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1
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Aftabi Y, Gilani N, Ansarin A, Amiri-Sadeghan A, Bakhtiyari N, Seyyedi M, Faramarzi E, Sharifi A, Ansarin K, Seyedrezazadeh E. Female-biased association of NOS2-c.1823C>T (rs2297518) with co-susceptibility to metabolic syndrome and asthma. Can J Physiol Pharmacol 2023; 101:200-213. [PMID: 36716438 DOI: 10.1139/cjpp-2022-0334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
The nitric oxide (NO) pathway contributes to the pathogeneses of metabolic syndrome (MetS) and asthma. NOS2 encodes inducible-NO synthase, which is an important enzyme of the pathway, and its variations could affect the risk of asthma and MetS and thereby co-susceptibility to them. This study aims to estimate the association of NOS2-c.1823C>T with risk of asthma, MetS, and asthma with MetS condition (ASMetS), and with asthma stages: intermittent, mild, moderate, and severe asthma. The study included asthmatics (n = 555), MetS (n = 334), and ASMetS cases (n = 232) and 351 controls, which were genotyped by the PCR-RFLP method. The T allele was significantly associated with an increased risk of asthma and MetS in the sample population and females. CT genotype and CT+TT model were significantly associated with increased risk of ASMetS in females. A significant association between CT genotype and increased risk of ASMetS in the sample population and females was found in ASMetS versus MetS. In the sample population and among females, the T allele was significantly associated with severe asthma. The rs2297518 single nucleotide polymorphism of NOS2 contributes to the risk of MetS, asthma, and co-susceptibility to them, and this contribution may be stronger in females compared to males.
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Affiliation(s)
- Younes Aftabi
- Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Rahat Breath and Sleep Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Neda Gilani
- Department of Statistics and Epidemiology, Faculty of Health, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Atefeh Ansarin
- Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amir Amiri-Sadeghan
- Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Nasim Bakhtiyari
- Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Maryam Seyyedi
- Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Elnaz Faramarzi
- Liver and Gastrointestinal Diseases Research Center, Clinical Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Akbar Sharifi
- Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Khalil Ansarin
- Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Rahat Breath and Sleep Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ensiyeh Seyedrezazadeh
- Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Rahat Breath and Sleep Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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2
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Salihi A, Al-Naqshabandi MA, Khudhur ZO, Housein Z, Hama HA, Abdullah RM, Hussen BM, Alkasalias T. Gasotransmitters in the tumor microenvironment: Impacts on cancer chemotherapy (Review). Mol Med Rep 2022; 26:233. [PMID: 35616143 PMCID: PMC9178674 DOI: 10.3892/mmr.2022.12749] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 04/07/2022] [Indexed: 11/23/2022] Open
Abstract
Nitric oxide, carbon monoxide and hydrogen sulfide are three endogenous gasotransmitters that serve a role in regulating normal and pathological cellular activities. They can stimulate or inhibit cancer cell proliferation and invasion, as well as interfere with cancer cell responses to drug treatments. Understanding the molecular pathways governing the interactions between these gases and the tumor microenvironment can be utilized for the identification of a novel technique to disrupt cancer cell interactions and may contribute to the conception of effective and safe cancer therapy strategies. The present review discusses the effects of these gases in modulating the action of chemotherapies, as well as prospective pharmacological and therapeutic interfering approaches. A deeper knowledge of the mechanisms that underpin the cellular and pharmacological effects, as well as interactions, of each of the three gases could pave the way for therapeutic treatments and translational research.
