فهرست مطالب

  • Volume:5 Issue:3, 2018
  • تاریخ انتشار: 1397/08/08
  • تعداد عناوین: 6
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  • Hamid Galehdari , Maryam Mohaghegh , * , Nastaran Majdinasab , Saeid Reza Khatami , Mahshid Hosseini Behbahani Page 1
    Background
    Multiple sclerosis (MS) is known as chronic inflammatory causes demyelination and results in neurodegenerative disease in central nervous system (CNS), which is known with progressive disability. MS is accepted and is a multifactorial disorder that is a result of genetic and environmental factors interaction. The set of genes coding for MHC (major histocompatibility complex) molecules exert the effect on disease development. HLA-A*03 (HLA-A3) is one of HLA class I alleles, which is associated with MS.
    Objectives
    Our goal is to survey the frequency of this allele in MS patients from the Khuzestan province.
    Methods
    HLA-A*03 alleles association was investigated in 200 MS patients in the province of Khuzestan then compared with 195 healthy controls. HLA-typing was performed by polymerase chain reaction (PCR) amplification with SSP-PCR method.
    Results
    Frequency of HLA-A*03 was significant among MS patients (47% vs. 26%, P < 0.001). There was no significant correlation among this allele and sex, course of disease, initial symptoms, and expanded disability status scale (EDSS).
    Conclusions
    Our findings suggested that HLA-A*03 allele has a significant association with MS, which is in line with other studies, and also confirmed that the presence of this allele could increase the risk of MS. Furthermore, positive association between the HLA-A*03 allele and the Arab population in the province of Khuzestan was found. CIS patients followed up for three years demonstrated that all patients were converted to RRMS
    Keywords: Multiple Sclerosis, Human Leucocyte Antigen (HLA), HLA-A*03
  • Saman Sargazi , , Ramin Saravani , , * , Javad Zavar Reza , , ** , Hossein Zarei Jaliani , Shekoufeh Mirinejad , Mahdiyeh Moudi , Hamidreza Galavi Page 2
    Background
    Treatments of advanced cervical cancer are limited to pelvic radiation and chemotherapy while outcomes are disappointing. Poly (ADP-ribose) polymerase inhibitors are highly toxic to cells with defects in DNA repair pathways. The purpose of the current study was to evaluate whether the combination of AZD2461 as a novel poly (ADP-ribose) polymerase 1 inhibitor and a histone deacetylase inhibitor, valproic acid, could be efficacious in Hela cells harboring no mutations in DNA repair pathways.
    Methods
    Cell morphology assay and MTT viability test were performed to determine cytotoxic effects of AZD2461 and valproic acid, separately and in combination. The combination effects were measured using the Chou-Talalay's method.
    Results
    Although the analysis of cell morphology revealed that the combination of the two inhibitors could decrease the viable cells compared to each drug separately, MTT results showed that there was a mild antagonistic effect in the affected fractions of AZD2461/valproic acid-treated Hela cells at all effective doses (CI > 1.1).
    Conclusions
    Our findings from this preliminary study conducted in Spring 2018 suggest that combining valproic acid with AZD2461 exerts mild antagonistic effects on Hela cells harboring no substantial defects in DNA repair pathways
    Keywords: Uterine Cervical Neoplasms, Valproic Acid, AZD2461, Cell Death
  • Elnaz Aghayi , Nazila Moghtaran Bonab , *, Zahra Hojjati Bonab Page 3
    Background
    Breast cancer (BC) is the most common malignancy in women and is the second cause of mortality among patients with different types of cancer. Interleukin 17 (IL-17) is the main cytokine secreted by T helper 17 (Th17) cells. This cytokine promotes a localized tissue inflammation by releasing pro-inflammatory cytokines and chemokines.
    Objectives
    The aim of this study was to investigate the association between rs763780T>C IL-17F and rs2275913G>A IL-17A polymorphisms and BC risk in East Azerbaijan population.
    Methods
    This case-control study consisted of 80 women with BC and 80 healthy controls. Genomic DNA was extracted from peripheral blood, using the salting out method. Genotyping was performed using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP). The statistical analysis was performed using the SPSS software package.
    Results
    The obtained results indicated that there is no significant difference between case and control groups in frequency of genotypes and alleles at rs763780T>C IL-17F and rs2275913G>A IL-17A polymorphisms (P > 0.05). Also, this study found no significant difference between case and control groups in demographic variables.
