OTHERS_CITABLE Precision Medicine: A New Revolution in Healthcare System Every human being is different based on genetics, lifestyle, and environmental factors. Novel medical technologies have become more precise owing to molecular information, including genomics, transcriptomics, proteomics, metabolomics, etc. The “omics” technologies have opened up new horizons for healthcare systems, enabling them to prevent and/or diagnose diseases more precisely, as well as to find the most effective treatments with fewer adverse events. Recently, the term ‘pre­cision medicine’ (PM), focusing on molecular-based medicine, has been introduced. PM empowered by “omics” technologies is going to be translated into precision healthcare. In other words, personalized healthcare is developed to improve the safety and efficacy of medical treatments and also to lower healthcare costs. Accordingly, some PM initiatives have been announced in the US and European countries to revolutionize healthcare systems. In the field of drug discovery, there are concerns about the role of genomics and proteomics in individual response to medicines. Information coming from “omics” such as genomics, proteomics, metabolomics, epigenomics, transcriptomics, and antibodyomics based on molecular characteristics of patients will enable physicians to administer safer and more effective drugs to each individual... http://ibj.pasteur.ac.ir/article-1-2062-en.pdf 2017-05-31 282 283 Babak Arjmand 1 Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran AUTHOR Mohammad Abdollahi 2 Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran; AUTHOR Bagher Larijani 3 Virtual Center for Review of Medical Sciences, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran; AUTHOR
OTHERS_CITABLE Misconduct in Research and Publication Dear Editor, I read the recent publication on “Misconduct in Research and Publication” with great interest[1]. I agree that misconduct in research and publication is not uncommon. Nevertheless, it is rarely mentioned. In fact, there are many incorrect conceptions among researchers on publication ethics. The milder examples are attempts to report only the “positive outcomes”, textual or data recycling as well as figure cropping and modification. These problems can be seen in published work of many academic members regardless of nationality or seniority. To provide the needed education and instructions aiming at primary prevention of the problem is widely practiced.  A secondary means of prevention is screening for misconduct for the purpose of early detection. Nevertheless, such misconduct is repeatedly observed. An important question is whether such measures are suitable corrective actions. In general, if the misconduct is detected, reporting to the researchers’ organization, as well as retraction of the articles with public announcement by the journal, are recommended. Nevertheless, there is often no incurred penalty or response from the researchers under question or their affiliated organizations. If those committing the misconducts are senior academics, they might receive no penalty and may even be further promoted based those questionable publications[2]. Sometimes, the journals, which are usually of poor quality and predatory type also support the misconduct incidence[2].  Such behavior sets fallacious examples for the rest. Of interest, although there are extensive attempts to promote anti-misconduct communities, which normally fail. A good example is the launching of Déjà vu database to combat plagiarism[3], which is currently non-functional. How to promote the ethical practice among the practitioners and promote the anti-misconduct community is a major challenge facing our scientific community. http://ibj.pasteur.ac.ir/article-1-2057-en.pdf 2017-05-29 284 284 10.18869/acadpub.ibj.21.5.284 Misconduct Publication Research Viroj Wiwanitkit 1 Visiiting Professor, Hainan Medical University, China; Honorary Professor, Dr. DY Patil University, China AUTHOR
