فهرست مطالب

  • Volume:23 Issue:5, 2019
  • تاریخ انتشار: 1398/05/05
  • تعداد عناوین: 8
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  • Reyhaneh Ravanbakhsh Gavgani, Esmaeil Babaei*, Mohammad Ali Hosseinpourfeizi, Ashraf Fakhrjou, Vahid Montazeri Pages 303-311
    Background
    Despite recent advances in diagnosis and treatment, breast cancer remains a leading cause of death in women worldwide. Long non-coding RNAs are a new class of RNA molecules that have been shown to participate in tumorigenesis. The aim of this study was to investigate the expression of lncUSMycN in tumor samples and to evaluate its potential role in the breast cancer cell line.
    Methods
    Real-time polymerase chain reaction was employed to assess lncUSMycN expression in breast tumor tissues and cancer cell lines. Furthermore, small interfering RNA was used to knockdown lncUSMycN.
    Results
    The data showed the significant up-regulation of lncUSMycN in tumor tissues compared to non-tumor specimens (95% CI, p = 0.002). Receiver operating characteristic (ROC) curve analysis demonstrated the biomarker potential of lncUSMycN (ROCAUC = 0.70, p < 0.001) for invasive breast ductal carcinoma. Furthermore, lncUSMycN knockdown induced apoptosis and suppressed cellular migration in breast cancer cells (p < 0.01).
    Conclusion
    The findings highlight the pivotal role of lncUSMycN in tumorigenesis, providing a new potential target for breast cancer therapy.
    Keywords: Breast cancer, Real-time polymerase chain reaction, siRNA
  • Saman Sargazi, Ramin Saravani*, Javad Zavar Reza, Hossein Zarei Jaliani, Hamidreza Galavi, Mahdiyeh Moudi, Najmeh Alsadat Abtahi Pages 312-323
    Background
    Prostate cancer (Pca) is a heterogeneous disease, and current treatments are not based on molecular stratification. Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors have recently been found to be remarkably toxic to cells with defects in homologous recombination, particularly cells with BRCA-mutated backgrounds. Therefore, this preliminary study was designed to evaluate whether PTEN expression status could have an impact on the sensitivity of invasive Pca cells to the PARP inhibitor, AZD2461.
    Methods
    MTT viability test, Annexin V‐FITC/propidium iodide double staining, and caspase3 activity assay were used to evaluate the apoptosis and relative expression of PTEN and VEGF in PC-3 and DU145 cell lines using real-time PCR.
    Results
    MTT results showed that the inhibitory effects of AZD2461 were higher in PC-3 than DU145 cells (with IC50 of 36.48 and 59.03 µM at 48 hours of treatment, respectively). Flow cytometric analysis also showed the same results. When exposed to 40 µM of AZD2461, PC-3 (38.8%) and DU145 (28%) cells underwent apoptosis (p < 0.05). Treatment of cells by AZD2461 also caused a significant increase in apoptosis through caspase3 activation in both cell lines. VEGF mRNA levels in PC-3 cells significantly decreased compared to adjusted untreated cells (p < 0.05) in all measured times while displaying different alteration patterns in DU145 cells (p < 0.05).
    Conclusion
    AZD2461 suppresses the growth of prostate tumor cells since AZD2461 monotherapy could prove to be efficacious, especially against cells not expressing PTEN besides activating the possible apoptosis-independent cell death pathways.
    Keywords: AZD2461, DNA repair, PARP, Prostate neoplasm
  • Mostafa Farzaneh, Mohammad Sayyah*, Hamid Reza Eshraghi, Negar Panahi, Hadi Mirzapourdelavar, Hamid Gholami Pourbadie Pages 324-329
    Background
    A human immunodeficiency virus type 1 (HIV-1)-based lentiviral vector (LV) pseudotyped by a variant of rabies envelope glycoprotein, FUG-B2, has previously been prepared and used in transfection of hippocampal CA1 ("Cornu Ammonis" area 1) neurons. This study aimed to verify reactive gliosis and neuronal damage after injection of the vector into the rat hippocampus.
