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Special Issue "The Role of Vitamin D in Human Health and Diseases"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 16683

Special Issue Editors

Dr. Loredana Bergandi
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Guest Editor
Department of Oncology, University of Torino, Via Santena 5 bis, 10126 Torino, Italy
Interests: nitric oxide; oxidative/nitrosative stress; in vitro bioglass compatibility; asbestos; epithelial–mesenchymal transition; oocytes competence; metabolic shift; chemoresistance
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Francesca Silvagno
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Co-Guest Editor
Department of Oncology, University of Torino, Via Santena 5 bis, 10126 Torino, Italy
Interests: cancer metabolism; vitamin D; TGF beta; mitochondrial metabolism; biochemistry; electromagnetic field; cancer growth; dermal wound healing; nutraceuticals
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Vitamin D has been described as a differentiative hormone, but this definition is reductive for a molecule targeting every tissue, produced in its active form by many kinds of cell and effective over the whole life of a cell by means of different mechanisms, which lead to nuclear, non-genomic, and mitochondrial effects. In fact, vitamin D not only controls the transcription of thousands of genes, directly or indirectly through the modulation of calcium fluxes, but it also influences cell metabolism to support specific nuclear programs. Given its broad spectrum of activity and molecular and cellular targets, it is not surprising that the deficiency of vitamin D is involved in many pathologies. In addition to its well-known impact on several functions, such as bone remodeling, skin differentiation, and the immune system, to cite just a few, many other tissues depend heavily on vitamin D for their health, and therefore the correlation between low levels of vitamin D and the onset of many diseases has been reported. However, many other links could be revealed. For example, considering the current COVID-19 pandemic, a recent discovery showed that a deficiency of vitamin D is among the risk factors associated with the severity of COVID-19 symptoms and outcome.

In vitro studies and those in animal models have demonstrated the efficacy of vitamin D treatment in many models of disease and have proposed the beneficial effects of vitamin D supplementation on health and prevention, as well as the regression of multiple diseases. As a result, several clinical trials are testing the efficacy of vitamin D supplementation in human disfunctions; although some results are encouraging, few discrepancies can be due to differences in therapy protocols and resistance to the hormone, and in general can be explained by an individual sensitivity to its action. More studies, both in vitro and in vivo, are needed to verify the mechanisms involved in successful or failed treatment with vitamin D, and further investigation is essential to set out an approach from bench to bedside, underlying personalized medicine.

This Special Issue gives insights into the evolving field of vitamin D regarding its mechanisms of action, causes of deficit, proper supplementation, health benefits, and clinical applications.

Dr. Loredana Bergandi
Guest Editor
Prof. Dr. Francesca Silvagno
Co-Guest Editor

Manuscript Submission Information

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Keywords

Vitamin D

vitamin D receptor

health

disease

inflammation

gene transcription

cell metabolism

differentiation

vitamin D deficiency

vitamin D supplementation

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Published Papers (11 papers)

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Editorial

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Editorial
Editorial of Special Issue “The Role of Vitamin D in Human Health and Diseases”
Int. J. Mol. Sci. 2022, 23(8), 4283; https://doi.org/10.3390/ijms23084283 - 13 Apr 2022
Viewed by 493
Abstract
Vitamin D has been described as a differentiative hormone, but this definition is reductive for a molecule targeting every tissue, produced in its active form by many kinds of cells and effective on the whole life of cells by different mechanisms, which lead [...] Read more.
Vitamin D has been described as a differentiative hormone, but this definition is reductive for a molecule targeting every tissue, produced in its active form by many kinds of cells and effective on the whole life of cells by different mechanisms, which lead to nuclear, non-genomic and mitochondrial effects [...] Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases)

