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Introduction: Dyslipidaemia is a major risk factor for cardiovascular diseases (CVD). Vitamin D deficiency has been found to be associated with CVD. However, the relationships between vitamin D and lipids are inconsistent. The aim of this study was to investigate the relationship between vitamin D status and serum lipids in Southern Thai subjects.Material and Methods: A total of 726 healthy subjects in Southern Thailand were enrolled in the study. Serum 25-hydroxyvitamin D (25(OH)D), lipid profiles, fasting plasma glucose, anthropometric data, blood pressure, and body composition were measured. The relationship between serum 25(OH)D levels and biochemical data was evaluated by partial correlation and multiple linear regression analyses. The association of serum 25(OH)D levels with dyslipidaemia was analysed using multivariate regression analysis.Results: Serum 25(OH)D levels were negatively correlated with body mass index (BMI), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and body composition parameters after adjusting for age in women. Multiple linear regression analysis showed that TC and BMI were independent predictors for 25(OH)D concentrations in women. Multivariate logistic regression analysis showed that the odds ratio of hypertriglyceridaemia (OR = 0.51; 95% CI: 0.32-0.80, p = 0.004) and reduced high-density lipoprotein cholesterol (HDL-C) (OR = 0.43; 95% CI: 0.26-0.71, p = 0.001) were significantly lower in vitamin D sufficiency when compared with hypovitaminosis D in women.Conclusions: Vitamin D sufficiency could reduce risk of hypertriglyceridaemia and reduced HDL-C, particularly in women, suggesting that vitamin D sufficiency may have beneficial effects on lipids and a decreased risk for CVD in Thai women. [ABSTRACT FROM AUTHOR]

Background: Keloid is a benign well‐demarcated overgrowth of fibrotic tissue which extends beyond the original boundaries of a defect. The treatment of keloids is a particular challenge to dermatologists. Intralesional corticosteroid injection has been considered the first‐line treatment for keloids. Vitamin D plays an important role in cell proliferation and differentiation as it slows the progression of tissue fibrosis by keloid fibroblasts and inhibits collagen synthesis in dermal fibrosis. Objectives: To evaluate the efficacy of intralesional injection of vitamin D in the treatment of keloids, both clinically and ultrasonically. Methods: Forty Egyptian patients with keloid scars were injected weekly with intralesional vitamin D with dose of 0.2 ml (200,000 IU) per 1 cm lesion. The keloid scars were evaluated with Vancouver Scar Scale (VSS) and by a high‐resolution ultrasound using B mode before and after treatment, the patients received 3 to 4 sessions. Results: There was statistically highly significant reduction in VSS after treatment with intralesional vitamin D injection (p value≤0.001). There was also statistically highly significant improvement in ultrasonic keloid scar thickness after treatment (P value ≤0.001). Conclusions: Intralesional vitamin D is an effective and safe method in treatment of keloid scars. Ultrasound is a useful method in assessing the improvement of keloids after treatment. [ABSTRACT FROM AUTHOR]

Context The effect of the anti-inflammatory and immunomodulatory actions of vitamin D on the duration of partial clinical remission (PR) in youth with type 1 diabetes (T1D) is unclear. Objective This work aimed to determine the effect of adjunctive ergocalciferol on residual β-cell function (RBCF) and PR in youth with newly diagnosed T1D who were maintained on a standardized insulin treatment protocol. The hypothesis was that ergocalciferol supplementation increases RBCF and prolongs PR. Methods A 12-month, randomized, double-blind, placebo-controlled trial was conducted of 50 000 IU of ergocalciferol per week for 2 months, and then once every 2 weeks for 10 months, vs placebo in 36 individuals aged 10 to 21 years, with T1D of less than 3 months and a stimulated C-peptide (SCP) level greater than or equal to 0.2 nmol/L (≥ 0.6 ng/mL). The ergocalciferol group had 18 randomly assigned participants (10 male/8 female), mean age 13.3 ± 2.8 years, while the control group had 18 participants (14 male/4 female), aged 14.3 ± 2.9 years. Results The ergocalciferol treatment group had statistically significantly higher serum 25-hydroxyvitamin D at 6 months (P  = .01) and 9 months (P  = .02) than the placebo group. At 12 months, the ergocalciferol group had a statistically significantly lower serum tumor necrosis factor α (TNF-α) concentration (P  = .03). There were no statistically significant differences between the groups at each time point from baseline to 12 months for SCP concentration (P  = .08), glycated hemoglobin A1c (HbA1c) (P  = .09), insulin dose–adjusted A1c (IDAA1c), or total daily dose of insulin. Temporal trends for rising HbA1c (P  = .04) and IDAA1c (P  = .02) were statistically significantly blunted in the ergocalciferol group. Conclusion Ergocalciferol statistically significantly reduced serum TNF-α concentration and the rates of increase both in A1c and IDAA1c, suggesting a protection of RBCF and PR in youth with newly diagnosed T1D. [ABSTRACT FROM AUTHOR]

