Th1 response was observed in groups that were vaccinated with BCG (prime) and then received recombinant protein CFP-10: Fcγ2a (booster).
    Conclusion
    The results demonstrated that binding mice Fc-domain to CFP-10 protein can increase the immunogenicity of the subunit vaccine. Further studies, might be able to design and produce a new generation of subunit vaccines based on the Fc-fused immunogen.
    Keywords: CFP-10, Fc?2a, Immunogenicity, Mycobacterium tuberculosis, Subunit vaccine
  • Xiao Peng Gao*, Dong Wei Qian, Zhen Xie, Hao Hui Pages 131-137
    Objective(s)
    Oxidative stress has been established as a key cause of alcohol-induced hepatotoxicity. Licochalcone B, an extract of licorice root, has shown antioxidative properties. This study was to investigate the effects and mechanisms of licochalcone B in ethanol-induced hepatic injury in an in vitro study.
    Materials And Methods
    An in vitro model of Ethanol-induced cytotoxicity in BRL cells was used in this study. Cell injury was assessed using WST-1 assay and lactate dehydrogenase, alanine transaminase, and aspartate aminotransferase release assay. Cell apoptosis were quantified by flow cytometric analysis. The intracellular oxidative level was evaluated by reactive oxidative species, malondialdehyde and glutathione detection. Furthermore, the expression level of Erk, p-Erk, Nrf-2 were assessed using Western blot.
    Results
    Treatment with ethanol induced marked cell injury and cell apoptosis in BRL cells. Licochalcone B significantly attenuated ethanol-induced cell injury, and inhibited cell apoptosis. Furthermore, licochalcone B significantly inhibited ethanol-induced intracellular oxidative level, upregulated the expression of p-Erk, and promoted nuclear localization of Nrf2. Additionally, this hepatoprotective role was significantly abolished by inhibition of Erk signaling. However, no apparent effects of Erk inhibition were observed on ethanol-induced hepatotoxicity.
    Conclusion
    This study demonstrates that licochalcone B protects hepatocyte from alcohol-induced cell injury, and this hepatoprotective role might be attributable to apoptosis reduction, inhibition of oxidative stress, and upregulation of Erk–Nrf2. Therefore, licochalcone B might possess potential as a novel therapeutic drug candidate for alcohol-related liver disorders.
    Keywords: Alcohol, BRL cells, Erk, Hepatotoxicity, Nrf, Oxidative Stress
  • Ameneh Ghadiri, Leila Etemad*, Mohammad Moshiri, Seyed Adel Moallem, Amir Hossein Jafarian, Farzin Hadizadeh, Mahmoud Seifi Pages 138-144
    Objective(s)
    The increasing use of methamphetamine (METH) in the last decades has made it the second most abused drug. Advancs in the area of intravenous lipid emulsion (ILE) have led to its potential application in the treatment of poisoning. The present study aims to investigate the potential role of ILE as an antidote for acute METH poisoning.
    Materials And Methods
    Two groups of six male rats were treated by METH (45 mg/kg), intraperitoneally. Five to seven min later, they received an infusion of 18.6 ml/kg ILE 20% through the tail vein or normal saline (NS). Locomotor and behavioral activity was assessed at different time after METH administration. Body temperature and survival rates were also evaluated. Brain and internal organs were then removed for histological examination and TUNEL assay.
    Results
    ILE therapy for METH poisoning in rats could prevent rats mortalities and returned the METH-induced hyperthermia to normal rates (P
    Conclusion
    ILE could reduce the severity of METH- induced toxicity as well as mortality rate in the animals. Intravenous infusion of lipid emulsion may save the life of patients with acute METH intoxication who do not respond to standard initial therapy.
    Keywords: Acute toxicity, Antidote, Intravenous lipid emulsion Methamphetamine
  • Seyyed Ali Mard*, Simin Mahini, Mahin Dianat, Yaghoob Farbood Pages 145-149
    Objective(s)
    Prostaglandins have been shown to mediate the gastro-protective effect of sodium hydrosulfide (NaHS) but effect of NaHS on mRNA expression of prostaglandin E2 receptors (EP1, 3-4; EPs) has not been investigated. Therefore, this study designed to evaluate the effect of NaHS on mRNA expression of EPs receptors in response to mucosal acidification and distention-induced gastric acid secretion in rats.