Research

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Article
The Effect of Vitamin D3 and Silver Nanoparticles on HaCaT Cell Viability
Int. J. Mol. Sci. 2022, 23(3), 1410; https://doi.org/10.3390/ijms23031410 - 26 Jan 2022
Cited by 1 | Viewed by 1167
Abstract
Vitamin D3, known to regulate bone homeostasis, has recently been shown to have many pleiotropic effects in different tissues and organs due to the presence of its receptor in a wide range of cells. Our previous study demonstrated that vitamin D3 was able [...] Read more.
Vitamin D3, known to regulate bone homeostasis, has recently been shown to have many pleiotropic effects in different tissues and organs due to the presence of its receptor in a wide range of cells. Our previous study demonstrated that vitamin D3 was able to increase the wound healing respect to the control sample, 24 h after cutting, without however leading to a complete repair. The aim of the study was to combine vitamin D3 with silver nanoparticles to possibly enable a faster reparative effect. The results showed that this association was capable of inducing a complete wound healing only after 18 h. Moreover, a treatment of vitamin D3 + silver nanoparticles yielded a small percentage of keratinocytes vimentin-positive, suggesting the possibility that the treatment was responsible for epithelial to mesenchymal transition of the cells, facilitating wound healing repair. Since vitamin D3 acts via sphingolipid metabolism, we studied the expression of gene encoding for the metabolic enzymes and protein level. We found an increase in neutral sphingomyelinase without involvement of neutral ceramidase or sphingosine kinase2. In support, an increase in ceramide level was identified by Ultrafast Liquid Chromatography–Tandem Mass Spectrometry, suggesting a possible involvement of ceramides in wound healing process. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases)
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Article
Vitamin D3 Treatment Alters Thyroid Functional Morphology in Orchidectomized Rat Model of Osteoporosis
Int. J. Mol. Sci. 2022, 23(2), 791; https://doi.org/10.3390/ijms23020791 - 12 Jan 2022
Cited by 1 | Viewed by 785
Abstract
Vitamin D plays an essential role in prevention and treatment of osteoporosis. Thyroid hormones, in addition to vitamin D, significantly contribute to regulation of bone remodeling cycle and health. There is currently no data about a possible connection between vitamin D treatment and [...] Read more.
Vitamin D plays an essential role in prevention and treatment of osteoporosis. Thyroid hormones, in addition to vitamin D, significantly contribute to regulation of bone remodeling cycle and health. There is currently no data about a possible connection between vitamin D treatment and the thyroid in the context of osteoporosis. Middle-aged Wistar rats were divided into: sham operated (SO), orchidectomized (Orx), and cholecalciferol-treated orchidectomized (Orx + Vit. D3; 5 µg/kg b.m./day during three weeks) groups (n = 6/group). Concentration of 25(OH)D in serum of the Orx + Vit. D3 group increased 4 and 3.2 times (p < 0.0001) respectively, compared to Orx and SO group. T4, TSH, and calcitonin in serum remained unaltered. Vit. D3 treatment induced changes in thyroid functional morphology that indicate increased utilization of stored colloid and release of thyroid hormones in comparison with hormone synthesis, to maintain hormonal balance. Increased expression of nuclear VDR (p < 0.05) points to direct, TSH independent action of Vit. D on thyrocytes. Strong CYP24A1 immunostaining in C cells suggests its prominent expression in response to Vit. D in this cell subpopulation in orchidectomized rat model of osteoporosis. The indirect effect of Vit. D on bone, through fine regulation of thyroid function, is small. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases)
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Article
Assessment of the Effects of Dietary Vitamin D Levels on Olanzapine-Induced Metabolic Side Effects: Focus on the Endocannabinoidome-Gut Microbiome Axis
Int. J. Mol. Sci. 2021, 22(22), 12361; https://doi.org/10.3390/ijms222212361 - 16 Nov 2021
Cited by 1 | Viewed by 1316
Abstract
Vitamin D deficiency is associated with poor mental health and dysmetabolism. Several metabolic abnormalities are associated with psychotic diseases, which can be compounded by atypical antipsychotics that induce weight gain and insulin resistance. These side-effects may be affected by vitamin D levels. The [...] Read more.