Microbe-associated molecular patterns, such as lipopolysaccharide (LPS) and β-glucan (BG), are surrogates of immune challenges like bacterial and fungal infections, respectively. The biologically active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), supports the immune system in its fight against infections. This study investigated significant and prominent changes of the transcriptome of human peripheral blood mononuclear cells that immediately after isolation are exposed to 1,25(OH)2D3-modulated immune challenges over a time frame of 24-48 h. In this in vitro study design, most LPS and BG responsive genes are downregulated and their counts are drastically reduced when cells are treated 24 h after, 24 h before or in parallel with 1,25(OH)2D3. Interestingly, only a 1,25(OH)2D3 pre-treatment of the LPS challenge results in a majority of upregulated genes. Based on transcriptome-wide data both immune challenges display characteristic differences in responsive genes and their associated pathways, to which the actions of 1,25(OH)2D3 often oppose. The joined BG/1,25(OH)2D3 response is less sensitive to treatment sequence than that of LPS/1,25(OH)2D3. In conclusion, the functional consequences of immune challenges are significantly modulated by 1,25(OH)2D3 but largely depend on treatment sequence. This may suggest that a sufficient vitamin D status before an infection is more important than vitamin D supplementation afterwards. [ABSTRACT FROM AUTHOR]

For maintaining the healthy metabolic status, vitamin D is a beneficial metabolite stored majorly in its pre-activated form, 25-hydroxyvitamin D3 (25(OH)D3). Due to its important role in bone strengthening, the study was planned to quantify 25(OH)D3 levels in our blood. Quantification techniques for 25(OH)D3 are costly thus requiring a need for a low cost, and sensitive detection methods. In this work, an economic, and sensitive sensor for the detection of 25(OH)D3 was developed using aptamer and graphene oxide (GO). Aptamer is an oligonucleotide, sensitive towards its target, whereas, GO with 2D nanosheets provides excellent quenching surface. Aptamer labeled with fluorescein (5', 6-FAM) is adsorbed by π–π interaction on the GO sheets leading to quenching of the fluorescence due to Förster resonance energy transfer (FRET). However, in the presence of 25(OH)D3, a major portion of aptamer fluorescence remains unaltered, due to its association with 25(OH)D3. However, in the absence, aptamer fluorescence gets fully quenched. Fluorescence intensity quenching was monitored using fluorescence spectrophotometer and agarose gel based system. The limit of detection of 25(OH)D3 by this method was found to be 0.15 µg/mL whereas when GO-COOH was used, limit of detection was improved to 0.075 µg/mL. Therefore, this method could come up as a new sensing method in the field of vitamin D detection. [ABSTRACT FROM AUTHOR]

For maintaining the healthy metabolic status, vitamin D is a beneficial metabolite stored majorly in its pre-activated form, 25-hydroxyvitamin D3 (25(OH)D3). Due to its important role in bone strengthening, the study was planned to quantify 25(OH)D3 levels in our blood. Quantification techniques for 25(OH)D3 are costly thus requiring a need for a low cost, and sensitive detection methods. In this work, an economic, and sensitive sensor for the detection of 25(OH)D3 was developed using aptamer and graphene oxide (GO). Aptamer is an oligonucleotide, sensitive towards its target, whereas, GO with 2D nanosheets provides excellent quenching surface. Aptamer labeled with fluorescein (5', 6-FAM) is adsorbed by π–π interaction on the GO sheets leading to quenching of the fluorescence due to Förster resonance energy transfer (FRET). However, in the presence of 25(OH)D3, a major portion of aptamer fluorescence remains unaltered, due to its association with 25(OH)D3. However, in the absence, aptamer fluorescence gets fully quenched. Fluorescence intensity quenching was monitored using fluorescence spectrophotometer and agarose gel based system. The limit of detection of 25(OH)D3 by this method was found to be 0.15 µg/mL whereas when GO-COOH was used, limit of detection was improved to 0.075 µg/mL. Therefore, this method could come up as a new sensing method in the field of vitamin D detection. [ABSTRACT FROM AUTHOR]