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Affiliation(s)
- Abbas Salihi
- Department of Biology, College of Science, Salahaddin University-Erbil, Erbil, Kurdistan Region 44001, Iraq
- Center of Research and Strategic Studies, Lebanese French University, Erbil, Kurdistan Region 44002, Iraq
- Department of Microbiology, Tumor and Cell Biology (MTC), Biomedicum, Karolinska Institutet, SE-17165 Stockholm, Sweden
| | - Mohammed A. Al-Naqshabandi
- Department of Clinical Biochemistry, College of Health Sciences, Hawler Medical University, Erbil, Kurdistan Region 44001, Iraq
| | - Zhikal Omar Khudhur
- Department of Medical Analysis, Faculty of Applied Science, Tishk International University, Erbil, Kurdistan Region 44001, Iraq
| | - Zjwan Housein
- Department of Medical Laboratory Technology, Technical Health and Medical College, Erbil Polytechnique University, Erbil, Kurdistan Region 44002, Iraq
| | - Harmand A. Hama
- Department of Biology, Faculty of Education, Tishk International University, Erbil, Kurdistan Region 44002, Iraq
| | - Ramyar M. Abdullah
- College of Medicine, Hawler Medical University, Erbil, Kurdistan Region 44002, Iraq
| | - Bashdar Mahmud Hussen
- Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Erbil, Kurdistan Region 44002, Iraq
| | - Twana Alkasalias
- General Directorate of Scientific Research Center, Salahaddin University-Erbil, Erbil, Kurdistan Region 44002, Iraq
- Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, SE-17176 Stockholm, Sweden
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3
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Abbaszadegan MR, Mojarrad M, Rahimi HR, Moghbeli M. Genetic and molecular biology of gastric cancer among Iranian patients: an update. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2022. [DOI: 10.1186/s43042-022-00232-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Abstract
Background
There is a declining trend of gastric cancer (GC) incidence in the world during recent years that is related to the development of novel diagnostic methods. However, there is still a high ratio of GC mortality among the Iranian population that can be associated with late diagnosis. Despite various reports about the novel diagnostic markers, there is not any general and standard diagnostic panel marker for Iranian GC patients. Therefore, it is required to determine an efficient and general panel of molecular markers for early detection.
Main body of the abstract
In the present review, we summarized all of the reported markers until now among Iranian GC patients to pave the way for the determination of a population-based diagnostic panel of markers. In this regard, we categorized these markers in different groups based on their involved processes to know which molecular process is more frequent during the GC progression among Iranians.
Conclusion
We observed that the non-coding RNAs are the main factors involved in GC tumorigenesis in this population.
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Ghaffari HR, Yunesian M, Nabizadeh R, Nasseri S, Sadjadi A, Pourfarzi F, Poustchi H, Eshraghian A. Environmental etiology of gastric cancer in Iran: a systematic review focusing on drinking water, soil, food, radiation, and geographical conditions. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2019; 26:10487-10495. [PMID: 30806933 DOI: 10.1007/s11356-019-04493-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/29/2018] [Accepted: 02/05/2019] [Indexed: 12/18/2022]
Abstract
The aim of this systematic review study was to investigate the causal relationship between environmental factors and gastric cancer (GC) in Iran. In a narrow definition, the environment includes water, soil, air, and food. This definition was the main criterion for the inclusion of articles in this study. In addition, exposure to radiation and geographical conditions were considered as less investigated environmental factors in the literatures. International (PubMed, Web of Science, ScienceDirect, Scopus, and Cochran) and national (Scientific Information Database) databases were searched for articles on GC and environmental risk factors in Iran. Twenty-six articles were found to meet the inclusion criteria after title, abstract, and full text review. Risk factors identified for GC include consumption of red meat; high fat, fried, and salted meat; smoked, salted, and fried foods; some dairy products; roasted and fried seeds; strong and hot tea; and un-piped and unchlorinated drinking water, as well as exposure to radiation, loess sediment, soft and grassy soil, soil containing low concentration of molybdenum, and proximity to volcanos. Fresh fruits and vegetable, fresh fish, and honey consumption were recognized as protective agents. Given the risk factors identified, strategies to prevent GC would be educating people to choose a healthy diet and to cook and store food properly, providing access to safe drinking water, taking into account topographical and geographical conditions in choosing a right location to build residential areas, and regulating the use of radiation-emitting devices.
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Affiliation(s)
- Hamid Reza Ghaffari
- Department of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Masud Yunesian
- Department of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
- Center for Air Pollution Research and Department of Research Methodology and Data Analysis, Institute for Environmental Research (IER), Tehran University of Medical Sciences, Tehran, Iran.
