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Special Issue "Vitamin D and Its Analogues: New Insights on Biological Effects and Therapeutic Uses"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry, Molecular and Cellular Biology".

Deadline for manuscript submissions: closed (30 September 2017)

Special Issue Editors

Guest Editor
Prof. Dr. George P. Studzinski

Department of Pathology, Rutgers-New Jersey Medical School, Newark, NJ 17101, USA
Website | E-Mail
Interests: signaling of cell differentiation; vitamin D and analogs; apoptosis and its control; cell cyle regulation; acute myeloid lekemia and its therapy
Guest Editor
Prof. Dr. Ewa Marcinkowska

Department of Biotechnology, University of Wroclaw, Wroclaw, Poland
Website 1 | Website 2 | E-Mail
Interests: blood cell differentiation; myeloid leukaemias; cell signaling; vitamin D analogues; retinoids; nuclear receptors
Guest Editor
Prof. Dr. Michael Danilenko

Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel
Website | E-Mail
Interests: cancer cell biology; leukemia; plant antioxidants; vitamin D derivatives

Special Issue Information

Dear Colleagues,

The proven importance of vitamin D for human health has stimulated extensive efforts, not only to understand the variety of its biological actions, but also attempts by organic chemists to modify the vitamin D structure to produce analogs that can be more potent in its effects on various body systems other than the skeletal system. The earliest modification occurred in nature. Animals, including humans, synthesize the secosteroid known as vitamin D3 (cholecalciferol), while plants synthesize vitamin D2 (ergocalciferol) with an unsaturated side-chain. Both have similar biological functions in humans, and both are used to treat rickets, osteoporosis, and osteomalacia. In order to be active as regulators of gene transcription, they need to be metabolically activated in the human body. Vitamin D2 and its derivatives were found to be somewhat less potent, but also less toxic, compared to vitamin D3 compounds. Numerous analogues have been synthesized with the primary goal of overcoming the hypercalcemic toxicity of active natural vitamin D derivatives, which limits their clinical use. Several such analogues have demonstrated reduced calcemic effects in model systems and human studies. Nevertheless, more work is necessary to develop clinically effective analogues. The ability of vitamin D compounds to cooperate with conventional drugs and with agents that sensitize abnormal cells to these compounds may offer a complementary approach towards an improved vitamin D-based therapy of human diseases.

This Special Issue will cover a selection of recent research topics and current review articles in the field of vitamin D and its analogues for biological actions and therapy of human diseases.

Prof. Dr. George P. Studzinski
Prof. Dr. Ewa Marcinkowska
Prof. Michael Danilenko
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

 

Keywords

  • vitamin D
  • analogs of vitamin D
  • vitamin D receptor
  • vitamin D metabolism
  • calcium-phosphate homeostasis
  • differentiation
  • apoptosis
  • cell cycle
  • intracellular signaling
  • regulation of immune system

Related Special Issue

Published Papers (17 papers)