Vitamin D is important for gonadal function in rodents, and improvement of vitamin D status in men with low sperm counts increases live birth rate. Vitamin D is a regulator of transcellular calcium transport in the intestine and kidney and may influence the dramatic changes in the luminal calcium concentration in epididymis. Here, we show spatial expression in the male reproductive tract of vitamin D receptor (VDR)-regulated factors involved in calcium transport: transient receptor potential vanilloid 5/6, sodium/ calcium exchanger 1, plasma membrane calcium ATPase 1, calbindin D9k, calciumsensing receptor (CaSR), and parathyroid hormone-related peptide (PTHrP) in mouse and human testis and epididymis. Testicular Casr expression was lower in Vdr ablated mice compared with controls. Moreover, expression levels of Casr and Pthrp were strongly correlated in both testis and epididymis and Pthrp was suppressed by 1,25(OH)2D3 in a spermatogonial cell line. The expression of CaSR in epididymis may be of greater importance than in the gonad in mice as germ cell-specific Casr deficient mice had no major reproductive phenotype, and coincubation with a CaSR-agon ist had no effect on human sperm--oocyte binding. In humans, seminal calcium concentration between 5 and 10 mM was associated with a higher fraction of motile and morphologically normal sperm cells, and the seminal calcium concentration was not associated with serum calcium levels. In conclusion, VDR regulates CaSR and PTHrP, and both factors may be involved in the regulation of calcium transport in the male reproductive tract with possible implications for sperm function and storage. [ABSTRACT FROM AUTHOR]

Active form of vitamin D (VitD) enhances human innate immunity against Mycobacterium tuberculosis (Mtb) infection. Our previous studies showed that MIR337-3p was highly expressed in lymphocytes of tuberculosis (TB) patients. Here, we identified the mechanism of MIR337-3p in the regulation of fast-acting anti-TB immunity by inhibiting VitD-dependent antimicrobial response pathways. While high-level MIR337-3p expression was induced by mycobacterial infection in cellular models and mice, TB patients exhibited significantly increased MIR337-3p in CD14+ monocytes/macrophages, innate-like Vγ2+ T cells, and CD8+ lymphocytes containing natural killer (NK)/innate lymphoid cells. MIR337-3p promoted the mycobacterial entry/infection and replication/growth in host target cells: macrophages and lung epithelial cells. Such MIR337-3p-enhanced pathogenicity coincided with the MIR337-3p depression of VitD-dependent antimicrobial response of cytochrome P450, family 27, subfamily b, polypeptide 1 (CYP27B1)/Beta-defensin 4 (DEFB4A)/ cathelicidin antimicrobial peptide CAMP pathways. Surprisingly, single MIR337-3p species could specifically target both the Toll-like receptor 4 (TLR4) and signal transducer and activator of transcription 3 (STAT3) 3′-untranslated regions (UTRs) to depress the TLR4/MYD88 and STAT3 signals and impair either of the two signals inhibiting the VitD-dependent antimicrobial pathways in macrophages. Concurrently, human peripheral blood mononuclear cells (PBMCs) expressing high-level MIR337-3p exhibited a reduced ability of innate cell populations to mount fast-acting cellular immunity against intracellular mycobacterial infection. Furthermore, a higher expression of Mir337-3p after mycobacterial infection of mice coincided with much greater colony-forming unit (CFU) counts in lungs and even the death of infected animals, whereas Mir337-3p inhibitor treatment of infected mice reduced Mir337-3p levels and reversed Mir337-3p-mediated increases in CFU counts. Thus, TB-driven single MIR337-3p species could specifically target/impair both TLR4/MYD88 and STAT3 activation signals, inhibiting VitD-dependent antimicrobial response and fast-acting anti-TB immunity, leading to enhanced pathogenicity. [ABSTRACT FROM AUTHOR]

Predictive toxicology plays an integral role in determining the toxicological profiles of chemicals for safety assessment. Vitamin D is an essential vitamin for the regulation of calcium absorption and homeostasis, as well as the treatment and prevention of several diseases such as rickets and osteomalacia. According to European Medicines Agency (EMA) Guideline on setting health-based exposure limits for use in risk identification in the manufacturing of different medicinal products in shared facilities, permitted daily exposure (PDE) calculation for active pharmaceutical ingredients (APIs) should be done by the medicinal product producers. PDE calculation is mainly based on critical toxicological endpoints such as repeated dose toxicity, genotoxicity, carcinogenicity, developmental and reproductive toxicity, and hypersensitivity potential. During this procedure, critical toxicological endpoints data of an API can be used to predict the PDE of another API that has a similar chemical structure. In the present paper, human toxicological endpoints of vitamin D2, D3, and their metabolites were evaluated and afterwards the data gaps in the toxicological endpoints were filled by forming a category. The read-across was justified by the structural and metabolic similarities. Molecular similarity and mechanistic relevance were found to be substantial, resulting in low uncertainty. The untested vitamin D analogs within the category can be read across with confidence to complete the data gaps related to the human health endpoints. [ABSTRACT FROM AUTHOR]

