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      Redox-fibrosis: Impact of TGFβ1 on ROS generators, mediators and functional consequences

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          Abstract

          Fibrosis is one of the most prevalent features of age-related diseases like obesity, diabetes, non-alcoholic fatty liver disease, chronic kidney disease, or cardiomyopathy and affects millions of people in all countries. Although the understanding about the pathophysiology of fibrosis has improved a lot during the recent years, a number of mechanisms still remain unknown. Although TGF-β1 signaling, loss of metabolic homeostasis and chronic low-grade inflammation appear to play important roles in the pathogenesis of fibrosis, recent evidence indicates that oxidative stress and the antioxidant system may also be crucial for fibrosis development and persistence. These findings point to a concept of a redox-fibrosis where the cellular oxidant and antioxidant system could be potential therapeutic targets. The current review aims to summarize the existing links between TGF-β1 signaling, generation and action of reactive oxygen species, expression of antioxidative enzymes, and functional consequences including epigenetic redox-mediated responses during fibrosis.

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          Highlights

          • Oxidative stress can be both a cause or a consequence of fibrotic events.

          • TGF-β1 is a key cytokine which contributes to production and reduction of ROS.

          • Feedback: ROS are able to activate TGF-β1.

          • ROS are powerful post-transcriptional and epigenetic regulators in fibrosis.

          • Are antioxidants a treatment option during fibrosis?

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          Most cited references162

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          Rapid planetesimal formation in turbulent circumstellar discs

          The initial stages of planet formation in circumstellar gas discs proceed via dust grains that collide and build up larger and larger bodies (Safronov 1969). How this process continues from metre-sized boulders to kilometre-scale planetesimals is a major unsolved problem (Dominik et al. 2007): boulders stick together poorly (Benz 2000), and spiral into the protostar in a few hundred orbits due to a head wind from the slower rotating gas (Weidenschilling 1977). Gravitational collapse of the solid component has been suggested to overcome this barrier (Safronov 1969, Goldreich & Ward 1973, Youdin & Shu 2002). Even low levels of turbulence, however, inhibit sedimentation of solids to a sufficiently dense midplane layer (Weidenschilling & Cuzzi 1993, Dominik et al. 2007), but turbulence must be present to explain observed gas accretion in protostellar discs (Hartmann 1998). Here we report the discovery of efficient gravitational collapse of boulders in locally overdense regions in the midplane. The boulders concentrate initially in transient high pressures in the turbulent gas (Johansen, Klahr, & Henning 2006), and these concentrations are augmented a further order of magnitude by a streaming instability (Youdin & Goodman 2005, Johansen, Henning, & Klahr 2006, Johansen & Youdin 2007) driven by the relative flow of gas and solids. We find that gravitationally bound clusters form with masses comparable to dwarf planets and containing a distribution of boulder sizes. Gravitational collapse happens much faster than radial drift, offering a possible path to planetesimal formation in accreting circumstellar discs.
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            The Dicke Quantum Phase Transition with a Superfluid Gas in an Optical Cavity

            A phase transition describes the sudden change of state in a physical system, such as the transition between a fluid and a solid. Quantum gases provide the opportunity to establish a direct link between experiment and generic models which capture the underlying physics. A fundamental concept to describe the collective matter-light interaction is the Dicke model which has been predicted to show an intriguing quantum phase transition. Here we realize the Dicke quantum phase transition in an open system formed by a Bose-Einstein condensate coupled to an optical cavity, and observe the emergence of a self-organized supersolid phase. The phase transition is driven by infinitely long-ranged interactions between the condensed atoms. These are induced by two-photon processes involving the cavity mode and a pump field. We show that the phase transition is described by the Dicke Hamiltonian, including counter-rotating coupling terms, and that the supersolid phase is associated with a spontaneously broken spatial symmetry. The boundary of the phase transition is mapped out in quantitative agreement with the Dicke model. The work opens the field of quantum gases with long-ranged interactions, and provides access to novel quantum phases.
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              Fibrosis--a common pathway to organ injury and failure.

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                Author and article information

                Contributors
                Journal
                Redox Biol
                Redox Biol
                Redox Biology
                Elsevier
                2213-2317
                28 August 2015
                December 2015
                28 August 2015
                : 6
                : 344-352
                Affiliations
                [a ]Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland
                [b ]Center of Excellence in Cell-Extracellular Matrix Research, Finland
                Author notes
                [* ]Corresponding author. tkietzm@ 123456gwdg.de
                [1]

                These authors contributed equally.

                Article
                S2213-2317(15)00105-6
                10.1016/j.redox.2015.08.015
                4565043
                26335400
                71b80020-7a01-417b-b1a8-9d91a5baa6b7
                © 2015 Published by Elsevier B.V.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 14 July 2015
                : 19 August 2015
                : 25 August 2015
                Categories
                Review Article

                ros,antioxidants,antioxidative enzymes,matrix,diet,fibrosis
                ros, antioxidants, antioxidative enzymes, matrix, diet, fibrosis

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