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Research

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Open AccessArticle Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-Degradation
Int. J. Mol. Sci. 2017, 18(12), 2764; https://doi.org/10.3390/ijms18122764
Received: 3 November 2017 / Revised: 1 December 2017 / Accepted: 13 December 2017 / Published: 19 December 2017
Cited by 1 | PDF Full-text (2834 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Alzheimer’s disease (AD) is characterized by extracellular plaques in the brain, mainly consisting of amyloid-β (Aβ), as derived from sequential cleavage of the amyloid precursor protein. Epidemiological studies suggest a tight link between hypovitaminosis of the secosteroid vitamin D and AD. Besides decreased
[...] Read more.
Alzheimer’s disease (AD) is characterized by extracellular plaques in the brain, mainly consisting of amyloid-β (Aβ), as derived from sequential cleavage of the amyloid precursor protein. Epidemiological studies suggest a tight link between hypovitaminosis of the secosteroid vitamin D and AD. Besides decreased vitamin D level in AD patients, an effect of vitamin D on Aβ-homeostasis is discussed. However, the exact underlying mechanisms remain to be elucidated and nothing is known about the potential effect of vitamin D analogues. Here we systematically investigate the effect of vitamin D and therapeutically used analogues (maxacalcitol, calcipotriol, alfacalcidol, paricalcitol, doxercalciferol) on AD-relevant mechanisms. D2 and D3 analogues decreased Aβ-production and increased Aβ-degradation in neuroblastoma cells or vitamin D deficient mouse brains. Effects were mediated by affecting the Aβ-producing enzymes BACE1 and γ-secretase. A reduced secretase activity was accompanied by a decreased BACE1 protein level and nicastrin expression, an essential component of the γ-secretase. Vitamin D and analogues decreased β-secretase activity, not only in mouse brains with mild vitamin D hypovitaminosis, but also in non-deficient mouse brains. Our results further strengthen the link between AD and vitamin D, suggesting that supplementation of vitamin D or vitamin D analogues might have beneficial effects in AD prevention. Full article
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Open AccessArticle Role of Vitamin D in Maintaining Renal Epithelial Barrier Function in Uremic Conditions
Int. J. Mol. Sci. 2017, 18(12), 2531; https://doi.org/10.3390/ijms18122531
Received: 29 September 2017 / Revised: 28 October 2017 / Accepted: 22 November 2017 / Published: 26 November 2017
Cited by 3 | PDF Full-text (5620 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
As current kidney replacement therapies are not efficient enough for end-stage renal disease (ESRD) treatment, a bioartificial kidney (BAK) device, based on conditionally immortalized human proximal tubule epithelial cells (ciPTEC), could represent an attractive solution. The active transport activity of such a system
[...] Read more.
As current kidney replacement therapies are not efficient enough for end-stage renal disease (ESRD) treatment, a bioartificial kidney (BAK) device, based on conditionally immortalized human proximal tubule epithelial cells (ciPTEC), could represent an attractive solution. The active transport activity of such a system was recently demonstrated. In addition, endocrine functions of the cells, such as vitamin D activation, are relevant. The organic anion transporter 1 (OAT-1) overexpressing ciPTEC line presented 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1) and vitamin D receptor (VDR), responsible for vitamin D activation, degradation and function, respectively. The ability to produce and secrete 1α,25-dihydroxy-vitamin D3, was shown after incubation with the precursor, 25-hydroxy-vitamin D3. The beneficial effect of vitamin D on cell function and behavior in uremic conditions was studied in the presence of an anionic uremic toxins mixture. Vitamin D could restore cell viability, and inflammatory and oxidative status, as shown by cell metabolic activity, interleukin-6 (IL-6) levels and reactive oxygen species (ROS) production, respectively. Finally, vitamin D restored transepithelial barrier function, as evidenced by decreased inulin-FITC leakage in biofunctionalized hollow fiber membranes (HFM) carrying ciPTEC-OAT1. In conclusion, the protective effects of vitamin D in uremic conditions and proven ciPTEC-OAT1 endocrine function encourage the use of these cells for BAK application. Full article
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Open AccessArticle IGFBP-3 Interacts with the Vitamin D Receptor in Insulin Signaling Associated with Obesity in Visceral Adipose Tissue
Int. J. Mol. Sci. 2017, 18(11), 2349; https://doi.org/10.3390/ijms18112349
Received: 28 September 2017 / Revised: 29 October 2017 / Accepted: 1 November 2017 / Published: 7 November 2017
Cited by 1 | PDF Full-text (1888 KB) | HTML Full-text | XML Full-text
Abstract
Adipose tissue has traditionally only been considered as an energy storage organ. Nevertheless, the importance of this tissue in systemic physiology and, especially, in systemic inflammation has been highlighted in recent years. Adipose tissue expresses proteins related to vitamin D (VD) metabolism, and
