Iranian Biomedical Journal Iranian Biomedical Journal - Journal articles for year 2018, Volume 22, Number 1 Yektaweb Collection - en 2018/1/11 Dr. Sabar Mirza Farman Farmaian; Benefactor and Former Director of Pasteur Institute of Iran <img alt="" src="./files/site1/images/Untitled.jpg" style="width: 130px; height: 149px; float: left;" >&nbsp;Pasteur Institute of Iran (PII) is known for its history of benefaction by exquisite characters, the most prominent of who is the family of Farman Farmaian.<br> Dr. Sabar Mirza Farman Farmaian, born in 1912 in Tehran, resided as the director of PII for a period of six years (1971-1977). Furthermore, he devoted his house (located in Shemiranat) for the establishment of a center to study and combat infectious diseases. Both of these events had a significant impact on the fate of PII.&nbsp;He was born to a famous family of Farman Farmaian. His father, Abdol-Hossein Mirza Farman Farmaian, the grandson of Abbas Mirza and Fath-Ali Shah, was born in 1852, in Tabriz. He was known as &ldquo;Salar Lashkar&rdquo; and &ldquo;Farman Farma&rdquo;. He finished his elementary studies at Dar ul-Funun, after which he went to an Austrian school to learn military skills. He held numerous critical positions during 1881-1919. These include the chief of Kerman and Azerbaijan military troops, governor of Kerman, Tehran, Fars, Khorasan, and Kermanshah, as well as the minister of War, Justice and the Interior. The most prominent of all is his chair as the prime minister during the reign of Ahmad Shah Qajar...&nbsp; Narges Shahbazi Optogenetics: Control of Brain Using Light Neuronal cells communicate with each other by producing electrical signals or action potentials (APs). Different ion channels, including Na<sup>+</sup>, K<sup>+</sup> and Ca<sup>2+</sup> channels, are involved in generation of AP. Once an AP is generated in the soma, it travels down entire the axon length toward its terminal in a self-generating fashion that ultimately conveys information between neurons in the neural circuit. Depending on the neurotransmitter, each neuron inhibits or excites other neurons in a certain network. For instance, glutamate released from glutamatergic neurons, opens AMPA and NMDA channels permitting influx of Na<sup>+</sup>/Ca<sup>2+</sup>, which leads to postsynaptic depolarization. On the other hand, GABA released from GABAergic neurons results in Cl<sup>- </sup>influx and postsynaptic hyperpolarization. One of the major challenges in neuroscience is how actions of individual cells in the brain could underlie a certain behavior such as attention, food consumption, aggression, cognition, and movement...&nbsp; Hamid Gholami Pourbadie Molecular Basis of α-Thalassemia in Iran Alpha-thalassemia (&alpha;-thal) is probably the most prevalent monogenic condition in the world. Deletions are the most common types of mutations in &alpha;-thal, followed by point mutations and small insertion/deletion. In the context of national screening program for prevention of thalassemia and hemoglobinopathies in Iran, &alpha;-thal carriers have come to more attention. Therefore, the frequency and distribution of &alpha;-globin mutations in various regions of the country have been studied in recent years. A comprehensive search was performed in PubMed, Scopus, and national databases for finding reports on mutation detection in &alpha;-thal carriers and HbH disease with Iranian origin. The mutation data of 10849 &alpha;-thal carriers showed that -&alpha;<sup>3.7</sup> and &alpha;<sup>-5NT</sup> were the most common deletional and nondeletional mutations, respectively. In HbH disease cases, the -&alpha;<sup>3.7</sup>/--<sup>MED</sup> was the most prevalent genotype. Overall, 42 different mutations have been identified in &alpha;-globin cluster reflecting the high heterogeneity of the mutations in Iranian populations. Morteza Karimipoor Low Level of Autophagy-Related Gene 10 (ATG10) Expression in the 6-Hydroxydopamine Rat Model of Parkinson's Disease <p><strong>Background:</strong> Autophagy is a mechanism disassembling the damaged organelles from the cell. This study attempted to examine the expression of several autophagy-related genes in Parkinson&rsquo;s disease (PD) rat model. <strong>Methods:</strong> The male Wistar rats were divided into three groups as control, sham, and lesion. In the latter group, the PD rat model was induced by the injection of 6-hydroxydopamine in the striatum. The behavioral test was conducted one (baseline) and four weeks after the surgery through apomorphine hydrochloride. Then the RT-PCR technique was employed to evaluate the expressions of <em>p62/SQSTM</em>, autophagy-related genes<em> (ATG)5</em>, <em>ATG12</em>, <em>ATG16L1</em>, <em>ATG10</em>, as well as <em>GAPDH</em> and <em>LC3</em>. <strong>Results:</strong> By injecting apomorphine, the striatal lesion group showed a significant contralateral rotation at fourth week as compared to the baseline. The examination of <em>p62</em>, <em>ATG5</em>, <em>ATG12</em>, <em>ATG16L1</em>, and <em>LC3</em> expressions using RT-PCR revealed that <em>p62</em>, <em>ATG5</em>, <em>ATG12</em>, <em>LC3</em>, and<em> ATG16L1</em> were expressed in the substantia nigra of PD rat model, while <em>ATG10</em> was not expressed. <strong>Conclusion:</strong> ATG10 expression is necessary for the initiation of autophagy. Thus, these results show that autophagy deregulation occurs in the initiation stages of the process in the rat model of PD.