فهرست مطالب

Basic Medical Sciences - Volume:20 Issue:4, 2017
  • Volume:20 Issue:4, 2017
  • تاریخ انتشار: 1396/02/18
  • تعداد عناوین: 15
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  • Gamal Badr *, Nancy K. Ramadan, Leila H. Sayed, Badr M. Badr, Hossam M. Omar, Zeliha Selamoglu Pages 338-349
    The balance between free radicals and antioxidants is an important factor for maintaining health and slowing disease progression. The use of antioxidants, particularly natural antioxidants, has become an important strategy for dealing with this cause of widespread diseases. Natural antioxidants have been used as therapeutic tools against many diseases because they are safe, effective, and inexpensive and are among the most commonly used adjuvants in the treatment of several diseases. Camel whey protein (CWP) is considered a strong natural antioxidant because it decreases oxidative stress, enhances immune system function, and increases glutathione levels. The structure of CWP is very similar to that of other types of whey protein from different types of milk. CWP contains many components, such as lactoferrin (LF), lactalbumin, lactoglobulins, lactoperoxidase, and lysozyme, and is rich in immunoglobulins. However, in contrast to other WPs, CWP lacks β-lactoglobulin, the main cause of milk allergies in children. The components of CWP have many beneficial effects, including stimulation of both innate and adaptive immunity and anti-inflammatory, anticancer, antibacterial, and antiviral activities. Recently, it has been shown that CWP and its unique components can facilitate the treatment of impaired diabetic wound healing. However, the molecular mechanisms underlying the protective effects of CWP in human and other animal disorders are not fully understood. Therefore, the current review presents a concise summary of the scientific evidence of the beneficial effects of CWP to support its therapeutic use in disease treatment and nutritional intervention.
    Keywords: Antioxidant, Camel whey protein, Free radicals, Health problems, Inflammation
  • Mohammad Javad Dehghan Esmatabadi, Baharak Farhangi, Maryam Montazeri, Hamideh Monfared, Roohollah Nakhaei Sistani, Majid Sadeghizadeh * Pages 350-359
    Objective(s)
    Despite the good results of anticancer activities by curcumin, there are some hurdles that limit the use of curcumin as an anticancer agent. Many methods were examined to overcome this defect like the use of the dendrosomal curcumin (DNC). There is increasing evidence that miRNAs play important roles in biological processes. In this study, we focus on the roles of microRNA-21 in the anti-cancer effects of DNC in breast cancer.
    Materials And Methods
    Also, we have used different methods such as MTT, apoptosis, cell cycle analysis, transwell migration assay and RT-PCR to find out more.
    Results
    We observed that miR-21 decreased apoptotic cells in both cells (from 6.35% to 0.34 % and from 7.72% to 1.32% orderly) and DNC increased it. As well as, our findings indicated that cell migration capacity was increased by miR-21 over expression and was decreased by DNC. The combination of miR-21 vector transfection and DNC treatment showed lower percentage of apoptotic cells or a higher level of penetration through the membrane compared with DNC treatment alone. Furthermore, DNC induced a marked increase in the number of cells in sub G1/G1 phase and a decrease in G2/M phase of the cell cycle in both; but, we observed reverse results compared it, after transfection with miR-21 vector.
    Conclusion
    We observed that miR-21 suppress many aspects of anti-cancer effects of DNC in breast cancer cells, it seems that co-treatment with DNC and mir-21 down-regulation may provide a clinically useful tool for drug-resistance breast cancer cells.
    Keywords: Breast cancer, Cell cycle, Cell proliferation, Curcumin, Dendrosomal curcumin, MicroRNA-21
  • Zhenhua Dai, Zhiqiang Liu, Bingshui Xiu, Xiqin Yang, Ping Zhao, Xuhui Zhang, Cuimi Duan, Haiping Que, Heqiu Zhang, Xiaoyan Feng * Pages 360-367
    Objective(s)
    Detection of circulating Mycobacterium tuberculosis (M. tuberculosis) antigens is promising in Tuberculosis (TB) diagnosis. However, not a single antigen marker has been found to be widely expressed in all TB patients. This study is aimed to prepare broadly reactive polyclonal antibodies targeting multiple antigen markers (multi-target antibodies) and evaluate their efficacies in TB diagnosis.