Vitamin D deficiency is associated with poor mental health and dysmetabolism. Several metabolic abnormalities are associated with psychotic diseases, which can be compounded by atypical antipsychotics that induce weight gain and insulin resistance. These side-effects may be affected by vitamin D levels. The gut microbiota and endocannabinoidome (eCBome) are significant regulators of both metabolism and mental health, but their role in the development of atypical antipsychotic drug metabolic side-effects and their interaction with vitamin D status is unknown. We studied the effects of different combinations of vitamin D levels and atypical antipsychotic drug (olanzapine) exposure on whole-body metabolism and the eCBome-gut microbiota axis in female C57BL/6J mice under a high fat/high sucrose (HFHS) diet in an attempt to identify a link between the latter and the different metabolic outputs induced by the treatments. Olanzapine exerted a protective effect against diet-induced obesity and insulin resistance, largely independent of dietary vitamin D status. These changes were concomitant with olanzapine-mediated decreases in Trpv1 expression and increases in the levels of its agonists, including various N-acylethanolamines and 2-monoacylglycerols, which are consistent with the observed improvement in adiposity and metabolic status. Furthermore, while global gut bacteria community architecture was not altered by olanzapine, we identified changes in the relative abundances of various commensal bacterial families. Taken together, changes of eCBome and gut microbiota families under our experimental conditions might contribute to olanzapine and vitamin D-mediated inhibition of weight gain in mice on a HFHS diet. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases)
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Article
High-Throughput Gene and Protein Analysis Revealed the Response of Disc Cells to Vitamin D, Depending on the VDR FokI Variants
Int. J. Mol. Sci. 2021, 22(17), 9603; https://doi.org/10.3390/ijms22179603 - 04 Sep 2021
Cited by 2 | Viewed by 782
Abstract
Vitamin D showed a protective effect on intervertebral disc degeneration (IDD) although conflicting evidence is reported. An explanation could be due to the presence of the FokI functional variant in the vitamin D receptor (VDR), observed as associated with spine pathologies. [...] Read more.
Vitamin D showed a protective effect on intervertebral disc degeneration (IDD) although conflicting evidence is reported. An explanation could be due to the presence of the FokI functional variant in the vitamin D receptor (VDR), observed as associated with spine pathologies. The present study was aimed at investigating—through high-throughput gene and protein analysis—the response of human disc cells to vitamin D, depending on the VDR FokI variants. The presence of FokI VDR polymorphism was determined in disc cells from patients with discopathy. 1,25(OH)2D3 was administered to the cells with or without interleukin 1 beta (IL-1β). Microarray, protein arrays, and multiplex protein analysis were performed. In both FokI genotypes (FF and Ff), vitamin D upregulated metabolic genes of collagen. In FF cells, the hormone promoted the matrix proteins synthesis and a downregulation of enzymes involved in matrix catabolism, whereas Ff cells behaved oppositely. In FF cells, inflammation seems to hamper the synthetic activity mediated by vitamin D. Angiogenic markers were upregulated in FF cells, along with hypertrophic markers, some of them upregulated also in Ff cells after vitamin D treatment. Higher inflammatory protein modulation after vitamin D treatment was observed in inflammatory condition. These findings would help to clarify the clinical potential of vitamin D supplementation in patients affected by IDD. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases)
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Article
Vitamin D Supplementation: Oxidative Stress Modulation in a Mouse Model of Ovalbumin-Induced Acute Asthmatic Airway Inflammation
Int. J. Mol. Sci. 2021, 22(13), 7089; https://doi.org/10.3390/ijms22137089 - 30 Jun 2021
Cited by 3 | Viewed by 1359
Abstract
Asthma oxidative stress disturbances seem to enable supplementary proinflammatory pathways, thus contributing to disease development and severity. The current study analyzed the impact of two types of oral vitamin D (VD) supplementation regimens on the redox balance using a murine model of acute [...] Read more.
Asthma oxidative stress disturbances seem to enable supplementary proinflammatory pathways, thus contributing to disease development and severity. The current study analyzed the impact of two types of oral vitamin D (VD) supplementation regimens on the redox balance using a murine model of acute ovalbumin-induced (OVA-induced) asthmatic inflammation. The experimental prevention group received a long-term daily dose of 50 µg/kg (total dose of 1300 µg/kg), whereas the rescue group underwent a short-term daily dose of 100 µg/kg (total dose of 400 µg/kg). The following oxidative stress parameters were analyzed in serum, bronchoalveolar lavage fluid (BALF) and lung tissue homogenate (LTH): total oxidative status, total antioxidant response, oxidative stress index, malondialdehyde and total thiols. Results showed that VD significantly reduced oxidative forces and increased the antioxidant capacity in the serum and LTH of treated mice. There was no statistically significant difference between the two types of VD supplementation. VD also exhibited an anti-inflammatory effect in all treated mice, reducing nitric oxide formation in serum and the expression of nuclear factor kappa B p65 in the lung. In conclusion, VD supplementation seems to exhibit a protective role in oxidative stress processes related to OVA-induced acute airway inflammation. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases)
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Review