</p> Shahram Darabi Immunization of C57BL/6 Mice with GRA2 Combined with MPL Conferred Partial Immune Protection against Toxoplasma gondii <p><strong>BBackground</strong>: We have previously reported that immunization with GRA 2 antigen of <em>Toxoplasma gondii </em>induces protective immunity in CBA /J (H2k) and BALB/c mice (H2d). We aimed to examine whether immunization of a distinct strain of rodent with recombinant dense granule antigens (GRA2) combined with monophosphorryl lipid A (MPL) adjuvant elicits protective immune response against <em>T. gondii.</em> <strong>Methods</strong>: C57BL/6 (H2b haplotype) mice were immunized with GRA 2, formulated in MPL adjuvant. <strong>Results</strong>: Strong humoral response, predominantly of IgG1 subclass and cellular response, IFN-&gamma;, was detected at three weeks post immunization. Mice immunized with GRA 2 had significantly (<em>p </em>< 0.01) fewer brain cysts than those in the adjuvant group, upon challenge infection. Despite the production of a strong antibody response, IFN-&gamma; production and brain cyst reduction were not significant when the immunized mice were infected four months after the immunization. <strong>Conclusions</strong>: We can conclude that GRA2 immunization partially protects against <em>T. gondii</em> infection in C57BL/6 mice, though the potency and longevity of this antigen as a standalone vaccine may vary in distinct genetic backgrounds. This observation further emphasizes the utility of GRA 2 for incorporation into a multi-antigenic vaccine against <em>T. gondii</em>.</p> Majid Golkar Molecular Identification and Antifungal Susceptibility Pattern of Non-albicans Candida Species Isolated from Vulvovaginal Candidiasis <p><strong>Background: </strong>Vulvovaginal candidiasis (VVC) is an important health problem caused by <em>Candida</em> spp. The aim of this study was molecular identification, phylogenetic analysis, and evaluation of antifungal susceptibility of non-<em>albicans</em> <em>Candida</em> isolates from VVC. <strong>Methods: </strong>Vaginal secretion samples were collected from 550 vaginitis patients at Sayyad Shirazi Medical and Educational Center of Gorgan (Golestan Province, Iran) from May to October 2015. Samples were analyzed using conventional mycological and molecular approaches. Clinical isolates were analyzed with specific PCR using CGL primers, and the internal transcribed spacer region and the D1-D2 domain of the large-subunit rRNA gene were amplified and sequenced. Susceptibility to amphotericin B, fluconazole, itraconazole, and clotrimazole was determined by the guidelines of the Clinical and Laboratory Standard Institute.<strong> Results:</strong> In total, 35 non-<em>albicans Candida </em>isolates were identified from VVC patients. The isolates included 27 strains of<em> Candida glabrata </em>(77.1%), 5 <em>Candida krusei </em>(<em>Pichia kudriavzevii</em>; 14.3%), 2 <em>Candida kefyr</em> (<em>Kluyveromyces marxianus</em>; 5.7%), and 1 <em>Candida lusitaniae</em> (<em>Clavispora lusitaniae</em>; 2.9%). The fungicides itraconazole and amphotericin B were effective against all species. One isolate of <em>C. glabrata</em> showed resistance to fluconazole and clotrimazole, and 26 isolates of <em>C. glabrata </em>indicated dose-dependent susceptibility to fluconazole. <em>C. lusitaniae</em> was susceptible in a dose-dependent manner to fluconazole and resistant to clotrimazole. <strong>Conclusions:</strong> Non-<em>albicans</em> <em>Candida</em> spp. are common agents of vulvovaginitis, and <em>C. glabrata</em> is the most common species in the tested patients.&nbsp;</p> Ziba Abbasi Nejat Analysis of NSP4 Gene and Its Association with Genotyping of Rotavirus Group A in Stool Samples <p><strong>Background</strong>: Non-structural protein 4 (<em>NSP4</em>) is a critical protein for rotavirus (RV) replication and assembly. This protein has multiple domains and motifs that predispose its function and activity. <em>NSP4</em> has a sequence divergence in human and animal RVs. Recently, 14 genotypes (E1-E14) of <em>NSP4</em> have been identified, and E1 and E2 have been shown to be the most common genotypes in human. <strong>Methods:</strong> The gene and protein sequence of <em>NSP4</em> in RV-positive samples were inspected with the aim of <em>NSP4</em> genotyping and variation analysis in viroporin and other domains. P and G typings of RV samples were carried out by WHO primers using a semi-multiplex PCR method. Non-typeable RV samples were amplified by conserved primers and sequenced. <strong>Results: </strong>In viroporin and enterotoxin, conserved sequence was detected, and amino acids substitution with the same biochemical properties was found. <strong>Conclusion</strong>: Association of <em>NSP4</em> genotype with P or G genotyping G1/G9 correlates with E1 genogroups. In electrophoretyping of RV, E2 genotype had a short pattern when compared to E1.