High levels of serum vitamin D-binding protein have been shown previously in patients with psoriasis compared with healthy controls; a possible role in inflammation is implied. The primary objective of this study was to investigate the impact of 24-week etanercept treatment on vitamin D status and vitamin D-binding protein in patients with psoriasis. The secondary aim was to explore whether pre-treatment vitamin D levels could predict the treatment effect. A prospective observational study was performed, including 20 patients with psoriasis and 15 controls. Serum samples were analyzed for, among others, vitamin D metabolites, vitamin D-binding protein and highly sensitive Creactive protein. Baseline levels of vitamin D-binding protein were higher in patients with self-reported arthropathy than in those without. After 24 weeks' treatment, an improvement in psoriasis was noted, as was a decrease in highly sensitive C-reactive protein. Vitamin D-binding protein decreased in those with self-reported arthropathy. Higher baseline levels of vitamin D were associated with faster and greater improvement in psoriasis. Vitamin D-binding protein may have an inflammatory biomarker role. [ABSTRACT FROM AUTHOR]

Background: The renin–angiotensin system (RAS) is activated in inflammatory bowel disease (IBD), and vitamin D deficiency aggravates the development of colitis, but the relationship between the local colonic RAS and vitamin D is unclear with regard to the pathogenesis of IBD. Aims: To investigate whether vitamin D suppresses the local colonic RAS to prevent colonic mucosal inflammation in a mouse model of experimental colitis. Methods: C57BL/6 mice fed vitamin D-deficient (VDD) diet for 8 weeks were induced to colitis by 2,4,6-trinitrobenzenesulfonic acid (TNBS), with mice fed vitamin D-sufficient (VDS) diet as controls. Colitis severity was assessed by histology, and pro-inflammatory cytokines, RAS components, and signaling pathways were quantified by real-time RT-PCR and Western blotting. Results: C57BL/6 mice fed the VDD diet for 8 weeks exhibited significantly lower serum 25(OH)D3 concentrations compared to mice fed the VDS diet. When these VDD mice were induced to colitis by TNBS, they exhibited more severe colonic inflammation and developed more severe colitis compared to the VDS counterparts. VDD diet feeding resulted in higher production of mucosal pro-inflammatory cytokines, higher activation of the myosin light chain kinase-tight junction regulatory pathway, and greater increases in mucosal permeability. VDD diet feeding also enhanced colonic RAS activation. Treatment with angiotensin II receptor blocker losartan markedly alleviated colitis in TNBS-induced VDD mice. Conclusion: Vitamin D deficiency promotes colonic inflammation at least in part due to over activation of the local RAS in the colon. [ABSTRACT FROM AUTHOR]