[...] Read more.
Adipose tissue has traditionally only been considered as an energy storage organ. Nevertheless, the importance of this tissue in systemic physiology and, especially, in systemic inflammation has been highlighted in recent years. Adipose tissue expresses proteins related to vitamin D (VD) metabolism, and it has been proposed that it can act as a VD storage tissue. The active form of VD, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), is able to modify adipocyte and adipose tissue physiology via the VD receptor (VDR), decreasing the expression of pro-inflammatory cytokines in adipose tissue. Moreover, VD deficiency and VDR has been reported to be associated with obesity and diabetes. However, the results of the different studies are not conclusive. Insulin growth binding proteins (IGFBPs) have been identified in adipose tissue, but their roles are poorly understood. Therefore, the objective of this study was to analyze the plasma levels of VD and the gene expression of VDR in the adipose tissue of subjects with morbid obesity (MO) and with different degrees of insulin resistance (IR), as well as the functionality of direct interaction between IGFBP-3 and VDR, which could explain its inhibitory role in adipogenesis. Our results show a novel role of the VD system in the regulation and activation of IGFBP-3 in visceral adipose tissue (VAT) of patients with MO, as a new and alternative mechanism proposed in the insulin signaling associated with obesity. Full article
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Open AccessArticle Seco-B-Ring Steroidal Dienynes with Aromatic D Ring: Design, Synthesis and Biological Evaluation
Int. J. Mol. Sci. 2017, 18(10), 2162; https://doi.org/10.3390/ijms18102162
Received: 28 September 2017 / Revised: 13 October 2017 / Accepted: 14 October 2017 / Published: 17 October 2017
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Abstract
Continuing our structure-activity studies on the vitamin D analogs with the altered intercyclic seco-B-ring fragment, we designed compounds possessing dienyne system conjugated with the benzene D ring. Analysis of the literature data and the docking experiments seemed to indicate that the target compounds
[...] Read more.
Continuing our structure-activity studies on the vitamin D analogs with the altered intercyclic seco-B-ring fragment, we designed compounds possessing dienyne system conjugated with the benzene D ring. Analysis of the literature data and the docking experiments seemed to indicate that the target compounds could mimic the ligands with a good affinity to the vitamin D receptor (VDR). Multi-step synthesis of the C/D-ring building block of the tetralone structure was achieved and its enol triflate was coupled with the known A-ring fragments, possessing conjugated enyne moiety, using Sonogashira protocol. The structures of the final products were confirmed by NMR, UV and mass spectroscopy. Their binding affinities for the full-length human VDR were determined and it was established that compound substituted at C-2 with exomethylene group showed significant binding to the receptor. This analog was also able to induce monocytic differentiation of HL-60 cells. Full article
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Open AccessArticle Long-Term Therapy Outcomes When Treating Chronic Kidney Disease Patients with Paricalcitol in German and Austrian Clinical Practice (TOP Study)
Int. J. Mol. Sci. 2017, 18(10), 2057; https://doi.org/10.3390/ijms18102057
Received: 23 August 2017 / Revised: 19 September 2017 / Accepted: 21 September 2017 / Published: 28 September 2017
PDF Full-text (5041 KB) | HTML Full-text | XML Full-text
Abstract
Paricalcitol is approved for prevention and therapy of secondary hyperparathyroidism (sHPT) in patients with chronic kidney disease (CKD), with only short-term data in clinical routine settings. A 12-month observational study was conducted in Germany and Austria (90 centers, 761 patients) from 2008 to
[...] Read more.
Paricalcitol is approved for prevention and therapy of secondary hyperparathyroidism (sHPT) in patients with chronic kidney disease (CKD), with only short-term data in clinical routine settings. A 12-month observational study was conducted in Germany and Austria (90 centers, 761 patients) from 2008 to 2013. Laboratory values, demographical, and clinical data were documented in 629 dialysis patients and 119 predialysis patients. In predialysis patients, median intact parathormone (iPTH) was 180.0 pg/mL (n = 105) at the start of the study, 115.7 pg/mL (n = 105) at last documentation, and 151.8 pg/mL (n = 50) at month 12, with 32.4% of the last documented iPTH values in the KDOQI (Kidney Disease Outcomes Quality Initiative) target range. In dialysis patients, median iPTH was 425.5 pg/mL (n = 569) at study start, 262.3 pg/mL (n = 569) at last documentation, and 266.1 pg/mL (n = 318) at month 12, with 36.5% of dialysis patients in the KDOQI target range. Intravenous paricalcitol showed more homogenous iPTH control than oral treatment. Combined analysis of all dialysis patients indicated comparable and stable mean serum calcium and phosphate levels throughout the study. Clinical symptoms, such as itching, bone pain, and fatigue, were improved compared with study entry. The spectrum and frequency of adverse events mirrored the known pattern for patients on dialysis. Paricalcitol is efficacious and has a consistent safety profile in sHPT over 12 months. Full article