    Materials And Methods
    A fusion gene consisting of 38kD, ESAT6, and CFP10 was constructed and overexpressed. The fusion polyprotein was used as an immunogen to elicit production of multi-target antibodies. Their reactivities were tested. Then, the multi-target antibodies and three corresponding antibodies elicited by each single antigen (mono-target antibodies) were evaluated with sandwich ELISA for detecting M. tuberculosis antigens. Their diagnostic efficacies for TB were also compared.
    Results
    The polyprotein successfully elicited production of multi-target antibodies targeting 38kD, ESAT6, and CFP10 as analyzed by Western blotting. When used as coating antibodies, the multi-target antibodies were more efficient in capturing the three antigens than the corresponding mono-target antibodies. By testing clinical serum, the multi-target antibodies demonstrated significantly higher sensitivity for clinical TB diagnosis than all three mono-target antibodies.
    Conclusion
    The multi-target antibodies allowed detecting multiple antigens simultaneously and significantly enhanced TB detection compared to routine mono-target antibodies. Our study may provide a promising strategy for TB diagnosis.
    Keywords: Antibodies, Antigen, Diagnosis, Tuberculosis, Elisa
  • Nuno M. FElix *, Rodolfo O. Leal, I. Goy-Thollot, Ronald S. Walton, Solange A. Gil, Lu, Iacute, Sa M. Mateus, Ana S. Matos, Maria M. R E. Niza Pages 368-379
    Objective(s)
    Buprenorphine is a common analgesic in experimental research, due to effectiveness and having few side-effects, including a limited influence in the immune and endocrine systems. However, how buprenorphine affects cytokine levels and the adrenal and thyroid response during general anesthesia and surgery is incompletely understood. This study aimed to assess whether buprenorphine modulated significantly those responses in rats submitted to general anesthesia, mechanical ventilation, and surgical insertion of intravascular catheters.
    Materials And Methods
    Animals were anesthetized with isoflurane, mechanically ventilated, and surgically instrumented for carotid artery and the femoral vein catheter placement. The test group (n=16), received buprenorphine subcutaneously before surgery, whereas the control group (n=16) received normal saline. Blood sampling to determine plasma levels of adrenocorticotropic hormone (ACTH), corticosterone (CS), total thyroxine (TT4), total triiodothyronine (TT3), thyroid-stimulating hormone (TSH), TNF-α, IL6, IL10, TNF-α, IL6, and IL10 mRNA was performed at 10 min after completion of all surgical procedures and at 90, 150, 240, and 300 min thereafter, with the animals still anesthetized and with mechanical ventilation.
    Results
    Buprenorphine-treated animals had higher levels of ACTH, CS, and TT4 at several time points (P
    Conclusion
    In this model, buprenorphine significantly modulated the intra-operative cytokine and endocrine response to anesthesia, mechanical ventilation, and surgical placement of intravascular catheters. The mechanism and significance of these findings remain undetermined. Researchers should be aware of these effects when considering the use of buprenorphine for analgesic purposes.
    Keywords: ACTH, Buprenorphine, Corticosterone, Cytokine, Intra- surgery, Rat
  • Mehdi Imani *, Hossein Zarei Jaliani, Mohammad Hassan Kheirandish, Mahnaz Azadpour Pages 380-385
    Objective(s)
    A newly-introduced protein toxin from a sea anemone, namely fragaceatoxin C is a protein with molecular weight of 20 kDa and pore-forming capability against cell membranes has recently grasped great attentions for its function. In this study, its coding sequence cloned as a fusion protein with His-tag for simple production and rapid purification.
    Materials And Methods
    After PCR amplification using NcoI and HindIII-harboring primers, the gene fragment was cloned into pET-28a(). Escherichia coli BL21 was used for expression of constructed vector and toxin expression was verified by SDS-PAGE. For one-step purification Ni-NTA sepharose affinity chromatography was employed. For examination of purified toxin function, RBC hemolytic test was conducted.
    Results
    The results showed that the FraC-coding gene was successfully cloned between NcoI and HindIII restriction sites and purified with affinity chromatography. Densitometric analysis represented the purity of approximately 97%. Hemolytic test indicated the purified FraC had remarkable lytic activity on RBC and almost lysed 50% of cells at the concentration value of 6.25 nM.