    Methods
    HEK 293T cells were transfected with transfer (fck-Jaws-GFP-ER2), envelope (FUG-B2), and packaging (pMDLg/pRRE, pRSV-Rev) plasmids, and the vector was injected into CA1 of the rat hippocampus. After one week, transduction efficiency, and the number of neuronal and astroglial cells were determined in CA1 and CA3 by double staining of the brain slices.
    Results
    Hippocampal cells were successfully transfected as 92.7% of CA1 and 95.8% of CA3 neuronal cells expressed GFP. The frequency of neuronal and astroglial cells in CA1 and CA3 of the vector-injected rats remained unchanged compared to those in the control and the saline-injected rats. Furthermore, no morphological change was found in hippocampal astrocytes and neuronal cells.
    Conclusion
    The HIV-1-based LV pseudotyped by FUG-B2 is safe and does not cause neuroinflammation and neuronal loss once directly delivered into the rat hippocampus.
    Keywords: Astrocytes, CA3 region, Rat Rabies virus glycoprotein
  • Fahimeh Yousefinejad, Farideh Jowkar, Shaghik Barani, Elham Jamali, Ebrahim Mahmoudi, Amin Ramezani, Elham Mahmoudi Maymand, Abbas Ghaderi* Pages 330-337
    Background
    The innate immune system against malignancies is mainly orchestrated by natural killer cells, which carry out killing mechanisms by using their receptors, such as killer immunoglobulin-like receptors (KIRs). This study was designed to determine the diversity of KIR genes in non-melanoma skin cancers.
    Methods
    A total of 160 subjects with skin cancer, including 60 cases of squamous cell carcinoma and 100 cases of basal cell carcinoma (BCC), and 270 healthy subjects formed the study groups. The sequence-specific polymerase chain reaction was carried out to detect the presence or absence of 16 KIR genes.
    Results
    KIR3DL1 (p = 0.0381, OR = 4.78, 95% CI = 1.108 to 20.62) increased in BCC patients compared to healthy controls.
    Conclusion
    We concluded that the higher frequency of KIR3DL1 in BCC patients compared with healthy controls may increase the probability of developing BCC in Iranians.
    Keywords: Basal cell carcinoma, KIR, Natural killer cells, Receptors, Squamous cell carcinoma
  • Ali Zare, Behnam Alipoor, Mir Davood Omrani*, Mohammad Reza Zali, Nasser Malekpour Alamdari, Hamid Ghaedi Pages 338-343
    Background
    Gastric cancer (GC) is one of the most prevalent cancers with a high rate of mortality in the world. In recent years, microRNAs (miRNAs) have been proposed to be involved in GC development. In this study, we aimed at investigating differential expression level of miR-155-5p, miR-15a, miR-15b, and miR-186 in GC.
    Methods
    For this research, we used qPCR to investigate miR-15b, miR-155, miR-15a, and miR-186 expression levels in a total of 29 normal gastric tissue, 45 gastric dysplasia, and 39 GC samples.
    Results
    We showed significant down-regulation of miR-155-5p (p = 0.0018), miR-15a (p = 0.0159), and miR-186 (p = 0.0005) expression in GC tissue.
    Conclusion
    This study provides evidence for deregulated expression of miR155-5p, miR-186, and miR-15a in GC and is providing new insights into the potential implication of these miRNAs in the pathogenesis of GC.
    Keywords: Dysplasia, Gastric cancer, MicroRNAs, MicroRNA stomach cancer
  • Hamid Kazemian, Mohammad Reza Pourmand*, Seyed Davar Siadat, Mehdi Mahdavi, Mohammad Hossein Yazdi, Peyman Avakh Majelan, Davoud Afshar, Mehdi Yaseri, Mehdi Davari, Muhammad Ibrahim Getso Pages 343-353
    Background
    Among the enterococci strains, Enterococcus faecalis is considered as one of the important nosocomial pathogens affecting immunocompromised patients. In this study, the immunogenicity of PpiC, GelE, and VS87_01105 proteins against enterococcal infection was investigated in a mice model.
    Methods
    The genes encoding these proteins were cloned into pET21a expression vector, and the recombinant proteins were produced. Mice and rabbits were immunized with the purified recombinant proteins, and subsequently, mice were challenged with E. faecalis for the evaluation of their survival and bacterial clearances. The antibody responses to recombinant proteins were determined by ELISA assay, and opsonophagocytic activities of the antibodies were also measured. Passive immunization was performed using purified antibodies. Mice were challenged, and their survival and bacterial clearance were determined.
