PMID: 

Rev Endocr Metab Disord. 2012 Mar ;13(1):21-9. PMID: 21845364

Abstract Title: 

Vitamin D metabolism and signaling in the immune system.

Abstract: 

Vitamin D has emerged as a pleiotropic regulator of human physiology, and recent work has revealed that it has several roles in control of human immune system function. Vitamin D was originally characterized for its role in calcium homeostasis, and the active form, 1,25-dihydroxyvitamin D (1,25D), can be produced in the kidney by 1α-hydroxylation of circulating 25-hydroxyvitamin D catalyzed by the enzyme CYP27B1. Renal CYP27B1 expression is regulated by calcium regulatory inputs, and 1,25D produced in the kidney was thought to function largely as an endocrine hormone. However, it is now clear that CYP27B1 is expressed in numerous tissues, and that 1,25D acts at several sites in the body in an intracrine or paracrine manner. In particular, both CYP27B1 and the vitamin D receptor (VDR) are expressed in several cell types in the immune system, where CYP27B1 production is controlled by a number of immune-specific inputs. Recent research has opened several windows on the molecular mechanisms by which 1,25D signaling regulates both innate and adaptive immune responses in humans. Moreover, intervention trials are beginning to provide evidence that vitamin D supplementation can bolster clinical responses to infection. This review will discuss recent developments in our understanding of how immune signaling controls local vitamin D metabolism and how, in turn, the 1,25D-bound VDR modulates immune system function. A particular emphasis will be placed on the interplay between vitamin D signaling and signaling throughdifferent classes of pattern recognition receptors in the production of antimicrobial peptides during innate immune responses to microbial infection.

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PMID: 

Curr Opin Endocrinol Diabetes Obes. 2014 Dec ;21(6):431-6. PMID: 25354043

Abstract Title: 

Vitamin D for infections.

Abstract: 

PURPOSE OF REVIEW: Current data clearly support an interaction of vitamin D with cells of the immune system apart from its regulatory role in calcium homeostasis. The discovery that immune cells express the vitamin D receptor and are capable of metabolizing circulating 25-hydroxyvitamin D into its active form, 1,25-dihydroxyvitamin D, has revolutionized the field and suggested a regulatory role on both the innate and adaptive immune systems.RECENT FINDINGS: Of particular interest with respect to infectious diseases, 1,25-dihydroxyvitamin D has been shown to trigger the production of antimicrobial peptides with a direct pathogen-killing capacity. Interestingly, pathogen-derived components influence the key players in the vitamin D metabolizing pathway, further supporting such an interaction.SUMMARY: Here, we review the potential mechanisms of vitamin D in promoting the innate immune response against infectious agents and discuss the possible implications for such a response in the prevention of or the intervention in various infectious diseases.

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PMID: 

Clin Calcium. 2015 Mar ;25(3):359-65. PMID: 25716808

Abstract Title: 

[Current Topics on Vitamin D. The effects of vitamin D on the immune system].

Abstract: 

Various kinds of immune cells-including macrophages, dendritic cells, T cells and B cells- express the vitamin D receptor and 1α-hydroxylase (CYP27B1), the enzyme necessary for the conversion of circulating 25-hydroxyvitamin D into its active form, 1,25-dihydroxyvitamin D. It suggests that vitamin D has a regulatory role on innate and adaptive immune responses. Vitamin D has been recently shown to promote antimicrobial responses through the production of antibacterial peptides, and stimulation of the autophagic activity in macrophages. Recent epidemiological evidence indicates a significant association between vitamin D deficiency and an increased incidence of several infectious diseases. Here, we review the essential roles of vitamin D in modulating the immune system and discuss the protective effects of vitamin D supplementation in diverse infections.

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PMID: 

J Steroid Biochem Mol Biol. 2014 Oct ;144 Pt A:74-80. Epub 2013 Jul 30. PMID: 23911725

Abstract Title: 

Non-classical mechanisms of transcriptional regulation by the vitamin D receptor: insights into calcium homeostasis, immune system regulation and cancer chemoprevention.