REVIEW_ARTICLE Therapeutic effects of Iranian herbal extracts against Trichomonas vaginalis Trichomonas vaginalis is a flagellated parasite affecting about 276 million people annually worldwide. Tricomoniasis is associated with different complications in pregnant women and infants. 5'-nitroimidazole derivatives (metronidazole, ornidazole, and tinidazole) are FDA approved drugs recommended for trichomoniasis treatment. Treatment with metronidazole 5'-nitroimidazole derivatives is associated with many side effects, and drug resistance to metronidazole has been reported in some cases. Recently, many attempts have been made to evaluate the effects of plants on causative agents of vaginal infections. In our research, the national and international databases were searched and the effects of various herbal extracts on T. vaginalis in Iran were reviewed from 2006 to 2016. In articles investigated, some plants had favorable antitrichomonal effects and needed to be further investigated. All the plant extracts have only been evaluated in vitro. Surveys of different articles in this review show that the active ingredients present in different parts of plants, including aerial parts, leaves, flowers, stems, and root can be suitable sources for introducing and developing new antitrichomonal compounds. http://ibj.pasteur.ac.ir/article-1-2134-en.pdf 2017-07-25 285 293 10.18869/acadpub.ibj.21.5.285 Trichomonas vaginalis Medicinal plants Iran Herbal Extract Zohreh Fakhrieh Kashan 1 Department of Medical Parasitology, School of Public Health , Tehran University of Medical Sciences, Tehran, Iran AUTHOR Mahdi Delavari 2 Department of Medical Parasitology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran AUTHOR Mohsen Arbabi 3 Department of Medical Parasitology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran AUTHOR Hossein Hooshyar 4 Department of Medical Parasitology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran AUTHOR
ORIGINAL_ARTICLE Homozygosity Mapping and Targeted Sanger Sequencing Identifies Three Novel CRB1 (Cumbs homologue 1) Mutations in Iranian Retinal Degeneration Families Background: Inherited retinal diseases (IRDs) are a group of genetic disorders with high degrees of clinical, genetic and allelic heterogeneity. IRDs generally show progressive retinal cell death resulting in gradual vision loss. IRDs constitute a broad spectrum of disorders including retinitis pigmentosa and Leber congenital amaurosis. In this study, we performed genotyping studies to identify the underlying mutations in three Iranian families. Methods: Having employed homozygosity mapping and Sanger sequencing, we identified the underlying mutations in the crumbs homologue 1 gene. The CRB1 protein is a part of a macromolecular complex with a vital role in retinal cell polarity, morphogenesis, and maintenance. Results: We identified a novel homozygous variant (c.1053_1061del; p.Gly352_Cys354del) in one family, a combination of a novel (c.2086T>C; p.Cys696Arg) and a known variant (c.2234C>T, p.Thr745Met) in another family and a homozygous novel variant (c.3090T>A; p.Asn1030Lys) in a third family. Conclusion: This study shows that mutations in CRB1 are relatively common in Iranian non-syndromic IRD patients. http://ibj.pasteur.ac.ir/article-1-2032-en.pdf 2017-05-02 294 302 10.18869/acadpub.ibj.21.5.294 Retinal degeneration Retinitis pigmentosa Leber congenital amaurosis Mutation Iran Mohammad Ghofrani 1 Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran. AUTHOR Mahin Yahyaei 2 Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran. AUTHOR Han G. Brunner 3 Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands. AUTHOR Frans P.M. Cremers 4 Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands. AUTHOR Morteza Movasat 5 Eye Research Center, Tehran University of Medical Sciences, Farabi Eye Hospital, Tehran, Iran AUTHOR Muhammad Imran Khan 6 Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands AUTHOR Mohammad Keramatipour 7 Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran AUTHOR
ORIGINAL_ARTICLE Expression Study and Clinical Correlations of MYC and CCAT2 in Breast Cancer Patients Background: Colon cancer-associated transcript 2 (CCAT2) is a newly recognized lncRNA transcribed from the 8q24 genomic region. It functions as an oncogene in various types of cancers including breast cancer, in which it affects Wnt/β-catenin pathway. Previous studies have shown a putative interaction between this lncRNA and MYC proto-oncogene. Methods: In the current study, we evaluated the expression of CCAT2 in breast cancer tissues with regards to the expression of its target MYC. In addition, we assessed the relationship between CCAT2 and MYC expression levels in tumor tissues and the clinical prognostic characteristics of breast cancer patients. Results: MYC expression levels were significantly up-regulated in tumor tissues compared with adjacent non-cancerous tissues (ANCTs), while such analysis showed no statistically significant difference between these two tissue types in CCAT2 expression. Starkly increased CCAT2 gene expression levels were found in 12/48 (25%) of cancer tissue samples compared with their