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Review
The Role of Vitamin D in Supporting Health in the COVID-19 Era
Int. J. Mol. Sci. 2022, 23(7), 3621; https://doi.org/10.3390/ijms23073621 - 25 Mar 2022
Cited by 2 | Viewed by 1511
Abstract
The genomic activity of vitamin D is associated with metabolic effects, and the hormone has a strong impact on several physiological functions and, therefore, on health. Among its renowned functions, vitamin D is an immunomodulator and a molecule with an anti-inflammatory effect, and, [...] Read more.
The genomic activity of vitamin D is associated with metabolic effects, and the hormone has a strong impact on several physiological functions and, therefore, on health. Among its renowned functions, vitamin D is an immunomodulator and a molecule with an anti-inflammatory effect, and, recently, it has been much studied in relation to its response against viral infections, especially against COVID-19. This review aims to take stock of the correlation studies between vitamin D deficiency and increased risks of severe COVID-19 disease and, similarly, between vitamin D deficiency and acute respiratory distress syndrome. Based on this evidence, supplementation with vitamin D has been tested in clinical trials, and the results are discussed. Finally, this study includes a biochemical analysis on the effects of vitamin D in the body’s defense mechanisms against viral infection. In particular, the antioxidant and anti-inflammatory functions are considered in relation to energy metabolism, and the potential, beneficial effect of vitamin D in COVID-19 is described, with discussion of its influence on different biochemical pathways. The proposed, broader view of vitamin D activity could support a better-integrated approach in supplementation strategies against severe COVID-19, which could be valuable in a near future of living with an infection becoming endemic. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases)
Review
An Overview of Systematic Reviews of the Role of Vitamin D on Inflammation in Patients with Diabetes and the Potentiality of Its Application on Diabetic Patients with COVID-19
Int. J. Mol. Sci. 2022, 23(5), 2873; https://doi.org/10.3390/ijms23052873 - 06 Mar 2022
Cited by 1 | Viewed by 1871
Abstract
Almost two years have passed since the outbreak reported for the first time in Wuhan of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome (SARS)-CoV-2 coronavirus, rapidly evolved into a pandemic. This infectious disease has stressed global health care systems. The [...] Read more.
Almost two years have passed since the outbreak reported for the first time in Wuhan of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome (SARS)-CoV-2 coronavirus, rapidly evolved into a pandemic. This infectious disease has stressed global health care systems. The mortality rate is higher, particularly in elderly population and in patients with comorbidities such as hypertension, diabetes mellitus, cardiovascular disease, chronic lung disease, chronic renal disease, and malignancy. Among them, subjects with diabetes have a high risk of developing severe form of COVID-19 and show increased mortality. How diabetes contributes to COVID-19 severity remains unclear. It has been hypothesized that it may be correlated with the effects of hyperglycemia on systemic inflammatory responses and immune system dysfunction. Vitamin D (VD) is a modulator of immune-response. Data from literature showed that vitamin D deficiency in COVID-19 patients increases COVID-19 severity, likely because of its negative impact on immune and inflammatory responses. Therefore, the use of vitamin D might play a role in some aspects of the infection, particularly the inflammatory state and the immune system function of patients. Moreover, a piece of evidence highlighted a link among vitamin D deficiency, obesity and diabetes, all factors associated with COVID-19 severity. Given this background, we performed an overview of the systematic reviews to assess the association between vitamin D supplementation and inflammatory markers in patients with diabetes; furthermore, vitamin D’s possible role in COVID-19 patients was assessed as well. Three databases, namely MEDLINE, PubMed Central and the Cochrane Library of Systematic Reviews, were reviewed to retrieve the pertinent data. The aim of this review is to provide insight into the recent advances about the molecular basis of the relationship between vitamin D, immune response, inflammation, diabetes and COVID-19. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases)
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Review
The Role of Vitamin D in Sleep Disorders of Children and Adolescents: A Systematic Review
Int. J. Mol. Sci. 2022, 23(3), 1430; https://doi.org/10.3390/ijms23031430 - 27 Jan 2022
Cited by 4 | Viewed by 2047
Abstract
This review investigates the association between vitamin D and sleep disorders. Vitamin D is an essential nutrient known to play an important role in the growth and bone health of the human body, but it also appears to play a role in sleep. [...] Read more.