    Conclusions
    It seems that rs763780T>C IL-17F and rs2275913G>A IL-17A polymorphisms may not play an important role in increasing the susceptibility of women to BC in the population of East Azerbaijan, Iran
    Keywords: Breast Cancer, IL-17F, IL-17A, Polymorphism
  • Nader Kazemi , *, Sadaf Beigi Shahrestani Page 4
    Background
    Stomach cancer is one of the most common cancers in modern societies. B-Cell Lymphoma-2 (Bcl-2) family members are classified to anti-apoptotic and pro-apoptotic groups, based on structural and functional features. The Bcl-2 inhibits apoptosis, while Bax (BCL-2 associated X protein) induces the apoptosis process. Saffron has anti-cancer properties and inhibits tumor genesis. The aim of this study was to investigate the anti-cancer properties of saffron extract and its effect on expression of Bcl-2 and Bax genes in gastric adenocarcinoma cell line (AGS) by real-time polymerase chain reaction (PCR).
    Methods
    In this experiment, aqueous extract of saffron was made and MTT test was performed on AGS cells at concentrations of 0, 200, 400, 800, 1200, and 2000 μg/mL from saffron extract at 48 and 72 hours. The 50% inhibitory concentration (IC50) was calculated for saffron extract at specific doses and times. The AGS cancer cell line was treated by saffron extract with concentrations of 800, 1200, and 2000 μg/mL at 48 and 72 hours. Total RNA was extracted from AGS cells and its concentration and purity was determined. Then, cDNA was synthesized and evaluating the expression of Bcl-2 and Bax genes was performed by real-time PCR. Finally, the obtained results were analyzed by a statistical software.
    Results
    The results of MTT test showed that with increasing concentration of extract and time, disappearance of cancer cells is increased. Thus, saffron extract has high cytotoxicity at high concentrations and in the long-term. The expression of Bax and Bcl-2 genes was also associated with significant increase (P < 0.05) in 800, 1200, and 2000 μg/mL extract doses and at 48 and 72 hours, compared to cells that were not treated with the saffron extract. The overall result of this experiment showed that the ratio of Bax on Bcl-2 expression (Bax/Bcl-2) increased with increasing extract concentration and time. This results in the apoptosis of cancerous cells.
    Conclusions
    Treatment of AGS cells with saffron extract caused an increase in the expression rate of Bax gene in comparison with Bcl-2 gene, and AGS cells were driven towards cell death. According to the obtained results, this effect is dependent on dose and time
    Keywords: Crocus sativus L., Bax, Bcl-2, Gastric Cancer Cell
  • Nassim Faridi , *, Arezou Ghahghaei , ** Page 5
    Heat shock protein 90 (HSP90) serves an essential role in stability and function of over-expressed proteins that promote malignancy. HSP90 guides various cellular and physiological processes/functions such as cell growth, cell survival and differentiation, hormone signaling, trafficking, response to cellular stress, and apoptosis. Conversely, HSP90 during oncogenesis causes malignant transformation and is critical for the maintenance and maturation of a broad range of mutated proteins activated and/or over-expressed in signaling pathways, promoting cancer cell growth and/or survival. Therefore, HSP90 is an attractive target strategy for tumor treatment. We described HSP90 structure and function in normal cells and in malignancy
    Keywords: Chaperones, Heat Shock Protein 90, Cancer
  • Sepehr Navid , Masoud Keikha , * Page 6
    Tuberculosis (TB) is one of the most important infectious diseases and the second leading cause of death by infectious agents after human immunodeficiency virus (HIV) (1). In 1982, all physicians in the worldwide believed that the disease would be controlled by the year 2000 and its discussion would be limited to case reports and medical literature, but this attitude lasted only for ten years where in 1993, TB was declared a global emergency by the World Health Organization (WHO) (2). Nowadays, with regard to the HIV epidemic growth around the world, as well as the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains, the eradication of tuberculosis is thought to be almost impossible (1, 2). According to the World Health Organization (WHO) in 2015, about 2 billion people worldwide are infected with Mycobacterium tuberculosis bacilli although they do not show any symptoms. In addition, 10.4 million new cases and 1.4 million TB-related deaths are estimated (1). Currently, Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is the only available vaccine against tuberculosis that has been used since 1921 to prevent tuberculosis. The BCG vaccine has only protective effects against meningitis and disseminated TB in children while it has minor protective effects and in some cases, no effects against tuberculosis in adults. Numerous clinical trial studies have shown that the protective effects of the BCG vaccine against pulmonary tuberculosis (PTB) range from 0 to 80% (3). In addition, the