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Open AccessArticle Vitamin D Supplementation Enhances C18(dihydro)ceramide Levels in Type 2 Diabetes Patients
Int. J. Mol. Sci. 2017, 18(7), 1532; https://doi.org/10.3390/ijms18071532
Received: 7 June 2017 / Revised: 7 July 2017 / Accepted: 11 July 2017 / Published: 15 July 2017
Cited by 2 | PDF Full-text (1372 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Sphingolipids are characterized by a broad range of bioactive properties. Particularly, the development of insulin resistance, a major pathophysiological hallmark of Type 2 Diabetes mellitus (T2D), has been linked to ceramide signaling. Since vitamin D supplementation may slow down T2D progression by improving
[...] Read more.
Sphingolipids are characterized by a broad range of bioactive properties. Particularly, the development of insulin resistance, a major pathophysiological hallmark of Type 2 Diabetes mellitus (T2D), has been linked to ceramide signaling. Since vitamin D supplementation may slow down T2D progression by improving glucose concentrations and insulin sensitivity, we investigated whether vitamin D supplementation impacts on plasma sphingolipid levels in T2D patients. Thus, plasma samples of 59 patients with non-insulin-requiring T2D from a placebo-controlled, randomized, and double-blind study were retrospectively analyzed. Once per week, patients received either 20 drops of Vigantol oil, corresponding to a daily dose of 1904 IU/d vitamin D (verum: n = 31), or a placebo oil consisting of medium chain triglycerides (placebo: n = 28). Blood samples were taken from all of the participants at three different time points: 1) at the beginning of the study (baseline), 2) after 6 months supplementation, and 3) after an additional 6 months of follow-up. Plasma sphingolipids were measured by high-performance liquid chromatography tandem mass spectrometry. At baseline and 6 months follow-up, no significant differences in plasma sphingolipid species were detected between the placebo and verum groups. After 6 months, vitamin D supplementation significantly enhanced plasma C18dihydroceramide (dhCer; N-stearoyl-sphinganine (d18:0/18:0)) and C18ceramide (Cer; N-stearoyl-sphingosine (d18:1/18:0)) levels were observed in the verum group compared to the placebo group. This was accompanied by significantly higher 25-hydroxyvitamin D3 (25(OH)D3) blood levels in patients receiving vitamin D compared to the placebo group. Taken together, vitamin D supplementation induced changes of the C18 chain-length-specific dhCer and Cer plasma levels in patients with T2D. The regulation of sphingolipid signaling by vitamin D may thus unravel a novel mechanism by which vitamin D can influence glucose utilization and insulin action. Whether this acts favorably or unfavorably for the progression of T2D needs to be clarified. Full article
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Open AccessArticle Fluorescence Analysis of Vitamin D Receptor Status of Circulating Tumor Cells (CTCS) in Breast Cancer: From Cell Models to Metastatic Patients
Int. J. Mol. Sci. 2017, 18(6), 1318; https://doi.org/10.3390/ijms18061318
Received: 11 May 2017 / Revised: 14 June 2017 / Accepted: 16 June 2017 / Published: 20 June 2017
PDF Full-text (3030 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The Vitamin D receptor (VDR) expressed in normal breast tissue and breast tumors has been suggested as a new prognostic biomarker in breast cancer (BC). Besides, increasing evidence supports the view that the detection of circulating tumor cells (CTCs) predicts outcome in early
[...] Read more.
The Vitamin D receptor (VDR) expressed in normal breast tissue and breast tumors has been suggested as a new prognostic biomarker in breast cancer (BC). Besides, increasing evidence supports the view that the detection of circulating tumor cells (CTCs) predicts outcome in early and metastatic BC. Consequently, an evaluation of VDR expression in the CTCs of BC patients may allow optimization of their treatment. As an attempt to profile and subtype the CTCs of metastatic patients, we established an innovative fluorescence technique using nine BC cell lines to visualize, define, and compare their individual VDR status. Afterwards, we tested the CTC presence and VDR expression in blood samples (cytospins) collected from 23 metastatic BC patients. The results demonstrated major differences in the VDR levels among the nine cell lines, and VDR positive CTCs were detected in 46% of CTC-positive patients, with a total of 42 CTCs individually analyzed. Due to the limited number of patients in this study, no correlation between VDR expression and BC subtype classification (according to estrogen receptor (ER), progesterone receptor (PR) and HER2) could be determined, but our data support the view that VDR evaluation is a potential new prognostic biomarker to help in the optimization of therapy management for BC patients. Full article
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Review

