فهرست مطالب

Cell Journal - Volume:17 Issue: 3, Autumn 2015

Cell Journal (Yakhteh)
Volume:17 Issue: 3, Autumn 2015

  • تاریخ انتشار: 1394/07/27
  • تعداد عناوین: 23
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  • Saeid Abroun*, Najmaldin Saki, Mohammad Ahmadvand, Farahnaz Asghari, Fatemeh Salari, Fakher Rahim Page 395
    Signal transducers and activators of transcription (STATs) are cytoplasmic transcriptionfactors that have a key role in cell fate. STATs, a protein family comprised ofseven members, are proteins which are latent cytoplasmic transcription factors thatconvey signals from the cell surface to the nucleus through activation by cytokinesand growth factors. The signaling pathways have diverse biological functions thatinclude roles in cell differentiation, proliferation, development, apoptosis, and inflammationwhich place them at the center of a very active area of research. In this reviewwe explain Janus kinase (JAK)/STAT signaling and focus on STAT3, which istransient from cytoplasm to nucleus after phosphorylation. This procedure controlsfundamental biological processes by regulating nuclear genes controlling cell proliferation,survival, and development. In some hematopoietic disorders and cancers,overexpression and activation of STAT3 result in high proliferation, suppression ofcell differentiation and inhibition of cell maturation. This article focuses on STAT3and its role in malignancy, in addition to the role of microRNAs (miRNAs) on STAT3activation in certain cancers.
    Keywords: JAK, STAT, Signaling Pathways, Malignancy, miRNA
  • Mahmoud Orazizadeh, Ali Khodadadi, Vahid Bayati, Sadegh Saremy, Maryam Farasat, Layasadat Khorsandi* Page 412
    Objective
    Zinc oxide nanoparticles (ZnO-NPs) are increasingly used in sunscreens, biosensors, food additives, pigments, manufacture of rubber products, and electronic materials. There are several studies about the effects of NPs on dermal fibroblast or keratinocytes, but very little attention has been directed towards adipose-derived mesenchymal stem cells (ASCs). A previous study has revealed that ZnO-NPs restricted the migration capability of ASCs. However, the potential toxicity of these NPs on ASCs is not well understood. This study intends to evaluate the effects of ZnO-NPs on subcutaneous ASCs.
    Materials And Methods
    In this experimental study, In order to assess toxicity, we exposed rat ASCs to ZnO-NPs at concentrations of 10, 50, and 100 μg/ml for 48 hours. Toxicity was evaluated by cell morphology changes, cell viability assay, as well as apoptosis and necrosis detection.
    Results
    ZnO-NPs concentration dependently reduced the survival rates of ASCs as revealed by the trypan blue exclusion and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium- bromide (MTT) tests. ZnO-NPs, at concentrations of 10 and 50 μg/ml, induced a significant increase in apoptotic indices as shown by the annexin V test. The concentration of 10 μg/ml of ZnO-NPs was more toxic.
    Conclusion
    Lower concentrations of ZnO-NPs have toxic and apoptotic effects on subcutaneous ASCs. We recommend that ZnO-NPs be used with caution if there is a dermatological problem.
    Keywords: Nanoparticles, Mesenchymal Stromal Cells, Apoptosis
  • Mohammad Reza Arab, Ramazan Mirzaei*, Fereydoon Sargolzaei Aval Page 422
    Objective
    The aim of the present study was to evaluate the protective effects of gadolinum on pneumotoxic effects of styrene in rats as an experimental model.
    Materials And Methods
    In this experimental study a total number of 40 adult male Sprague Dawley rats that weighed 200 ± 13 g were randomly divided into five groups: i. styrene (St, N=10), ii. styrene+gadolinium chloride (GdCl3, N=10), iii. control (N=10), iv. GdCl3 (N=5) and v. normal saline (Nor.Sal, as a solvent of GdCl3, N=5). Normal saline, as a sham control group, was otherwise treated identically. Rats from the experimental groups were exposed to St in an exposure chamber for 6 days/week, 4 hours/day for up to 3 weeks. At the end of the experiment, rats from all groups were killed by deep anesthesia. Their lungs were removed, then fixed in formalin and weighed. Tissue samples were processed routinely and sections stained by the hematoxylin and eosin (H&E) and periodic acid Schiff (PAS) methods. We measured the thicknesses of the respiratory epithelia and interalveolar septa. Obtained data were analyzed by ANOVA, the Tukey test and the paired t test.
