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The Importance of Iron in Pathophysiologic Conditions

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195244 Year: Pages: 479 DOI: 10.3389/978-2-88919-524-4 Language: English
Publisher: Frontiers Media SA
Subject: Therapeutics --- Science (General)
Added to DOAB on : 2015-12-10 11:59:06
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Abstract

The iron element (Fe) is strictly required for the survival of most forms of life, including bacteria, plants and humans. Fine-tuned regulatory mechanisms for Fe absorption, mobilization and recycling operate to maintain Fe homeostasis, the disruption of which leads to Fe overload or Fe depletion. Whereas the deleterious effect of Fe deficiency relies on reduced oxygen transport and diminished activity of Fe-dependent enzymes, the cytotoxicity induced by Fe overload is due to the ability of this metal to act as a pro-oxidant and catalyze the formation of highly reactive hydroxyl radicals via the Fenton chemistry. This results in unfettered oxidative stress generation that, by inducing protein, lipid and DNA oxidation, leads to Fe-mediated programmed cell death and organ dysfunction. Major and systemic Fe overloads occurring in hemochromatosis and Fe-loading anemias have been extensively studied. However, localized tissue Fe overload was recently associated to a variety of pathologies, such as infection, inflammation, cancer, cardiovascular and neurodegenerative disorders. In keeping with the existence of cross-regulatory interactions between Fe homeostasis and the pathophysiology of these diseases, further investigations on the mechanisms that provide cellular and systemic adaptation to tissue Fe overload are instrumental for future therapeutic approaches. Thus, we encourage our colleagues to submit original research papers, reviews, perspectives, methods and technology reports to contribute their findings to a current state of the art on a comprehensive overview of the importance of iron metabolism in pathophysiologic conditions.

Iron as Therapeutic Targets in Human Diseases Volume 1

Authors: --- ---
ISBN: 9783039280827 9783039280834 Year: Pages: 472 DOI: 10.3390/books978-3-03928-083-4 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology --- Biochemistry
Added to DOAB on : 2020-04-07 23:07:08
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Abstract

Iron is an essential element for almost all organisms, a cofactor playing a crucial role in a number of vital functions, including oxygen transport, DNA synthesis, and respiration. However, its ability to exchange electrons renders excess iron potentially toxic, since it is capable of catalyzing the formation of highly poisonous free radicals. As a consequence, iron homeostasis is tightly controlled by sophisticated mechanisms that have been partially elucidated. Because of its biological importance, numerous disorders have been recently linked to the deregulation of iron homeostasis, which include not only the typical disorders of iron overload and deficiency but also cancer and neurodegenerative diseases. This leads iron metabolism to become an interesting therapeutic target for novel pharmacological treatments against these diseases. Several therapies are currently under development for hematological disorders, while other are being considered for different pathologies. The therapeutic targeting under study includes the hepcidin/ferroportin axis for the regulation of systemic iron homeostasis, complex cytosolic machineries for the regulation of the intracellular iron status and its association with oxidative damage, and reagents exploiting proteins of iron metabolism such as ferritin and transferrin receptor. A promising potential target is a recently described form of programmed cell death named ferroptosis, in which the role of iron is essential but not completely clarified. This Special Issue has the aim to summarize the state-of-the-art, and the latest findings published in the iron field, as well as to elucidate future directions.