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Open AccessReview Health Risks of Hypovitaminosis D: A Review of New Molecular Insights
Int. J. Mol. Sci. 2018, 19(3), 892; https://doi.org/10.3390/ijms19030892
Received: 26 January 2018 / Revised: 13 March 2018 / Accepted: 15 March 2018 / Published: 17 March 2018
Cited by 3 | PDF Full-text (930 KB) | HTML Full-text | XML Full-text
Abstract
Hypovitaminosis D has become a pandemic, being observed in all ethnicities and age groups worldwide. Environmental factors, such as increased air pollution and reduced ultraviolet B (UVB) irradiation, as well as lifestyle factors, i.e., decreased outdoor activities and/or poor intake of vitamin D-rich
[...] Read more.
Hypovitaminosis D has become a pandemic, being observed in all ethnicities and age groups worldwide. Environmental factors, such as increased air pollution and reduced ultraviolet B (UVB) irradiation, as well as lifestyle factors, i.e., decreased outdoor activities and/or poor intake of vitamin D-rich food, are likely involved in the etiology of a dramatic reduction of vitamin D circulating levels. The insufficiency/deficiency of vitamin D has long been known for its association with osteoporosis and rickets. However, in the last few decades it has become a serious public health concern since it has been shown to be independently associated with various chronic pathological conditions such as cancer, coronary heart disease, neurological diseases, type II diabetes, autoimmune diseases, depression, with various inflammatory disorders, and with increased risk for all-cause mortality in the general population. Prevention strategies for these disorders have recently involved supplementation with either vitamin D2 or vitamin D3 or their analogs at required daily doses and tolerable upper-limit levels. This review will focus on the emerging evidence about non-classical biological functions of vitamin D in various disorders. Full article
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Open AccessReview The Role of Vitamin D in Non-Scarring Alopecia
Int. J. Mol. Sci. 2017, 18(12), 2653; https://doi.org/10.3390/ijms18122653
Received: 29 October 2017 / Revised: 2 December 2017 / Accepted: 3 December 2017 / Published: 7 December 2017
Cited by 1 | PDF Full-text (202 KB) | HTML Full-text | XML Full-text
Abstract
Non-scarring hair loss is a common problem that affects both male and female patients. Since any disturbances in the hair follicle cycle may lead to hair shedding, or alopecia, it is not surprising that the possible role of vitamin D in alopecia was
[...] Read more.
Non-scarring hair loss is a common problem that affects both male and female patients. Since any disturbances in the hair follicle cycle may lead to hair shedding, or alopecia, it is not surprising that the possible role of vitamin D in alopecia was investigated in many studies. Vitamin D has been shown to have many important functions. A growing body of evidence shows that vitamin D and its receptor are responsible for maintaining not only calcium homeostasis but also skin homeostasis. Moreover, vitamin D could also regulate cutaneous innate and adaptive immunity. This paper presents a review of current literature considering the role of vitamin D in alopecia areata, telogen effluvium, and female pattern hair loss. The majority of studies revealed decreased serum 25-hydroxyvitamin D levels in patients with different types of non-scarring alopecia, which could suggest its potential role in the pathogenesis of hair loss. According to the authors, vitamin D supplementation could be a therapeutic option for patients with alopecia areata, female pattern hair loss, or telogen effluvium. However, further studies on a larger group of patients are required. Full article
Open AccessReview Vitamin D and Neurological Diseases: An Endocrine View
Int. J. Mol. Sci. 2017, 18(11), 2482; https://doi.org/10.3390/ijms18112482
Received: 23 October 2017 / Revised: 18 November 2017 / Accepted: 20 November 2017 / Published: 21 November 2017
Cited by 6 | PDF Full-text (702 KB) | HTML Full-text | XML Full-text
Abstract
Vitamin D system comprises hormone precursors, active metabolites, carriers, enzymes, and receptors involved in genomic and non-genomic effects. In addition to classical bone-related effects, this system has also been shown to activate multiple molecular mediators and elicit many physiological functions. In vitro and