    Results
    Shedding of apical cytoplasm in the bronchiole was a prominent feature of the St group. PAS staining revealed histochemical changes in goblet cells in the epithelium of the St group. While there were no significant changes in lung weights and respiratory epithelial thicknesses between all studied groups, statistical analysis showed a significant alteration in the thickness of interalveolar septa in the St and St+GdCl3 group compared to the control groups (P<0.001).
    Conclusion
    Styrene induced structural and histochemical changes in bronchiole, interalveolar septa and alveolar organization in the rats’ lungs. Gadolinium appeared to partially reduce the toxic effects of styrene on the lungs.
    Keywords: Styrene, Gadolinum, Respiratory, Toxic, Rat
  • Shahnaz Razavi*, Saeed Karbasi, Mohammad Morshed, Hamid Zarkesh Esfahani, Mohammad Golozar, Sedigheh Vaezifar Page 429
    Objective
    In this study, nano-biocomposite composed of poly (lactide-co-glycolide) (PLGA) and chitosan (CS) were electrospun through a single nozzle by dispersing the CS nano-powders in PLGA solution. The cellular behavior of human adipose derived stem cells (h-ADSCs) on random and aligned scaffolds was then evaluated.
    Materials And Methods
    In this experimental study, the PLGA/CS scaffolds were prepared at the different ratios of 90/10, 80/20, and 70/30 (w/w) %. Morphology, cell adhesion and proliferation rate of h-ADSCs on the scaffolds were assessed using scanning electron microscope (SEM), 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and trypan blue staining respectively.
    Results
    H-ADSCs seeded on the matrices indicated that the PLGA/CS composite matrix with aligned nanofibres and higher content of CS nano-powders gave significantly better performance than others in terms of cell adhesion and proliferation rate (P<0.05).
    Conclusion
    We found that CS enhanced cell adhesion and proliferation rate, and aligned nanofibers guided cell growth along the longitudinal axis of the nanofibers, which would provide a beneficial approach for tissue engineering.
    Keywords: Chitosan, Mesenchymal Stem Cell, PLGA, Scaffold
  • Mehdi Sharifi Tabar, Mahdi Hesaraki, Fereshteh Esfandiari, Fazel Sahraneshin Samani, Haghighat Vakilian, Hossein Baharvand* Page 438
    Objective
    Genetic modification of human embryonic stem cells (hESCs) is critical for their extensive use as a fundamental tool for cell therapy and basic research. Despite the fact that various methods such as lipofection and electroporation have been applied to transfer the gene of interest (GOI) into the target cell line, however, there are few reports that compare all parameters, which influence transfection efficiency. In this study, we examine all parameters that affect the efficiency of electroporation and lipofection for transient and long-term gene expression in three different cell lines to introduce the best method and determinant factor.
    Materials And Methods
    In this experimental study, both electroporation and lipofection approaches were employed for genetic modification. pCAG-EGFP was applied for transient expression of green fluorescent protein in two genetically different hESC lines, Royan H5 (XX) and Royan H6 (XY), as well as human foreskin fibroblasts (hFF). For long-term EGFP expression VASA and OLIG2 promoters (germ cell and motoneuron specific genes, respectively), were isolated and subsequently cloned into a pBluMAR5 plasmid backbone to drive EGFP expression. Flow cytometry analysis was performed two days after transfection to determine transient expression efficiency. Differentiation of drug resistant hESC colonies toward primordial germ cells (PGCs) was conducted to confirm stable integration of the transgene.
    Results
    Transient and stable expression suggested a variable potential for different cell lines against transfection. Analysis of parameters that influenced gene transformation efficiency revealed that the vector concentrations from 20-60 μg and the density of the subjected cells (5×105 and 1×106 cells) were not as effective as the genetic background and voltage rate. The present data indicated that in contrast to the circular form, the linearized vector generated more distinctive drug resistant colonies.
    Conclusion
    Electroporation was an efficient tool for genetic engineering of hESCs compared to the chemical method. The genetic background of the subjected cell line for transfection seemed to be a fundamental factor in each gene delivery method. For each cell line, optimum voltage rate should be calculated as it has been shown to play a crucial role in cell death and rate of gene delivery.
    Keywords: Electroporation, Lipofectamine, Genetic Modification
  • Laleh Parsa Yeganeh, Reza Azarbaijani, Hossein Mousavi, Seyed Abolhassan Shahzadeh Fazeli, Mohammad Ali Amoozgar, Ghasem Hosseini Salekdeh* Page 451
    Objective
    The bacterium Oceanimonas sp. (O. sp.) GK1 is a member of the Aeromonadaceae family and its genome represents several virulence genes involved in fish and human pathogenicity. In this original research study we aimed to identify and characterize the putative virulence factors and pathogenicity of this halotolerant marine bacterium using genome wide analysis.
