فهرست مطالب

Iranian Biomedical Journal
Volume:22 Issue: 3, May 2018

  • تاریخ انتشار: 1397/01/15
  • تعداد عناوین: 10
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  • Marjan Mohammadi * Pages 138-139
    There is an enormous number of astounding scientists, who have made their mark in science. Very few of them also serve as a true mentor, ready to provide a helping hand to young researchers, especially those in developing countries, who must constantly struggle to remain optimistic. Professor David Y. Graham is one of these rare characters.
    He received his undergraduate degree from the University of Notre Dame in South Bend, Indiana, his M.D. degree with honor from Baylor College of Medicine in 1966, and is board-certified in Medicine and Gastroenterology. He is currently a staff physician at the Michael E. DeBakey VA Medical Center and a professor in the Departments of Medicine and Molecular Virology and Microbiology at Baylor College of Medicine, in Houston, Texas. His first research paper was published in 1967. Since then, his research interests have varied widely, but have generally been focused on the acid-peptic diseases and the role of infectious agents in gastrointestinal disorders. He has also been interested in the exocrine pancreatic insufficiency and his first paper on this subject (as a single-authored paper) was published in the New England Journal of Medicine in 1977[1]. His latest paper on this topic was published in 2016[2]. His interest in the possible infectious etiology of inflammatory bowel disease took him into the area of viral gastroenteritis, where he, working with Dr. Mary K. Estes, made major advances in both rotavirus and norovirus gastroenteritis, including the recent report of finally being able to cultivate the previously uncultivable noroviruses in vitro[3]. He has continued his work on the infectious cause of Crohn’s disease and is currently the lead investigator on a multicenter trial of antimicrobials to treat Mycobacterium paratuberculosis in Crohn’s patients...
  • Farzin Roohvand * Pages 140-140
    Thrombotic disorders, such as myocardial infarction, ischemic stroke, peripheral arterial disease, deep venous thrombosis, pulmonary embolism, or other embolic diseases that are responsible for worldwide mortality and morbidity, are manifestations of the formed thrombi by blood clots during a pathologic blood coagulation process. Once thrombi are formed, the only way to resolve the blood clot is treatment with specific thrombolytic agents, so called plasminogen activators (PAs), such as tissue-PAs (tPAs), urokinase, and streptokinase (SK). PAs convert the endogenous human plasminogen (HPG: the inactive proenzyme) to plasmin (HPM: the active enzyme), which cleaves the fibrin network of the blood clot, a process known as fibrinolysis (Fig. 1)...
  • Fatemeh Khatami, Seyed Mohammad Tavangar * Pages 142-150
    Medullary thyroid carcinoma (MTC) is an infrequent calcitonin-producing neuroendocrine tumor that initiates from the parafollicular C cells of the thyroid gland. Several genetic and epigenetic alterations are collaterally responsible for medullary thyroid carcinogenesis. In this review article, we shed light on all the genetic and epigenetic hallmarks of MTC. From the genetic perspective, RET, HRAS, and KRAS are the most important genes that are characterized in MTC. From the epigenetic perspective, Ras-association domain family member 1A, telomerase reverse transcriptase promoter methylations, overexpression of histone methyltransferases, EZH2 and SMYD3, and wide ranging increase and decrease in non-coding RNAs can be responsible for medullary thyroid carcinogenesis.
    Keywords: Thyroid carcinoma, Genetic markers, Proto, oncogene
  • Mahshid Bazrafkan *, Banafsheh Nikmehr, Abdolhossein Shahverdi, Seyed Reza Hosseini, Fatemeh Hassani, Mahnaz Poorhassan, Tahmineh Mokhtari, Farid Abolhassani, Hamid Choobineh, Cordian Beyer, Gholamreza Hassanzadeh Pages 151-159
    Background
    The majority of male patients with spinal cord injury (SCI) suffer from infertility. Nucleotide-binding oligomerization domain-like receptors NOD-like receptors (NLRs) are a kind of receptors that corporate in the inflammasome complex. Recent studies have introduced the inflammasome as the responsible agent for secreting cytokines in semen. Reactive oxygen species (ROS) is one of the elements that trigger inflammasome activation. Genital infections in SCI can lead to ROS generation. We investigated the relation between lipid peroxidation and inflammasome complex activity in testicular tissue of SCI rats.
    Methods
    Adult male rats (n=20), weighting 200-250 g, were included and divided into four groups: three experimental groups, including SCI1, SCI3, and SCI7, i.e. the rats were subjected to SCI procedure and sacrificed after one, three, and seven days, respectively and a control group. We performed a moderate, midline spinal contusion injury at thoracic level 10. The animals were anesthetized, and testes were collected for measurement of gene expression by real-time PCR. Caudal parts of epididymis were collected for malondialdehyde (MDA) measurement.
