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Genome-wide view on the physiology of vitamin D

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193493 Year: Pages: 194 DOI: 10.3389/978-2-88919-349-3 Language: English
Publisher: Frontiers Media SA
Subject: Physiology --- Science (General)
Added to DOAB on : 2016-03-10 08:14:32
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The main physiological actions of the biologically most active metabolite of vitamin D, 1a,25-dihydroxyvitamin D3(1a,25(OH)2D3), are calcium and phosphorus uptake and transport and thereby controlling bone formation. Other emergent areas of 1a,25(OH)2D3 action are in the control of immune functions, cellular growth and differentiation. This fits both with the widespread expression of the VDR and the above described consequences of vitamin D deficiency. Transcriptome-wide analysis indicated that per cell type between 200 and 600 genes are primary targets of vitamin D. Since most of these genes respond to vitamin D in a cell-specific fashion, the total number of vitamin D targets in the human genome is far higher than 1,000. This is supported by the genome-wide view on VDR binding sites in human lymphocytes, monocytes, colon and hepatic cells. All genomic actions of 1a,25(OH)2D3 are mediated by the transcription factor vitamin D receptor (VDR) that has been the subject of intense study since the 1980’s. Thus, vitamin D signaling primarily implies the molecular actions of the VDR. In this research topic, we present in 15 chapters different perspectives on the action of vitamin D and its receptor, such as the impact of the genomewide distribution of VDR binding loci, ii) the transcriptome- and proteome-wide effects of vitamin D, iii) the role of vitamin D in health, iv) tissue-specific functions of vitamin D and v) the involvement of vitamin D in different diseases, such as infections, autoimmune diseases, diabetes and different types of cancer.

Vitamin D and Human Health

ISBN: 9783038420569 9783038420576 Year: Pages: 476 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Added to DOAB on : 2015-10-22 08:50:54
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Vitamin D research has expanded greatly over the last 10 years, with a more than two-fold increase in annual publications listed in Pubmed with the key word ‘vitamin D’ from 1675 in 2005 to 3953 in 2014. Part of this increase is due to research showing that vitamin D deficiency is associated with a wide range of diseases and health outcomes. Until the 1980s, the primary focus of vitamin D research (in combination with calcium supplementation) was on bone diseases. Since then, observational studies have linked vitamin D deficiency with increased risk of many diseases: both acute and chronic. This book contains publications on several of these disease groups linked to vitamin D deficiency.