[...] Read more.
Vitamin D system comprises hormone precursors, active metabolites, carriers, enzymes, and receptors involved in genomic and non-genomic effects. In addition to classical bone-related effects, this system has also been shown to activate multiple molecular mediators and elicit many physiological functions. In vitro and in vivo studies have, in fact, increasingly focused on the “non-calcemic” actions of vitamin D, which are associated with the maintenance of glucose homeostasis, cardiovascular morbidity, autoimmunity, inflammation, and cancer. In parallel, growing evidence has recognized that a multimodal association links vitamin D system to brain development, functions and diseases. With vitamin D deficiency reaching epidemic proportions worldwide, there is now concern that optimal levels of vitamin D in the bloodstream are also necessary to preserve the neurological development and protect the adult brain. The aim of this review is to highlight the relationship between vitamin D and neurological diseases. Full article
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Open AccessReview Vitamin D Axis in Inflammatory Bowel Diseases: Role, Current Uses and Future Perspectives
Int. J. Mol. Sci. 2017, 18(11), 2360; https://doi.org/10.3390/ijms18112360
Received: 1 October 2017 / Revised: 27 October 2017 / Accepted: 29 October 2017 / Published: 7 November 2017
PDF Full-text (249 KB) | HTML Full-text | XML Full-text
Abstract
Increasing evidence supports the concept that the vitamin D axis possesses immunoregulatory functions, with vitamin D receptor (VDR) status representing the major determinant of vitamin D’s pleiotropic effects. Vitamin D promotes the production of anti-microbial peptides, including β-defensins and cathelicidins, the shift towards
[...] Read more.
Increasing evidence supports the concept that the vitamin D axis possesses immunoregulatory functions, with vitamin D receptor (VDR) status representing the major determinant of vitamin D’s pleiotropic effects. Vitamin D promotes the production of anti-microbial peptides, including β-defensins and cathelicidins, the shift towards Th2 immune responses, and regulates autophagy and epithelial barrier integrity. Impairment of vitamin D-mediated pathways are associated with chronic inflammatory conditions, including inflammatory bowel diseases (IBD). Interestingly, inhibition of vitamin D pathways results in dysbiosis of the gut microbiome, which has mechanistically been implicated in the development of IBD. Herein, we explore the role of the vitamin D axis in immune-mediated diseases, with particular emphasis on its interplay with the gut microbiome in the pathogenesis of IBD. The potential clinical implications and therapeutic relevance of this interaction will also be discussed, including optimizing VDR function, both with vitamin D analogues and probiotics, which may represent a complementary approach to current IBD treatments. Full article
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Open AccessReview Role of Placental VDR Expression and Function in Common Late Pregnancy Disorders
Int. J. Mol. Sci. 2017, 18(11), 2340; https://doi.org/10.3390/ijms18112340
Received: 26 September 2017 / Revised: 24 October 2017 / Accepted: 26 October 2017 / Published: 6 November 2017
Cited by 2 | PDF Full-text (709 KB) | HTML Full-text | XML Full-text
Abstract
Vitamin D, besides its classical role in bone metabolism, plays a distinct role in multiple pathways of the feto-maternal unit. Calcitriol is the major active ligand of the nuclear vitamin D receptor (VDR). The vitamin D receptor (VDR) is expressed in different uteroplacental
[...] Read more.
Vitamin D, besides its classical role in bone metabolism, plays a distinct role in multiple pathways of the feto-maternal unit. Calcitriol is the major active ligand of the nuclear vitamin D receptor (VDR). The vitamin D receptor (VDR) is expressed in different uteroplacental parts and exerts a variety of functions in physiologic pregnancy. It regulates decidualisation and implantation, influences hormone secretion and placental immune modulations. This review highlights the role of the vitamin D receptor in physiologic and disturbed pregnancy, as preeclampsia, fetal growth restriction, gestational diabetes and preterm birth. We discuss the existing literature regarding common VDR polymorphisms in these pregnancy disorders. Full article