This review investigates the association between vitamin D and sleep disorders. Vitamin D is an essential nutrient known to play an important role in the growth and bone health of the human body, but it also appears to play a role in sleep. The goal of our review is to examine the association between vitamin D and sleep disorders in children and adolescents. We summarize the evidence about the role and the mechanism of action of vitamin D in children and adolescents with sleep disorders such as insomnia, obstructive sleep apnea (OSA), restless legs syndrome (RLS), and other sleep disorders. Systematic electronic database searches were conducted using Pubmed and Cochrane Library. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. The studies that met the established inclusion criteria were analyzed and compared. Results suggest a strict relationship between vitamin D deficiency in children and sleep disorders. There is evidence that vitamin D is implicated in the different neurochemical mechanisms involved in sleep regulation and mainly in the serotonergic and dopaminergic pathways. This might be responsible for the association of vitamin D deficiency and restless sleep, sleep hyperhidrosis, OSA, and RLS. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases)
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Review
Combinations of Calcitriol with Anticancer Treatments for Breast Cancer: An Update
Int. J. Mol. Sci. 2021, 22(23), 12741; https://doi.org/10.3390/ijms222312741 - 25 Nov 2021
Cited by 6 | Viewed by 1010
Abstract
Preclinical, clinical, and epidemiological studies indicate that vitamin D3 (VD) deficiency is a risk factor for the development of breast cancer. Underlying mechanisms include the ability of calcitriol to induce cell differentiation, inhibit oncogenes expression, and modify different signaling pathways involved in the [...] Read more.
Preclinical, clinical, and epidemiological studies indicate that vitamin D3 (VD) deficiency is a risk factor for the development of breast cancer. Underlying mechanisms include the ability of calcitriol to induce cell differentiation, inhibit oncogenes expression, and modify different signaling pathways involved in the control of cell proliferation. In addition, calcitriol combined with different kinds of antineoplastic drugs has been demonstrated to enhance their beneficial effects in an additive or synergistic fashion. However, a recognized adjuvant regimen based on calcitriol for treating patients with breast cancer has not yet been fully established. Accordingly, in the present work, we review and discuss the preclinical and clinical studies about the combination of calcitriol with different oncological drugs, aiming to emphasize its main therapeutic benefits and opportunities for the treatment of this pathology. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases)
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Review
Vitamin D and Rheumatic Diseases: A Review of Clinical Evidence
Int. J. Mol. Sci. 2021, 22(19), 10659; https://doi.org/10.3390/ijms221910659 - 01 Oct 2021
Cited by 10 | Viewed by 2670
Abstract
Vitamin D plays an important role in maintaining a healthy mineralized skeleton. It is also considered an immunomodulatory agent that regulates innate and adaptive immune systems. The aim of this narrative review is to provide general concepts of vitamin D for the skeletal [...] Read more.
Vitamin D plays an important role in maintaining a healthy mineralized skeleton. It is also considered an immunomodulatory agent that regulates innate and adaptive immune systems. The aim of this narrative review is to provide general concepts of vitamin D for the skeletal and immune health, and to summarize the mechanistic, epidemiological, and clinical evidence on the relationship between vitamin D and rheumatic diseases. Multiple observational studies have demonstrated the association between a low level of serum 25-hydroxyvitamin D [25(OH)D] and the presence and severity of several rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), spondyloarthropathies, and osteoarthritis (OA). Nevertheless, the specific benefits of vitamin D supplements for the treatment and prevention of rheumatic diseases are less accepted as the results from randomized clinical trials are inconsistent, although some conceivable benefits of vitamin D for the improvement of disease activity of RA, SLE, and OA have been demonstrated in meta-analyses. It is also possible that some individuals might benefit from vitamin D differently than others, as inter-individual difference in responsiveness to vitamin D supplementation has been observed in genomic studies. Although the optimal level of serum 25(OH)D is still debatable, it is advisable it is advisable that patients with rheumatic diseases should maintain a serum 25(OH)D level of at least 30 ng/mL (75 nmol/L) to prevent osteomalacia, secondary osteoporosis, and fracture, and possibly 40–60 ng/mL (100–150 nmol/L) to achieve maximal benefit from vitamin D for immune health and overall health. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases)
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