    Materials And Methods
    The genome data of O. sp. GK1 was obtained from NCBI. Comparative genomic study was done using MetaCyc database.
    Results
    Whole genome data analysis of the O. sp. GK1 revealed that the bacterium possesses some important virulence genes (e.g. ZOT, RTX toxin, thermostable hemolysin, lateral flagella and type IV pili) which have been implicated in adhesion and biofilm formation and infection in some other pathogenic bacteria.
    Conclusion
    This is the first report of the putative pathogenicity of O. sp.GK1. The genome wide analysis of the bacterium demonstrates the presence of virulence genes causing infectious diseases in many warm- and cold-blooded animals.
    Keywords: Pathogenicity, Virulence Factors, Halotolerant
  • Maryam Honardoost, Masoud Soleimani, Ehsan Arefian, Mohammad Reza Sarookhani* Page 461
    Objective
    MicroRNAs (miRNAs) are a class of small non-coding RNAs that play pivotal roles in many biological processes such as regulating skeletal muscle development where alterations in miRNA expression are reported during myogenesis. In this study, we aimed to investigate the impact of predicted miRNAs and their target genes on the myoblast to myocyte differentiation process.
    Materials And Methods
    This experimental study was conducted on the C2C12 cell line. Using a bioinformatics approach, miR-214 and miR-135 were selected according to their targets as potential factors in myoblast to myocyte differentiation induced by 3% horse serum. Immunocytochemistry (ICC) was undertaken to confirm the differentiation process and quantitative real-time polymerase chain reaction (PCR) to determine the expression level of miRNAs and their targets.
    Results
    During myoblast to myocyte differentiation, miR-214 was significantly downregulated while miRNA-135, Irs2, Akt2 and Insr were overexpressed during the process.
    Conclusion
    miR-214 and miR-135 are potential regulators of myogenesis and are involved in skeletal muscle development through regulating the IRS/PI3K pathway.
    Keywords: Myoblast, Differentiation, miR, 214, miR, 135
  • Golnesa Kazemi Oula, Soudeh Ghafouri Fard*, Maryam Beigom Mobasheri, Lobat Geranpayeh, Mohammad Hossein Modarressi Page 471
    Objective
    During the past decade, the importance of biomarker discovery has been highlighted in many aspects of cancer research. Biomarkers may have a role in early detection of cancer, prognosis and survival evaluation as well as drug response. Cancer-testis antigens (CTAs) have gained attention as cancer biomarkers because of their expression in a wide variety of tumors and restricted expression in testis. The aim of this study was to find putative biomarkers for breast cancer.
    Materials And Methods
    In this applied-descriptive study, the expression of 4 CTAs, namely acrosin binding protein (ACRBP), outer dense fiber 4 (ODF4), Rhox homeobox family member 2 (RHOXF2) and spermatogenesis associated 19 (SPATA19) were analyzed at the transcript level in two breast cancer lines (MCF-7 and MDA-MB-231), 40 invasive ductal carcinoma samples and their adjacent normal tissues as well as 10 fibroadenoma samples by means of quantitative real-time reverse transcription polymerase chain reaction (RT-PCR).
    Results
    All four genes were expressed in both cell lines. Expression of ODF4 and RHOXF2 was detected in 62.5% and 60% of breast cancer tissues but in 22.5 and 17.5% of normal tissues examined respectively. The expression of both RHOXF2 and ODF4 was upregulated in cancerous tissues compared with their normal adjacent tissues by 3.31- and 2.96-fold respectively. The expression of both genes was correlated with HER2/neu overexpression. RHOXF2 expression but not ODF4 was correlated with higher stages of tumors. However, no significant association was seen between expression patterns and estrogen and progesterone receptors status.
    Conclusion
    ODF4 and RHOXF2 are proposed as putative breast cancer biomarkers at the transcript level. However, their expression at protein level should be evaluated in future studies.
    Keywords: Breast Cancer, Cancer, Testis Antigen, ODF4, RHOXF2
  • Maryam Eslami*, Gholamreza Javadi, Nasser Agdami, Mohammad Ali Shokrgozar Page 478
    Objective
    The incidence of heart valve disease is increasing worldwide and the number of heart valve replacements is expected to increase in the future. By mimicking the main tissue structures and properties of heart valve, tissue engineering offers new options for the replacements. Applying an appropriate scaffold in fabricating tissue-engineered heart valves (TEHVs) is of importance since it affects the secretion of the main extracellular matrix (ECM) components, collagen 1 and elastin, which are crucial in providing the proper mechanical properties of TEHVs.