Abstract: 

Hormonal 1,25-dihydroxyvitamin D [1,25(OH)2D] signals through the nuclear vitamin D receptor (VDR), a ligand-regulated transcription factor. Gene expression profiling studies have revealed that 1,25(OH)2D signaling through the VDR can lead to activation or repression of target gene transcription in roughly equal proportions. Classically, transcriptional regulation by the VDR, similar to other nuclear receptors, has been characterized by its capacity to recognize high affinity cognate vitamin D response elements (VDREs), located in the regulatory regions of target genes. Several biochemical studies revealed that the VDRE-bound receptor recruits a series of coregulatory proteins, leading to transactivation of adjacent target genes. However, genome-wide and other analyses of VDR binding have revealed that a subset of VDR binding sites does not contain VDREs, and that VDREs are not associated with transcriptionally repressed VDR target genes. Work over the last∼20 years and in particular recent findings have revealed a diverse array of mechanisms by which VDR can form complexes with several other classes of transcriptional activators, leading to repression of gene transcription. Moreover, these efforts have led to several insights into the molecular basis for the physiological regulation of calcium homeostasis, immune system function and cancer chemoprevention by 1,25(OH)2D/VDR signaling. This article is part of a Special Issue entitled '16th Vitamin D Workshop'.

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PMID: 

Nutr Clin Pract. 2007 Jun ;22(3):305-22. PMID: 17507731

Abstract Title: 

Vitamin d and its role in cancer and immunity: a prescription for sunlight.

Abstract: 

Vitamin D has been recognized for more than a century as essential for the normal development and mineralization of a healthy skeleton. More extensive roles for vitamin D were suggested by the discovery of the vitamin D receptor (VDR) in tissues that are not involved in calcium and phosphate metabolism. VDR has been discovered in most tissues and cells in the body and is able to elicit a wide variety of biologic responses. These observations have been the impetus for a reevaluation of the physiologic and pharmacologic actions of vitamin D. Here, we review the role of vitamin D in regulation of the immune system and its possible role in the prevention and treatment of cancer and immune-mediated diseases.

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PMID: 

Clin Endocrinol (Oxf). 2020 Apr ;92(4):273-281. Epub 2020 Jan 16. PMID: 31889334

Abstract Title: 

Exploring vitamin D signalling within skin cancer.

Abstract: 

Sunlight exposure of the skin is associated with both risks and benefits. On one hand, sunlight ultraviolet (UV) radiation can cause skin cancer through signature DNA mutations. On the other hand, it can be absorbed in the skin by 7-dehydrocholesterol to instigate endogenous synthesis of vitamin D to regulate anticancer effects. Thus, protecting one's skin from sunlight to avoid skin cancer may lead to impaired vitamin D levels arguing for sensible sun exposure practices. To limit cancer, vitamin D metabolites can promote uncharacterized and diverse sets of events such as repair responses to DNA damage, apoptosis of malignant cells, and suppression of immune surveillance, proliferation and angiogenesis. Recent findings also suggest that part of the anticancer effects of vitamin D within squamous cell carcinoma-a type of skin cancer most directly linked to sun exposure-involves the DDIT4-mTOR catabolic signalling pathway to enhance cell autophagy. As mTOR activity and cellular metabolism are modulated as part of the DNA damage response, insights into the means by which mTOR can be controlled by vitamin D to suppress cancer is of molecular and clinical importance. Overall, the research so far suggests that presence of vitamin D through sunlight exposure and supplementation are beneficial for human health in the face of cancer.

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PMID: 

Eur J Clin Nutr. 2020 Mar ;74(3):366-376. Epub 2020 Jan 29. PMID: 31996793

Abstract Title: 

Targeted 25-hydroxyvitamin D concentration measurements and vitamin Dsupplementation can have important patient and public health benefits.

Abstract: 

Over the past two decades, many studies reported the benefits of higher 25-hydroxyvitamin D [25(OH)D] concentrations for nonskeletal effects. Researchers found significant benefits in reducing risk of acute respiratory tract infections, many types of cancer, type 2 diabetes mellitus, premature death, and adverse pregnancy and birth outcomes. In addition, 25(OH)D concentrations are low for various reasons in several categories of people, including the obese, those with dark skin living at higher latitudes, the elderly, and those who do not eat much eggs, fish, meat, or vitamin D fortified milk. Measuring 25(OH)D concentrations is one way to both increase the awareness of vitamin D's importance in maintaining good health and to encourage vitamin D supplementation or increased solar ultraviolet-B exposure to sustain well-being throughout life by reducing disease incidence. Although 20 ng/ml seems adequate to reduce risk of skeletal problems and acute respiratory tract infections, concentrations above 30 ng/ml have been associated with reduced risk of cancer, type 2 diabetes mellitus, and adverse pregnancy and birth outcomes. Thus, judicious testing of 25(OH)D concentrationscould reduce disease incidence and make treatment expenditures more cost-effective.