Keywords

cinnamic acid derivatives --- soybean seed ferritin --- iron release --- binding ability --- Fe2+-chelating activity --- reducibility --- adverse event profile --- anaemia --- bioengineering --- labile iron --- intravenous iron --- iron-carbohydrate complex --- iron processing --- iron metabolism --- infection --- innate immunity --- hepcidin --- ferritin --- anemia of inflammation --- pharmaceutical targets --- iron deficiency anemia --- nutrient iron --- oral iron therapy --- FeSO4 --- NaFeEDTA --- non-transferrin-bound iron (NTBI) --- developing countries --- Indonesia --- neurodegeneration --- mitochondria --- therapy --- heme --- haem --- Iron-sulfur --- Friedreich Ataxia --- Oxidative stress --- Iron chelators --- iron deficiency --- anemia --- cancer --- hepcidin --- patient blood management --- malaria --- iron deficiency --- hepcidin --- TNF --- children --- Africa --- Anemia --- iron deficiency --- oral iron salts --- intravenous iron --- Sucrosomial® iron --- M cells --- bioavailability --- tolerability --- efficacy --- iron --- gut microbiota --- iron supplementation --- iron transporters --- mucosal immunity --- SCFA --- intestinal inflammation --- inflammatory bowel disease (IBD) --- colorectal cancer --- oxidative stress --- anaemia --- cardiovascular disease --- chronic kidney disease --- IV iron therapy --- bone homeostasis --- iron overload --- iron deficiency --- osteoclast --- osteoblast --- osteoporosis --- neurodegeneration with brain iron accumulation --- iron chelation therapy --- multifunctional iron chelators --- fluorescent iron chelator --- 3-hydroxy-4-pyridinone --- fluorophore --- rhodamine --- membrane interactions --- bacteria --- antibacterial activity --- histidine --- iron --- anemia --- oxidative stress --- kidney --- chelation --- iron --- retina --- age-related macular degeneration (AMD) --- iron --- lipid --- obesity --- cancer --- neurodegeneration --- iron chelation --- phlebotomy --- NCOA4 --- ferritinophagy --- iron homeostasis --- erythropoiesis --- ferroptosis --- cancer --- Tfr2 --- iron metabolism --- hepcidin --- erythropoiesis --- SNC --- ferritin --- iron mobilization --- chaotropes --- flavin nucleotide --- electron transfer --- kinetics --- ferritin --- iron --- iron delivery --- nanotechnology --- nanocage --- drug delivery --- inflammation --- serum biomarker --- iron metabolism --- hepcidin --- ferroportin --- hemochromatosis --- anemia --- hepcidin --- iron deficiency anemia --- iron dextran --- neonatal period --- pig --- supplementation --- Alzheimer’s disease --- neuroinflammation --- neurodegeneration --- cytokines --- neuroimmune responses --- iron --- genetic hemochromatosis --- non transferrin bound iron --- hepcidin --- ferroportin --- venesections --- Anemia of chronic disease --- anemia of inflammation --- hepcidin --- anti-hepcidin therapy --- iron supplementation --- macrophage --- central nurse macrophage --- red pulp macrophage --- Kupffer cell --- iron metabolism --- erythropoiesis --- erythroblastic islands --- erythrophagocytosis --- inflammation --- iron homeostasis --- lung diseases --- oxygen sensing --- hypoxia --- ferritin --- hereditary hyperferritinemia --- hereditary hypoferritinemia --- iron metabolism --- cataracts syndrome --- neurodegenerative disease --- n/a --- iron --- neurodegeneration --- NBIA --- hepcidin --- iron --- lung --- acute lung injury --- COPD --- lung infection --- cystic fibrosis --- iron --- anaemia --- infection --- malaria --- immunity --- brain development --- growth --- microbiome --- hepcidin --- ferritin --- iron supplementation --- infants --- children --- low and middle income countries --- liver --- iron --- hepcidin --- Mek/Erk --- Hfe --- Bmp/Smad --- iron --- mycobacteria --- immunity --- Alzheimer’s disease --- iron homeostasis --- ferroptosis --- senescence --- chelators --- macrophages --- iron --- metabolism --- inflammation --- iron --- ferritin --- acute kidney injury --- chronic kidney disease --- vascular calcification --- iron --- hepcidin --- ferroportin --- Interleukin-6 --- infection --- rheumatoid arthritis --- iron homeostasis --- iron absorption --- non-haem iron --- flavonoids --- developmental --- iron deficiency anemia --- neonatal --- transferrin receptor --- treatment --- hemochromatosis --- HFE --- natural history --- T lymphocytes --- MHC --- CD8+ T cells --- prevention --- iron homeostasis --- hepcidin --- protein binding --- peritoneal dialysis --- iron --- hepcidin --- iron regulatory proteins --- cardiomyocyte --- chronic heart failure --- pulmonary arterial smooth muscle cells --- pulmonary arterial hypertension --- iron --- brain --- neurophysiology --- cognition --- social behavior --- didox --- iron chelators --- antitumor compound --- iron metabolism --- RRM2 --- SLC40A1 --- ferroportin --- iron overload --- non-HFE --- ferritin --- hemochromatosis --- iron --- chelation --- neurodegenerative diseases --- pituitary --- brain --- hemopexin --- heme homeostasis --- iron homeostasis --- hemolysis --- haptoglobin --- ferroptosis --- inflammation --- biomarker --- heme oxygenase --- liver --- microbiome --- trauma --- hemorrhage --- iron metabolism --- hepcidin --- iron homeostasis --- ferroportin --- n/a