Purpose. Vitamin D deficiency is highly prevalent among the very elderly and is associated with a wide variety of clinical conditions other than musculoskeletal diseases. This study aims to ascertain the efficacy and safety of high-dose intramuscular vitamin D2 in very elderly Chinese patients with vitamin D deficiency. Methods. Very elderly (aged 80 years or over) Chinese patients with vitamin D deficiency were recruited to receive monthly intramuscular injections of 600,000 IU vitamin D2 until their serum 25-hydroxyvitamin D (25(OH)D) reached ≥30 ng/mL. The serum levels of 25(OH)D2, 25(OH)D3, iPTH, BTMs, immune parameters, and other biochemical parameters were measured at baseline and one month after each dose. Results. Of the 30 very elderly Chinese patients who had been recruited into the study, 27 (90.0%) had their vitamin D deficiency corrected, and 26 (86.7%) reached vitamin D sufficiency. The mean time (±SD) was 3.1 (±1.3) months for vitamin D deficiency to be corrected, and 6.1 (±0.8) months for vitamin D sufficiency to be reached. The mean (±SD) serum level of 25(OH)D2 increased from 0.69 (±1.51) ng/mL to 29.07 (±5.68) ng/mL, while the mean (±SD) serum level of 25(OH)D3 decreased from 9.82 (±2.75) ng/mL to 5.30 (±3.09) ng/mL (both P < 0.001). The total T cells in serum remained unchanged (P > 0.05), and the CD4 and B cells (CD19+) were increased significantly (both P < 0.05). In addition, no significant change was observed in the serum levels of iPTH and BTMs. Conclusion. Monthly intramuscular injection of 600,000 IU vitamin D2 is an effective and safe dosing regimen to reach vitamin D sufficiency and enhances immune function in the very elderly Chinese patients with vitamin D deficiency. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency has been linked with different health problems including male infertility. Its function is mediated by the vitamin D receptor, which acts as a transcription factor. Epigenetic mechanisms such as DNA methylation may affect the vitamin D receptor gene and result in gene silencing. The present study aimed to assess serum vitamin D level and seminal methylation of vitamin D receptor gene in idiopathic male infertility. Blood and semen samples were collected from 60 men with idiopathic infertility and 40 healthy fertile men. Vitamin D levels were detected using enzyme‐linked fluorescent assay technique and methylation status was assessed by methylation‐specific PCR. Results revealed that serum levels of 25OHD were significantly lower in patients compared to controls. Positive correlation was found between serum level of 25OHD and sperm concentration in patients group and progressive motility in total studied group. Methylation of vitamin D receptor gene was significantly higher in patients compared to control group. Negative correlation was found between methylation of vitamin D receptor gene and both sperm concentration and progressive motility in total studied group. Results of the present study suggest that vitamin D deficiency and vitamin D receptor gene methylation may be involved in aetiopathogenesis of idiopathic male infertility. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD) is a complex psychiatric disease characterized by mood swings that include episodes of mania and depression. Given its cyclical nature, BD is especially hard to model; however, the standard practice has been to mimic manic episodes in animal models. Despite scientific advances, the pathophysiology of BD is not fully understood, and treatment remains limited. In the last years, natural products have emerged as potential neuroprotective agents for the treatment of psychiatric diseases. Thus, the aim of this review was to explore the therapeutic potential of natural compounds and derivatives against BD, taking into account preclinical and clinical studies. Reliable articles indexed in databases such as PubMed, Web of Science and Science Direct were used. In clinical studies, treatment with herbal plants extracts, omega-3, inositol, n-acetylcysteine and vitamin D has been associated with a clinical improvement in symptoms of mania and depression in BD patients. In animal models, it has been shown that red fruits extracts, curcumin, quercetin, gallic acid, alpha-lipoic acid and carvone can modulate many neurochemical pathways involved in the pathophysiology of manic episodes. Thus, this review appointed the advances in the consumption of natural compounds and derivatives as an important therapeutic strategy to mitigate the symptoms of BD. [ABSTRACT FROM AUTHOR]

Introduction: Vitamin D plays a protective role against COVID-19. Patients with deficiency of vitamin D are more prone to severe SARS-CoV-2 infections. It is known to enhance human β-defensin 2 and antimicrobial peptide. Vitamin D can easily stabilise and manage immunological reactions against SARS-CoV-2. It can also suppress the cytokine storm by boosting the innate system. Material and methods: RT-PCR confirmed COVID-19 positive subjects were divided into two groups, one comprising asymptomatic subjects (Group 1) and the other one ICU admitted patients (Group 2). In both groups, various comorbidities such as obesity, diabetes mellitus, hypertension, cardiovascular disease, respiratory disease, renal disease and malignancy were taken into consideration. Vitamin D estimation was performed along with serum levels of interleukin-6 (IL-6) and ferritin using automated immunoassays on Siemens Advia Centaur XP. Results: On acknowledging the cut-off serum concentration level of vitamin D as < 30 ng/mL for establishing vitamin D deficiency the prevalence of vitamin D deficiency was 66.18% in Group 1 and 98.30% in Group 2. Diabetes mellitus, followed by hypertension was associated comorbidity in both groups. In total, 33 patients were found to be severely deficient (<10 ng/mL) in vitamin D, out of which 27 were critically ill and six asymptomatic. In both groups, diabetes mellitus, followed by hypertension were the highest comorbid associations. Fatality rate (discharge vs fatality) was 0% in Group 1 and 16.94% (10 patients died) in Group 2.Conclusion: To conclude, the present study addressed the significant relationship between vitamin D levels and clinical outcomes of COVID-19 patients. Vitamin D deficiency distinctly upswings the chance of disease severity as well as mortality after SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Ergosterol, an important pharmaceutical intermediate, is the precursor of liposoluble vitamin D2 and cortisone. It is also a main sterol in yeast cells and responsible for structural features of membranes such as the integrity, fluidity, permeability and activity of membrane-bound enzymes. Kluyveromyces marxianus is able to utilize various sugars such as lactose, xylose and arabinose against Saccharomyces cerevisiae and is also thermotolerant. Based on these aforementioned characteristics, K. marxianus can be of great importance in the utilization of whey and lignocellulosic biomass. In this paper, the effect of four factors on the specific ergosterol content and yeast growth was investigated using two statistical experimental designs. The factors examined were initially added alcohol, temperature, salt concentration and pH. The initially added alcohol had a positive effect on the specific ergosterol content, resulted in 37 % specific ergosterol content increasement. The temperature had a negative effect on yeast growth reducing the biomass concentration by 50 % when increased from 25 °C to 30 °C. The pH had a significant effect only on the specific ergosterol content, having an optimum at pH 5.5. The salt concentration had no significant effect in either case. Based on the results, it is suggested that the setup which facilitates higher ergosterol content but does not slow down the growth of the yeast remarkably should be selected, which are 25 °C, pH 5.3 and 3 % of initial ethanol content. [ABSTRACT FROM AUTHOR]