    Materials And Methods
    Using real-time polymerase chain reaction (PCR) in this experimental study, the relative expression levels of COLLAGEN 1 and ELASTIN were obtained for three samples of each examined sheep mitral valvular interstitial cells (MVICs)-seeded onto electrospun poly (glycerol sebacate) (PGS)-poly (ε-caprolactone) (PCL) microfibrous, gelatin and hyaluronic acid based hydrogel-only and composite (PGS-PCL/hydrogel) scaffolds. This composite has been shown to create a synthetic three-dimensional (3D) microenvironment with appropriate mechanical and biological properties for MVICs.
    Results
    Cell viability and metabolic activity were similar among all scaffold types. Our results showed that the level of relative expression of COLLAGEN 1 and ELASTIN genes was higher in the encapsulated composite scaffolds compared to PGS-PCL-only and hydrogel- only scaffolds with the difference being statistically significant (P<0.05).
    Conclusion
    The encapsulated composite scaffolds are more conducive to ECM secretion over the PGS-PCL-only and hydrogel-only scaffolds. This composite scaffold can serve as a model scaffold for heart valve tissue engineering.
    Keywords: Tissue Engineering, Heart Valve, ELASTIN, COLLAGEN I, Real, Time PCR
  • Mostafa Ganjuri, Jamal Moshtaghian*, Kamran Ghaedi Page 489
    Objective
    Nanotechnology focuses on materials having at least one dimension of less than 100 nanometers. Nanomaterials such as Nanosilver (NS) have unique physical and chemical properties such as size, shape, surface charge. NS particles are thought to induce neuronal degeneration and necrosis in the brain. It has been reported that NS particles generate free radicals and oxidative stress which alters gene expression and induces apoptosis. This study was designed to evaluate whether the detrimental effect of NS particles is through the activation of Procaspase-3 during fetal neural development.
    Materials And Methods
    In this experimental study, thirty Wistar female rats at day one of pregnancy were semi-randomly distributed into three groups of ten. Group 1, the control group, had no treatment. From day 1 to the end of pregnancy, groups 2 and 3 received 1 and 10 ppm NS respectively via drinking water. Newborn rats were sacrificed immediately after birth and their brains were dissected and kept frozen. Total RNA, extracted from brain homogenates, was reverse transcribed to cDNA. Quantitative real-time polymerase chain reaction (PCR) analysis was undertaken to estimate the expression level of Procaspase-3.
    Results
    Developmental exposure to NS induced neurotoxicity and apoptosis. This correlated with a significant increase in Procaspase-3 expression level especially at 10 ppm NS.
    Conclusion
    The pro-apoptotic activity of NS in cells is likely to due to the dysregulation of Procaspase-3.
    Keywords: Apoptosis, Brain, Blood, Brain Barrier, Procaspase, 3
  • Sedigheh Gharbi, Mehdi Shamsara*, Shahriar Khateri, Mohammad Reza Soroush, Nassim Ghorbanmehr, Mahmood Tavallaei, Mohammad Reza Nourani, Seyed Javad Mowla Page 494
    Objective
    In spite of accumulating information about pathological aspects of sulfur mustard (SM), the precise mechanism responsible for its effects is not well understood. Circulating microRNAs (miRNAs) are promising biomarkers for disease diagnosis and prognosis. Accurate normalization using appropriate reference genes, is a critical step in miRNA expression studies. In this study, we aimed to identify appropriate reference gene for microRNA quantification in serum samples of SM victims.
    Materials And Methods
    In this case and control experimental study, using quantitative real-time polymerase chain reaction (qRT-PCR), we evaluated the suitability of a panel of small RNAs including SNORD38B, SNORD49A, U6, 5S rRNA, miR-423-3p, miR-191, miR-16 and miR-103 in sera of 28 SM-exposed veterans of Iran-Iraq war (1980-1988) and 15 matched control volunteers. Different statistical algorithms including geNorm, Normfinder, best-keeper and comparative delta-quantification cycle (Cq) method were employed to find the least variable reference gene.
    Results
    miR-423-3p was identified as the most stably expressed reference gene, and miR- 103 and miR-16 ranked after that.
    Conclusion
    We demonstrate that non-miRNA reference genes have the least stability in serum samples and that some house-keeping miRNAs may be used as more reliable reference genes for miRNAs in serum. In addition, using the geometric mean of two reference genes could increase the reliability of the normalizers.
