فهرست مطالب

Research in Molecular Medicine
Volume:6 Issue: 3, Aug 2018

  • تاریخ انتشار: 1397/05/10
  • تعداد عناوین: 6
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  • Leili Sadeghi Amiri*, Ali Barzegar, Alireza Rafiei, Omolbanin Amjadi Pages 1-19
    The five leading causes of cancer-related deaths are lung (1,760,000 deaths), colorectal (862,000 deaths), stomach (783,000 deaths), liver (782,000 deaths), and breast (627,000 deaths) cancers. Epigenetic changes can alter chromatin compaction, leading to the regulation of geneexpression without changing the primary DNA sequence.Epigenetic mechanisms are normally involved incellular processes such asgenomic stability, chromosome X inactivation, and embryonic development and differentiation. Similar to other types of chromatin modifications, DNA methylation has been verifiedto affect the expression of various genes. Any impairment in these mechanisms alters the regulation of gene expression and can contribute to malignant cell transformation. Over the past few years, extensive innovations within the field of epigenetics have encouraged its application as a major strategy for the treatment of important diseases such as cancer.
    Keywords: Cancer, epigenetic, methylation, gene expression
  • Sepideh Khalili Savadkouhi, Abbasali Karimpour Malekshah, Mehri Mirhoseini*, Mahmood Moosazadeh, Maryam Shahidi Pages 20-28
    Background
    In vitro culture of mammalian embryos can slow or stop growth completely. This may be due to the medium used, pH, temperature, or light. There is considerable concern about the harmful effect of light in the laboratory environment.
    Cell number and apoptosis are useful parameters that indicate embryonic development and health. In this study, we assessed these two factors in the blastocyst.
    Materials and methods
    A total of 128 embryos were extracted from NMRI mice at the 2-cell stage and were divided into 4 groups. The embryos were exposed to light for 0, 5, 15, and 30 min, and then cultured for 96 h. The degree of embryonic development were recorded every 24 h. Furthermore, several morphologically normal blastocysts were evaluated using the TUNEL assay.
    Results
    There was no significant difference in developmental stages between the experimental and control groups. An evaluation of the percentage of blastomeres and apoptotic cells revealed significant differences among the four groups. The maximum number of apoptotic blastomeres was observed in the group exposed to light for 30 minutes.
    Conclusion
    Up to thirty minutes of white fluorescent light can induce apoptosis in blastomeres, but it does not prevent embryo development.
    Keywords: Apoptosis, Blastocyst, Mice, light, Embryonic Structures
  • Farhad Gilavand, Amirarsalan Kavyanifard, Abdolrazagh Marzban* Pages 29-44
    Background
    L-Asparaginase (L-Asp) is used as an efficient anti-cancer drug, especially for acute lymphoblastic leukemia (ALL). Currently, two bacterial asparaginase isoenzymes are used for cancer treatment. Therefore, this research focused on isolating native bacteria with the ability to produce L-Asp.
    Materials and methods
    L-Asp producing bacteria were isolated from soil samples on 9K medium supplemented with L-Asp as nitrogen source. Detection of L-Asp activity was performed by observing color change of the agar medium from yellow to orange due to the release of ammonia around the colonies. After the isolation and identification of the bacterium, L-Asp production was first optimized by the one factor-at-the-time (OFAT) technique followed by the response surface method. Next, the enzyme was extracted, purified, and assessed for antileukemia activity on U937 and MRC-5 cell lines.
    Results
    The results revealed that L-Asp produced by Rouxiella sp. AF1 significantly inhibited the growth of U937 cells at a dose of up to 0.04 IU/ml, while MRC-5 was not affected at any enzyme doses. The final purification of the enzyme was achieved by column chromatography (Sephadex G-100) at approximately 0.31 mg/ml, and its specific activity was determined to be 0.51 IU/mg. The OFAT optimization experiments were performed primarily to determine optimal enzyme conditions, which were found to be neutral pH (pH7), 30 °C temperature, and 3 % NaCl, 1 % peptone, and 1% glucose concentrations. Statistical optimization   was based on five factors obtained from OFAT, and response surface method  (RSM) analysis introduced a quadratic model for enzyme production at the optimal range of these variables. This model provided an equation for measuring the effect of physiochemical conditions on final enzyme production.
    Conclusion
    We showed that native bacteria may be novel candidates for isolating new metabolites such as L-Asp. Because many bacteria grow in unknown environments with unique ecological properties, the probability of discovering novel bacterial species producing bioactive compounds is high.
    Keywords: L- Asapaginase, Antileukemia activity, Rouxiella sp. AF1, Response Surface Method
  • Faezeh Namazi, Nasrin Hadi, Mansour Moghimi, Amir Eshaghiyan, Behnaz Nateghi* Pages 45-53
    Background
    Chronic lymphocytic leukemia (CLL) is the most common adult human leukemia. Studies revealed that microRNAs (miRNAs) can function as oncogenes or tumor suppressors in CLL and that the expression of miRNAs, such as miR-193b-3p and miR-376a-3p change in several diseases. We aimed to elucidate the changes in miR-193b-3p and miR-376a-3p expression in CLL and determine their potential as diagnostic biomarkers for this disease.