Iron as Therapeutic Targets in Human Diseases Volume 2

Authors: --- ---
ISBN: 9783039281145 9783039281152 Year: Pages: 440 DOI: 10.3390/books978-3-03928-115-2 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology --- Biochemistry
Added to DOAB on : 2020-04-07 23:07:08
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Abstract

Iron is an essential element for almost all organisms, a cofactor playing a crucial role in a number of vital functions, including oxygen transport, DNA synthesis, and respiration. However, its ability to exchange electrons renders excess iron potentially toxic, since it is capable of catalyzing the formation of highly poisonous free radicals. As a consequence, iron homeostasis is tightly controlled by sophisticated mechanisms that have been partially elucidated. Because of its biological importance, numerous disorders have been recently linked to the deregulation of iron homeostasis, which include not only the typical disorders of iron overload and deficiency but also cancer and neurodegenerative diseases. This leads iron metabolism to become an interesting therapeutic target for novel pharmacological treatments against these diseases. Several therapies are currently under development for hematological disorders, while other are being considered for different pathologies. The therapeutic targeting under study includes the hepcidin/ferroportin axis for the regulation of systemic iron homeostasis, complex cytosolic machineries for the regulation of the intracellular iron status and its association with oxidative damage, and reagents exploiting proteins of iron metabolism such as ferritin and transferrin receptor. A promising potential target is a recently described form of programmed cell death named ferroptosis, in which the role of iron is essential but not completely clarified. This Special Issue has the aim to summarize the state-of-the-art, and the latest findings published in the iron field, as well as to elucidate future directions.