    Conclusion
    The results indicated that not only purified toxin preserved its activity during expression and purification processes but also exerted its function at lower concentrations so that even the 0.09 nM displayed hemolytic effect.
    Keywords: Fragaceatoxin C, Recombinant protein, Gene cloning, Hemolysis, Sea Anemone
  • Yu Jie, Wang Pan, Yan Wenxia, Gao Feng, He Liting, Li Wenmei, Xu Jie * Pages 386-391
    Objective(s)
    To investigate the effects of Nonylphenol (NP) in pups from dams exposed during gestational and lactational periods on immediate early genes (c-jun, c-fos) in hippocampus and the learning and memory of F1 rats.
    Materials And Methods
    Twenty eight pregnant dams, stratified by pregnancy date, were randomly assigned into 4 groups, which were gavaged with NP at the doses of 50 mg/kg/day, 100 mg/kg/day, 200 mg/kg/day and groundnut oil, respectively. Step-down avoidance test, and learning and memory effects of NP were evaluated on 8-weeks-old pups. The expressions of c-jun and c-fos and the activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) were evaluated in hippocampus of pups.
    Results
    Compared to the control, reaction time (RT) that pups spent to jump to the platform was longer (P=0.02), the number of errors were higher (P=0.01), and the step-down latency was shorter in the 200 mg/kg/day NP-treated group (P=0.04). Exposure to NP induced a significant reduction in ChAT activity in hippocampus in the 100 (P=0.005) and 200 mg/kg/day NP-treated groups (P=0.002), whereas exposure to 200 mg/kg/day caused a significant increase in AchE activity (P=0.004); a dose–response relationship was revealed between ChAT and AchE activities and NP exposure in the hippocampus of pups (r=-0.821, P=0.01; r=0.757, P=0.04). Exposure to NP in the 100 and 200 mg/kg/day NP-treated groups exhibited an increase in number of c-fos and c-jun positive cells.
    Conclusion
    Exposure to NP might negatively affect learning and memory ability in F1 rats, possibly due to the alterations in the expression of c-jun and c-fos, and ChAT, AchE activities in hippocampus of pups.
    Keywords: Learning, memory, Neurotransmitters Nonylphenol, Pups
  • Shahnaz Razavi *, Nazem Ghasemi, Mohammad Mardani, Hossein Salehi Pages 392-398
    Objective(s)
    Neurotrophic factors secreting cells (NTS-SCs) may be a superior cell source for cell-based therapy in neurodegenerative diseases. NTS-SCs are able to secrete some neurotrophic Such as nerve growth factor and glia-derived neurotrophic factor. Our primary aim was to assess transplantation of neurotrophic factor secreting cells derived from human adipose-derived stem cells (hADSCs) into the damaged spinal cord rats and determine the potential of these cells in remyelination.
    Materials And Methods
    To this end, 40 adult male Wistar rats were categorized into four groups including; control, lysolecithin (Lysophosphatidylcholines or LPC), vehicle, and NTS-SCs transplan-tation. Local demyelination was induced using LPC injection into the lateral column of spinal cord. Seven days after the lysolecithin lesion, the cells transplantation was performed. The ultrastructure of myelinated fibers was examined with a transmission electron microscope to determine the extent of myelin destruction and remyelinization 4 weeks post cell transplantation. Moreover, the presence of oligodendrocyte in the lesion of spinal cord was assessed by immunohistochemistry procedure.
    Results
    The results of current study indicated that in NTF-SCs transplantation group, the remyelination process and the mean of myelin sheath thickness as well as axonal diameters were significantly higher than other groups (P
    Conclusion
    NTF-SCs transplantation represents a valuable option for cell-based therapy in the nervous tissue damages.
    Keywords: Lysolecithin lesion, Myelination, Neurotrophic factor-secreting cells (NTF-SCs), Spinal cord injury
  • Shahram Mashhadizadeh, Yaghoub Farbood, Mahin Dianat, Ali Khodadadi, Alireza Sarkaki * Pages 399-407
    Objective(s)
    Cognitive defects such as learning and memory impairment are amongst the most repetitious sequelae after sever and moderate traumatic brain injury (TBI). It was suggested that ellagic acid (EA), an innate phenol product, display neuroprotective properties against oxidative and inflammatory damages after brain injury. The object of the current study was therapeutic properties of EA on blood-brain barrier (BBB) interruption and elevated content of TNF-α in brain tissue followed by neurologic aftereffects, cognitive and brain electrophysiology deficits as outcomes of diffuse TBI in rat.
