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For decades we have known that the overgrowth, hardening and scarring of tissues (so-called fibrosis) represents the final common pathway and best histological predictor of disease progression in most organs. Fibrosis is the culmination of both excess extracellular matrix deposition due to ongoing or severe injury, and a failure to regenerate. An inadequate wound repair process ultimately results in organ failure through a loss of function, and is therefore a major cause of morbidity and mortality in disease affecting both multiple and individual organs.Whilst the pathology of fibrosis and its significance are well understood, until recently we have known little about its molecular regulation. Current therapies are often indirect and non-specific, and only slow progression by a matter of months. The recent identification of novel therapeutic targets, and the development of new treatment strategies based on them, offers the exciting prospect of more efficacious therapies to treat this debilitating disorder.This Research Topic therefore compromises several up-to-date mini-reviews on currently known and emerging therapeutic targets for fibrosis including: the Transforming Growth Factor (TGF)-family; epigenetic factors; Angiotensin II type 2 (AT2) receptors; mineralocorticoid receptors; adenosine receptors; caveolins; and the sphingosine kinase/sphingosine 1-phosphate and notch signaling pathways. In each case, mechanistic insights into how each of these factors contribute to regulating fibrosis progression are described, along with how they can be targeted (by existing drugs, small molecules or other mimetics) to prevent and/or reverse fibrosis and its contribution to tissue dysfunction and failure. Two additional reviews will discuss various anti-fibrotic therapies that have demonstrated efficacy at the experimental level, but are not yet clinically approved; and the therapeutic potential vs limitations of stem cell-based therapies for reducing fibrosis while facilitating tissue repair. Finally, this Research Topic concludes with a clinical perspective of various anti-fibrotic therapies for cardiovascular disease (CVD), outlining limitations of currently used therapies, the pipeline of anti-fibrotics for CVD and why so many anti-fibrotic drugs have failed at the clinical level.

treatment strategies --- Fibrosis --- pharmacology --- collagen --- fibrogenesis --- therapeutic targets

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For decades we have known that the overgrowth, hardening and scarring of tissues (so-called fibrosis) represents the final common pathway and best histological predictor of disease progression in most organs. Fibrosis is the culmination of both excess extracellular matrix deposition due to ongoing or severe injury, and a failure to regenerate. An inadequate wound repair process ultimately results in organ failure through a loss of function, and is therefore a major cause of morbidity and mortality in disease affecting both multiple and individual organs.Whilst the pathology of fibrosis and its significance are well understood, until recently we have known little about its molecular regulation. Current therapies are often indirect and non-specific, and only slow progression by a matter of months. The recent identification of novel therapeutic targets, and the development of new treatment strategies based on them, offers the exciting prospect of more efficacious therapies to treat this debilitating disorder.This Research Topic therefore compromises several up-to-date mini-reviews on currently known and emerging therapeutic targets for fibrosis including: the Transforming Growth Factor (TGF)-family; epigenetic factors; Angiotensin II type 2 (AT2) receptors; mineralocorticoid receptors; adenosine receptors; caveolins; and the sphingosine kinase/sphingosine 1-phosphate and notch signaling pathways. In each case, mechanistic insights into how each of these factors contribute to regulating fibrosis progression are described, along with how they can be targeted (by existing drugs, small molecules or other mimetics) to prevent and/or reverse fibrosis and its contribution to tissue dysfunction and failure. Two additional reviews will discuss various anti-fibrotic therapies that have demonstrated efficacy at the experimental level, but are not yet clinically approved; and the therapeutic potential vs limitations of stem cell-based therapies for reducing fibrosis while facilitating tissue repair. Finally, this Research Topic concludes with a clinical perspective of various anti-fibrotic therapies for cardiovascular disease (CVD), outlining limitations of currently used therapies, the pipeline of anti-fibrotics for CVD and why so many anti-fibrotic drugs have failed at the clinical level.

treatment strategies --- Fibrosis --- pharmacology --- collagen --- fibrogenesis --- therapeutic targets