corresponding ANCTs. Furthermore, significant inverse correlations were found between CCAT2 expression and stage, as well as lymph node involvement. Besides, a significant inverse correlation was found between the relative MYC expression in tumor tissues compared with their corresponding ANCTs and disease stage. Conclusions: These results highlight the significance of MYC and CCAT2 expressions in the early stages of breast cancer development and suggest a potentially significant role for CCAT2 in a subset of breast cancer patients, which could applied as a potential therapeutic target in these patients. http://ibj.pasteur.ac.ir/article-1-2036-en.pdf 2017-05-08 303 311 10.18869/acadpub.ibj.21.5.303 Long non-coding RNA Breast cancer c-MYC Shaghayegh Sarrafzadeh 1 Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran AUTHOR Lobat Geranpayeh 2 Department of Surgery, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran AUTHOR Behnoosh Tasharrofi 3 Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran AUTHOR Mohammad Soudyab 4 Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran AUTHOR Elahe Nikpayam 5 Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran AUTHOR Mostafa Iranpour 6 Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran AUTHOR Reza Mirfakhraie 7 Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran AUTHOR Jalal Gharesouran 8 Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran AUTHOR Somayyeh Ghafouri-Fard 9 Department of Community and Preventive Medicine, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran AUTHOR Soudeh Ghafouri-Fard 10 Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran AUTHOR
ORIGINAL_ARTICLE Accuracy of Soluble Endoglin for Diagnosis of Preeclampsia and its Severity Background: The use of biomarkers for diagnosis of Preeclampsia (PE), a life-threatening pregnancy disorder, could reduce serious complications of this disease. In this study, we investigated dysregulation of endoglin (Eng) expression and diagnostic accuracy of soluble endoglin (sEng) in PE patients. Methods: For this case-control study, 26 mild and 15 severe preeclamptic women along with 20 normotensive controls were recruited. The expression level of Eng (the co-receptor TGF-β1) was evaluated using qRT-PCR. Also, the serum concentration of soluble Eng and expression of membranous Eng were determined by ELISA and immunohistochemistry. Results:  A significant up-regulation in Eng mRNA and sEng levels was observed in PE patients versus normal controls. Immunohistochemistry (IHC) showed up-regulation of membranous Eng staining in syncytiotrophoblast and cytotrophoblast cells of PE patients. The serum levels of sEng were significantly increased in all patients (mild, sever, early- and late-onset) as compared to healthy pregnant women (P˂0.001). Receiver-operating characteristic (ROC) curve analysis revealed that sEng had the highest accuracy in distinguishing PE from normal pregnancies with cut-off value of 20.4, sensitivity of 92.1%, specificity of 90%, and area under the curve (AUC) of 0.94 (95% CI: 0.88-1.00). Conclusions: Our data showed that the up-regulation of Eng mRNA along with its membranous and soluble form in PE patients leads to defect in angiogenesis pathway. Also, the results of this study revealed sEng potential as a marker for diagnosis of PE and its severity. http://ibj.pasteur.ac.ir/article-1-2063-en.pdf 2017-05-31 312 320 10.18869/acadpub.ibj.21.5.312 Preeclampsia Endoglin Biomarkers Pregnancy Pooneh Nikuei 1 Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran; AUTHOR Minoo Rajaei 2 Fertility and Infertility Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran; AUTHOR Kianoosh Malekzadeh 3 Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran AUTHOR Azim Nejatizadeh 4 Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran AUTHOR Fatemeh Mohseni 5 Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran AUTHOR Ali AtashAbParvar 6 Pathology Department, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran AUTHOR