    Results
    No NLRP1a mRNA overexpression was seen in the testes of control and SCI groups. After seven days from SCI surgery, NLRP3 mRNA expression was significantly increased in SCI7 animals (p ≤ 0.05). There was a significant difference in MDA level in SCI7 versus control group, as well as SCI1 and SCI3 animals (p ≤ 0.05).
    Conclusion
    NLRP3 overexpression occurs due to the increased ROS production in testis tissue of SCI rats.
    Keywords: Infertility, Lipid peroxidation, Testis, Spinal cord injuries
  • Mandana Afsharpad *, Mohammad Reza Nowroozi, Mohsen Ayati, Mojtaba Saffari, Saeed Nemati, Elham Mohebbi, Leila Nekoohesh, Kazem Zendehdel, Mohammad Hossein Modarressi Pages 160-170
    Background
    This study aimed to evaluate the diagnostic value of outer dense fiber 4 (ODF4), melanoma-associated antigen A3 (MAGEA3), and MAGEAB4 mRNAs in transitional cell carcinoma (TCC), using a small amount of cell reverse transcriptase-polymerase chain reaction (RT-PCR) on urinary exfoliated cells.
    Methods
    We recruited a total of 105 suspected TCC patients and 54 sex- and age-matched non-TCC controls. The candidates’ genetic expression patterns were investigated with RT-PCR, while reverse transcription quantitative PCR was applied to quantify and compare each mRNA level between cases and control groups.
    Results
    The sensitivity of ODF4, MAGEA3, and MAGEAB4 RT-PCR was 54.8%, 63%, and 53.4%, whereas the specificity was 73.7%, 86%, and 94.7%, respectively. Combining ODF4, MAGEA3, and MAGEAB4 RT-PCR offered a relatively higher sensitivity (83.6%).
    Conclusion
    RT-PCR with ODF4, MAGEA3, and MAGEAB4 on urinary exfoliated cells could provide clinicians with a promising method to improve TCC diagnosis, especially in the case of gross hematuria and catheterization. The method used here is non-invasive, simple and convenient, and unlike cytology, it does not rely directly on expert professional opinions. These features can be of particular importance to the management of TCC patients in whom regular and lifelong surveillance is required.
    Keywords: Transitional cell carcinoma_Clinical markers_Cancer testis antigen_Human outer dense fiber of sperm tails 4 protein
  • Molood Shariati, Samira Hajigholami, Ziba Veisi Malekshahi, Maliheh Entezari, Narges Bodaghabadi, Majid Sadeghizadeh * Pages 171-179
    Background
    Curcumin, extracted from turmeric, represents enormous potential to serve as an anticancer agent. Telomerase is viewed as a prominent molecular target of curcumin, and transforming growth factor-β1 (TGFβ1) has proven to be a major inhibitory signaling pathway for telomerase activity. In the current study, we aimed to explore suppressive effects of nanocurcumin on telomerase expression through TGFβ1 pathway in a hepatocellular carcinoma cell line (Huh7).
    Methods
    MTT assay was used to determine the effect of nonocurcumin on viability of Huh7 cells. RT-PCR was used to analyze the gene expression patterns.
    Results
    MTT assay revealed that nanocurcumin acts in a dose- and time-dependent manner to diminish the cell viability.
    RT-PCR analysis indicated that nanocurcumin results in augmentation of TGFβ1 72 hours post treatment and leads to the reduction of telomerase expression 48 and 72 hours post exposure. Also, up-regulation of Smad3 and E2F1 and down-regulation of Smad7 confirmed the effect of nanocurcumin on intermediate components of TGFβ1 pathway. Furthermore, transfection of the proximal promoter of telomerase triggered a significant
    reduction in luciferase activity.
    Conclusion
    The data from the present study lead us to develop a deeper understanding of the mechanisms underlying nanocurcumin-mediated regulation of telomerase expression, thereby presenting a new perspective to the landscape of using nanocurcumin as a cancer-oriented therapeutic agent.
    Keywords: Hepatocellular carcinoma, Telomerase, Gene expression
  • Zahra Payandeh, Masoumeh Rajabibazl *, Yousef Mortazavi, Azam Rahimpour, Amir Hossein Taromchi Pages 180-192
    Background
    Ofatumumab, an anti-CD20 mAb, was approved in 2009 for the treatment of chronic lymphocytic leukemia. This mAb acts through immune-mediated mechanisms, in particular complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity by natural killer cells as well as antibody-dependent phagocytosis by macrophages. Apoptosis induction is another mechanism of this antibody. Computational docking is the method of predicting the conformation of an antibody-antigen from its separated elements. Validation of the designed antibodies is carried out by docking tools. Increased affinity enhances the biological action of the antibody, which in turn improves the therapeutic effects. Furthermore, the increased antibody affinity can reduce the therapeutic dose of the antibody, resulting in lower toxicity and handling cost.