    Keywords: MicroRNA, Quantitative Real Time, PCR, Normalization, Sulfur Mustard, miR, 423
  • Iman Sadeghi, Mehrdad Behmanesh*, Najmeh Ahmadian Chashmi, Mohsen Sharifi, Bahram Mohammad Soltani Page 502
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    Objective
    Podophyllotoxin (PTOX), a natural compound in numerous plants, contains remarkable biological properties that include anti-tumor, anti-viral such as anti-human immunodeficiency virus (HIV) activities. In order to avoid its adverse effects, various compounds have been derived from PTOX. 6-methoxy PTOX (MPTOX) is one of the natural PTOX derivatives with an extra methoxy group. MPTOX is mostly isolated from the Linum species. This study has sought to determine the biological effects of MPTOX on cancer cell lines, 5637 and K562.
    Materials And Methods
    In this experimental study, we treated the 5637 and K562 cancer cell lines with MPTOX in a dose- and time-dependent manner. Apoptosis was examined by flow cytometry and viability rate was analyzed by the MTT assay. Expressions of the tubulin (TUBB3) and topoisomerase II (TOPIIA) genes were determined by real-time polymerase chain reaction (PCR).
    Results
    Treatment with MPTOX led to significant induction of apoptosis in cancer cells compared to control cells. Gene expression analysis showed reduced levels of TUBB3 and TOPIIA mRNA following MPTOX treatment.
    Conclusion
    MPTOX inhibited TUBB3 and TOPIIA gene expression and subsequently induced cell death through apoptosis. These results suggested that MPTOX could be considered a potential anti-tumor agent.
    Keywords: Podophyllotoxin, Cancer, Apoptosis, Gene Expression, Real, Time PCR
  • Samyuktha Lakkireddy, Sangeetha Aula, Swamy Avn, Atya Kapley, Raghunadha Rao Digumarti, Kaiser Jamil * Page 510
    Objective
    Cytochrome P450 is one of the major drug metabolizing enzyme families and its role in metabolism of cancer drugs cannot be less emphasized. The association between single nucleotide polymorphisms (SNPs) in CYP1A1 and pathogenesis of chronic myeloid leukemia (CML) has been investigated in several studies, but the results observed vary based on varied risk factors. The objective of this study was to investigate the risk factors associated with the CYP1A1*2C [rs1048943: A>G] polymorphism in CML patients and its role in therapeutic response to imatinib mesylate (IM) affecting clinico-pathological parameters, in the Indian population.
    Materials And Methods
    In this case-control study, CYP1A1*2C was analysed in CML patients. After obtaining approval from the Ethics Committee of oncology hospital, we collected blood samples from 132 CML patients and 140 matched controls. Genomic DNA was extracted and all the samples were analysed for the presence of the CYP1A1*2C polymorphism using allele-specific polymerase chain reaction, and we examined the relationship of genotypes with risk factors such as gender, age, phase of the disease and other clinical parameters.
    Results
    We observed a significant difference in the frequency distribution of CYP1A1*2C genotypes AA (38 vs. 16%, P=0.0001), AG (57 vs. 78%, P=0.0002) and GG (5 vs. 6%, P=0.6635) between patients and controls. In terms of response to IM therapy, significant variation was observed in the frequencies of AA vs. AG in major (33 vs. 67%) and poor 62 vs. 31%) hematological responders, and AA vs. AG in major (34 vs. 65%) and poor (78 vs. 22%) cytogenetic responders. However, the patients with the GG homozygous genotype did not show any significant therapeutic outcome.
    Conclusion
    The higher frequency of AG in controls indicates that AG may play a protective role against developing CML. We also found that patients with the AG genotype showed favorable treatment response towards imatinib therapy, indicating that this polymorphism could serve as a good therapeutic marker in predicting response to such therapy.
    Keywords: Cytochrome P, 450 Enzyme System, CYP1A1, Polymorphism, Chronic Myeloid Leukemia, Imatinib
  • Maryam Salavatifar, Sedigheh Zakeri *, Nasim Hayati Roodbari, Navid Dinparast Djadid Page 520
    Objective
    The apical membrane antigen-1 (AMA-1) is considered as a promising candidate for development of a malaria vaccine against Plasmodium parasites. The correct conformation of this protein appears to be necessary for the stimulation of parasite inhibitory responses, and these responses, in turn, seem to be antibody-mediated. Therefore, in the present investigation, we expressed the Plasmodium vivax AMA-1 (PvAMA-1) ectodomain in Escherichia coli (E. coli), purified it using standard procedures and characterized it to determine its biological activities for it to be used as a potential target for developing a protective and safe vivax malaria vaccine.
    Materials And Methods
    In this experimental investigation, the ectodomain of PvAMA- 1 antigen (GenBank accession no. JX624741) was expressed in the E. coli M15- pQE30 expression system and purified with immobilized-metal affinity chromatography. The correct conformation of the recombinant protein was evaluated by Western blotting and indirect immunofluorescence antibody (IFA) test. In addition, the immunogenic properties of PvAMA-1 were evaluated in BALB/c mice with the purified protein emulsified in Freund’s adjuvant.