| | - Ramin Nabizadeh
- Department of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
- Center for Air Pollution Research (CAPR), Institute for Environmental Research (IER), Tehran University of Medical Sciences, Tehran, Iran
| | - Simin Nasseri
- Department of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
- Center for Water Quality Research, Institute for Environmental Research (IER), Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Sadjadi
- Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- No Way New Way Company, the Hauge, the Netherlands
| | - Farhad Pourfarzi
- Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Hossein Poustchi
- Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Ahad Eshraghian
- Avicenna Hospital, Avicenna Center for Medicine and Organ Transplant, Shiraz, Iran
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Zhu Y, Jiang H, Chen Z, Lu B, Li J, Peng Y, Shen X. The genetic association between iNOS and eNOS polymorphisms and gastric cancer risk: a meta-analysis. Onco Targets Ther 2018; 11:2497-2507. [PMID: 29765229 PMCID: PMC5939909 DOI: 10.2147/ott.s161925] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Objective There are a number of susceptible factors for an increased risk of gastric cancer. Nitric oxide (NO) is considered to be associated with the development of a range of cancers. In particular, inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) are known to play a central role in the production of NO. Published studies relating to the association between eNOS rs1799983, rs2070744, and iNOS rs2297518 polymorphisms and the risk of gastric cancer risk are conflicting and inconclusive and require further analysis. Materials and methods This study involved a meta-analysis of case–control studies relating to eNOS rs1799983, rs2070744, and iNOS rs2297518 polymorphisms published prior to January 2018. Literature searches were carried out in PubMed, Embase, Web of Science, the Cochrane Library databases, and the Chinese National Knowledge Infrastructure. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of association based on genotype data. Results A total of 1,356 cases and 1,791 controls were included from nine case–control studies involving eNOS rs1799983 (G894T), rs2070744 (T-786C), and iNOS rs2297518 (C150T) polymorphisms. Data analysis indicated that iNOS rs2297518 was a risk factor for Helicobacter pylorus-positive gastric cancer when compared with H. pylorus-negative gastric cancer (p=0.003, OR [95% CI] =2.19 [1.31–3.66]). In addition, the allelic, dominant, and recessive models of eNOS rs2070744 were significantly associated with a risk of gastric cancer (allelic model: p<0.00001, OR [95% CI] =0.23 [0.16–0.34]; dominant model: p<0.00001, OR [95% CI] =0.25 [0.15–0.42]; recessive model: p<0.00001, OR [95% CI] =0.16 [0.08–0.30]). No association was identified between eNOS rs1799983 and the risk of gastric cancer (p>0.05). Conclusion iNOS rs2297518 and eNOS rs2070744 polymorphisms may represent susceptible factors for gastric cancer.
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Affiliation(s)
- Yi Zhu
- Department of Gastroenterological Surgery, The First Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People's Republic of China
| | - Honggang Jiang
- Department of Gastroenterological Surgery, The First Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People's Republic of China
| | - Zhiheng Chen
- Department of Gastroenterological Surgery, The First Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People's Republic of China
| | - Bohao Lu
- Department of Gastroenterological Surgery, The First Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People's Republic of China
| | - Jin Li
- Department of Gastroenterological Surgery, The First Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People's Republic of China
| | - Yuping Peng
- Department of Gastroenterological Surgery, The First Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People's Republic of China
| | - Xuning Shen
- Department of Gastroenterological Surgery, The First Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People's Republic of China
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de Oliveira GA, Cheng RYS, Ridnour LA, Basudhar D, Somasundaram V, McVicar DW, Monteiro HP, Wink DA. Inducible Nitric Oxide Synthase in the Carcinogenesis of Gastrointestinal Cancers. Antioxid Redox Signal 2017; 26:1059-1077. [PMID: 27494631 PMCID: PMC5488308 DOI: 10.1089/ars.2016.6850] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
SIGNIFICANCE Gastrointestinal (GI) cancer taken together constitutes one of the most common cancers worldwide with a broad range of etiological mechanisms. In this review, we have examined the impact of nitric oxide (NO) on the etiology of colon, colorectal, gastric, esophageal, and liver cancers. Recent Advances: Despite differences in etiology, initiation, and progression, chronic inflammation has been shown to be a common element within these cancers showing interactions of numerous pathways. NO generated at the inflammatory site contributes to the initiation and progression of disease. The amount of NO generated, time, and site vary and are an important determinant of the biological effects initiated. Among the nitric oxide synthase enzymes, the inducible isoform has the most diverse range, participating in numerous carcinogenic processes. There is emerging evidence showing that inducible nitric oxide synthase (NOS2) plays a central role in the process of tumor initiation and/or development. CRITICAL ISSUES Redox inflammation through NOS2 and cyclooxygenase-2 participates in driving the mechanisms of initiation and progression in GI cancers. FUTURE DIRECTIONS Understanding the underlying mechanism involved in NOS2 activation can provide new insights into important prevention and treatment strategies. Antioxid. Redox Signal. 26, 1059-1077.
