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      Parkinson’s Disease: A Systemic Inflammatory Disease Accompanied by Bacterial Inflammagens

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          Abstract

          Parkinson’s disease (PD) is a well-known neurodegenerative disease with a strong association established with systemic inflammation. Recently, the role of the gingipain protease group from Porphyromonas gingivalis was implicated in Alzheimer’s disease and here we present evidence, using a fluorescent antibody to detect gingipain R1 (RgpA), of its presence in a PD population. To further elucidate the action of this gingipain, as well as the action of the lipopolysaccharide (LPS) from P. gingivalis, low concentrations of recombinant RgpA and LPS were added to purified fluorescent fibrinogen. We also substantiate previous findings regarding PD by emphasizing the presence of systemic inflammation via multiplex cytokine analysis, and demonstrate hypercoagulation using thromboelastography (TEG), confocal and electron microscopy. Biomarker analysis confirmed significantly increased levels of circulating proinflammatory cytokines. In our PD and control blood analysis, our results show increased hypercoagulation, the presence of amyloid formation in plasma, and profound ultrastructural changes to platelets. Our laboratory analysis of purified fibrinogen with added RgpA, and/or LPS, showed preliminary data with regards to the actions of the protease and the bacterial membrane inflammagen on plasma proteins, to better understand the nature of established PD.

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          Porphyromonas gingivalis: An Overview of Periodontopathic Pathogen below the Gum Line

          Periodontal disease represents a group of oral inflammatory infections initiated by oral pathogens which exist as a complex biofilms on the tooth surface and cause destruction to tooth supporting tissues. The severity of this disease ranges from mild and reversible inflammation of the gingiva (gingivitis) to chronic destruction of connective tissues, the formation of periodontal pocket and ultimately result in loss of teeth. While human subgingival plaque harbors more than 500 bacterial species, considerable research has shown that Porphyromonas gingivalis, a Gram-negative anaerobic bacterium, is the major etiologic agent which contributes to chronic periodontitis. This black-pigmented bacterium produces a myriad of virulence factors that cause destruction to periodontal tissues either directly or indirectly by modulating the host inflammatory response. Here, this review provides an overview of P. gingivalis and how its virulence factors contribute to the pathogenesis with other microbiome consortium in oral cavity.
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            Interleukin-1 Beta as a Target for Atherosclerosis Therapy: Biological Basis of CANTOS and Beyond.

            Inflammatory pathways drive atherogenesis and link conventional risk factors to atherosclerosis and its complications. One inflammatory mediator has come to the fore as a therapeutic target in cardiovascular disease. The experimental and clinical evidence reviewed here support interleukin-1 beta (IL-1β) as both a local vascular and systemic contributor in this regard. Intrinsic vascular wall cells and lesional leukocytes alike can produce this cytokine. Local stimuli in the plaque favor the generation of active IL-1β through the action of a molecular assembly known as the inflammasome. Clinically applicable interventions that interfere with IL-1 action can improve cardiovascular outcomes, ushering in a new era of anti-inflammatory therapies for atherosclerosis. The translational path described here illustrates how advances in basic vascular biology may transform therapy. Biomarker-directed application of anti-inflammatory interventions promises to help us achieve a more precise and personalized allocation of therapy for our cardiovascular patients.
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              The dormant blood microbiome in chronic, inflammatory diseases

              Blood in healthy organisms is seen as a ‘sterile’ environment: it lacks proliferating microbes. Dormant or not-immediately-culturable forms are not absent, however, as intracellular dormancy is well established. We highlight here that a great many pathogens can survive in blood and inside erythrocytes. ‘Non-culturability’, reflected by discrepancies between plate counts and total counts, is commonplace in environmental microbiology. It is overcome by improved culturing methods, and we asked how common this would be in blood. A number of recent, sequence-based and ultramicroscopic studies have uncovered an authentic blood microbiome in a number of non-communicable diseases. The chief origin of these microbes is the gut microbiome (especially when it shifts composition to a pathogenic state, known as ‘dysbiosis’). Another source is microbes translocated from the oral cavity. ‘Dysbiosis’ is also used to describe translocation of cells into blood or other tissues. To avoid ambiguity, we here use the term ‘atopobiosis’ for microbes that appear in places other than their normal location. Atopobiosis may contribute to the dynamics of a variety of inflammatory diseases. Overall, it seems that many more chronic, non-communicable, inflammatory diseases may have a microbial component than are presently considered, and may be treatable using bactericidal antibiotics or vaccines.
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                Author and article information

                Contributors
                Journal
                Front Aging Neurosci
                Front Aging Neurosci
                Front. Aging Neurosci.
                Frontiers in Aging Neuroscience
                Frontiers Media S.A.
                1663-4365
                27 August 2019
                2019
                : 11
                : 210
                Affiliations
                [1] 1Department of Physiological Sciences, Faculty of Science, Stellenbosch University , Stellenbosch, South Africa
                [2] 2Department of Biochemistry, Institute of Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool , Liverpool, United Kingdom
                [3] 3Division of Neurology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University , Stellenbosch, South Africa
                Author notes

                Edited by: Simone Engelender, Technion–Israel Institute of Technology, Israel

                Reviewed by: Rebecca L. Cunningham, University of North Texas Health Science Center, United States; Liu Jun, Shanghai Jiao Tong University, China

                *Correspondence: Douglas B. Kell, dbk@ 123456liv.ac.uk
                Etheresia Pretorius resiap@ 123456sun.ac.za

                ORCID: Douglas B. Kell, orcid.org/0000-0001-5838-7963; Etheresia Pretorius, orcid.org/0000-0002-9108-2384

                Article
                10.3389/fnagi.2019.00210
                6718721
                31507404
                74306bd7-e9c8-4682-a239-c0df11981ddd
                Copyright © 2019 Adams, Nunes, Page, Roberts, Carr, Nell, Kell and Pretorius.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 14 May 2019
                : 26 July 2019
                Page count
                Figures: 8, Tables: 4, Equations: 0, References: 118, Pages: 17, Words: 0
                Funding
                Funded by: Biotechnology and Biological Sciences Research Council 10.13039/501100000268
                Funded by: National Research Foundation 10.13039/100011512
                Funded by: South African Medical Research Council 10.13039/501100001322
                Categories
                Neuroscience
                Original Research

                Neurosciences
                parkinson’s disease,systemic inflammation,cytokines,lps from porphyromonas gingivalis,gingipains,amyloid formation

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