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      Is Open Access

      Advanced Glycation End Products: New Clinical and Molecular Perspectives

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          Abstract

          Diabetes mellitus (DM) is considered one of the most massive epidemics of the twenty-first century due to its high mortality rates caused mainly due to its complications; therefore, the early identification of such complications becomes a race against time to establish a prompt diagnosis. The research of complications of DM over the years has allowed the development of numerous alternatives for diagnosis. Among these emerge the quantification of advanced glycation end products (AGEs) given their increased levels due to chronic hyperglycemia, while also being related to the induction of different stress-associated cellular responses and proinflammatory mechanisms involved in the progression of chronic complications of DM. Additionally, the investigation for more valuable and safe techniques has led to developing a newer, noninvasive, and effective tool, termed skin fluorescence (SAF). Hence, this study aimed to establish an update about the molecular mechanisms induced by AGEs during the evolution of chronic complications of DM and describe the newer measurement techniques available, highlighting SAF as a possible tool to measure the risk of developing DM chronic complications.

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          Most cited references206

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          RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides.

          S100/calgranulin polypeptides are present at sites of inflammation, likely released by inflammatory cells targeted to such loci by a range of environmental cues. We report here that receptor for AGE (RAGE) is a central cell surface receptor for EN-RAGE (extracellular newly identified RAGE-binding protein) and related members of the S100/calgranulin superfamily. Interaction of EN-RAGEs with cellular RAGE on endothelium, mononuclear phagocytes, and lymphocytes triggers cellular activation, with generation of key proinflammatory mediators. Blockade of EN-RAGE/RAGE quenches delayed-type hypersensitivity and inflammatory colitis in murine models by arresting activation of central signaling pathways and expression of inflammatory gene mediators. These data highlight a novel paradigm in inflammation and identify roles for EN-RAGEs and RAGE in chronic cellular activation and tissue injury.
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            Müller cells in the healthy and diseased retina.

            Müller glial cells span the entire thickness of the tissue, and ensheath all retinal neurons, in vertebrate retinae of all species. This morphological relationship is reflected by a multitude of functional interactions between neurons and Müller cells, including a 'metabolic symbiosis' and the processing of visual information. Müller cells are also responsible for the maintenance of the homeostasis of the retinal extracellular milieu (ions, water, neurotransmitter molecules, and pH). In vascularized retinae, Müller cells may also be involved in the control of angiogenesis, and the regulation of retinal blood flow. Virtually every disease of the retina is associated with a reactive Müller cell gliosis which, on the one hand, supports the survival of retinal neurons but, on the other hand, may accelerate the progress of neuronal degeneration: Müller cells protect neurons via a release of neurotrophic factors, the uptake and degradation of the excitotoxin, glutamate, and the secretion of the antioxidant, glutathione. However, gliotic Müller cells display a dysregulation of various neuron-supportive functions. This contributes to a disturbance of retinal glutamate metabolism and ion homeostasis, and causes the development of retinal edema and neuronal cell death. Moreover, there are diseases evoking a primary Müller cell insufficiency, such as hepatic retinopathy and certain forms of glaucoma. Any impairment of supportive functions of Müller cells, primary or secondary, must cause and/or aggravate a dysfunction and loss of neurons, by increasing the susceptibility of neurons to stressful stimuli in the diseased retina. On the contrary, Müller cells may be used in the future for novel therapeutic strategies to protect neurons against apoptosis (somatic gene therapy), or to differentiate retinal neurons from Müller/stem cells. Meanwhile, a proper understanding of the gliotic responses of Müller cells in the diseased retina, and of their protective vs. detrimental effects, is essential for the development of efficient therapeutic strategies that use and stimulate the neuron-supportive/protective-and prevent the destructive-mechanisms of gliosis.
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              Diabetic retinopathy.

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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Environ Res Public Health
                Int J Environ Res Public Health
                ijerph
                International Journal of Environmental Research and Public Health
                MDPI
                1661-7827
                1660-4601
                06 July 2021
                July 2021
                : 18
                : 14
                : 7236
                Affiliations
                [1 ]Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela; jjsv18@ 123456gmail.com (J.S.); cpnm24@ 123456gmail.com (C.N.); angelort94@ 123456hotmail.com (Á.O.); manuelnava_14@ 123456hotmail.com (M.N.); wheelertorres16@ 123456gmail.com (W.T.)
                [2 ]Faculty of Medicine, School of Medicine, University of Buenos Aires, Buenos Aires 1121, Argentina; danielalemv@ 123456gmail.com
                [3 ]Faculty of Medicine, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela; marlonjh79@ 123456gmail.com
                [4 ]City of Houston Health Department, Houston, TX 77054, USA; mayela.cabreradebravo@ 123456houstontx.gov
                [5 ]Escuela de Nutrición y Dietética, Facultad de Medicina, Universidad Andrés Bello, Sede Concepción 4260000, Chile; lisse.angarita@ 123456unab.cl
                [6 ]Facultad de Medicina, Universidad Católica de Cuenca, Cuenca 010105, Ecuador; rortiz@ 123456ucacue.edu.ec
                [7 ]Facultad de Ciencias de la Salud, Universidad Simón Bolívar, Barranquilla 080002, Colombia; m.chacin@ 123456unisimonbolivar.edu.co
                [8 ]Department of Nephrology, Hospital Clinico Universitario de Valencia, INCLIVA, University of Valencia, 46010 Valencia, Spain
                Author notes
                Author information
                https://orcid.org/0000-0003-4211-528X
                https://orcid.org/0000-0002-1321-9568
                https://orcid.org/0000-0002-7180-4765
                https://orcid.org/0000-0001-9769-1693
                https://orcid.org/0000-0001-9902-7438
                https://orcid.org/0000-0001-7860-5112
                https://orcid.org/0000-0003-0148-891X
                https://orcid.org/0000-0003-1880-8887
                Article
                ijerph-18-07236
                10.3390/ijerph18147236
                8306599
                34299683
                63ccc8d2-a0dd-40fd-afd8-4c1d52357bda
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 02 June 2021
                : 03 July 2021
                Categories
                Review

                Public health
                advanced glycation end products,diabetes mellitus,chronic complications,skin fluorescence

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