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Affiliation(s)
- Graciele Almeida de Oliveira
- 1 Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Frederick, Maryland
| | - Robert Y S Cheng
- 1 Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Frederick, Maryland
| | - Lisa A Ridnour
- 1 Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Frederick, Maryland
| | - Debashree Basudhar
- 1 Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Frederick, Maryland
| | - Veena Somasundaram
- 1 Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Frederick, Maryland
| | - Daniel W McVicar
- 1 Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Frederick, Maryland
| | - Hugo Pequeno Monteiro
- 2 Laboratório de Sinalização Celular, Universidade Federal de São Paulo , São Paulo, Brazil
| | - David A Wink
- 1 Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Frederick, Maryland
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7
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Neumann L, Mueller M, Moos V, Heller F, Meyer TF, Loddenkemper C, Bojarski C, Fehlings M, Doerner T, Allers K, Aebischer T, Ignatius R, Schneider T. Mucosal Inducible NO Synthase-Producing IgA+ Plasma Cells in Helicobacter pylori-Infected Patients. THE JOURNAL OF IMMUNOLOGY 2016; 197:1801-8. [PMID: 27456483 DOI: 10.4049/jimmunol.1501330] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/12/2015] [Accepted: 06/20/2016] [Indexed: 12/20/2022]
Abstract
The mucosal immune system is relevant for homeostasis, immunity, and also pathological conditions in the gastrointestinal tract. Inducible NO synthase (iNOS)-dependent production of NO is one of the factors linked to both antimicrobial immunity and pathological conditions. Upregulation of iNOS has been observed in human Helicobacter pylori infection, but the cellular sources of iNOS are ill defined. Key differences in regulation of iNOS expression impair the translation from mouse models to human medicine. To characterize mucosal iNOS-producing leukocytes, biopsy specimens from H. pylori-infected patients, controls, and participants of a vaccination trial were analyzed by immunohistochemistry, along with flow cytometric analyses of lymphocytes for iNOS expression and activity. We newly identified mucosal IgA-producing plasma cells (PCs) as one major iNOS(+) cell population in H. pylori-infected patients and confirmed intracellular NO production. Because we did not detect iNOS(+) PCs in three distinct infectious diseases, this is not a general feature of mucosal PCs under conditions of infection. Furthermore, numbers of mucosal iNOS(+) PCs were elevated in individuals who had cleared experimental H. pylori infection compared with those who had not. Thus, IgA(+) PCs expressing iNOS are described for the first time, to our knowledge, in humans. iNOS(+) PCs are induced in the course of human H. pylori infection, and their abundance seems to correlate with the clinical course of the infection.
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Affiliation(s)
- Laura Neumann
- Medical Clinic I, Gastroenterology, Infectious Diseases and Rheumatology, Charité-University Medicine Berlin, 12203 Berlin, Germany;
| | - Mattea Mueller
- Medical Clinic I, Gastroenterology, Infectious Diseases and Rheumatology, Charité-University Medicine Berlin, 12203 Berlin, Germany
| | - Verena Moos
- Medical Clinic I, Gastroenterology, Infectious Diseases and Rheumatology, Charité-University Medicine Berlin, 12203 Berlin, Germany
| | - Frank Heller
- Practice for Gastroenterology, 12163 Berlin, Germany
| | - Thomas F Meyer
- Department of Molecular Biology, Max Planck Institute for Infection Biology, 10117 Berlin, Germany
| | | | - Christian Bojarski
- Medical Clinic I, Gastroenterology, Infectious Diseases and Rheumatology, Charité-University Medicine Berlin, 12203 Berlin, Germany
| | - Michael Fehlings
- Department of Molecular Biology, Max Planck Institute for Infection Biology, 10117 Berlin, Germany
| | - Thomas Doerner
- Department of Medicine, Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, 10117 Berlin, Germany
| | - Kristina Allers
- Medical Clinic I, Gastroenterology, Infectious Diseases and Rheumatology, Charité-University Medicine Berlin, 12203 Berlin, Germany
| | | | - Ralf Ignatius
- Institute for Microbiology and Hygiene, Charité-University Medicine Berlin, 12203 Berlin, Germany
| | - Thomas Schneider
- Medical Clinic I, Gastroenterology, Infectious Diseases and Rheumatology, Charité-University Medicine Berlin, 12203 Berlin, Germany
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Jiao J, Wu J, Huang D, Liu L. Lack of association of the iNOS gene polymorphism with risk of cancer: a systematic review and Meta-Analysis. Sci Rep 2015; 5:9889. [PMID: 26391304 PMCID: PMC4585729 DOI: 10.1038/srep09889] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2015] [Accepted: 03/19/2015] [Indexed: 12/20/2022] Open
Abstract
In order to investigate the association between the iNOS gene polymorphisms and susceptibility to cancer, a search of English papers was done using Pubmed, the Cochrane Library, Embase, ISI Web of Science, Google (scholar) database, and all Chinese reports were conducted using CBMDisc, Chongqing VIP database, and CNKI database. A total of eight studies were included in this meta-analysis including 1,920 cases and 2,373 controls. The results indicated that the polymorphisms in iNOS gene (C150T(Ser(608) Leu) polymorphism and polymorphic (CCTTT)n repeats) had no association with cancer risk for all genetic models. This meta-analysis suggested that the polymorphisms in the iNOS gene were not associated with cancer risk.
