فهرست مطالب

Basic Medical Sciences - Volume:20 Issue: 12, 2017
  • Volume:20 Issue: 12, 2017
  • تاریخ انتشار: 1396/08/29
  • تعداد عناوین: 16
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  • Zeynab Noorimotlagh, Mahla Babaie, Mahdi Safdarian, Tahereh Ghadiri, Vafa Rahimi-Movaghar * Pages 1287-1296
    Objective(s)
    To determine the molecular and cellular mechanisms of spinal cord regeneration in zebrafish.
    Materials And Methods
    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.
    Results
    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.
    Conclusion
    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.
    Keywords: Regeneration recovery of function, Spinal cord regeneration, Spinal cord injuries, Zebrafish
  • Akram Ahangarpour, Leila Zeidooni *, Mohsen Rezaei, Soheila Alboghobeish, Azin Samimi, Ali Akbar Oroojan Pages 1297-1305
    Objective(s)
    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.
    Materials And Methods
    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.
    Results
    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.
    Conclusion
    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.
    Keywords: Arsenic, Butyric acid, Islet insulin secretion, Liver mitochondrial, Metformin, Oxidative stress
  • Sara Chenari, Fatemeh Safari, Ali Moradi * Pages 1306-1311
    Objective(s)
    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.
    Materials And Methods
    The study consisted of four groups (n=8 for each of Wistar rats): sham group, sham狪�梧 (sham૪) group (received curcumin 100 mg/kg/day), BDL૪ 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.
    Results
    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 (P-value
    Conclusion
    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.
    Keywords: Curcumin, Gene expression, Liver Cirrhosis, Rats, SIRT3 protein
  • Faeze Daghigh, Alireza Alihemmati, Pouran Karimi, Parisa Habibi, Naser Ahmadiasl * Pages 1312-1317
    Objective(s)
    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.
    Materials And Methods
    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.
    Results
    Treatment with genistein significantly decreased inflammatory and apoptotic biomarkers in the ovariectomized diabetic rats compared to non-treated animals (P
    Conclusion
    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.
    Keywords: Apoptosis, Diabetes, Genistein, Inflammation, Ovariectomy
  • Saied Goodarzi, Mehdi Nateghpour, Parina Asgharian, Abbas Hadjiakhoondi, Narguess Yassa, Saeed Tavakoli, Jalal Mirzaei, Leila Farivar, Afsaneh Motevalli Haghi, Zahra Tofighi * Pages 1318-1323
    Objective(s)
    Astrodaucus persicus (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 A. persicus fruits and roots extracts.
    Materials And Methods
    Ripe fruits and roots of A. persicuswere extracted and fractionated by hexane, chloroform, ethyl acetate and methanol, separately. Antimalarial activities of fractions were performed based on Plasmodium berghei 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 IC50 of them were measured.
    Results
    Hexane fraction of roots extract (RHE) and ethyl acetate fraction of fruits extract (FEA) of A. persicus demonstrated highest parasite inhibition (73.3 and 72.3%, respectively at 500 mg/kg/day) which were significantly different from negative control group (P
    Conclusion
    According to the results, RHE and FEA fractions of A. persicus could be introduced as excellent choice for antimalarial drug discovery. In addition, cytotoxic activity of RHE was noticeable.
    Keywords: Antimalaria, Apiaceae, Astrodaucus persicus, Cytotoxic, MTT assay, Plasmodium berghei
  • Chang-Tsen Hung, Li-Dian Chen, Chien-Wei Hou * Pages 1324-1330
    Objective(s)
    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.
    Materials And Methods
    The infaction of Sprague Dawley (SD) rats and hypoxia models of BV-2 microglia or PC12 cells were investigated for in vivo and in vitro test respectively. Lipid peroxidation and reactive oxygen species (ROS), prostaglandin E2 (PGE2) and related signaling pathways from hypoxic cells were analyzed by ELISA or Western blot assay, respectively.
    Results
    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 PGE2 release from hypoxic BV-2 or PC12 cells. MMEDA significantly reduced hypoxia-induced JNK and caspase-3 (survival and apoptotic pathways) in PC12 cells.
    Conclusion
    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.
    Keywords: Anti-inflammatory, Cerebral ischemia, Hypoxia, Neuroprotection, Reactive oxygen species, Sesamin derivative
  • Aylin Moayedi, Jamileh Nowroozi *, Abbas Akhavan Sepahy Pages 1331-1338
    Objective(s)
    Pyocyanin is a blue-greenish redox-active pigment, produced by Pseudomonas aeruginosa, 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.
    Materials And Methods
    The presence of pyocyanin-producing specific genes and proteins in clinical and soil isolates of P. aeruginosa 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.
    Results
    Adding ABS to P. aeruginosa 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-1 and 126.80±2.036 vs. 30.56±0.382 μg.ml-1 of C11 and E8 pyocyanin concentration in the presence of 10% FBS vs. control, respectively).
    Conclusion
    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.