    Results
    In the present study, the PvAMA-1 ectodomain was expressed at a high-level (65 mg/L) using a bacterial system. Reduced and non-reduced sodium dodecyl sulfate- polyacrylamide gel electrophoresis (SDS-PAGE) as well as Western blot analysis confirmed the appropriate conformation and folding of PvAMA-1. The evaluation of immunogenic properties of PvAMA-1 showed that both T helper-1 and 2 cells (Th1 and Th2) responses were present in mice after three immunizations and persisted up to one year after the first immunization. Moreover, the antibodies raised against the recombinant PvAMA-1 in injected mice could recognize the native protein localized on P. vivax parasites.
    Conclusion
    We demonstrate that our recombinant protein had proper conformation and folding. Also, there were common epitopes in the recombinant forms corresponding to native proteins. These results; therefore, indicate that the expressed PvAMA-1 has the potential to be used as a vivax malaria vaccine.
    Keywords: Malaria, Plasmodium vivax, Apical Membrane Antigen, 1, Vaccine
  • Gholamhossein Meftahi, Zohreh Ghotbedin, Mohammad Javad Eslamizade, Narges Hosseinmardi, Mahyar Janahmadi* Page 532
    Objective
    Resveratrol, a phytoalexin, has a wide range of desirable biological actions. Despite a growing body of evidence indicating that resveratrol induces changes in neuronal function, little effort, if any, has been made to investigate the cellular effect of resveratrol treatment on intrinsic neuronal properties.
    Materials And Methods
    This experimental study was performed to examine the acute effects of resveratrol (100 μM) on the intrinsic evoked responses of rat Cornu Ammonis (CA1) pyramidal neurons in brain slices, using whole cell patch clamp recording under current clamp conditions.
    Results
    Findings showed that resveratrol treatment caused dramatic changes in evoked responses of pyramidal neurons. Its treatment induced a significant (P<0.05) increase in the after hyperpolarization amplitude of the first evoked action potential. Resveratrol-treated cells displayed a significantly broader action potential (AP) when compared with either control or vehicle-treated groups. In addition, the mean instantaneous firing frequency between the first two action potentials was significantly lower in resveratrol-treated neurons. It also caused a significant reduction in the time to maximum decay of AP. The rheobase current and the utilization time were both significantly greater following resveratrol treatment. Neurons exhibited a significantly depolarized voltage threshold when exposed to resveratrol.
    Conclusion
    Results provide direct electrophysiological evidence for the inhibitory effects of resveratrol on pyramidal neurons, at least in part, by reducing the evoked neural activity.
    Keywords: Resveratrol, Electrophysiology, Action Potential, Neurons, Whole Cell Patch Clamp
  • Mahdieh Azin, Javad Mirnajafi Zadeh, Mohammad Javan* Page 540
    Objective
    Hippocampal insults have been observed in multiple sclerosis (MS) patients. Fibroblast growth factor-2 (FGF2) induces neurogenesis in the hippocampus and enhances the proliferation, migration and differentiation of oligodendrocyte progenitor cells (OPCs). In the current study, we have investigated the effect of FGF2 on the processes of gliotoxin induced demyelination and subsequent remyelination in the hippocampus.
    Materials And Methods
    In this experimental study adult male Sprague-Dawley rats received either saline or lysolecithin (LPC) injections to the right hippocampi. Animals received intraperitoneal (i.p.) injections of FGF2 (5 ng/g) on days 0, 5, 12 and 26 post-LPC. Expressions of myelin basic protein (Mbp) as a marker of myelination, Olig2 as a marker of OPC proliferation, Nestin as a marker of neural progenitor cells, and glial fibrillary acidic protein (Gfap) as a marker of reactive astrocytes were investigated in the right hippocampi by reverse transcriptase-polymerase chain reaction (RT-PCR).
    Results
    There was reduced Mbp expression at seven days after LPC injection, increased expressions of Olig2 and Nestin, and the level of Gfap did not change. FGF2 treatment reversed the expression level of Mbp to the control, significantly enhanced the levels of Olig2 and Nestin, but did not change the level of Gfap. At day-28 post- LPC, the expression level of Mbp was higher than the control in LPC-treated animals that received FGF2. The levels of Olig2, Nestin and Gfap were at the control level in the non-treated LPC group but significantly higher in the FGF2-t reated LPC group.
    Conclusion
    FGF2 enhanced hippocampal myelination and potentiated the recruitment of OPCs and neural stem cells (NSCs) to the lesion area. Long-term application of FGF2 might also enhance astrogliosis in the lesion site.