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Affiliation(s)
- Jinghua Jiao
- Department of Anesthesiology, Central Hospital, Shenyang Medical College. Shenyang, 110024, China
| | - Jingyang Wu
- Department of Ophthalmology, The First Affiliated Hospital, China Medical University. Shenyang, 110001, China
| | - Desheng Huang
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang, 110001, China
| | - Lei Liu
- Department of Ophthalmology, The First Affiliated Hospital, China Medical University. Shenyang, 110001, China.,Department of Epidemiology, School of Public Health, China Medical University, Shenyang, 110001, China
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Inducible nitric oxide synthase (iNOS) regulatory region variation in non-human primates. INFECTION GENETICS AND EVOLUTION 2015; 31:236-44. [PMID: 25675838 DOI: 10.1016/j.meegid.2015.01.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/15/2014] [Revised: 01/07/2015] [Accepted: 01/19/2015] [Indexed: 01/26/2023]
Abstract
Inducible nitric oxide synthase (iNOS) is an enzyme that plays a key role in intracellular immune response against respiratory infections. Since various species of nonhuman primates exhibit different levels of susceptibility to infectious respiratory diseases, and since variation in regulatory regions of genes is thought to play a key role in expression levels of genes, two candidate regulatory regions of iNOS were mapped, sequenced, and compared across five species of nonhuman primates: African green monkeys (Chlorocebus sabaeus), pig-tailed macaques (Macaca nemestrina), cynomolgus macaques (Macaca fascicularis), Indian rhesus macaques (Macaca mulatta), and Chinese rhesus macaques (M. mulatta). In addition, we conducted an in silico analysis of the transcription factor binding sites associated with genetic variation in these two candidate regulatory regions across species. We found that only one of the two candidate regions showed strong evidence of involvement in iNOS regulation. Specifically, we found evidence of 13 conserved binding site candidates linked to iNOS regulation: AP-1, C/EBPB, CREB, GATA-1, GATA-3, NF-AT, NF-AT5, NF-κB, KLF4, Oct-1, PEA3, SMAD3, and TCF11. Additionally, we found evidence of interspecies variation in binding sites for several regulatory elements linked to iNOS (GATA-3, GATA-4, KLF6, SRF, STAT-1, STAT-3, OLF-1 and HIF-1) across species, especially in African green monkeys relative to other species. Given the key role of iNOS in respiratory immune response, the findings of this study might help guide the direction of future studies aimed to uncover the molecular mechanisms underlying the increased susceptibility of African green monkeys to several viral and bacterial respiratory infections.
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10
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Shadifar M, Ataee R, Ataie A, Heydari Gorgi AM, Nasri Nasrabadi N, Nouri S. Genetic and molecular aspects of Helicobacter pylori in gastritis, pre- cancerous conditions and gastric adenocrcinoma. GASTROENTEROLOGY AND HEPATOLOGY FROM BED TO BENCH 2015; 8:S15-22. [PMID: 26171133 PMCID: PMC4495423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/12/2014] [Accepted: 03/18/2015] [Indexed: 10/26/2022]
Abstract
Gastric adenocarcinoma is one of the most common malignancies worldwide. Many ethological causes have been introduced among which helicobacter pylori, as a gram-negative bacterium has been considered as an important pathological facilitating factor. This agent is also associated with different digestive diseases, such as gastritis, peptic ulcer, and mucosa-associated lymphoid tissue lymphoma. Recently, scientists have been described some molecular aspects that show the role of some apoptotic genes and proteins; for example: P53, Bcl2, C-Myc and Rb-suppressor systems in the H. pylori pathogenesis. Also the relationship between nitric oxide (NOSi genotype) with H. pylori infection has been shown. The aim of this mini-review is to explain better these genetically aspects of H.pylori pathogenesis.