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Open AccessReview Vitamin D and VDR in Gynecological Cancers—A Systematic Review
Int. J. Mol. Sci. 2017, 18(11), 2328; https://doi.org/10.3390/ijms18112328
Received: 29 September 2017 / Revised: 27 October 2017 / Accepted: 30 October 2017 / Published: 4 November 2017
Cited by 3 | PDF Full-text (728 KB) | HTML Full-text | XML Full-text
Abstract
In recent years, a vast amount of studies have centered on the role of vitamin D in the pathogenesis of certain types of cancers such as breast, colorectal and lung cancer. Increasing evidence suggests that vitamin D and its receptor play a crucial
[...] Read more.
In recent years, a vast amount of studies have centered on the role of vitamin D in the pathogenesis of certain types of cancers such as breast, colorectal and lung cancer. Increasing evidence suggests that vitamin D and its receptor play a crucial role in the development of gynecological cancers. In this review, we systematically analyzed the effect of vitamin D and the vitamin D receptor on endometrial, ovarian, cervical, vulvar and vaginal cancer. Our literature research shows that vitamin D levels and vitamin-D-related pathways affect the risk of gynecological cancers. Numerous ecological studies give evidence on the inverse relationship between UVB exposure and gynecological cancer risk. However, epidemiologic research is still inconclusive for endometrial and ovarian cancer and insufficient for rarer types of gynecological cancers. The vitamin D receptor (VDR) is upregulated in all gynecological cancers, indicating its influence on cancer etiology. The VDR polymorphism FokI (rs2228570) seems to increase the risk of ovarian cancer. Other nuclear receptors, such as the RXR, also influence gynecological cancers. Although there is limited knowledge on the role of the VDR/RXR on the survival of endometrial, cervical, vulvar or vaginal cancer patients, some studies showed that both receptors influence survival. Therefore, we suggest that further studies should focus on the vitamin D- and its hetero dimer receptor RXR in gynecological cancers. Full article
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Open AccessReview The Role of Toll-Like Receptors and Vitamin D in Cardiovascular Diseases—A Review
Int. J. Mol. Sci. 2017, 18(11), 2252; https://doi.org/10.3390/ijms18112252
Received: 30 September 2017 / Revised: 24 October 2017 / Accepted: 25 October 2017 / Published: 27 October 2017
Cited by 4 | PDF Full-text (881 KB) | HTML Full-text | XML Full-text
Abstract
Cardiovascular diseases are the leading cause of mortality worldwide. Therefore, a better understanding of their pathomechanisms and the subsequent implementation of optimal prophylactic and therapeutic strategies are of utmost importance. A growing body of evidence states that low-grade inflammation is a common feature
[...] Read more.
Cardiovascular diseases are the leading cause of mortality worldwide. Therefore, a better understanding of their pathomechanisms and the subsequent implementation of optimal prophylactic and therapeutic strategies are of utmost importance. A growing body of evidence states that low-grade inflammation is a common feature for most of the cardiovascular diseases in which the contributing factors are the activation of toll-like receptors (TLRs) and vitamin D deficiency. In this article, available data concerning the association of cardiovascular diseases with TLRs and vitamin D status are reviewed, followed by a discussion of new possible approaches to cardiovascular disease management. Full article
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Open AccessReview Vitamin D as a Novel Regulator of Tumor Metabolism: Insights on Potential Mechanisms and Implications for Anti-Cancer Therapy
Int. J. Mol. Sci. 2017, 18(10), 2184; https://doi.org/10.3390/ijms18102184
Received: 30 September 2017 / Revised: 14 October 2017 / Accepted: 16 October 2017 / Published: 19 October 2017
Cited by 5 | PDF Full-text (510 KB) | HTML Full-text | XML Full-text
Abstract
1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the bioactive form of vitamin D, has been shown to possess significant anti-tumor potential. While most studies so far have focused on the ability of this molecule to influence the proliferation and apoptosis of cancer