    Materials And Methods
    TBI was induced by a 200 g weight falling by a 2-m height through a free-falling tube onto the head of anesthetized rat. TBI rats treated immediately after trauma with EA (100 mg/kg, IP) once every 8 hr until 48 hr later. Neurologic outcomes, passive avoidance task (PAT), hippocampal long-term potentiation (LTP), BBB permeability and content of TNF-α in brain tissue were evaluated.
    Results
    TBI induced significant impairments in neurological score, BBB function, PAT and hippocampal LTP in TBI嗨 group in compare with Sham嗨 (P
    Conclusion
    Our findings propose that EA can restore NSS, cognitive and LTP deficits and prevent brain inflammation may by restore BBB permeability as well as lowering brain content of TNF-α following TBI.
    Keywords: Blood-brain barrier, Ellagic acid, LTP, Memory, TNF-? Traumatic brain injury
  • Huichao Wang, Chunbo Li, Jianming Li, Yingjie Zhu, Yudong Jia, Ying Zhang, Xiaodong Zhang, Wenlong Li, Lei Cui, Wuyin Li, Youwen Liu * Pages 408-414
    Objective(s)
    Naringin has been reported to regulate bone metabolism. However, its effect on osteogenesis remains unclear. The aim was to investigate the effect of naringin on osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) through the activation of the ERK signaling pathway in osteogenic differentiation.
    Materials And Methods
    Annexin V-FITC assay and MTT assay were used to measure the effect of naringin on cytotoxicity and proliferation of hBMSCs, respectively. Alkaline phosphatase activity analysis, Alizarin Red S staining, Western blotting, and real-time PCR assay were used to evaluate both the potential effect of naringin on osteogenic differentiation and the role of ERK signaling pathway in osteogenic differentiation.
    Results
    Our results showed that naringin had no obvious toxicity on hBMSCs, and could significantly promote the proliferation of hBMSCs. Naringin also enhanced the osteogenic differentiation of hBMSCs and increased the protein and mRNA expression levels of osteogenic markers such as Runx-2, OXS, OCN, and Col1 in a dose-dependent manner. In addition, we found that the enhancing effect of naringin on osteogenic differentiation was related to the activation of phosphor-ERK, with an increase in duration of activity from 30 min to 120 min. More importantly, both the enhancing effect of naringin on osteogenic differentiation and the activity effect of naringin on ERK signaling pathway were reversed by U0126 addition.
    Conclusion
    Our findings demonstrated that naringin promoted proliferation and osteogenesis of hBMSCs by activating the ERK signaling pathway and it might be a potential therapeutic agent for treating or preventing osteoporosis.
    Keywords: Bone marrow-mesenchymal stem cells, ERK signaling pathway, Naringin, Osteogenic differentiation
  • Mohammad Hossein Feiz Haddad *, Hamidreza Mahbodfar, Zahra Zamani, Ali Ramazani Pages 415-422
    Objective(s)
    In an attempt to discover new natural active extracts against malaria parasites, the present study evaluated the antiplasmodial properties of selected plants based on Iranian traditional medicine.
    Materials And Methods
    Ten plant species found in Iran were selected and collected based on the available literature about the Iranian traditional medicine. The methanolic extracts of these plants were investigated for in vitro antimalarial properties against chloroquine-sensitive (3D7) and multi-drug resistant (K1) strains of Plasmodium falciparum. Their in vivo activity against Plasmodium berghei infection in mice was also determined. Cytotoxicity tests were carried out using the Raji cells line using the MTT assay. The extracts were phytochemically screened for their active constituents.
    Results
    According to the IC50 and selectivity index (SI) values, of the 10 selected plant species, Citrullus colocynthis, Physalis alkekengi, and Solanum nigrum displayed potent in vitro antimalarial activity against both 3D7 and K1 strains with no toxicity (IC50= 2.01-18.67 µg/ml and SI=3.55 to 19.25). Comparisons between treated and untreated control mice showed that the mentioned plant species reduced parasitemia by 65.08%, 57.97%, and 60.68%, respectively. The existence of antiplasmodial compounds was detected in these plant extracts.