The aim of this research was to determine the effect of different growth stages on ergocalciferol content, yield, some morphological characters and forage quality properties of six field pea genotypes (Töre, Ateş, Taşkent, 16-K, DYK and Kr). Genotypes were planted in two-factor factorial randomized block design with three replications. Some morphological characters (main stem length, number of branches per plant, number of leaves per main stem and leaf length), herbage and hay yields, ergocalciferol, crude protein, crude fiber, acid detergent fiber, acid detergent lignin and neutral detergent fiber contents were determined at the pre-bud, ¼ bloom and full-bloom stages. The maximum main stem length (127.35-130.07 cm), herbage yield (50.12-50.33 t ha-1) and hay yield (10.85-11.77 t ha-1) were observed from field pea genotypes 'Ateş' and 'Töre' at full-bloom stage. The lowest leaf length (22.08 cm) and number of leaves per main stem (20.09) were found in field pea genotype '16-K', whereas number of branches per plant (6.42) had its highest in same genotype. Full-bloom stage showed the highest ergocalciferol (9.33 μg kg-1 in fresh matter), crude fiber (20.63 %), neutral detergent fiber (41.46 %), acid detergent fiber (30.54 %) and acid detergent lignin (5.84 %) contents between the other growth stages, whereas crude protein (18.37 %) had its lowest content at same growth stage. According to ergocalciferol content, forage yield and other quality properties, genotypes 'Ateş' and 'Töre' can be sown and cut at full-bloom stage in the Thrace and other regions of Turkey, and probably in similar subtropical conditions.

Supplementation of food products with mushroom powder increases their health-promoting value, but at the same time affects technological quality, which often play a key role for consumers. The aim of the research was to determine the effect of adding freeze-dried white and brown button mushrooms (2.5% and 5%) to wheat bread on its health-promoting properties such as antioxidant activity (DPPH, FRAP), total polyphenols and vitamin D2 content and as well as the technological quality as colour and texture. The breads were supplemented with mushroom lyophilisates, which were exposed to UVB radiation in order to increase their vitamin D2 content. The content of total polyphenols and antioxidant properties were determined spectrophotometrically, and the content of vitamin D2 by ultra-high performance liquid chromatography coupled to triple quadrupole spectrometer (UHPLC/MS/MS analysis). Colour parameters were determined in the CIE-Lab system and texture profile analysis (TPA) and sensory evaluation of the baked products were performed. The addition of dried mushrooms significantly increased the content of bioactive compounds (total polyphenols, vitamin D2) and the antioxidant properties of bread. A small addition of mushrooms caused a significant change in the basic technological quality of breads (colour parameters, specific volume, hardness, cohesiveness, springiness). At the same time, supplementation with mushroom lyophilisates has a positive effect on most analysed attributes in the nine-point hedonic scale. Based on the conducted research, it can be concluded that mushroom lyophilisates can be a valuable raw material for the fortification of bread, which is a good matrix and carrier of substances with documented biological activities.

Tremella fuciformis Berk. ( TF ), or the white jelly mushroom, is well known for its myriad of pharmacological properties, such as immunomodulatory, anti-inflammatory, antidiabetic, antitumor, and antioxidant activities, and hypocholesterolemic and hepatoprotective effects that boost human health. Most of the studies of TF are concentrated on its polysaccharide (glucuronoxylomannan) composition, which is responsible for its pharmacological as well as rheological properties. It is well established that mushrooms are a great source of dietary vitamin D due to the presence of ergosterol in their cell membrane. There is a lack of published data on TF as a source of vitamin D 2 . Therefore, this study aimed to evaluate the vitamin D 2 composition of the fruiting bodies of TF using triple quadrupole liquid chromatography-mass spectrometry (LC-MS/QQQ). The results showed highest vitamin D 2 content (292.02 µg/g dry weight) in the sample irradiated with ultraviolet B (UVB; 310 nm) for 180 min as compared with the control group (52.47 µg/g dry weight) ( P ≤ 0.001). The results showed higher accumulation potential of vitamin D 2 in TF as compared with published data available for other extensively studied culinary mushrooms, such as Agaricus bisporus, Lentinula edodes, Pleurotus ostreatus, Cordiceps militaris , and Calocybe indica . Moreover, the impact of UV treatment on antioxidant capacities and total polyphenol content of TF was also studied. The accumulation potential of vitamin D in TF reveals a novel commercial source for this nutrient.