[...] Read more.
1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the bioactive form of vitamin D, has been shown to possess significant anti-tumor potential. While most studies so far have focused on the ability of this molecule to influence the proliferation and apoptosis of cancer cells, more recent data indicate that 1,25(OH)2D3 also impacts energy utilization in tumor cells. In this article, we summarize and review the evidence that demonstrates the targeting of metabolic aberrations in cancers by 1,25(OH)2D3, and highlight potential mechanisms through which these effects may be executed. We shed light on the ability of this molecule to regulate metabolism-related tumor suppressors and oncogenes, energy- and nutrient-sensing pathways, as well as cell death and survival mechanisms such as autophagy. Full article
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Open AccessReview Vitamin D in Pain Management
Int. J. Mol. Sci. 2017, 18(10), 2170; https://doi.org/10.3390/ijms18102170
Received: 25 August 2017 / Revised: 29 September 2017 / Accepted: 11 October 2017 / Published: 18 October 2017
PDF Full-text (222 KB) | HTML Full-text | XML Full-text
Abstract
Vitamin D is a hormone synthesized in the skin in the presence of sunlight. Like other hormones, vitamin D plays a role in a wide range of processes in the body. Here we review the possible role of vitamin D in nociceptive and
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Vitamin D is a hormone synthesized in the skin in the presence of sunlight. Like other hormones, vitamin D plays a role in a wide range of processes in the body. Here we review the possible role of vitamin D in nociceptive and inflammatory pain. In observational studies, low vitamin D levels have been associated with increased pain and higher opioid doses. Recent interventional studies have shown promising effects of vitamin D supplementation on cancer pain and muscular pain—but only in patients with insufficient levels of vitamin D when starting intervention. Possible mechanisms for vitamin D in pain management are the anti-inflammatory effects mediated by reduced cytokine and prostaglandin release and effects on T-cell responses. The recent finding of vitamin D-mediated inhibition of Prostaglandin E2 (PGE2) is especially interesting and exhibits a credible mechanistic explanation. Having reviewed current literature, we suggest that patients with deficient levels defined as 25-hydroxyvitamin D (25-OHD) levels <30 nmol/L are most likely to benefit from supplementation, while individuals with 25-OHD >50 nmol/L probably have little benefit from supplementation. Our conclusion is that vitamin D may constitute a safe, simple and potentially beneficial way to reduce pain among patients with vitamin D deficiency, but that more randomized and placebo-controlled studies are needed before any firm conclusions can be drawn. Full article
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Open AccessReview The Role of Vitamin D in Thyroid Diseases
Int. J. Mol. Sci. 2017, 18(9), 1949; https://doi.org/10.3390/ijms18091949
Received: 14 July 2017 / Revised: 6 September 2017 / Accepted: 7 September 2017 / Published: 12 September 2017
Cited by 6 | PDF Full-text (254 KB) | HTML Full-text | XML Full-text
Abstract
The main role of vitamin D is regulating bone metabolism and calcium and phosphorus homeostasis. Over the past few decades, the importance of vitamin D in non-skeletal actions has been studied, including the role of vitamin D in autoimmune diseases, metabolic syndromes, cardiovascular
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The main role of vitamin D is regulating bone metabolism and calcium and phosphorus homeostasis. Over the past few decades, the importance of vitamin D in non-skeletal actions has been studied, including the role of vitamin D in autoimmune diseases, metabolic syndromes, cardiovascular disease, cancers, and all-cause mortality. Recent evidence has demonstrated an association between low vitamin D status and autoimmune thyroid diseases such as Hashimoto’s thyroiditis and Graves’ disease, and impaired vitamin D signaling has been reported in thyroid cancers. This review will focus on recent data on the possible role of vitamin D in thyroid diseases, including autoimmune thyroid diseases and thyroid cancers. Full article
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