    Conclusion
    This was the first study to highlight the in vitro and in vivo antiplasmodial effects of C. colocynthis, P. alkekengi, and S. nigrum in Iran. Future studies can use these findings to design further biological tests to identify the active constituents of the mentioned plant species and clarify their mechanism of action.
    Keywords: Antimalarials, Cytotoxicity, Phytochemicals, Plasmodium falciparum, Traditional medicine
  • Hadi Yousefi, Alireza Alihemmati, Pouran Karimi, Mohammad Reza Alipour, Parisa Habibi, Nasser Ahmadiasl * Pages 423-429
    Objective(s)
    Genistein is reported to have anti-diabetic and anti-inflammatory functions, in particular, direct effects on β-cell proliferation and insulin secretion. In this study, we investigated the anti-inflammatory effect of genistein on the pancreatic β-cells in ovariectomized diabetic rat.
    Materials And Methods
    Forty female rats were divided into four groups: sham, bilateral ovariectomy (OVX), OVX.D (OVX瘦魺힬) and OVX.D.G (OVX.D臩힢). After bilateral ovariectomy, rats in the diabetic groups were fed high-fat diet (HFD), ad libitum for 4 weeks, and then a low dose of streptozotocin (STZ) (30 mg/kg) injected intraperitoneally. Genistein (1 mg/kg/day; SC) was administrated for 8 weeks. At the end of 8 weeks, pancreas tissue was removed and used for western blotting and Hematoxylin-Eosin staining.
    Results
    Treatment with genistein declined inflammation and tissue injury, and this decline was correlated with the expression of SIRT1. OVX and OVX.D significantly increased Nf-кB and IL-1β expression and decreased SIRT1 levels compared to sham group (P
    Conclusion
    Estrogen deficiency alone or with HFD increased pancreatic inflammation. However, subcutaneous administration of gtenistein prevented from these inflammatory changes in the pancreas of a surgery animal model of ovariectomy with or without diabetes. Our results support the potential preventing effect of genistein from pancreatic injury.
    Keywords: Diabetes, Genistein, Inflammatory cytokines-ovariectomy, SIRT1
  • Asghar Davood *, Maryam Iman, Hanieh Pouriaiee, Hamed Shafaroodi, Sepideh Akhbari, Leila Azimidoost, Erfan Imani, Somaieh Rahmatpour Pages 430-437
    Objective(s)
    Phthalimide-based derivatives have anticonvulsant activity like as phenytoin by inhibition of sodium channel. In our previously research we mentioned about some phthalimide derivatives as potent anticonvulsant agents.
    Materials And Methods
    Fourteen analogs of 2-substituted phthalimide pharmacophore were synthesized and then were evaluated for the anticonvulsant activities in pentylenetetrazole-induced seizures (PTZ) and maximal electroshock seizure (MES) models.
    Results
    The in vivo screening results showed that all the analogs have the ability to protect against the maximal electroshock and PTZ. The compounds 3 and 9 elevated clonic seizure thresholds at 30 min which were more active than the standard medicine phenytoin. Compounds 3, 6, 7, 11, 13 and 14 with 100% protection were the most potent ones in tonic seizure. The most potent compound in the both PTZ and MES models was compound 3. Using a model of the open pore of sodium channel, all of the compounds were docked. Results of docking showed that the ligands interacted mainly with residues II-S6 of NaV1.2 by making hydrogen bonds and have additional hydrophobic interactions with other domains in the channel's inner pore.
    Conclusion
    Some of these compounds are more potent than phenytoin simultaneously in the clonic and tonic seizures.
    Keywords: Anticonvulsant, Docking, MES seizure, Phthalimide, PTZ seizure, Sodium channel
  • Yald Shokoohinia, Shekoufeh Khajouei, Farahnaz Ahmadi, Nastaran Ghiasvand, Leila Hosseinzadeh * Pages 438-445
    Objective(s)
    The present study aims to evaluate the protective effect of the compounds isolated from Echinophora cinerea (E. cinerea) against oxidative stress and apoptosis induced by cisplatin (CIS) in PC12 cells.