    Keywords: FGF2, Hippocampus, Neural Stem Cells
  • Mina Sharbatoghli, Mojtaba Rezazadeh Valojerdi*, Mohammad Hadi Bahadori, Reza Salman Yazdi, Leila Rashki Ghaleno Page 547
    Objective
    Melatonin, the chief secretory product of the pineal gland, regulates dynamic physiological adaptations that occur in seasonally breeding mammals as a response to changes in daylight hours. Because of the presence of melatonin in semen and the membrane melatonin receptor in spermatozoa, the impact of melatonin on the regulation of male infertility is still questionable. The aim of this study was to determine the effects of endogenous melatonin on human semen parameters (sperm concentration, motility and normal morphology), DNA fragmentation (DF) and nuclear maturity.
    Materials And Methods
    In this clinical prospective study, semen samples from 75 infertile men were routinely analyzed and assessed for melatonin and total antioxidant capacity (TAC) levels using the enzyme-linked immunosorbent assay (ELISA) and colorimetric assay kits, respectively. DF was examined by the sperm chromatin dispersion (SCD) test. Acidic aniline blue staining was used to detect chromatin defects in the sperm nuclei.
    Results
    There was no significant correlation between seminal plasma melatonin and TAC with sperm parameters and nuclear maturity. However, we observed a positive significant correlation between DF and melatonin level (r=0.273, P<0.05).
    Conclusion
    Melatonin in seminal plasma is positively correlated with damaged sperm DNA of infertile patients. The mechanism of this phenomenon needs further study.
    Keywords: Melatonin, DNA Fragmentation, Antioxidant, Sperm Maturation
  • Hossein Malekzadeh, Maryam Robati, Hojatollah Yousefimanesh *, Mehri Ghafourian Boroujerdnia, Reza Nadripour Page 554
    Objective
    Oral lichen planus (OLP) is a chronic inflammatory disease. Immunological factor may act as etiological factor. The cellular immune cells such as T cells are important in pathogenesis. Interferon gamma (IFN-γ) and interleukin 4 (IL-4) are secreted by T-helper 1 (Th1) and Th2, respectively. The aim of this study was to investigate the correlation between salivary levels of IFN-γ and IL-4 with OLP.
    Materials And Methods
    This case control study included sixty three Iranian OLP patients who were selected from the Department of Oral Medicine of Ahvaz Jundishapur University of Medical Sciences from January to July 2013. An equal number of healthy volunteers were also selected as a control group. The OLP patients were then divided into two following sub-groups: reticular (n=30) and erythematous/ulcerative (n=33). All patients had no systemic disease and received no medication. IFN-γ and IL-4 levels in whole unstimulated saliva (WUS) were measured using the enzyme-linked immunosorbent assay (ELISA) test. Data analysis was done using t test, ANOVA, least significant difference (LSD) test, and the Kruskal-Wallis test.
    Results
    Reticular OLP patients showed higher salivary IFN-γ (7.74 ± 0.09 pg/ml) and IL-4 (3.876 ± 0.05 pg/ml) levels compared with the control group, indicating that difference was significant. Salivary IFN-γ/IL-4 ratio significantly increased compared with control group (P=0.042). Salivary IFN-γ and IL-4 levels between sub-groups (reticular and erythematous/ulcerative) were not significantly different (2.6 ± 0.06 and 2.3 ± 0.05, respectively, P<0.05).
    Conclusion
    Salivary IFN-γ and IL-4 levels were increased in OLP patients. An increase of salivary IFN-γ/IL-4 ratio in OLP patients showed that Th1 might have a dominant role in the OLP pathogenesis.
    Keywords: Lichen Planus, Interleukin, 4, Saliva, Interferon Gamma
  • Hojatollah Yousefimanesh*, Maryam Robati, Hossein Malekzadeh, Mahmoud Jahangirnezhad, Mehri Ghafourian Boroujerdnia, Khadijeh Azadi Page 559
    Objective
    Chronic periodontitis is the most common form of periodontal disease. Changes in biomarkers seem to be associated with the disease progression. Procalcitonin (PCT) is one of these biomarkers that are altered during infection. This study was established to investigate the relationship between periodontitis as an infectious disease and salivary PCT.
    Materials And Methods
    This case-control study was performed on 30 patients with generalized chronic periodontitis and 30 health individuals as control group who were referred to Dental School, Jundishapur University of Ahvaz, Ahvaz, Iran at Feb to Apr 2014. The saliva samples were collected and analyzed by the enzyme-linked immunosorbent assay (ELISA) method. Data analysis was performed using t test with the SPSS (SPSS Inc., Chicago, IL, USA) version 13.
