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      Exacerbation of colon carcinogenesis by Blastocystis sp.

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          Abstract

          Colorectal cancer (CRC) is one the most commonly diagnosed cancers worldwide and the number is increasing every year. Despite advances in screening programs, CRC remains as the second leading cause of cancer deaths in the United States. Oxidative stress plays an important role in the molecular mechanisms of colorectal cancer (CRC) and has been shown to be associated with Blastocystis sp., a common intestinal microorganism. In the present study, we aimed to identify a role for Blastocystis sp. in exacerbating carcinogenesis using in vivo rat model. Methylene blue staining was used to identify colonic aberrant crypt foci (ACF) and adenomas formation in infected rats whilst elevation of oxidative stress biomarker levels in the urine and serum samples were evaluated using biochemical assays. Histological changes of the intestinal mucosa were observed and a significant number of ACF was found in Blastocystis sp. infected AOM-rats compared to the AOM-controls. High levels of urinary oxidative indices including advanced oxidative protein products (AOPP) and hydrogen peroxide were observed in Blastocystis sp. infected AOM-rats compared to the uninfected AOM-rats. Our study provides evidence that Blastocystis sp. has a significant role in enhancing AOM-induced carcinogenesis by resulting damage to the intestinal epithelium and promoting oxidative damage in Blastocystis sp. infected rats.

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          Most cited references58

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          New insights on classification, identification, and clinical relevance of Blastocystis spp.

          Blastocystis is an unusual enteric protozoan parasite of humans and many animals. It has a worldwide distribution and is often the most commonly isolated organism in parasitological surveys. The parasite has been described since the early 1900s, but only in the last decade or so have there been significant advances in our understanding of Blastocystis biology. However, the pleomorphic nature of the parasite and the lack of standardization in techniques have led to confusion and, in some cases, misinterpretation of data. This has hindered laboratory diagnosis and efforts to understand its mode of reproduction, life cycle, prevalence, and pathogenesis. Accumulating epidemiological, in vivo, and in vitro data strongly suggest that Blastocystis is a pathogen. Many genotypes exist in nature, and recent observations indicate that humans are, in reality, hosts to numerous zoonotic genotypes. Such genetic diversity has led to a suggestion that previously conflicting observations on the pathogenesis of Blastocystis are due to pathogenic and nonpathogenic genotypes. Recent epidemiological, animal infection, and in vitro host-Blastocystis interaction studies suggest that this may indeed be the case. This review focuses on such recent advances and also provides updates on laboratory and clinical aspects of Blastocystis spp.
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            Protein oxidation in aging, disease, and oxidative stress.

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              Observation and quantification of aberrant crypts in the murine colon treated with a colon carcinogen: preliminary findings.

              R P Bird (1987)
              In the present study a methodological approach is taken which quantitates aberrant dysplastic crypts in the unsectioned murine colon. C57BL/6J or CF1 female mice (7-8 weeks old) were injected (i.p.) with azoxymethane (5 mg/kg body wt./week) for 4 weeks. Their colons were excised, cut open on the median axis and fixed flat in buffered formalin. Unsectioned colons were stained with methylene blue. The mucosal side was examined under a light microscope. The aberrant crypts, which are larger and have a thicker epithelial lining, were easily visualized using X 4 or X 10 objectives. CF1 mice, which are more sensitive to developing colon tumors, had a higher number of aberrant crypts/colon than their less sensitive counterparts, C57BL/6J mice (5.0 +/- 0.7 vs. 2.4 +/- 0.7). The usefulness of this observation as a possible measure of neoplastic events is discussed in the animal and human situation.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draft
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: Project administrationRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: Formal analysisRole: ResourcesRole: Validation
                Role: ConceptualizationRole: MethodologyRole: SupervisionRole: VisualizationRole: Writing – review & editing
                Role: Data curationRole: MethodologyRole: Visualization
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                31 August 2017
                2017
                : 12
                : 8
                : e0183097
                Affiliations
                [1 ] Department of Microbiology, Faculty of Medicine, MAHSA University, Bandar Saujana Putra, Shah Alam, Malaysia
                [2 ] Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
                [3 ] Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
                [4 ] Department of Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
                [5 ] Department of Biomedical Science, Faculty of Medicine, Mahsa University, Bandar Saujana Putra, Shah Alam, Malaysia
                [6 ] Department of Parasitology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
                University of Illinois at Chicago, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-8895-1796
                http://orcid.org/0000-0002-3426-0201
                Article
                PONE-D-17-09200
                10.1371/journal.pone.0183097
                5578604
                28859095
                a5702361-5e07-4b9f-bcc9-1b577b5eab58
                © 2017 Kumarasamy et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 8 March 2017
                : 28 July 2017
                Page count
                Figures: 12, Tables: 4, Pages: 19
                Funding
                Funded by: University Malaya High Impact Research Grant
                Award ID: UM.C/625/1/HIR/MOHE/MED/44.
                Award Recipient :
                Funding for this study was provided by University Malaya High Impact Research Grant UM.C/625/1/HIR/MOHE/MED/44. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Organisms
                Protozoans
                Parasitic Protozoans
                Blastocystis
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Colorectal Cancer
                Medicine and Health Sciences
                Parasitic Diseases
                Biology and Life Sciences
                Anatomy
                Digestive System
                Gastrointestinal Tract
                Medicine and Health Sciences
                Anatomy
                Digestive System
                Gastrointestinal Tract
                Research and Analysis Methods
                Microscopy
                Light Microscopy
                Fluorescence Recovery after Photobleaching
                Biology and Life Sciences
                Cell Biology
                Oxidative Stress
                Biology and Life Sciences
                Anatomy
                Digestive System
                Gastrointestinal Tract
                Colon
                Medicine and Health Sciences
                Anatomy
                Digestive System
                Gastrointestinal Tract
                Colon
                Research and Analysis Methods
                Specimen Preparation and Treatment
                Staining
                Group-Specific Staining
                Hematoxylin Staining
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

                Uncategorized
                Uncategorized

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