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Mitochondria are subcellular organelles evolved by the endosymbiosis of bacteria with eukaryotic cells. They are the main source of ATP in the cell and engaged in other aspects of cell metabolism and cell function, including the regulation of ion homeostasis, cell growth, redox status, and cell signaling. Due to their central role in cell life and death, mitochondria are also involved in the pathogenesis and progression of human diseases/conditions, including neurodegenerative and cardiovascular disorders, cancer, diabetes, inflammation, and aging. However, despite the increasing number of studies, precise mechanisms whereby mitochondria are involved in the regulation of basic physiological functions, as well as their role in the cell under pathophysiological conditions, remain unknown. A lack of in-depth knowledge of the regulatory mechanisms of mitochondrial metabolism and function, as well as interplay between the factors that transform the organelle from its role in pro-survival to pro-death, have hindered the development of new mitochondria-targeted pharmacological and conditional approaches for the treatment of human diseases. This book highlights the latest achievements in elucidating the role of mitochondria under physiological conditions, in various cell/animal models of human diseases, and in patients.

hypoglycemia --- sodium dichloroacetate --- pyruvate dehydrogenase kinase --- pyruvate dehydrogenase --- oxidative stress --- neuron death --- cholangiocellular carcinoma --- mitochondria --- energy metabolism --- oxidative phosphorylation --- 4-HNE --- DRP1 --- ERK1/2 --- hippocampus --- JNK --- mitochondrial dynamics --- PKA --- protein phosphatases --- TUNEL --- DDE --- high-fat diet --- mitochondrial UCP2 --- ROS --- antioxidant system --- uncoupling protein --- mitochondria: energy metabolism --- lipid handling --- fatty acid oxidation --- potassium channel --- reactive oxygen species --- antioxidants --- life span --- aging --- BKCa channels --- pravastatin --- gemfibrozil --- liver --- colon --- mitochondrial function --- cyclosporin A --- mitochondria calcium buffering --- mitochondria bioenergetics --- mitochondria permeability transition pore --- inorganic phosphate --- hepatic fibrogenesis --- HtrA2/Omi --- reactive oxygen species stress --- mitochondrial homeostasis --- complex I (CI) deficiency --- metabolome and proteome profiling --- reactive oxygen species (ROS) --- respirasome assembly --- electron tunneling (ET) --- perilipin 5 --- lipid droplet --- H9c2 cardiomyoblasts --- adenine nucleotide translocase --- respiratory supercomplexes --- ETC complexes --- dentate granule cell --- epilepsy --- hyperforin --- LONP1 --- neuroprotection --- pilocarpine --- seizure --- siRNA --- cardioprotection --- mitochondrial permeability transition pores --- mitochondrial connexin 43 --- cardiolipin --- iron overload --- hepcidin --- transferrin --- ferritin --- ZIP --- inflammation --- mtDNA --- mitochondrial dysfunction --- muscle aging --- physical performance --- LHON --- Siberian population --- ancient mutation --- specific genetic background --- apoptosis --- human amniotic membrane --- mitochondrial cell death --- BAX --- BCL-2 --- tensile strength --- mitochondrial gene expression --- mtDNA transcription --- mtRNA --- post-transcriptional mtRNA processing --- dsRNA --- innate immunity --- interferon response --- amino acid neurotransmitter --- cerebellar amino acid metabolism --- hypoxia --- 2-oxoglutarate dehydrogenase --- tricarboxylic acid cycle --- heart --- cytoskeletal proteins --- mitochondrial interactions --- plectin --- tubulin beta --- signaling --- GW9662 --- ischemia reperfusion injury --- Langendorff --- myocardial --- pioglitazone --- redox state --- rosiglitazone --- TZD --- uncoupling --- ADP/ATP carrier --- KmADP --- dextran --- morphology --- cardiomyocytes --- telomere length --- telomerase activity --- development --- regeneration --- intranuclear mitochondria --- healthy cells --- electron and confocal microscopy --- signaling pathways --- ion homeostasis --- human diseases