Purpose: To investigate the effect of leaf extract of Dioscorea deltoidea (Dioscoreaceae) leaf (DDE) on atherosclerosis-induced aorta wall damage in a rat model, and the underlying mechanism of action. Methods: Rats were fed high-fat diet containing vitamin D2 for 16 weeks to induce atherosclerosis. Histopathological changes in the aorta were examined using hematoxylin and eosin (H & E) staining, while ELISA kits were used to measure cytokine levels. Results: Treatment with DDE significantly (p < 0.05) alleviated atherosclerosis-induced increase in mean lesion area in the rat aorta. The mean lesion area in atherosclerotic rats was decreased to 51.5, 21.2 and 2.3 mm2, on treatment with DDE at doses of 2.5, 5 and 10 mg/kg, respectively. Furthermore, DDE significantly suppressed atherosclerosis-induced elevation in IL-1β and IL-6 levels in the rat aorta (p < 0.05). The levels of MCP-1 and TNF-α decreased in the artherosclerotic rats on treatment with DDE. In DDE-treated rats, the atherosclerosis-induced increase in the levels of Ang II, AT1, AT2, p- STAT3, p-p65 and p-p38 were significantly decreased, relative to the model group (p < 0.05). However, DDE treatment did not alter the levels of total STAT3, p65 and p38 in the rat aorta tissues. Conclusion: These results indicate that DDE inhibits inflammatory response and atherosclerosisinduced damage to aorta wall. Moreover, RAAS expression, inflammatory cytokines and JAK/STAT signalling pathway were down-regulated in atherosclerotic rats on treatment with DDE. Thus, DDE may be a potential source of drug for the management of atherosclerosis. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effects of 1,25-Vit D3 and 24,25-Vit D3 on corneal fibroblast expression of the vitamin D-associated enzymes CYP27B1 and CYP24A1 and the roles of the vitamin D receptor (VDR) and protein disulfide isomerase, family A, member 3 (Pdia3) in these cells. Methods: CYP24A1, CYP27B1, VDR, and Pdia3 expression in corneas was detected using immunohistochemistry. Western blotting was used to measure protein expression in human and mouse fibroblasts, including VDR KO mouse cells, treated with 1,25-Vit D3 (20 nM) and 24,25-Vit D3 (100 nM). The Pdia3 inhibitor LOC14 was used to explore the role of Pdia3 as a Vit D3 receptor in these cells. Results: CYP24A1, CYP27B1, VDR, and Pdia3 were all expressed in mouse and human corneal fibroblasts. 1,25-Vit D3 significantly increased VDR expression in human and mouse fibroblasts. 1,25-Vit D3 and 24,25-VitD3 significantly increased CYP24A1 and CYP27B1 expression level in human, VDR WT mouse, and VDR KO mouse corneal fibroblasts. CYP24A1 and CYP27B1 expression was unchanged in VDR KO mouse fibroblasts treated with 1,25-Vit D3 or 24,25-Vit D3 plus LOC14. Human fibroblast VDR, CYP24A1, and CYP27B1 expression were unaffected by LOC14. Conclusions: Vitamin D metabolic enzymes, VDR, and Pdia3 are all expressed in mouse and human corneal fibroblasts. 1,25-Vit D3 modulates fibroblast vitamin D enzymes through both the VDR and Pdia3 pathways in a species-dependent manner. 24,25-Vit D3 can increase expression of fibroblast CYP24A1 and CYP27B1 in the absence of VDR and is likely involved in fibroblast regulation independent of 1,25-Vit D3 or VDR. [ABSTRACT FROM AUTHOR]