    Materials And Methods
    Six compounds were isolated as quercetrin-3-O-β-D-glucopyranoside (QUE), osthol (OST), verbenone-5-O-β-D-glycopyranoside (VER), Isoimperatorin (ISO), kaempferol-3-O-β-D-glucopyranoside (KAM), and echinophorin B (ECH). For this study, we used MTT reduction assay for detection of protective effects of isolated compounds on CIS-induced cytotoxicity in PC12 cells. The effects of isolated compounds against apoptosis induced by CIS were investigated through the measurement of mitochondrial membrane potential (MMP), Bax and Bcl2 mRNA expression, and caspase-3 activation. We also assessed oxidative stress by measuring reactive oxygen species (ROS) generation with 2′, 7′-dichlorofluorescein diacetate (DCFH-DA).
    Results
    Treatment of cells with QUE and OST before exposure to the CIS increased cell viability, i.e., these compounds protected the cells against CIS -induced cytotoxicity. In addition, pre-treatment with QUE and OST decreased CIS-induced apoptosis through up-regulation of Bcl-2, inhibition of caspase-3 activity, and mitochondrial membrane potential (MMP) increase. OST decreased ROS generation induced by CIS, as well.
    Conclusion
    Our in vitro experiment showed that QUE and OST are apoptotic inhibitors that effectively block CIS-induced neurotoxicity predicting their therapeutic potential in the prevention of chemotherapy-induced neurotoxicity.
    Keywords: Apoptosis, Cisplatin, Echinophora cinerea, Neuroprotection, Osthole, Quercetin
  • Hossein Hosseinzadeh, Fatemeh Mazaheri, Razieh Ghodsi * Pages 446-450
    Objective(s)
    In the present study, we investigated the potential anti-nociceptive activity and acute anti-inflammatory effect of a synthetic quinoline compound (2-(4-Methoxyphenyl)benzo[h]quinoline-4-carboxylic acid, QC), possessing structural elements of both naproxen and tomoxiprole drugs.
    Materials And Methods
    The anti-nociceptive activity of QC was evaluated using chemical- and thermal-induced nociception models and its acute anti-inflammatory effect was evaluated by xylene-induced ear edema test in mice.
    Results
    QC displayed a dose dependent effect in both acute anti-nociceptive tests (writhing and hot plate). This compound at dose of 6.562 mg/kg showed a high anti-nociceptive effect near equal to diclofenac 5 mg/kg. It also showed high anti-inflammatory effects (less than 6.562 mg/kg) comparable to those of reference drugs diclofenac (5 mg/kg) and celecoxib (100 mg/kg). Docking study showed that this quinoline derivative could inhibit COX-2 enzyme strongly.
    Conclusion
    QC showed high anti-nociceptive and anti-inflammatory effects comparable to reference drugs and can exert its anti-nociceptive and anti-inflammatory activities through COX-2 inhibition.
    Keywords: Anti-inflammation, COX-2, Molecular modeling, Naproxen, NSAIDs, Quinoline, Tomoxiprole
  • Ali Shakerimoghaddam, Ezzat A. Ghaemi, Ailar Jamalli * Pages 451-456
    Objective(s)
    This study aimed to investigate the effect of zinc oxide nanoparticles (ZnO-np) on biofilm formation and expression of the flu gene in uropathogenic Escherichia coli (UPEC) strains.
    Materials And Methods
    Minimum inhibitory concentration (MIC) of ZnO-np was determined by agar dilution method. The effect of MIC and sub-MIC concentrations of ZnO-np on biofilm formation were determined by microtiter plate assay. The expression level of the flu gene was assessed by Real-Time PCR assay.
    Results
    MIC and sub-MIC ZnO-np concentrations reduced biofilm formation by 50% and 33.4%, respectively. Sub-MIC ZnO-np concentration significantly reduced the flu gene expression in the UPEC isolates (P
    Conclusion
    The sub-MIC concentration of ZnO-np reduces biofilm formation and flu gene expression in UPEC isolates. It is suggested to use nanoparticles for coating medical devices to prevent bacterial colonization.
    Keywords: Biofilm, Urinary tract infection, Uropathogenic Escherichia coli, Zinc oxide nanoparticle