    Results
    In both groups, age and sex distribution values were not significantly different. The concentrations of salivary PCT in controls and patients ranged from 0.081 pg/ mL to 0.109 pg/mL and from 0.078 pg/mL to 0.114 pg/mL, respectively. The statistically significant differences between the two groups were not observed (P=0.17).
    Conclusion
    It seems that salivary PCT concentration is not affected by disease progression. Therefore, PCT is not a valuable marker for the existence of periodontal disease.
    Keywords: Procalcitonin, Periodontal Disease, Saliva, ELISA
  • Mohammad Fazeltabar Malekshah*, Mahsa Sedighi, Kazem Parivar, Homa Mohseni Kouchesfahani, Mohamadali Bigdeli Page 564
    Objective
    Oximes are important materials in organic chemistry. Synparamethyl benzaldehyde oxime (toloaldoxime) is structurally similar to other oximes, hence we have studied its effects on the neonatal and adult female Balb/c mice reproductive systems in order to provide a platform for future studies on the production of female contraceptive drugs.
    Materials And Methods
    In experimental study, we studied the effects of toloaldoxime on ovary growth and gonadal hormones of neonatal and adult Balb/c mice. A regression model for prediction was presented.
    Results
    The effects of toloaldoxime on neonatal mice were more than adult mice. The greatest effect was on the number of Graafian follicles (59.6% in adult mice and 31.83% in neonatal mice). The least effect was on ovary weight, and blood serum levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH).
    Conclusion
    According to the data obtained, toloaldoxime can be considered an antipregnancy substance.
    Keywords: Toloaldoxime, Ovary, Balb, c Mouse, Fertility
  • Ensieh Zahmatkesh*, Gholamreza Najafi, Vahid Nejati Page 569
    Objective
    This study aimed to investigate the effects of royal jelly (RJ) on catalase, total antioxidant capacity and embryo development in adult mice treated with oxymetholone (OXM).
    Materials And Methods
    In this exprimental study, 32 male and 96 female adult Naval Medical Research Institute (NMRI) mice (7-9 weeks of age) with a ratio of 1:3 for fertilization purposes were randomly divided into 4 groups as follows: i. Control group (n=8) receiving 0.1 ml/mice saline daily by gavage for 30 day, ii. RJ group (n=8) treated with RJ at a dose of 100 mg/kg daily by gavage for 30 days, iii. OXM group (n=8) receiving OXM at the dose of 5 mg/kg daily by gavage for 30 days and iv. RJ+OXM group (n=8) receiving RJ at the dose of 100 mg/kg daily by gavage concomitant with 100 mg/kg OXM administration for 30 days.
    Results
    Analysis revealed a significant reduction in catalase, total antioxidant, as well as embryo development in OXM group (P<0.05). However, RJ group showed a salient recovery in the all of the above mentioned parameters and embryo toxicity.
    Conclusion
    The results of this study indicated a partially protective effect of RJ against OXM-induced embryo toxicity.
    Keywords: Catalase, Embryo, Fertilization, Oxymetholone, Royal Jelly
  • Deming Li, Ziwei Li, Xueqiang Guo, Cunshuan Xu* Page 576
    Epidermal growth factor (EGF) is an important factor for healing after tissue damage in diverse experimental models. It plays an important role in liver regeneration (LR). The objective of this experiment is to investigate the methylation variation of 10 CpG sites in the Egf promoter region and their relevance to Egf expression during rat liver regeneration. As a follow up of our previous study, rat liver tissue was collected after rat 2/3 partial hepatectomy (PH) during the re-organization phase (from days 14 to days 28). Liver DNA was extracted and modified by sodium bisulfate. The methylation status of 10 CpG sites in Egf promoter region was determined using bisulfite sequencing polymerase chain reaction (PCR), as BSP method. The results showed that 3 (sites 3, 4 and 9) out of 10 CpG sites have strikingly methylation changes during the re-organization phase compared to the regeneration phase (from 2 hours to 168 hours, P=0.002, 0.048 and 0.018, respectively). Our results showed that methylation modification of CpGs in the Egf promoter region could be restored to the status before PH operation and changes of methylation didn’t affect Egf mRNA expression during the re-organization phase.
    Keywords: Epidermal Growth Factor, Methylation, Liver Regeneration
  • Xiaoguang Chen, Cunshuan Xu* Page 582
    In this article which was published in Cell J, Vol 17, No 2, Summer 2015, on pages 339-354, the name of the first author was published incorrectly as: «Xiaguang Chen». The correct one is «Xiaoguang Chen». This correction was requested by the Corresponding author.