Vitamin K and Vitamin K-Dependent Proteins in Relation to Human Health

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ISBN: 9783038428312 9783038428329 Year: Pages: X, 192 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Nutrition and Food Sciences
Added to DOAB on : 2018-04-17 12:23:54
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Vitamin K comprises a group of highly lipophilic molecules that possess a common 2-methyl-1, 4-naphthoquinone nucleus and a variable polyisoprenoid side chain at the 3-position that can vary in both length and degree of saturation. In nature, these forms are found as a single plant form (phylloquinone or vitamin K1) and a series of bacterial forms (menaquinones or vitamin K2). Vitamin K acts as a cofactor for a microsomal enzyme, γ-carboxyglutamyl carboxylase (GGCX), that serves to transform specific peptide-bound glutamate residues found in certain specialized proteins to γ-carboxyglutamate (Gla). This posttranslational protein modification is the only firmly established biochemical function of vitamin K. The resultant vitamin K-dependent (VKD) proteins, or Gla proteins, are diverse in both structure and function and are found in many cell and tissue types. The best-known example of the health role of vitamin K-mediated protein γ-carboxylation is in the synthesis of several VKD blood coagulation proteins, which are essential for the maintenance of extracellular haemostasis. An overt deficiency of vitamin K results in bleeding and although rare in most populations, vitamin K deficiency bleeding (VKDB) in early infancy has potentially devastating and fatal consequences because bleeding commonly occurs within the brain. For this reason it is recommended that all newborn infants should receive vitamin K prophylaxis. On the other hand, the deliberate lowering of circulating VKD-coagulation factors by the therapeutic administration of vitamin K antagonists (VKA) such as warfarin is used to treat and prevent thrombotic disorders. The functions of most non-coagulation Gla proteins remain uncertain, but are suspected to play roles in processes as diverse as bone and cardiovascular mineralization, vascular integrity, energy metabolism, immune response, brain metabolism, and in cellular growth, survival, and signalling. For the most part, extrapolations of the cellular properties of extrahepatic Gla proteins to tangible health benefits are unclear or fuzzy, as are the health consequences of their undercarboxylation. However, there is evidence that higher nutritional intakes of vitamin K are required to enable maximal γ-carboxylation of certain extrahepatic Gla proteins, such as osteocalcin and matrix Gla protein (MGP). Osteocalcin and MGP currently represent the best-studied extrahepatic Gla proteins with respect to their putative roles in bone and cardiovascular health, respectively. In addition, osteocalcin may play a role in regulating energy metabolism. Much current interest focuses on the role of MGP as an inhibitor of vascular mineralization, particularly in renal disease and in patients taking VKA. Interestingly, although VKA have been in clinical use for decades, recent evidence suggests that they may cause unintended health consequences by disrupting the function of MGP resulting in calcification and loss of the functional integrity of the vessel wall. Apart from the role of vitamin K in γ-carboxylation there is evidence that some forms, particularly menaquinone-4 (MK-4), have a direct influence on cellular functions.This Special Issue of Nutrients focuses on advances that extend our knowledge of the biochemical functions and health roles played by both the micronutrient vitamin K and its target Gla proteins. The scope of potential topics is wide and may include studies in population and patient groups, animal models and at the cellular level. Examples include the presentation, diagnosis, incidence, causes, and prevention of deficiency syndromes, of which the most obvious is bleeding in infancy, but also extends to other putative roles of vitamin K such as in bone and cardiovascular health. In trying to define extrahepatic functions of vitamin K it is important to obtain evidence of pathophysiological signatures that may derive from chronic suboptimal vitamin K intakes or as a consequence of vitamin K antagonists. An important related question is whether the pathophysiology can be ameliorated or prevented by judicious vitamin K supplementation. Equally important to our understanding of the human physiology of vitamin K are studies that define the relative functional importance of individual vitamers and how differences in their availability and metabolism affect their biological activity. Recent highlights in metabolism include the delineation of the importance of vitamin K epoxide reductase (VKOR) in maintaining vitamin K status and the intriguing hypothesis that its paralog VKOR-like 1 enzyme (VKORL1) may serve an antioxidant function. Another highlight illustrating the importance of metabolism to vitamin K function is the discovery that the enzyme UbiA prenyltransferase-containing domain 1 (UBIAD1) participates in the cellular conversion of phylloquinone to MK-4 with menadione as a metabolic intermediate. We invite authors to submit reviews or original research on any of the above topics.

Vitamin D and Human Health

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ISBN: 9783038975861 / 9783038975878 Year: Pages: 306 DOI: 10.3390/books978-3-03897-587-8 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Biology
Added to DOAB on : 2019-02-21 10:04:11
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Over the past decades, researchers have gathered data demonstrating that vitamin D and its metabolites possess activities far beyond the classic regulation of calcium–phosphate homeostasis. It is now well established that vitamin D is essential for the proper functioning of the musculoskeletal, cardiovascular, nervous, and immune systems. Furthermore, vitamin D and its analogs were shown to regulate proliferation and differentiation of keratinocyte, immune cells, and numerous cancer-derived cells, both in vivo and in vitro. On the other hand, population base studies have provided evidence that global vitamin D deficiency is correlated with the occurrence and aggravation of symptoms of skeletal, cardiovascular autoimmune, and skin disease; infections; metabolic and cognitive disorders; multiple types of cancers; as well as overall mortality. This Special Issue of International Journal of Molecular Sciences, entitled “Vitamin D and Human Health”, summarizes recent advances in our understanding of pleiotropic activity of vitamin D with a focus on its protective role against cancer, hypertension, viral infections, and neurological diseases, as well as its impact on the immune system and mitochondria. Furthermore, eight research papers provide new insight into vitamin D research and highlight new directions and targets in the prevention and treatment of human diseases.