    Results
    Immunized mice with PpiC, GelE, and VS87_01105 recombinant proteins showed 80%, 70%, and 40% survival rate, respectively. The survival rates among passively immunized mice that received 500 µg of IgG fraction in 100 µl PBS buffer of each of anti-PpiC, anti-GelE, and anti-VS87_01105 were 60%, 50%, and 20%, respectively. The rates of opsonization with anti-PpiC, anti-GelE, and anti-VS87_01105 antibodies at 1/10 dilution were 77%, 64%, and 23%, respectively.
    Conclusion
    Based on our findings, PpiC, and GelE proteins can protect the mice against E. faecalis ATCC 29212 and effectively induce a protective antibody response. Thus, these proteins could be used as an additional therapeutic tool against enterococcal infections. Further studies to determine the role of PpiC in ligand binding and demonstration of epitope mapping may establish a credible target for vaccination.
    Keywords: Enterococcus, Immunogenicity, Molecular cloning
  • Salman Khan*, Molly Madan, Sunil Kumar Virmani Pages 354-361
    Background
    Genetic changeability of hepatitis B virus (HBV) signifies a challenge for the sensitivity of immunologic and molecular diagnostics. Therefore, knowing the spread of HBV genotypes (GENs) and mutation has considerable impacts on treatment strategies, vaccination program, diagnosis, and prevention. The present study aimed to detect HBV GENs and mutants in HBsAg-positive patients.
    Methods
    The study conducted on 4927 patients in Meerut, India, between March 2013 and April 2017. The blood specimens were analyzed for HBsAg using an ELISA kit, then the blood samples from HBsAg-positive patients were subjected to HBeAg assay and DNA isolation. Amplification of the HBV DNA of pre-S gene and pre-core or basal core promoter region were performed by RT-PCR and sequenced to analyze both GEN and mutation.
    Results
    According to the results, 245 cases were positive for HBsAg, and 55 were HBeAg-positive. With regard to HBV DNA levels, 16 samples were found positive in PCR assay with 7 (43.8%) less than 2000 IU/mL, 4 (25%) between >2000 and 20,000 IU/mL, and 5 (3.25%) >20,000 IU/mL. No mutations were detected in GENs B and A. The prevalence of HBV GENs B and A were 68.8% (n = 11) and 31.25% (n = 6), respectively.
    Conclusion
    GEN-B was more prevalent in comparison to GEN-A. The genetic diversity of HBV and distribution of its GENs and mutation improve the current knowledge of epidemiological, clinical and virological patterns of hepatitis B in this region, which help physicians to prescribe proper antiviral/interferon therapy according to current genotyping pattern.
    Keywords: Genotype, Hepatitis B surface antigens, Hepatitis B virus, India, Mutation
  • Mohammad Saberi, Zahra Golchehre, Arezou Karamzade, Mona Entezam, Yeganeh Eshaghkhani, Elaheh Alavinejad, Hassan Khojasteh Jafari, Mohammad Keramatipour* Pages 362-368
    Background
    Leber congenital amaurosis (LCA) is a rare inherited retinal disease causing severe visual impairment in infancy. It has been reported that 9-15% of LCA cases have mutations in CRB1 gene. The complex of CRB1 protein with other associated proteins affects the determination of cell polarity, orientation, and morphogenesis of photoreceptors. Here, we report three novel pathogenic variants in CRB1 gene and then briefly review the types, prevalence, and correlation of reported mutations in CRB1 gene.
    Methods
    Whole exome sequencing and targeted gene panel were employed. Then validation in the patient and segregation analysis in affected and unaffected members was performed.
    Results
    Our detected novel pathogenic variants (p.Glu703*, c.2128+1G>A and p.Ser758SerfsX33) in CRB1 gene were validated by Sanger sequencing. Segregation analysis confirmed the inheritance pattern of the pathogenic variants.
    Conclusion
    Our findings show that emerging the next-generation sequencing-based techniques is very efficient in identifying causative variants in disorders with locus heterogeneity.
    Keywords: CRB1, Leber congenital amaurosis, Retinal dystrophies, Whole exome sequencing