    Materials And Methods
    Fasted rats were randomly assigned into 4 groups (n=6/group). They were control, and NaHS-treated groups. To evaluate the effect of NaHS on mucosal mRNA expression of EPs receptors, the gastric mucosa exposed to stimulated gastric acid output and mucosal acidification. The pylorus sphincter catheterized for instillation of isotonic neutral saline or acidic solution. Ninety min after beginning the experiments, animals sacrificed and the gastric mucosa collected to determine the pH, mucus secretion and to quantify the mRNA expression of EPs receptors by quantitative real-time PCR.
    Results
    present results showed that a) NaHS increased the mucus secretion, mRNA expression of EP3 and EP4 receptors in response to distention-induced expression; b) The mRNA expression of EP1 receptors increased while EP4 mRNA receptors decreased in response to mucosal acidification in NaHS-pretreated rats; and c) NaHS increased pH of gastric contents both in response to distention-induced gastric acid secretion and mucosal acidification.
    Conclusion
    NaHS behaves in a different manner. It effectively only increased the pH of gastric contents to reinforce the gastric mucosa against a highly acidic solution but modulated both acid and mucus secretion when the rate of acid increase in the stomach was slower.
    Keywords: Mucosal acidification, Prostaglandin E2 receptors, Rat, Sodium hydrosulfide
  • Zahra Nazari, Mohammad Nabiuni *, Mohsen Saeidi, Mohammad Jafar Golalipour Pages 150-154
    Objective(s)
    The link between a hyperglycemic intrauterine environment and the development of diabetes later in life has been observed in offspring exposed to gestational diabetes mellitus (GDM), but the underlying mechanisms for this phenomenon are still not clear. Reduced β-cells mass is a determinant in the development of diabetes (type 1 and type 2 diabetes). Some recent studies have provided evidence that the CDK4-pRB-E2F1 regulatory pathway is involved in β-cells proliferation. Therefore, we postulated that GDM exposure impacts the offspring’s β-cells by disruption in the CDK4-pRB-E2F1 pathway.
    Materials And Methods
    Adult Wistar rats were randomly allocated in control and diabetic group. The experimental group received 40 mg/kg/body weight of streptozotocin (STZ) on day zero of gestation. After delivery, diabetic offspring of GDM mothers and control dams at the age of 15 week were randomly scarified and pancreases were harvested. Langerhans islets of diabetic and control groups were digested by collagenase digestion technique. After RNA extraction, we investigated the expressions of the kir 6.2 and CDK4-pRB-E2F1 pathway genes by quantitative real-time PCR.
    Results
    GDM reduced the expression of CDK4-pRB-E2F1 pathway genes in Langerhans islets cells of offspring. CDK4, pRB and E2F1 pathway genes were downregulated in diabetic islets by 51%, 35% and 84%, respectively. Also, the expression of Kir 6.2 was significantly decreased in diabetic islets by 88%.
    Conclusion
    We suggest that the effect of gestational diabetes on offspring’s β-cells may be primarily caused by the suppression of CDK4-pRB-E2F1 pathway.
    Keywords: Gene expression, Gestational diabetes mellitus, Langerhans islets, Offspring
  • Farzaneh Shakeri, Mohammad Soukhtanloo, Mohammad Hossein Boskabady* Pages 155-165
    Objective(s)
    The effects of Curcuma longa (C. longa) and curcumin on total and differential WBC count and oxidant, antioxidant biomarkers, in rat model of asthma were evaluated.
    Materials And Methods
    Total and differential WBC count in the blood, NO2, NO3, MDA, SOD, CAT and thiol levels in serum were examined in control, asthma, Asthmatic rats treated with C. longa (0.75, 1.50, and 3.00 mg/ml), curcumin (0.15, 0.30, and 0.60 mg/ml), and dexamethasone (1.25 μg/ml) rats.
    Results
    Total and most differential WBC count, NO2, NO3 and MDA were increased but lymphocytes, SOD, CAT and thiol were decreased in asthmatic animals compared to controls (P
    Conclusion
    Antioxidant and anti-inflammatory effects of C. longa extract and its constituent curcumin in animal model of asthma was observed which suggest a therapeutic potential for the plant and its constituent on asthma.
