فهرست مطالب

Iranian Biomedical Journal - Volume:23 Issue: 3, May 2019

Iranian Biomedical Journal
Volume:23 Issue: 3, May 2019

  • تاریخ انتشار: 1398/01/17
  • تعداد عناوین: 8
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  • Shirin Shahbazi, Reza Mahdian* Pages 165-174
    Coagulation factors belong to a family of plasma glycosylated proteins that should be activated for appropriate blood coagulation. Congenital deficiencies of these factors cause inheritable hemorrhagic diseases. Factor VII (FVII) deficiency is a rare bleeding disorder with variable clinical symptoms. Various mutations have been identified throughout the F7 gene and can affect all the protein domains. The results of previous experiments have partly revealed the correlation between genotype and phenotype in patients with FVII deficiency. Nevertheless, each particular variant may affect the coagulative function of FVII, mainly via altering its expression level, extra-cellular secretion, tissue factor binding affinity, or proteolytic activity. The pathogenicity of the variants and molecular mechanisms responsible for clinical symptoms in patients with FVII deficiency should be characterized via in silico and in vitro, as well as in vivo functional studies. This review has highlighted the most important functional studies reported on F7 gene variants, including relevant reports regarding Iranian FVII deficiency patients.
    Keywords: Factor VII deficiency, in vitro techniques, mutation
  • Saeid Afshar, Sepideh Afshar, Emily Warden, Hamed Manochehri, Massoud Saidijam* Pages 175-183
    Background
    The early diagnosis of colorectal cancer (CRC) is associated with improved survival rates, and development of novel non-invasive, sensitive, and specific diagnostic tests is highly demanded. The objective of this paper was to identify commonly circulating microRNA (miRNA) biomarkers for use in CRC diagnosis.
    Methods
    For this purpose, an artificial neural network (ANN) model was proposed. Among miRNAs retrieved from the Gene Expression Omnibus dataset, four miRNAs with the best miRNA score were selected by ANN units.
    Results
    The simulation results showed that the designed ANN model could accurately classify the sample data into cancerous or non-cancerous. Furthermore, based on the results of evaluated ANN model, the area under the ROC curve (AUC) of the designed ANN model as well as the regression coefficient between the output of the ANN and the expected output was one. The confusion matrix of the ANN model indicated that all non-cancerous patients were predicted as normal, and the cancerous patients as cancerous.
    Conclusion
    Our findings suggest that the improved model can be used as a robust prediction toolbox for cancer diagnosis. In conclusion, by using ANN, circulatory miRNAs can be used as a non-invasive, sensitive and specific diagnostic marker.
    Keywords: Artificial neural network, Biomarkers, Colorectal neoplasms, Diagnosis, MicroRNAs
  • Omid Emadian Saravi, Farshad Naghshvar, Zhila Torabizadeh*, Somayeh Sheidaei Pages 184-189
    Background
    Cancer stem cells (CSCs) are a group of tumor cells with self-renewal property and differentiation potential. CSCs play a crucial role in malignant progression of several types of tumors. However, what is still controversial is the clinicopathological relationship between Nanog marker and its prognostic value in the patients with breast cancer. The expression of Nanog in the patients with breast cancer and its correlation with clinicopathological prognostic factors was explored in the present study.
    Methods
    A sample of 120 breast cancer tissues was obtained from the patients who referred to Imam Khomeini Hospital in Sari city, Iran during January 2012 and December 2016. The associations between Nanog expression and clinicopathological factors were analyzed based on immunohistochemical analysis.
    Results
    It was found that 67 (55.8%) patients had Nanog expression, and high expression rate was observed in 24 (36%) cases (staining index ≥3). Moreover, there was a statistically significant relationship between Nanog expression and clinicopathological factors, including tumor grade (p = 0.001), lymph node metastasis (p = 0.01), and the stage of the disease (p = 0.003).
    Conclusion
    Findings of the study indicate that Nanog is a biomarker for prognostic prediction in patients with breast cancer. However, further studies of Nanog are suggested to provide novel therapeutic targets for curing breast cancer.
    Keywords: Breast cancer, Immunohistochemistry, Nanog homeobox protein
  • Pawan Kumar*, Brijnandan S. Dehiya, Anil Sindhu Pages 190-199
    Background
    This study addressed the development of biodegradable and biocompatible scaffolds with enhanced biomechanical characteristics. The biocompatibility and the cationic nature of chitosan (CTS) make it more effective as a bone grafting material.