ORIGINAL_ARTICLE Serum Antibodies against Helicobacter pylori Neutrophil Activating Protein in Carriers of IL-4 C-590T Genetic Polymorphism Amplify the Risk of Gastritis and Gastric Cancer http://ibj.pasteur.ac.ir/article-1-1895-fa.pdf 2016-12-20 321 329 10.18869/acadpub.ibj.21.5.321 Serum Antibodies against Helicobacter pylori Neutrophil Activating Protein in Carriers of IL-4 C-590T Genetic Polymorphism Amplify the Risk of Gastritis and Gastric Cancer Background: Gastric cancer arises, mainly, on an inflammatory background. Helicobacter pylori neutrophil activating (HP-NAP) protein functions as a potent pro-inflammatory mediator.  Similarly, IL-4 plays a critical role in the inflammation pathway, the levels of which are altered by C to T transition at position -590 in its promoter region. Here, we have aimed to assess the risk of gastritis and gastric cancer in the co-presence of these two inflammation modulating mediators. Methods: Gastritis (n=58) and gastric cancer (n=31) patients were evaluated and compared with H. pylori-positive asymptomatic controls (n=46), for serum antibodies against recombinant HP-NAP and IL-4 C-590T single nucleotide polymorphism using immunoblotting and PCR-RFLP, respectively. Multivariable logistic regression, adjusting for age, gender and ethnicity, was used for data analysis. Results: In terms of susceptibility to gastritis, seropositivity to HP-NAP projected a risk impact of 4.62 fold (OR=4.62, 95% CI=1.50-14.22), which when present in IL-4 -590 T carriers augmented the risk up to 9.7 fold (OR=9.70, 95% CI=2.06-45.69). A similar pattern, but of a stronger magnitude, occurred for the risk of gastric cancer, which was estimated at 9.07 fold (OR=9.07, 95% CI=1.99-42.0) for HP-NAP-seropositive subjects and was drastically amplified (OR=33.64, 95% CI=2.06-548.68), when double-positive (HP-NAP seropositive/IL-4 -590 T carrier) subjects were examined against double negatives (HP-NAP seronegative/IL-4 -590 CC). Conclusion: Our preliminary data indicate that serum antibodies against HP-NAP represent a state of risk, which is further exacerbated in IL-4 -590 T carriers. These biomarkers, if validated in larger prospective studies, can be used to screen for gastric cancer susceptibility. http://ibj.pasteur.ac.ir/article-1-1895-en.pdf 2016-12-20 321 329 10.18869/acadpub.ibj.21.5.321 Biomarkers Genetic Polymorphism Recombinant Yeganeh Talebkhan 1 HPGC Group, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran AUTHOR Mohsen Doozbakhshan 2 HPGC Group, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran AUTHOR Samaneh Saberi 3 HPGC Group, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran AUTHOR Maryam Esmaeili 4 HPGC Group, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran AUTHOR Najmeh Karami 5 HPGC Group, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran AUTHOR Nazanin Mohajerani 6 HPGC Group, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran AUTHOR Afshin Abdirad 7 Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran AUTHOR Mahmoud Eshagh Hosseini 8 Department of Gastroenterology, Amiralam Hospital, Tehran University of Medical Sciences, Tehran, Iran AUTHOR Azin Nahvijou 9 Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran AUTHOR Mohammad Ali Mohagheghi 10 Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran AUTHOR Marjan Mohammadi 11 HPGC Group, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran AUTHOR
ORIGINAL_ARTICLE Synergistic Effects of Arsenic Trioxide and Radiation: Triggering the Intrinsic Pathway of Apoptosis Background: Arsenic trioxide (ATO) has been reported as an effective anti-cancer and a US Food and Drug Administration (FDA) approved drug for treatment of some cancers. The aim of this study is to determine the underlying apoptosis molecular and cellular mechanisms of ATO in the presence or absence of ionizing radiation (IR) in vitro in the glioblastoma multiforme (GBM) cell line, U87MG. Methods: Cells were treated by different concentrations of ATO either in presence or absence of IR. Viability and apoptosis pathway of both treated and control groups were evaluated using MTT assay and the expression analysis of Bax, Bcl-2, and caspase-3 genes, respectively. All treatments were performed on 100-μm diameter spheroids. Results: Results showed a significant reduction in the survival of the cells in all treated groups. As expected, cell survival was much less in combination treatment than treatment with only ATO. Moreover, combination therapy made Bax and caspase-3 up-regulated and Bcl-2 down-regulated. Conclusion: ATO and radiation had a synergistic apoptotic effect on GBM cells by up-regulation of caspase-3 and alteration of the Bax-Bcl-2 balance; therefore, ATO may act as a potential anti-cancer agent against GBM cells through triggering the mitochondrial pathway of apoptosis. http://ibj.pasteur.ac.ir/article-1-2029-en.pdf 2017-05-01 330 337 10.18869/acadpub.ibj.21.5.330 Arsenic trioxide Radiation Apoptosis Glioblastoma Spheroids Kave Moloudi 1 Radiation Sciences Department, Faculty of allied Medicine school, Iran University of Medical Sciences, Tehran, Iran AUTHOR Ali