    Keywords: Adult bovine serum, Fetal bovine serum, PhzM, Pseudomonas aeruginosa, Pyocyanin
  • Jinjun Wang, Ziqiang Xu, Bicheng Chen, Shaoling Zheng, Peng Xia, Yong Cai * Pages 1339-1344
    Objective(s)
    The aim of this study was to observe the impact of sirolimus on proteinuria in streptozotocin (STZ) induced diabetic rats.
    Materials And Methods
    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 8th and 20th 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.
    Results
    In the early stage of diabetic nephropathy (DN), sirolimus reduced the proteinuria significantly (P
    Conclusion
    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.
    Keywords: Diabetic nephropathies, mTOR protein, Podocytes, Proteinuria, Sirolimus
  • Fakhroddin Mesbah *, Aris Donic Pracha, Tahereh Talaei Khozani, Soghra Bahmanpour Pages 1345-1353
    Objective
    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 in vitro oocyte maturation. This study was designed to assess the effect of activated-omental extract (AOE) on in vitro maturation (IVM) of rat cumulus-oocyte complexes (COCs).
    Materials And Methods
    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.
    Results
    Expansion of CCs and nuclear maturation of the oocytes in in vitro for 24 hr was significantly higher in AOE- and FBS-supplemented groups (P=0.000 and 0.013) and (P=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.
    Conclusion
    Although AOE supplementation induced a higher rate of the CCs expansion, and resuming meiosis, it was not as potent as FBS to provide cytoplasmic maturation of rat oocytes.
    Keywords: Cumulus cells, Cytoplasm, In vitro oocyte maturation, Nucleus, Omentum, Rats
  • Vida Mohammadi, Abbas Behzad Behbahani, Gholam Reza Rafiee, Seyed Younes Hosseini, Marzieh Alizadeh Zarei, Mohammad Ali Okhovat, Mohammad Ali Takhshid * Pages 1354-1359
    Objective(s)
    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.
    Materials And Methods
    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 of 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.
    Results
    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 (P
    Conclusion
    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.
    Keywords: Apoptin protein, Apoptosis, Prostate-specific antigen, Prostate-specific membrane antigen, Prostate cancer
  • Syuhada Zakaria, Siti-Zulaikha Mat-Husain, Kong Ying-Hwey, Kek Xin-Kai, Abdullah Mohd-Badawi, Nurul-Amiza Abd-Ghani, Muhamad-Arizi Aziz, Mohamed Norazlina * Pages 1360-1367
    Objective(s)
    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.
    Materials And Methods
    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.
    Results
    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 (P
    Conclusion
    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.
    Keywords: Alcohol-induced disorder, Bone minerals, Bone strength, Palm oil, Vitamin E
  • Malihe Sadeghi, Parham Reisi *, Maryam Radahmadi Pages 1368-1376
    Objective(s)
    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.
    Materials And Methods
    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.
    Results
    Stress impaired spatial memory significantly (P
    Conclusion
    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.
    Keywords: CA1, Cholecystokinin sulfated octapeptide, Hippocampus, Long term potentiation, Memory, Stress
  • Arehzoo Zaker, Javad Asili, Parvaneh Abrishamchi, Zahra Tayarani-Najaran, Seyed Hadi Mousavi * Pages 1377-1384
    Objective(s)
    Perovskia abrotanoides 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 P. abrotanoides. 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.
    Materials And Methods
    Alamar Blue® 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.
    Results
    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.
    Conclusion
    The findings suggest that root extract of P. abrotanoides 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.
    Keywords: Apoptosis, Cytotoxicity, HeLa, MCF-7, Perovskia abrotanoides, Root extract, Tanshinone
  • Ghaidafeh Akbari, Seyyed Ali Mard *, Seyed Esmaeil Khoshnam, Iraj Ahmadi Pages 1385-1389
    Objective(s)
    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.
    Materials And Methods
    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.
    Results
    The stimulated gastric acid upregulated expression levels of TGF-α in gastric mucosa. These levels were higher in animals pretreated with NaHS.
    Conclusion
    TGF-α upregulatory effect of sodium hydrosulfate implied that TGF-α is involved in the acid inhibitory effect of NaHS.
    Keywords: Gastric acid secretion, NaHS, Rat, TGF-? Western blot
  • Uma Dharshini Karuppiah Vijayamuthuramalingam, Rajeswari Rajaram, Kalaivani Madhavaram Kuppusamy, Bhavana Jonnalagadda, Sumathy Arokiasamy * Pages 1390-1397
    Objective(s)
    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 Croton bonplandianusagainst these pancreatic enzymes.
    Materials And Methods
    The methanol extract of C. bonplandianusleaf 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.
    Results
    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 (IC5095.78 µg/ml) and α glucosidase (IC50 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.
    Conclusion
    The study findings suggest that the components present in the leaves of C. bonplandianus, may provide a potential therapeutic source in developing treatment forhyperglycemia. Further bioassay guided fractionation procedure is required to identify the active constituents.
    Keywords: Antihyperglycemia, ?-Amylase, ?-Glucosidase, Polyphenols, Postprandial hyperglycemia
  • Pages 1398-1400