PMID: 

Exp Ther Med. 2020 Feb ;19(2):1570-1573. Epub 2019 Dec 27. PMID: 32010341

Abstract Title: 

Regulation of immune response by-1-propenylcysteine through autophagy-mediated protein degradation.

Abstract: 

Autophagy is a key event in cellular recycling processes due to its involvement in the intracellular degradation of proteins. It has been demonstrated that-1-propenylcysteine (S1PC), a characteristic sulfur compound in aged garlic extract, induces the activation of autophagy. S1PC degrades the adaptor protein myeloid differentiation response protein 88 (MyD88) of downstream of Toll-like receptor (TLR) by activating autophagyand. The degradation of MyD88 inhibits the TLR signaling pathway, including the phosphorylation of interleukin 1 receptor associated kinase 4 (IRAK4) and nuclear factor (NF)-κB p65, and eventually leads to the inhibition of interleukin (IL)-6 productionand C-C motif chemokine ligand 2 () mRNA expression. S1PC also increases the level of intestinal immunoglobulin A (IgA) and the number of IgA-producing cells in Peyer's patches. In addition, S1PC triggers the mRNA expression of X-box binding protein 1 (), an inducer of IgA-producing cell differentiation via the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and the degradation of paired box protein 5 (Pax5), a suppressor ofmRNA expression. The present review summarizes the mechanisms through which the activation of autophagy by S1PC modulates the immune response.

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PMID: 

Int J Clin Pract. 2020 Mar 11:e13498. Epub 2020 Mar 11. PMID: 32159257

Abstract Title: 

A randomized, double-blind, placebo-controlled clinical trial, evaluating the garlic supplement effects on some serum biomarkers of oxidative stress, and quality of life in women with rheumatoid arthritis.

Abstract: 

AIM: Rheumatoid arthritis (RA), is a prevalent immune-inflammatory disease, which is associated with disabling pain. Oxidative stress might play a role in RA pathogenesis and outcomes. According to the antioxidant properties of garlic, the current study was performed to evaluate the garlic supplement effects on some serum levels of oxidative stress biomarkers, and quality of life in patients with rheumatoid arthritis.METHODS: Seventy women with RA participated in this randomized, double-blind, placebo-controlled, parallel-design trial. The patients were randomly divided into two groups, receiving two tablets of either 500 mg garlic or placebo daily for 8 weeks. Serum levels of total antioxidant capacity (TAC) and malondialdehyde (MDA) and quality of life were determined at baseline and end of week 8. A health assessment questionnaire (HAQ) was used to evaluate the quality of life related to health.RESULTS: Of 70 patients enrolled in the trial, 62 subjects were included in the final analysis. At the end of the study, there was a significant increase in serum levels of TAC in the garlic group as compared with the placebo group (26.58 ± 77.30 nmol of Trolox equivalent/ml vs 16.11 ± 0.92 nmol of Trolox equivalent/mL; P = .026). In addition, MDA levels were significantly decreased in the intervention group compared with the control group (-0.82 ± 1.99 nmol/mL vs 0.36 ± 2.57 nmol/mL; P = .032). Pain after activity and HAQ scores decreased in the garlic group compared with the placebo (-11.96 ± 13.43 mm vs -0.06 ± 13.41 mm; P 

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PMID: 

Breast Cancer Res Treat. 2020 Apr ;180(3):707-714. Epub 2020 Mar 12. PMID: 32166478

Abstract Title: 

Vitamin D deficiency increases severity of paclitaxel-induced peripheral neuropathy.

Abstract: 

PURPOSE: Approximately 25% of patients receiving weekly paclitaxel for breast cancer require treatment disruptions to avoid severe, irreversible peripheral neuropathy (PN). Vitamin insufficiencies are PN risk factors in many diseases, but their relevance to chemotherapy-induced PN is unknown.METHODS: We investigated whether baseline insufficiency of vitamin D, vitamin B12, folate, or homocysteine increased PN in patients with breast cancer receiving weekly paclitaxel in a retrospective analysis of a prospective observational study. Patient-reported PN was collected at baseline and during treatment on the Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy (CIPN20). The primary analysis tested associations between vitamin deficiency and the maximum increase from baseline in the CIPN20 sensory subscale (ΔCIPN8). Secondary analyses tested for association with PN-induced treatment disruptions and adjusted associations for treatment and clinical variables.RESULTS: 25-hydroxy-vitamin D was the only nutrient with sufficient deficiency (

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