</p> Ali Teimoori Chemical Composition and Antimicrobial Activities of Iranian Propolis <p><strong>Background</strong>: With considering the importance of natural products for their remedial and therapeutic value, this research was aimed to analyze the chemical compositions and antimicrobial activity of four propolis samples from different areas of Iran (Chenaran, Taleghan, Morad Beyg, and Kalaleh) with various climates and flora. <strong>Methods</strong>: Ethanolic (70% EtOH) and dichlromethane (DCM) extracts of Iranian propolis were analyzed by gas chromatography-mass spectrometry (GC-MS) methods, and antimicrobial activity was evaluated against <em>Candida albicans, Escherichia coli, </em>and <em>Staphylococcus aureus </em>using disk diffusion antimicrobial method. <strong>Results:</strong> The results of GC-MS analysis showed the presence of fatty acids, flavonoids, terpenes, aromatic-aliphatic acids, and their related esters. The total flavonoids in DCM extract of Chenaran, Taleghan, Morad Beyg, and Kalaleh propolis were pinocembrin and pinostrobin chalcone. The common phenolic and terpene compounds detected in all four tested EtOH extracts were <em>P</em>-cumaric acid and dimethyl -1,3,5,6-tetramethyl-[1,3-(13C2)] bicycloce [5.5.0] dodeca-1,3,5,6,8,10-hexaene-9,10-dicarboxylate, respectively. The highest inhibitory diameter zone of the Iranian propolis against <em>C. albicans</em>, <em>E. coli</em>, and<em> S. aureus </em>was for DCM extract of Kalaleh propolis (13.33 mm), Morad Beyg propolis (12 mm), and Kalaleh (11.67 mm), respectively. <strong>Conclusion</strong>: Iranian propolis showed antimicrobial activities against <em>C. albicans</em>, <em>E. coli</em>, and <em>S. aurous</em>, perhaps due to the presence of flavonoids, phenolic acids, and terpenes as active components that can be used alone or in combination with the selected antibiotics to<br> synergize antibiotic effect, as well as to prevent microbial resistance to available antimicrobial drugs.</p> Houshang Afrouzan Expression Optimization of Anti-CD22 scFv-Apoptin Fusion Protein Using Experimental Design Methodology <p><strong>Background:</strong> Design of experiments is a rapid and cost-effective approach for optimization of recombinant protein production process. In our previous study, we generated a potent dual-acting fusion protein, anti-CD22 scFv-apoptin, to target B-cell malignant cell lines. In the present investigation, we report the effect of different variables on the expression levels of this fusion protein. <strong>Methods:</strong> Four variables (cell optical density at induction, IPTG concentration, induction temperature, and induction time) were tested using experimental design. <strong>Results:</strong> Our findings demonstrated that among the examined variables, only the induction time had a significant positive effect on the protein expression yield. <strong>Conclusion:</strong> Experimental design was successfully applied in this study. The optimized condition obtained in the current study can be applied in future commercial production of this novel fusion protein.</p> Solmaz Agha Amiri Effect of Passage Number and Culture Time on the Expression and Activity of Insulin-Degrading Enzyme in Caco-2 Cells <p><strong>Background: </strong>Insulin-degrading enzyme (IDE) is a conserved zinc metallopeptidase. Here, we have evaluated the effect of passage number and culture time on IDE expression and activity in colorectal adenocarcinoma cell line (Caco-2). <strong>Methods: </strong>Caco-2 cells were cultured with different passage ranges of 5-15, 25-35, 52-63 for 48, 72, and 120 hours. Subsequently, IDE expression and enzyme activity were assessed by Western blot analysis and fluorescent assay, respectively. <strong>Results: </strong>Our results confirmed that the amount of IDE was higher in cell extract compared to supernatant, and different passage numbers and culture times had small effect on IDE expression. However, when cells were cultured in the passage number range of 5-15 for 72 hours, the IDE activity was&nbsp;35% higher compared to other passage numbers (<em>p</em> < 0.05). <strong>Conclusion:</strong> The use of Caco-2 cells at passage number range of 5-15 and culture time of 72 hours provides proper conditions for IDE-related studies.</p> Taiebeh Mohammadi Farsani