T Cell Regulation by the Environment

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197330 Year: Pages: 115 DOI: 10.3389/978-2-88919-733-0 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-04-07 11:22:02
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Naïve T cells get activated upon encounter with their cognate antigen and differentiate into a specific subset of effector cells. These T cells are themselves plastic and are able to re-differentiate into another subset, changing both phenotype and function. Differentiation into a specific subset depends on the nature of the antigen and of the environmental milieu. Notably, certain nutrients, such as vitamins A and D, sodium chloride, have been shown to modulate T cell responses and influence T cell differentiation. Parasite infection can also skew Th differentiation. Similarly, the gut microbiota regulates the development of immune responses. Lastly, the key role of metabolism on T cells has also been demonstrated. This series of articles highlights some of the multiple links existing between environmental factors and T cell responses.

Vitamin C and Human Health

ISBN: 9783906980614 9783906980621 Year: Pages: 236 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Added to DOAB on : 2015-01-12 11:52:06
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Ascorbic acid is a small, simple, water soluble molecule, synthesised by most plants and animals, with the exception of humans and some animal species due to mutations in the gene encoding the terminal enzyme in the biosynthetic pathway. For humans, it is thus a vitamin (vitamin C) that must be obtained from the diet, with complete deficiency resulting in the fatal disease scurvy. Many functions have been attributed to this fascinating molecule and, despite nearly 90 years of research since its discovery, new roles are still being uncovered, including recent discoveries that it acts as a regulator of epigenetic marks and transcription factors (1). In this volume we begin with a review by Michels and Frei on specific factors that need to be taken into consideration when carrying out vitamin C research. Translational research normally comprises a progression from in vitro/cell culture studies to animal models and finally to clinical trials. At each of these stages, there are requirements specific to vitamin C research that need to be integrated into study designs and this review describes these in detail. [...]

Pediatric Integrative Medicine: An Emerging Field of Pediatrics

ISBN: 9783038420620 9783038420637 Year: Pages: 172 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Added to DOAB on : 2015-10-22 07:30:21
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Pediatric integrative medicine is a specialty that blends conventional medicine with evidence-based complementary therapies. Research shows that use of integrative medicine is common in children, especially in those living with chronic illness. Knowledge in several important areas of pediatric integrative medicine has expanded exponentially over the last decade. Despite this progress, many pediatricians and practitioners who work with children remain unaware of developments in this field.The goal of this special issue is to: define pediatric integrative medicine in its modern context, provide a history of the field’s evolution, highlight areas where research for its use in children is most robust at this time, and identify areas where research is lacking or evolving. Models of the use of integrative medicine in clinical pediatrics will be examined. Bioethics, informed consent, and provider credentialing will be discussed.Some of the most exciting clinical applications of integrative medicine in pediatrics include the use of mind-body medicine therapies such as guided imagery, hypnosis, and biofeedback for the treatment of pain. Mitigation of toxic stress and its health manifestations in children are another area of great potential application of the mind-body therapies. Other areas include integrative approaches to chronic illness, such as cancer, asthma, arthritis, bowel disease, and other chronic conditions where conventional therapies are necessary, yet leave treatment gaps that can be filled with evidence-based integrative therapies targeting lifestyle elements such as nutrition, sleep, physical activity, and social support that are often overlooked in this patient population. Integrative approaches have great potential in preventative heath. Conditions such as obesity and the metabolic syndrome affect a sobering number of children across all age ranges. Few successful treatment models exist for this patient population. Healthy lifestyle measures learned early in life can be a critical factor in providing a foundation for lifelong health for the child and family. Successful models for the use of integrative medicine in these patient populations are needed and will be explored.