    Methods
    The hydroxyapatite nanoparticles (nHA) were synthesized by hydrothermal method, and bioglass (nBG) (50% SiO2-45% CaO-5% P2O5) was synthesized using sol-gel method. The ibuprofen-loaded CTS/nHA and CTS/nBG scaffolds were fabricated by using freeze-drying method.
    Results
    Transmission electron microscopy image of nHA and nBG revealed the particles of less than 200 nm. The scanning electron microscopy (SEM) images of CTS/nHA and CTS/nBG scaffolds showed pore sizes ranging from 84-190 µm. The physiochemical characteristics of synthesized ceramic nanoparticles and scaffolds analyzed by XRD were confirmed by ICDD 9-432. The porosity of scaffolds was measured by using SEM, Brunauer-Emmett-Teller method and Archimedes’ principle. The open porosities of CTS/nBG and CTS/nHA samples were 29% and 31%, respectively. The compressive strength of scaffolds was evaluated by stress vs. strain curve. The CTS/nHA scaffold revealed 4% more water retention capacity than CTS/nBG scaffold. In the presence of lysozyme, CTS/nBG scaffold degraded 32.8%, while CTS/nHA degraded 26.1% in PBS solution at pH 7.4. The density of all scaffolds was found (1.9824 g/cm-3 and 1.9338 g/cm-3) to be nearly similar to that of the dry bone (0.8-1.2 g/cm-3). Fibroblast cells multiplied two times in the sample medium of CTS/nBG after 14 days. After 72 h, CTS/nBG and CTS/nHA scaffolds demonstrated 52% and 46% drug release, respectively.
    Conclusion
    Based on our findings, ibuprofen-loaded scaffolds could be an effective drug delivery system for tissue engineering applications.
    Keywords: Chitosan, Fibroblast, Ibuprofen, Nanoparticles
  • Ladan Jalalie, Mohammad Jafar Rezaie*, Ali Jalili, Mohammad Ali Rezaee, Zakaria Vahabzadeh, Mohammad Reza Rahmani, Mojtaba Karimipoor, Mohammad Saeed Hakhamaneshi Pages 200-208
    Background
    Mesenchymal stem cells (MSCs) can be used to treat premature ovarian failure (POF). Different methods have already been applied to detect MSCs in tissues. This study aimed to investigate the quantitative distribution of CM-DiI-labeled human umbilical cord vein MSCs (hUCV-MSCs) in different regions of the ovarian tissue of the cyclophosphamide ( CTX )-induced POF in mice.
    Methods
    Adult female C57BL/6 mice (n = 40) were divided into four groups: (1) Mice receiving PBS as control (Ctrl) group; (2) mice receiving hUCV-MSCs intravenously as Ctrl + hUCV-MSCs group; (3) mice receiving CTX intraperitoneally (i.p.) as CTX group; (4) mice receiving CM-DiI-labeled hUCV-MSCs after CTX injection as CTX + hUCV-MSCs group. Histological changes and CM-DiI-labeled hUCV-MSCs distribution were analyzed in the ovarian tissues. Quantitative real-time PCR was performed to detect human mitochondrial cytochrome b (MTCYB) gene in the ovarian tissues of the mice.
    Results
    The mean number of the fluorescent hUCV-MSCs was 20 ± 2.5 (57.1%) in the medulla, 11.3 ± 2.8 (32.2%) in the cortex, and 5.5 ± 1 (15%) in the germinal epithelium of the ovarian tissue (p < 0.05). Moreover, MTCYB gene was detected in the mice ovaries of the CTX + hUCV-MSCs group, but not in other groups.
    Conclusion
    Our findings suggest that the distribution of the transplanted hUCV-MSCs in different regions of the ovarian tissue is not equal, and it is greater in the medulla than the cortex and germinal epithelium. This is the first report of quantitative distribution of MSCs in different regions of ovarian tissue in the POF model.