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Affiliation(s)
| | - Ramin Ataee
- Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari Iran,Thalassemia Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari Iran
| | - Amin Ataie
- Department of Physiology and pharmacology, Babol University of medical sciences, Babol, Iran
| | | | - Nafiseh Nasri Nasrabadi
- Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari Iran
| | - Somayyeh Nouri
- Pharmaceutical Sciences Research Center, Islamic Azad University, Tehran Iran
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11
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Hazam RK, Deka M, Kar P. Role of nitric oxide synthase genes in hepatitis E virus infection. J Viral Hepat 2013; 21:671-9. [PMID: 24215170 DOI: 10.1111/jvh.12186] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2013] [Accepted: 07/20/2013] [Indexed: 12/16/2022]
Abstract
Hepatitis E virus (HEV) is the most common cause of endemic and epidemic acute hepatitis. A correlation between iNOS, eNOS polymorphisms, levels and severity of disease has been reported, and here, we examined the role of iNOS and eNOS gene polymorphisms and their levels in HEV-related acute viral hepatitis and acute liver failure. Hepatitis E virus-related cases of acute hepatitis (294 patients) and liver failure (82 patients) and age- and sex-matched healthy controls (331 subjects) were included in the study. PCR-RFLP was performed to identify the polymorphisms in the iNOS and eNOS genes. iNOS and eNOS levels were studied using ELISA assays and HEV viral load, genotype and combined effects of iNOS genotype, levels and parameters for disease severity were examined. The frequency of iNOS (CT + TT) and eNOS (GT + TT) genotypes was higher in subjects with liver failure compared with controls. iNOS and eNOS levels in patients with acute liver failure (55.51 ± 6.33 IU/mL, 60.2 ± 3.69) cases were significantly increased as compared to patients with acute viral hepatitis (17.8 ± 6.08 IU/mL, 23.7 ± 6.57) and controls (P < 0.05). A significant positive correlation was observed between the iNOS and eNOS levels in our study population when compared with the severity of disease parameters. Hence, the iNOS C150T polymorphism and the eNOS G894T polymorphism and high levels of iNOS and eNOS are associated with an increased risk of HEV-related acute hepatitis and liver failure. This study supports the possible role of nitric oxide synthase genes (iNOS and eNOS) in determining the severity of HEV infection.
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Affiliation(s)
- R K Hazam
- PCR Hepatitis Lab, Department of Medicine, Maulana Azad Medical College, University of Delhi, New Delhi, India
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12
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Rafiei A, Gilbreath JJ, Merrell DS. Response to Abadi and Kusters, World J Gastroenterol 19: 429-430. World J Gastroenterol 2013; 19:3711-3712. [PMID: 23801878 PMCID: PMC3691030 DOI: 10.3748/wjg.v19.i23.3711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2013] [Revised: 04/16/2013] [Accepted: 05/20/2013] [Indexed: 02/06/2023] Open
Abstract
In a recent study, Rafiei et al, reported a link between a C150T polymorphism in the human inducible nitric oxide gene and Helicobacter pylori infection as a risk factor for gastric cancer among an Iranian population. Subsequently, Abadi and Kusters published a letter to the editor questioning the validity of the study because of a supposed flaw in primer design. Here we respond to the claims of Abadi and Kusters and show that the results reported in the original article are valid.
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Abadi ATB, Kusters JG. Association of inducible nitric oxide synthetase genotype and Helicobacter pylori infection gastric cancer risk may be due to faulty primer design. World J Gastroenterol 2013; 19:429-430. [PMID: 23372371 PMCID: PMC3554833 DOI: 10.3748/wjg.v19.i3.429] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2012] [Revised: 10/11/2012] [Accepted: 12/20/2012] [Indexed: 02/06/2023] Open
Abstract
Rafiei et al recently described an association between the presence of the C150T polymorphism of the inducible nitric oxide synthase (iNOS) gene and Helicobacter pylori (H. pylori) induced gastric cancer. When we used primer-BLAST to find the polymerase chain reaction (PCR) product that would be generated by the primers used by these authors no products against any of the sequences present in the GenBank database were found. Further analysis of the iNOS sequences present in the GenBank suggest that the result from their study might come from a faulty primer design and may thus represent an artifact. Alternatively they may be correct and have identified a truly interesting explanation for the mechanism whereby H. pylori induces gastric cancer but some additional experiments would be in order to exclude the possibility of a PCR artifact.
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