Lipid Signaling in T Cell Development and Function

Authors: ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196975 Year: Pages: 142 DOI: 10.3389/978-2-88919-697-5 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2016-08-16 10:34:25
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Lipids are best known as energy storing molecules and core-components of cellular membranes, but can also act as mediators of cellular signaling. This is most prominently illustrated by the paramount importance of the phospholipase C (PLC) and phosphoinositide 3-kinase (PI3K) signaling pathways in many cells, including T cells and cancer cells. Both of these enzymes use the lipid phosphatidylinositol(4,5)bisphosphate (PIP2) as their substrate. PLCs produce the lipid product diacylglycerol (DAG) and soluble inositol(1,4,5)trisphosphate (IP3). DAG acts as a membrane tether for protein kinase C and RasGRP proteins. IP3 is released into the cytosol and controls calcium release from internal stores. The PI3K lipid product phosphatidylinositol(3,4,5)trisphosphate (PIP3) controls signaling by binding and recruiting effector proteins such as Akt and Itk to cellular membranes. Recent research has unveiled important signaling roles for many additional phosphoinositides and other lipids. The articles in this volume highlight how multiple different lipids govern T cell development and function through diverse mechanisms and effectors. In T cells, lipids can orchestrate signaling by organizing membrane topology in rafts or microdomains, direct protein function through covalent lipid-modification or non-covalent lipid binding, act as intracellular or extracellular messenger molecules, or govern T cell function at the level of metabolic regulation. The cellular activity of certain lipid messengers is moreover controlled by soluble counterparts, exemplified by symmetric PIP3/inositol(1,3,4,5)tetrakisphosphate (IP4) signaling in developing T cells. Not surprisingly, lipid producing and metabolizing enzymes have gained attention as potential therapeutic targets for immune disorders, leukemias and lymphomas.

Keywords

Lipid --- T cell --- eicosanoid --- PI3K --- Vitamin D --- diacylglyerol --- Inositol --- Pten --- SHIP --- Adipokine

Vitamin C: Current Concepts in Human Physiology

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ISBN: 9783038972945 9783038972952 Year: Pages: 148 DOI: 10.3390/books978-3-03897-295-2 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Therapeutics --- Biology
Added to DOAB on : 2018-11-05 12:11:11
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ca. 200 words; this text will present the book in all promotional forms (e.g. flyers). Please describe the book in straightforward and consumer-friendly terms.[Vitamin C is synthesized by almost all animals. However, for humans, it is a vitamin that needs constant replenishment in the diet. While its role as an anti-oxidant and for preventing scurvy have been known for a long time, novel functions and unrecognized associations continue to be identified for this enigmatic molecule. In the past decade, new details have emerged regarding differences in its uptake by oral and intravenous modes. While vitamin C deficiency remains largely unknown and poorly addressed in many segments of the population, novel pharmacological roles for high-dose, intravenous vitamin C in many disease states have now been postulated and investigated. This has shifted its role in health and disease from the long-perceived notion as merely a vitamin and an anti-oxidant to a pleiotropic molecule with a broad anti-inflammatory, epigenetic, and anti-cancer profile.This Special Issue comprises original research papers and reviews on vitamin C metabolism and function that relate to the following topics: understanding its role in the modulation of inflammation and immunity, therapeutic applications and safety of pharmacological ascorbate in disease, and the emerging role of vitamin C as a pleiotropic modulator of critical care illness and cancer.]

Vitamin C in Health and Disease

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ISBN: 9783038970293 9783038970309 Year: Pages: X, 288 Language: english
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Cardiovascular
Added to DOAB on : 2018-08-09 11:31:26
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Vitamin C is a pivotal water soluble electron donor in nature and an essential nutrient in man. Despite its many years as a research focus, new and increasingly regulatory functions of vitamin C in human health are continually being unravelled. This improved mechanistic insight is starting to provide rationales explaining the extensive epidemiological literature that, for decades, has consistently shown strong associations between poor vitamin C status and increased morbidity and mortality.In this Special Issue, we include original research and literature reviews by experts in the field outlining the roles of vitamin C in early, daily and late life, as well as the roles of deficiency in cardiovascular disease, inflammation and cancer.

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