    Materials and methods
    We investigated miR-193b-3p and miR-376a-3p expression by quantitative real-time PCR in peripheral blood mononuclear cells of 30 patients with CLL and 30 healthy individuals. Moreover, in silico molecular enrichment analysis was conducted on predicted and validated targets of miR-193b-3p and miR-376a-3p from the miRecords and miRTarBase databases.
    Results
    The expression of miR-193b-3p and miR-376a-3p was significantly different between the two groups (P<0.0001 and P < 0.0001, respectively).
    Conclusion
    Based on these findings, miR-193b-3p and miR-376a-3p could be novel biomarkers for the early diagnosis of CLL and could be used to design new CLL control strategies.
    Keywords: chronic lymphocytic leukemia, miR-193b-3p, miR-376a-3p, miRNA
  • Jaber Zafari*, Hossein Vazini, Fatemeh Javani Jouni, Parviz Abdolmaleki, Ramesh Monajemi, Elahe Shams, Mohammad Satari Pages 54-64
    Background
    Expansion of the use of magnetic fields in metals, mining, transport, research, and medicine industries has led to a discussion about the effects of magnetic fields and whether their strength is negligible. The aim of this study was to investigate the effects of magnetic field on the viability and proliferation rate of HeLa cells.
    Materials and methods
    We studied the effects of magnetic field on the viability, proliferation rate and membrane lipid peroxidation of cells, thus, HeLa cells (cancer cells) and human fibroblast cells (normal cells) were used. Initially, the cells were cultured in DMEM and to determine the impact of the magnetic field, the cells were treated with magnetic field at 4 specific intensity levels (0, 7, 14 and 21 mT) and 2 exposure times (24 h and 48 h). The viability percentage and inhibition of cell proliferation were calculated by MTT assay and Trypan blue staining, respectively.
    Results
    Lipid peroxidation of the cell membrane was examined by malondialdehyde (MDA) method. As the intensity and exposure time of the static magnetic field (SMF) increased, the viability percentage and proliferation rate decreased and the lipid peroxidation levels increased in the Hela cells.
    Conclusion
    In this study, we have shown the anticancer effects of static magnetic field and propose a suitable intensity range that can be effective for the treatment of cancer.
    Keywords: Fibroblast cells, Human cervical cancer (HeLa) cell line, Pproliferation rate, Viability percent, Lipid peroxidation
  • Golzar Farhadi, Jamal Fayazi*, Hedayat Allah Roshanfekr, Mahmoud Nazari, Elham Behdani Pages 65-89
    Background
     Oocyte maturity includes nuclear and cytoplasmic maturity, both of which are important for embryo fertilization. The development of oocyte is not limited to the period of follicular growth, and starts from the embryonic period and continues throughout life. In this study, for the purpose of evaluating the effect of the FSH hormone on the expression of genes, GEO access codes for this data set, GSE38345, were used.
    Materials and methods
    The data are microarray and contain the gene expression information for cow's oocyte cells, that their maturation is influenced by the FSH hormone under laboratory conditions. Data analysis was performed by using the GEO2R software link. After identifying the genes and examining the different genes expressed, two gene groups included Increased and decreased expression genes are formed. The interaction of each of the gene groups was examined by using a string database, based on the co-expression information. The meaningful sub networks were explored using the clusterone software. Gene ontology was performed using the comparative GO database. The miRNA-mRNA interaction network was also studied based on the miRWalk database. Finally, meaningful networks and subnets obtained by cytoscape software were drawn.
    Results
     In a comparison between oocyte gene expression data in the pre-maturation and the post- maturation stage after treatment with FSH, 5958 increased genes and 4275 decreased genes expression were found. By examining the protein interaction network in the set of increased and decreased expression genes, based on string information, 262 increased and 147 decreased genes (high confidence (0.7) data) were found. In network of Increased expression genes in oocyte maturation, the RPS3, NUSAP1, TBL3 and ATP5H genes which are effective in the biological pathways of positive regulation of rRNA processing, cell division, mitochondrial ATP synthesis coupled proton, also in functional pathways, oxidative phosphorylation and progesterone-mediated were effective, also in decreased expression genes, WDR46 and MRPL22 genes are the most important that were effective in the biological pathways of SRP-dependent cotranslational proteins in targeting to membrane, RNA secondary structure, unwinding and functional pathways of ribosomal and RNA polymerase. The most important microarray gene in the protein network of increased and decreased expression genes bta-miR-10b-5p and miR-29b-2-5p gene were reported.
    Conclusion
    In examining the genes expressed in the pathway of oocyte maturation, three groups of nuclear, mitochondria, microarray genes were determined. Increasing and decreasing gene expression helps maintain balance, which can be considered as a marker.
    Keywords: Oocyte maturation, Microarray data, expressed genes, FSH hormone