    Keywords: Curcuma longa, Curcumin, Inflammation, Oxidative Stress, Rat model of asthma, WBC
  • Zahra Tayarani, Najaran, Farideh Sadat Makki, Nafiseh Sadat Alamolhodaei, Mahdi Mojarrab, Seyed Ahmad Emami * Pages 166-171
    Objective(s)
    Artemisia is a genus of herbs and small shrubs forms an important part of natural vegetation in Iran. It has been reported that several Artemisia species possess anti-proliferative effects. Considering the value of this genus in anti-cancer researches we have chosen Artemisia biennis for cytotoxic and mechanistic studies.
    Materials And Methods
    In this study we have investigated the cytotoxic and apoptotic effects of petroleum ether, dichloromethane, ethyl acetate, ethanol, and ethanol:water (1:1 v/v) extracts of A. biennis Willd. on two cancer human cell lines (K562 and HL-60) and J774 as normal cells.
    Results
    CH2Cl2 extract was found to have the highest anti-proliferative effect on cancer cells. IC50 values obtained in AlamarBlue® assay for CH2Cl2 extract were 64.86 and 54.31 µg/ml on K562 and HL-60 cells respectively. In flow cytometry histogram of the cells treated with CH2Cl2 extract, sub-G1 peak was induced. DNA fragmentation, increased in the level of Bax and cleavage of PARP protein all showed the induction of apoptosis with CH2Cl2 extract after 48 hr contact with cells.
    Conclusion
    The results can corroborate the cytotoxic and apoptotic effects of the CH2Cl2 extract of A. biennis on the K562 and HL-60 cancer cell lines.
    Keywords: Artemisia biennis, Asteraceae, Apoptosis, Leukemic cell lines
  • Mina Zarei, Amir Hossein Jafarian, Azadeh Harandi, Maryam Javidi, Maryam Gharechahi * Pages 172-177
    Objective(s)
    The purpose of the present study was the immunohistochemical evaluation of VEGF and VII factors in dog’s teeth pulp revascularized with MTA and propolis.
    Materials And Methods
    144 mature and immature two rooted dog’s premolar canals were selected. Pulp necrosis and infection were established after 2 weeks and the disinfection of the canals was done with copious NaOCl irrigation and triantibiotic mixture (ciprofloxacin, metronidazole, and minocycline) for 3 weeks. Subsequently, the blood clot was evoked in the canal by periapical tissue irritation with a k-file. The samples were randomly divided into 6 experimental groups: propolis (groups 1, 2), MTA (groups 3, 4), and parafilm (groups 5, 6) in immature and mature teeth. The animals were sacrificed and samples were prepared for immunohistochemical evaluation of VEGF and the VIII factor.
    Results
    Tissue regeneration was seen in 64.5% of MTA, 38% of propolis, and 0% of parafilm group samples. Expression of VEGF and VIII factor in the propolis group was more than the MTA group and it showed a reduction after 3 months in comparison to 1 month. VEGF and VIII factor were seen in stromal cells in addition to endothelial vessel cells. Overall, expression of angiogenic factors was more in the open apex teeth compared to close apex ones.
    Conclusion
    According to the results of this study, propolis can induce the expression of VEGF and VIII factor in infected mature and immature dog’s teeth and is a suitable biomaterial for the revascularization technique.
    Keywords: Regeneration, Propolis, VIII Factor, VEGF
  • Vajiheh Zarrinpour, Zahra Hajebrahimi *, Mojtaba Jafarinia Pages 178-186
    Objective(s)
    Studies have confirmed that microgravity, as a mechanical factor, influences both differentiation and function of mesenchymal stem cells. Here we investigated the effects of simulated microgravity on neural differentiation of human adipose-derived stem cells (ADSCs).
    Materials And Methods
    We have used a fast rotating clinostat (clinorotation) to simulate microgravity condition. Real-time PCR and flow cytometry analysis were used to evaluate the regulation of neurotrophins, their receptors, and neural markers by simulated microgravity and their impact on neural differentiation of cells.
    Results
    Our data revealed that simulation microgravity up-regulated the expression of MAP-2, BDNF, TrkB, NT-3, and TrkC both before and after neural differentiation. Also, the neural cells derived from ADSCs in microgravity condition expressed more MAP-2, GFAP, and synaptophysin protein in comparison to the 1G control.