    Keywords: Cyclophosphamide, Mesenchymal stem cells, Premature ovarian failure, Transplantation
  • Leila Hatami, Giklou Jajan, Seyed Nezamedin Hosseini, Masoud Ghorbani, Seyed Fazlollah Mousavi, Behzad Ghareyazie, Mohsen Abolhassani* Pages 209-219
    Background
     Magnetotactic bacteria are a heterogeneous group of Gram-negative prokaryote cells that produce linear chains of magnetic particles called magnetosomes, intracellular organelles composed of magnetic iron particles. Many important applications have been defined for magnetic nanoparticles in biotechnology, such as cell separation applications and  acting as carriers of enzymes, antibodies or anti-cancer drugs. Since the bacterial growth is difficult and the yield of magnetosome production is low, the application of magnetosome has not been developed on a commercial scale.
    Methods
    Magnetospirillum gryphiswaldense strain MSR-1 was used in a modified current culture medium supplemented by different concentrations of oxygen, iron, carbon, and nitrogen, to increase the yield of magnetosomes.
    Results
    Our improved MSR-1 culture medium increased magnetosome yield, magnetosome number per bacterial cell, magnetic response, and bacterial cell growth yield significantly.  The yield of magnetosome increased approximately four times. The optimized culture medium containing 25 mM of Na-pyruvate, 40 mM of NaNO3, 200 µM of ferrous sulfate, and 5-10 ppm of dissolved oxygen (DO) resulted in 186.67 mg of magnetosome per liter of culture medium.  The iron uptake increased significantly, and the magnetic response of the bacteria to the magnetic field was higher than threefold as compared to the previously reported procedures.
    Conclusion
    This technique not only decreases the cultivation time but also reduces the production cost. In this modified method, the iron and DO are the major factors affecting the production of magnetosome by M. gryphiswaldense strain MSR-1. However, refining this technique will enable a further yield of magnetosome and cell density.
    Keywords: Conditioned culture medium, Magnetosomes, Magnetospirillum gryphiswaldense MSR-1
  • Zohreh Hojati*, Elaheh Soleimanpour, Seyed, Morteza Javadirad, Mohammad Hossein Nasr, Esfahani Pages 220-227
    Background
    KDM3A is a key epigenetic regulator that is expressed in the testis and is required for packaging and condensation of sperm chromatin. To this point, the association of the KDM3A gene and infertility has not been studied in human. The aim of this study was to screen any new mutation in KDM3A gene to explore more details of human male infertility.
    Methods
    In this work, 150 infertile men (oligozoospermia and azoospermia) and 150 normal healthy fathers were studied.  Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and sequencing were used to screen for any mutation in exons 12, 22, and 24 of KDM3A.  
    Results
    The infertile men showed various SSCP patterns for the exons 12 and 24, but not for exon 22. A transversion point mutation in exon 12 and a single nucleotide deletion in exon 24 were detected using sequencing analysis. The transversion mutation was located in the preceding exon of lysine-specific demethylase1 and Jumonji (Jmj)-C domain and the later one (deletion) in the cupin-like motif of KDM3A protein. Neither Y chromosome microdeletions nor partial azoospermia factor deletion was found in these patients.
    Conclusion
    The mutations found in infertile men with otherwise unexplained severe spermatogenic failure could be considered as the origin of their abnormalities.
    Keywords: KDM3A, Male infertility, Spermatogenic failure
  • Azam Amirian, Zahra Zafari, Morteza Karimipoor, Alireza Kordafshari, Mohammad Dalili, Siamak Saber, Amir Farjam Fazelifar, Sirous Zeinali* Pages 228-234
    Background
    Long QT syndrome (LQTS) is characterized by the prolongation of QT interval, which results in syncope and sudden cardiac death in young people. KCNQ1 is the most common gene responsible for this syndrome.
    Methods
    Molecular investigation was performed by DNA Sanger sequencing in Iranian families with a history of syncope. In silico examinations were performed for predicting the pathogenicity of the novel variant.
    Results
    A novel homozygous KCNQ1 frameshift mutation, c.1426_1429delATGC (M476Pfs*4), was identified, and then the current literatures of five patients were reviewed regarding the LQTS.
    Conclusion
    The novel frameshift mutation has been reported for the first time among the Iranian population. Our finding along with the case series study of LQTS patients illustrates the importance of genetic and case series in precise detection of the frequency of LQTS carriers.
    Keywords: Jervell-Lange‐Nielsen syndrome, KCNQ1, Long QT syndrome, Romano-Ward syndrome