Keywords

cinnamic acid derivatives --- soybean seed ferritin --- iron release --- binding ability --- Fe2+-chelating activity --- reducibility --- adverse event profile --- anaemia --- bioengineering --- labile iron --- intravenous iron --- iron-carbohydrate complex --- iron processing --- iron metabolism --- infection --- innate immunity --- hepcidin --- ferritin --- anemia of inflammation --- pharmaceutical targets --- iron deficiency anemia --- nutrient iron --- oral iron therapy --- FeSO4 --- NaFeEDTA --- non-transferrin-bound iron (NTBI) --- developing countries --- Indonesia --- neurodegeneration --- mitochondria --- therapy --- heme --- haem --- Iron-sulfur --- Friedreich Ataxia --- Oxidative stress --- Iron chelators --- iron deficiency --- anemia --- cancer --- hepcidin --- patient blood management --- malaria --- iron deficiency --- hepcidin --- TNF --- children --- Africa --- Anemia --- iron deficiency --- oral iron salts --- intravenous iron --- Sucrosomial® iron --- M cells --- bioavailability --- tolerability --- efficacy --- iron --- gut microbiota --- iron supplementation --- iron transporters --- mucosal immunity --- SCFA --- intestinal inflammation --- inflammatory bowel disease (IBD) --- colorectal cancer --- oxidative stress --- anaemia --- cardiovascular disease --- chronic kidney disease --- IV iron therapy --- bone homeostasis --- iron overload --- iron deficiency --- osteoclast --- osteoblast --- osteoporosis --- neurodegeneration with brain iron accumulation --- iron chelation therapy --- multifunctional iron chelators --- fluorescent iron chelator --- 3-hydroxy-4-pyridinone --- fluorophore --- rhodamine --- membrane interactions --- bacteria --- antibacterial activity --- histidine --- iron --- anemia --- oxidative stress --- kidney --- chelation --- iron --- retina --- age-related macular degeneration (AMD) --- iron --- lipid --- obesity --- cancer --- neurodegeneration --- iron chelation --- phlebotomy --- NCOA4 --- ferritinophagy --- iron homeostasis --- erythropoiesis --- ferroptosis --- cancer --- Tfr2 --- iron metabolism --- hepcidin --- erythropoiesis --- SNC --- ferritin --- iron mobilization --- chaotropes --- flavin nucleotide --- electron transfer --- kinetics --- ferritin --- iron --- iron delivery --- nanotechnology --- nanocage --- drug delivery --- inflammation --- serum biomarker --- iron metabolism --- hepcidin --- ferroportin --- hemochromatosis --- anemia --- hepcidin --- iron deficiency anemia --- iron dextran --- neonatal period --- pig --- supplementation --- Alzheimer’s disease --- neuroinflammation --- neurodegeneration --- cytokines --- neuroimmune responses --- iron --- genetic hemochromatosis --- non transferrin bound iron --- hepcidin --- ferroportin --- venesections --- Anemia of chronic disease --- anemia of inflammation --- hepcidin --- anti-hepcidin therapy --- iron supplementation --- macrophage --- central nurse macrophage --- red pulp macrophage --- Kupffer cell --- iron metabolism --- erythropoiesis --- erythroblastic islands --- erythrophagocytosis --- inflammation --- iron homeostasis --- lung diseases --- oxygen sensing --- hypoxia --- ferritin --- hereditary hyperferritinemia --- hereditary hypoferritinemia --- iron metabolism --- cataracts syndrome --- neurodegenerative disease --- n/a --- iron --- neurodegeneration --- NBIA --- hepcidin --- iron --- lung --- acute lung injury --- COPD --- lung infection --- cystic fibrosis --- iron --- anaemia --- infection --- malaria --- immunity --- brain development --- growth --- microbiome --- hepcidin --- ferritin --- iron supplementation --- infants --- children --- low and middle income countries --- liver --- iron --- hepcidin --- Mek/Erk --- Hfe --- Bmp/Smad --- iron --- mycobacteria --- immunity --- Alzheimer’s disease --- iron homeostasis --- ferroptosis --- senescence --- chelators --- macrophages --- iron --- metabolism --- inflammation --- iron --- ferritin --- acute kidney injury --- chronic kidney disease --- vascular calcification --- iron --- hepcidin --- ferroportin --- Interleukin-6 --- infection --- rheumatoid arthritis --- iron homeostasis --- iron absorption --- non-haem iron --- flavonoids --- developmental --- iron deficiency anemia --- neonatal --- transferrin receptor --- treatment --- hemochromatosis --- HFE --- natural history --- T lymphocytes --- MHC --- CD8+ T cells --- prevention --- iron homeostasis --- hepcidin --- protein binding --- peritoneal dialysis --- iron --- hepcidin --- iron regulatory proteins --- cardiomyocyte --- chronic heart failure --- pulmonary arterial smooth muscle cells --- pulmonary arterial hypertension --- iron --- brain --- neurophysiology --- cognition --- social behavior --- didox --- iron chelators --- antitumor compound --- iron metabolism --- RRM2 --- SLC40A1 --- ferroportin --- iron overload --- non-HFE --- ferritin --- hemochromatosis --- iron --- chelation --- neurodegenerative diseases --- pituitary --- brain --- hemopexin --- heme homeostasis --- iron homeostasis --- hemolysis --- haptoglobin --- ferroptosis --- inflammation --- biomarker --- heme oxygenase --- liver --- microbiome --- trauma --- hemorrhage --- iron metabolism --- hepcidin --- iron homeostasis --- ferroportin --- n/a

Genetic and Epigenetic Modulation of Cell Functions by Physical Exercise

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ISBN: 9783039284801 / 9783039284818 Year: Pages: 170 DOI: 10.3390/books978-3-03928-481-8 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology --- Genetics
Added to DOAB on : 2020-06-09 16:38:57
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From an evolutionary perspective, our species has relied upon physical activity for most of its history to survive and has had to escape from predators, to scavenge for food, and to use physique to work or build necessary means for everyday life. Physical activity has been part of our evolution and progress since the very beginning and, consequently, our entire body has been programmed to be active physically. In the last 20 years, scientific research has increasingly shown that our ancient survival principle has beneficial effects not only on the cells and organs involved in physical activities but on the metabolism of the entire organism, influencing the homeostasis and integration of all bodily functions, likely stimulating the production of hormones and other regulatory molecules, with each affecting vital signalling pathways. Most of the web of factors involved in molecular signalling upon exercise are suspected to be centrally controlled by the brain, which has been reported to be deeply modified by physical activity. Such complexity requires a multifaceted approach to shed light on the molecular interactions that occur between physical activity and its outcome at a cellular level.

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