    Conclusion
    We showed that simulated microgravity can enhance the differentiation of mesenchymal stem cells into neurons. Our findings provide a new strategy for differentiation of ADSCs to neural-like cells and probably other cell lineages. Meanwhile, microgravity simulation had no adverse effects on the viability of the cells and could be used as a new environment to successfully manipulate cells.
    Keywords: ADSCs, Microgravity, Neural differentiation Neurotrophin
  • Zhixiong Fang, Langqiu He, Hui Jia, Qiusheng Huang, Dan Chen, Zhiwei Zhang* Pages 187-192
    Objective(s)
    To explore the correlation between expression patterns and functions of miR-383 and LDHA in hepatocellular cancer (HCC).
    Materials And Methods
    We detected the expression of miR-383 and LDHA in 30 HCC tissues and their matched adjacent normal tissues using qRT-PCR. Then we performed MTT assay, foci formation assay, transwell migration assay, glucose uptake assay and lactate production assay to explore the function of miR-383 in cell proliferation, invasion and glycolysis in HCC cell lines. Luciferase reporter assay was used to explore whether LDHA was a target gene of miR-383. Western blot and qRT-PCR were used to further confirm LDHA was targeted by miR-383. Then the above functional experiments were repeated to see whether the function of LDHA could be inhibited by miR-383.
    Results
    The results of qRT-PCR showed that miR-383 was down-regulated in HCC tissues compared with their matched adjacent normal tissues. Functional experiments showed that overexpression of miR-383 significantly suppressed cell proliferation, invasion and glycolysis. Luciferase reporter assay showed LDHA was a target gene of miR-383 and expression of LDHA was inversely correlated with that of miR-383 in HCC. Besides, increased cell proliferation, invasion and glycolysis triggered by LDHA could be inhibited by overexpression of miR-383 in HCC cell lines.
    Conclusion
    Our study proved that miR-383 is down-regulated in HCC and acts as a tumor suppressor through targeting LDHA. Targeting the miR-383-LDHA axis might be a promising strategy in HCC treatment.
    Keywords: Hepatocellular cancer, LDHA, MiR-383
  • Ali Reza Khosravi *, Hojjatollah Shokri, Shahin Eshghi Pages 193-198
    Objective(s)
    Systemic candidiasis is an infection of Candida albicans (C. albicans) causing disseminated disease and sepsis, invariably when host defenses are compromised. We investigated the histopathological changes as well as the lymphoproliferative responses and cytokine production of splenic cells after stimulation with Concanavalin A (Con A) and Pokeweed mitogen (PWM) in mice with disseminated candidiasis.
    Materials And Methods
    Lymphoproliferative responses were stimulated in vitro with Con A (1 µg/ml) and PWM (1 µg/ml) mitogens in Roswell Park Memorial Institute (RPMI) 1640 media, and the production of interferon (IFN)-γ and interleukin-4 (IL-4) in the supernatants was measured by enzyme-linked immunosorbent assay (ELISA).
    Results
    The results revealed that C. albicans organisms multiplied to a greater extent in the kidneys than in the liver and spleen of infected mice. The most predominant forms of C. albicans in different parts of the kidneys were yeast mixed with hyphal forms. Infected mice had a significantly increased proliferative response when splenocytes were stimulated with PWM (2.0±0.16) and Con A (1.9±0.19) (P
    Conclusion
    These findings demonstrated a significant increase in both cell proliferation and IFN-γ secretion in supernatants of PWM and Con A- stimulated splenocyte cultures obtained from mice with disseminated candidiasis.
    Keywords: Candida albicans, Cytokine production, Lymphocyte proliferation, Mitogens, Mice, Systemic candidiasis
  • Maryam Mosadegh, Shapour Hasanzadeh*, Mazdak Razi Pages 199-208
    Objective(s)
    Present study was performed in order to uncover new aspects for nicotine-induced damages on spermatogenesis cell lineage.