    Methods
    Considering the importance of this issue, using in silico analysis such as docking and molecular dynamics, we aimed to find the important amino acids of the Ofatumumab antibody and then replaced these amino acids with others to improve antibody-binding affinity. Finally, we examined the binding affinity of antibody variants to antigen.
    Results
    Our findings showed that variant 3 mutations have improved the characteristics of antibody binding compared to normal Ofatumumab antibodies.
    Conclusion
    The designed anti-CD20 antibodies showed potentiality for improved affinity in comparison to commercial Ofatumumab.
    Keywords: Monoclonal antibody, Ofatumumab, Protein engineering
  • Kimia Mirzakhani *, Seyed Latif Mousavi Gargari, Iraj Rasooli, Samaneh Rasoulinejad Pages 193-201
    Background
    Artificial oligonucleotides like DNA or RNA aptamers can be used as biodiagnostic alternatives for antibodies to detect pathogens. Comparing to antibodies, artificial oligonucleotides are produced easily at lower costs and are more stable. Neisseria meningitidis, the causative agent of meningitis, is responsible for about 1% of infections in an epidemic period. Specific DNA aptamers that bind to N. meningitidis serogroup B were identified by whole-cell Systemic Evolution of Ligands by EXponential Enrichment (SELEX).
    Methods
    The SELEX begins with a library of labeled ssDNA molecules. After six rounds of selection and two rounds of counter-selection, 60 clones were obtained, of which the binding efficiency of 21 aptamers to the aforementioned bacterium was tested by flow cytometry.
    Results
    The aptamers K3 and K4 showed the highest affinity to N. meningitidis serogroup B and no affinity to N. meningitidis serogroups Y, A, and C, or to other meningitis causing bacteria. The dissociation constant (Kd value) for K3 and K4 were calculated as 28.3 ± 8.9 pM and 39.1 ± 8.6 pM, respectively. K3 aptamer with the lowest Kd was chosen as the main aptamer. K3 could detect N. meningitidis in patients’ cerebrospinal fluid (CSF) samples and in CSF from healthy volunteers inoculated with N. meningitidis serogroup B (ATCC 13090) at 200 and 100 CFU ml-1, respectively.
    Conclusion
    The findings suggest the application of the developed aptamer in specific detection of N. meningitidis serogroup B amongst a group of meningitis causing bacteria.
    Keywords: Aptamer, Flow cytometry, Neisseria meningitidis, Serogroup
  • Mehrnoosh Fathi-Roudsari *, Mehrdad Behmanesh, Ali-Hatef Salmanian, Majid Sadeghizadeh, Khosro Khajeh Pages 202-209
    Background
    Phenolic compounds, which are produced routinely by industrial and urban activities, possess dangers to live organisms and environment. Laccases are oxidoreductase enzymes with the ability of remediating a wide variety of phenolic compounds to more benign molecules. The purpose of the present research is surface display of a laccase enzyme with adhesin involved in diffuse adhesion (AIDA-I) autotransporter system on the surface of Escherichia coli cells for bioremediation of phenolic compounds.
    Methods
    The expression of laccase was regulated by a phenol-responsive promoter (a σ54 promoter). The constitutively-expressed CapR transcription activator was able to induce laccase expression in the presence of phenolic compounds.
    Results
    Western blot analysis showed the expression and correct transfer of the enzyme to the outer membrane of E. coli cells in the presence of phenol. Activity assay confirmed the correct folding of the enzyme after translocation through the autotransporter system. HPLC analysis of residual phenol in culture medium showed a significant reduction of phenol concentration in the presence of cells displaying laccase on the surface.
    Conclusion
    Our findings confirm that autodisplay enables functional surface display of laccase for direct substrate-enzyme availability by overcoming membrane hindrance.
    Keywords: Laccase, Phenol, Bioremediation, AIDA, I
  • Farzaneh Darbeheshti, Pantea Izadi *, Amir Nader Emami Razavi, Mir Saeed Yekaninejad, Javad Tavakkoly Bazzaz Pages 210-214
    Background
    Previous studies have suggested that BRCA1 dysregulation has been shown to have a role in triple-negative phenotypic manifestation. However, differences of BRCA1 expression, as a tumor suppressor gene, have rarely been investigated between luminal and triple-negative breast tumors. Therefore, the present study attempted to compare the BRCA1 expression in triple-negative with luminal breast tumors and its association with the clinicopathologic characteristics of patients.
    Methods
    BRCA1 expression was evaluated by real-time PCR in 26 triple-negative and 27 luminal breast tumors.
    Results
    The results revealed that there is a high frequency of BRCA1 underexpression in both triple-negative and luminal breast tumors. The BRCA1 underexpression was related to young age at diagnosis, lymph node involvement, and grade ІІІ tumors.
    Conclusion
    The observations suggest that decreased BRCA1 expression, regardless of tumor subtype, has a general role in breast malignancy and associated with poor prognostic features in breast tumors.
    Keywords: Breast cancer, BRCA1, Triple, negative breast neoplasm