Neshasteriz 2 Radiation biology research center, Iran University of medical sciences, Tehran, Iran AUTHOR Arshad Hosseini 3 Department of Medical Biotechnology, Faculty of allied Medicine, Iran University of Medical Sciences, Tehran, Iran AUTHOR Nazila Eyvazzadeh 4 Radiation Research Center, Faculty of Paramedicine, AJA University of Medical sciences, Tehran, Iran AUTHOR Mehdi Shomali 5 Radiology Department, Faculty of allied Medicine, Tehran University of Medical Sciences, Tehran, Iran AUTHOR Samira Eynali 6 Medical physics and Biomedical Engineering Department, school of Medicine, Tran University of Medical Sciences, Tehran, Iran AUTHOR Elahe Mirzaei 7 Microbiology Department, Faculty of Science, Islamic Azad University, Tehran, Iran AUTHOR Asaad Azarnezhad 8 Cellular & Molecular Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran AUTHOR
SHORT_COMMUNICATION Next-Generation Sequencing Reveals One Novel Missense Mutation in COL1A2 Gene in an Iranian Family with Osteogenesis imperfecta Background: Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous disorder characterized by bone loss and bone fragility. The aim of this study was to investigate the variants of three genes involved in the pathogenesis of OI. Methods: Molecular genetic analyses were performed for COL1A1, COL1A2, and CRTAP genes in an Iranian family with OI. The DNA samples were analyzed by next-generation sequencing (NGS) gene panel and Sanger sequencing. Results: Five different variants were identified in COL1A1 and COL1A2, including two variants in COL1A1 and three variants in COL1A2. Among the five causative COL1A1 and COL1A2 variants, one novel variants, c.1081 G>A, was found in COL1A2, which was identified in two siblings. Conclusion: Our finding extends the variant spectrum of the COL1A2 gene and has important implications for genetic counseling of families. The NGS is a powerful molecular diagnostic strategy for OI, a heterogeneous disorder. http://ibj.pasteur.ac.ir/article-1-2012-en.pdf 2017-04-22 338 341 10.18869/acadpub.ibj.21.5.338 Collagen type I COL1A2 Mutation Osteogenesis imperfecta Next-generation sequencing Farah Talebi 1 Department of Genetic, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran AUTHOR Farideh Ghanbari Mardasi 2 Department of Midwifery, Shoushtar Faculty of Medical Science, Shoushtar, Iran AUTHOR Javad Mohammadi Asl 3 Department of Medical Genetics, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran AUTHOR Amir Hooshang Bavarsad 4 Department of Internal Medicine, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran AUTHOR Masoumeh Salehi Kambo 5 Department of Midwifery, Shoushtar Faculty of Medical Sciences, Shoushtar, Iran AUTHOR
SHORT_COMMUNICATION Molecular Characterization and Biodiversity of a Putative Chlorotoxin from the Iranian Yellow Scorpion Odontobuthus doriae Background: Chloride channels have already been over-expressed in the different types of cancer. Chlorotoxins, as the blocking agent of these channels, have been indicated to be an effective drug against tumors. In this study, we characterized a putative chlorotoxin from a cDNA library of the venom glands obtained from the Iranian scorpion Odontobuthus doriae. Methods: A cDNA library was constructed from venom gland transcriptome of six scorpions. The cDNA encoding Odontobuthus doriae chlorotoxin was isolated from the library, and its putative peptide was characterized by some bioinformatics software such as protein blast, SignalP4.0, DISULFIND and Clustal Omega. Results: The mature Odontobuthus doriae chlorotoxin peptide has a 35-amino-acid residue and four disulfide bounds. This putative chlorotoxin is a small, compact, and stable molecule. Moreover, based on the open reading frame sequence similarity, this peptide is similar to Buthus martensii Karsch chlorotoxin‑like toxin and Bm12-b neurotoxins from the Chinese scorpion Mesobuthus martensii. Conclusion: The small size of this putative chlorotoxin and its stability make it as a suitable candidate for medical and pharmacological research, especially in the cancer research. http://ibj.pasteur.ac.ir/article-1-2002-en.pdf 2017-04-18 342 346 10.18869/acadpub.ibj.21.5.342 Chlorotoxin Scorpion Odontobuthus doriae cDNA library Maryam Naderi Soorki 1 Department of Genetics, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran AUTHOR Amir Jalali 2 Department of Pharmacology and Toxicology, School of Pharmacy and Toxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran AUTHOR Hamid Galehdari 3 Department of Genetics, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran AUTHOR