    Materials And Methods
    For this purpose, 36 mature male Wistar rats were divided into three groups as; control-sham (0.2 ml, saline normal, IP), low dose (0.2 mg/kg BW-1, IP) nicotine-received and high dose (0.4 mg/kg BW-1, IP) nicotine-received groups. Following 7 weeks, the expression of bcl-2, p53 and caspase-3 at mRNA and protein levels were investigated by using reverse-transcriptase PCR (RT-PCR) and immunohistochemical (IHC) analyses, respectively. Moreover, the serum level of FSH, LH and testosterone were evaluated. Finally, the mRNA damage was analyzed by using special fluorescent staining.
    Results
    Nicotine, at both dose levels, decreased tubular differentiation, spermiogenesis and repopulation indices and enhanced cellular depletion. Animals in nicotine-received groups exhibited a significant (P
    Conclusion
    Our data showed that, nicotine by suppressing the testosterone biosynthesis, reducing mRNA and protein levels of bcl-2 and up regulating the p53 and caspase-3 mRNA and protein levels adversely affects the spermatogenesis and results in cellular depletion.
    Keywords: Apoptosis, Bcl-2, Caspase-3, Nicotine, p53, Testis, Testosterone
  • Javad Mahmoudi, Babak Sabermarouf, Behzad Baradaran, Leila Sadat Hatamnezhad, Siamak Sandoghchian Shotorbani * Pages 209-215
    Objective(s)
    High Mobility Group Box1 (HMGB1) is a nonhistone, DNA-binding protein that serves a crucial role in regulating gene transcription and is involved in a variety of proinflammatory, extracellular activities. The aim of this study was to explore whether HMGB1 stimulation can up-regulate the expression of Toll-like Receptor 2 (TLR2) and Toll-like Receptor 4 (TLR4) on macrophages from pulpitis and to clarify the subsequent events involving Th17 cells and Th17 cell-associated cytokine changes.
    Materials And Methods
    Having prepared dental pulp tissues of pulpitis and healthy controls, macrophage were isolated and cultured. Macrophages were thereafter stimulated by HMGB1 time course. RT-QPCR, flowcytometer, immunofluorescence, Western blotting, and ELISA techniques were used in the present research.
    Results
    Our results showed that the expression of TLR2 and TLR4 on macrophages stimulated with HMGB1 increased in pulpitis compared with controls (macrophages without HMGB1 stimulation) with a statistical significance (P
    Conclusion
    The evidence from the present study suggests that the enhanced TLR2 and TLR4 pathways and Th17 cell polarization may be due to HMGB1 stimulation in pulpitis.
    Keywords: HMGB1, Pulpitis, TLR2, TLR4
  • Akramsadat Tabasi, Soraya Ghafari, Mehdi Mehdizadeh, Majid Asadi Shekari, Mohammad Jafar Golalipour * Pages 216-221
    Objective(s)
    The Muller cell is the principal glial cell of the vertebrate retina. The expression of Glial fibrillary acidic protein (GFAP) in the Muller cells was used as a cellular marker for retinal damage. This study was done to evaluate the effect of gestational diabetes on retinal Muller cells in rat's offspring.
    Materials And Methods
    In this experimental study, 12 Wistar rat dams were randomly allocated in control and diabetic groups. Gestational diabetes was induced by 40 mg/kg/body weight of streptozotocin at the first day of gestation, intraperitoneally. Dams in control group received an equivalent volume normal saline. Eye of six offspring of each group were removed at postnatal day 28 (P28). The histopathological changes in retina were examined through H&E staining and ultrastructure transmission electron microscopy (TEM). The expression of GFAP was examined using Immunohisto-chemical staining of GFAP in Muller cells. Photographs of retina were taken using Olympus BX51 microscope and a digital camera DP12 and EM LEO906; Zeiss, Germany.
    Results
    In the control rat's offspring, GFAP expression was not significant in Muller cells. According to the optical microscope images, GFAP expression was observed in the processes of the Muller cell in the inner plexiform layer of retina in offspring of diabetic mothers. In TEM technique, nuclear fragmentation and apoptotic bodies were observed in Muller cell of diabetic offspring.
    Conclusion
    This study showed that the uncontrolled gestational diabetes can increase GFAP expression in Muller cells and retinal thickness of retinal layer in rat offsprings, therefore uncontrolled gestational can damage the Muller cells.
    Keywords: Gestational diabetes, GFAP, Mellitus, Muller cell, Retina