BCG vaccine does not prevent the reactivation of latent TB. Therefore, it is imperative to develop efficient vaccines against TB in all forms, in particular, latent tuberculosis (4). It is clear that vaccination is one of the most important protection and immunization strategies against infectious diseases, especially tuberculosis. In this regard, various tuberculosis vaccines such as DNA vaccines, viral vector vaccines, subunit vaccines, live-attenuated M. tuberculosis vaccines, recombinant BCG vaccines, and some M. tb antigens have been proposed, among which subunit vaccines are of particular importance. The most important principle in vaccine design is the correct recognition of immunogenic antigen and its presentation to the target system. In this context, adjuvants are very useful because they enhance antigen uptake and presentation of antigen-derived peptides by major histocompatibility complex (MHC) class II on antigen-presenting cells (APCs). Based on clinical studies, it is suggested selecting the early antigens of M. tb during the proliferative phase and the latent phase (4, 5). The most important early antigens include ESAT-6 (6-kDa early-secreted antigen target), CFP-10 (10-kDa culture filtrate protein), peptide 190 - 198 of MPT64, and Ag85B. In addition, HspX protein (16-kDa α-crystallin) and DosR (dormancy survival regulon) are the most important and effective antigens of M. tb during the latent phase of the infection, which can induce proper immune responses in animal and human hosts (6, 7). The immune system is based on two major classes: innate and acquired immunity. An effective immune response is the consequence of the interaction between these two classes. In addition, the acquired immunity consists of humoral and cell-mediated immunity, and the synergy between them is essential for events like affinity maturation, antibody class switching, memory cells formation, IFN-γ production, T follicular helper (Tfh) cells formation, etc. (8). In this regard, it has been suggested that protein fusion containing primary and latent phase antigens attach to the FC region of immunoglobulin G (IgG), which can lead to the longevity of antigen-presenting, facilitation of antigen uptake by APCs (dendritic cells, macrophages, and B lymphocytes), enhanced possibility of cross-priming by dendritic cell (DC), increased solubility of antigens, stability and antigen protection from hydrolysis, correct folding of the antigens (due to the flexible hinge region), easy detection by staphylococcal protein A or polyhistidine-tag (6xHis tag), and easy purification of fusion protein (9, 10). Typically, antigen-derived peptides are expressed by MHC II on DCs, which can stimulate TH1, activate macrophages containing M. tb by IFN-γ production, and eventually eliminate bacteria within the phagolysosome by producing nitric oxide. Moreover, after antigen uptake during cross-priming by DC and antigen processing, antigen-derived peptides are presented to Cytotoxic T lymphocytes (CTLs) by MHC I, ultimately activating CTLs and eliminating the reservoirs of infection (10). The important steps in fusion protein expression are choosing a suitable cloning vector, Codon optimization, and selecting an appropriate host. According to the literature, pUC57 is one of the best vectors, which contains multiple sites for restriction enzymes and it can carry a DNA fragment up to 300,000 nucleotides long. In addition, Pichia pastoris is one of the best systems for the expression of synthetic peptides compared to similar organisms because of its high growth rate, high proliferation capacity on the routine laboratory media, glycosylation, and post-translational modifications. The fusion peptides have been evaluated as one of the most important tuberculosis vaccines. There are 15 candidate vaccines (construction synthetic fusion peptide), which are being evaluated in clinical trials. Of these, H56 and ID93 that lead to an efficient immune response are of BCG vaccine boosters. These candidate vaccines are in phase I of clinical trials while Ag85B and ESAT-6 fusion peptide have entered phase IIa of clinical trials (11). According to the satisfactory results of studies on eukaryotic cell categories, animal models (such as mice, guinea pigs, goats, and monkeys), and clinical trials, there is a strong hope that the synthetic fusion proteins will be developed by the researchers and change to M. tb vaccines with higher potentials in comparison with the present vaccine, Mycobacterium bovis Bacille Calmette-Guérin (BCG vaccine) (6, 11-13). So far, multiple vaccines consisting of fusion protein constructs containing M. tb antigens have been synthesized and used in numerous laboratory animal studies and clinical trials, leading to satisfactory results (12, 14, 15). Currently, fusion proteins are widely used in such studies, and there is almost a general belief in the acceptance of synthetic peptides as a vaccine for tuberculosis (TB). However, this strategy requires more evolution in clinical trials for final approval (16).