Clinical evaluation of vitamin D status is conventionally performed by measuring serum levels of a single vitamin D metabolite, 25-hydroxyvitamin D predominantly by immunoassay methodology. However, this neglects the complex metabolic pathways involved in vitamin D bioactivity, including two canonical forms D3 and D2, bioactive 1,25-dihydroxy metabolites and inactive 24-hydroxy and other metabolites. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) can measure multiple analytes in a sample during a single run with high sensitivity and reference level specificity. We therefore aimed to develop and validate a LC-MS/MS method to measure simultaneously 13 circulating vitamin D metabolites and apply it to 103 human serum samples. The LC-MS/MS method using a Cookson-type derivatization reagent phenyl-1,2,4-triazoline-3,5-dione (PTAD) quantifies 13 vitamin D metabolites, including mono and dihydroxy-metabolites, as well as CYP11A1-derived D3 and D2 metabolites in a single run. The lower limit of quantitation was 12.5 pg/mL for 1,25(OH)2D3 with accuracy verified by analysis of National Institute of Standards and Technology (NIST) 972a standards. Quantification of seven metabolites (25(OH)D3, 25(OH)D2, 3-epi-25(OH)D3, 20(OH)D3, 24,25(OH)2D3, 1,25(OH)2D3 and 1,20S(OH)2D3) was consistently achieved in human serum samples. This profiling method can provide new insight into circulating vitamin D metabolite pathways forming the basis for improved understanding of the role of vitamin D in health and disease. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of daily supplementation of 200 mL milk fortified with 240 IU of vitamin D2 (ergocalciferol). Design: Double-blind randomized controlled trial. Settings: School-based study in Delhi between October and December, 2019. Participants: 235 healthy children aged 10–14 years. Intervention: Daily supplementation of 200 mL milk fortified with 240 IU of ergocalciferol in intervention group (n=119) and 200 mL of plain milk in control group (n =116) for 3 months. Outcome Measures: Change in serum 25 hydroxy vitamin D (25(OH)D), parathyroid hormone (PTH), bone formation and resorption markers, and urinary calcium creatinine ratio (U-Ca/CrR). Results: The mean (SD) baseline serum 25(OH) D level in control and fortification groups was 11.9 (3.8) and 11.4 (3.6) ng/mL (P=0.23), respectively. The serum 25(OH)D levels did not increase post-intervention with the dose used for fortification, but were significantly higher in intervention group as compared to control group [10.8 (3.4) vs 6.7 (3.5) ng/mL; P<0.001]. A higher proportion of secondary hyperparathyroidism was observed post-intervention in control (39%) than in intervention group (13.3%); P<0.001. Serum carboxy-terminal telopeptide levels were similar in both groups but the serum procollagen type1 N-terminal propeptide levels were higher in the control than intervention group (P<0.007), following supplementation. Conclusion: Supplementation of milk fortified with approximately 240 IU vitamin D2 for three months did not achieve sufficient serum 25(OH)D levels in Indian children with vitamin D deficiency during winter. [ABSTRACT FROM AUTHOR]

Vitamin D (VitD) deficiency has been shown to be a risk factor for a plethora of disorders. We have shown that dogs with clinical leishmaniasis presented lower VitD serum levels than non-infected dogs, and even lower than those with asymptomatic infection. However, if VitD deficiency is a risk factor to develop clinical leishmaniasis remains to be answered. It is also unknown if VitD participates in Leishmania control. First, we retrospectively analysed VitD concentration in serum samples from 36 healthy dogs collected in different periods of the year concluding that there isn't a seasonal variation of this vitamin in dogs. We also included 9 dogs with clinical leishmaniasis and 10 non-infected healthy dogs, in which we measured VitD levels at the beginning of the study, when all dogs were negative for serology and qPCR, and 1 year later. Whereas non-infected dogs showed no change in VitD levels along the study, those developing clinical leishmaniasis showed a significant VitD reduction at the end of the study (35%). When we compared VitD concentration between the two groups at the beginning of the study, no differences were detected (43.6 (38–59) ng/mL, P = 0.962). Furthermore, an in vitro model using a canine macrophage cell line proved that adding active VitD leads to a significant reduction in L. infantum load (31.4%). Analyzing expression of genes related to VitD pathway on primary canine monocytes, we showed that CBD103 expression was significantly enhanced after 1,25(OH)2D addition. Our results show that VitD concentration is neither seasonal nor a risk factor for developing canine leishmaniasis, but it diminishes with the onset of clinical disease suggesting a role in parasitic control. Our in vitro results corroborate this hypothesis and point out that VitD regulates infection through CBD103 expression. These results open the possibility for studies testing VitD as an adjuvant in leishmaniasis therapy. Author summary: Vitamin D (VitD), the precursor of the powerful steroid hormone calcitriol, has been widely known to regulate the calcium and phosphate homeostasis. Several studies have shown that VitD plays also an important role on innate immunity. The mechanisms by which VitD modulates the immune function have been studied within different contexts involving multiple pathogens, but not Leishmania sp. It is known that VitD strengthens the innate immune system by inducing the expression of anti-microbial peptides in Mycobacterium tuberculosis-infected human macrophages. Antimicrobial peptides act on the bacterial wall, increasing the formation of reactive oxygen species, modulating cytokine expression, and inducing autophagy. Immune system plays a key role in leishmaniasis disease control, thus VitD could have a relevant contribution in leishmaniasis. In a previous study, we shown that clinical leishmaniasis is associated with VitD deficiency. This research aims to determine whether vitamin D is seasonal and a risk factor for developing canine leishmaniasis and, also, to study the possible VitD anti-parasitic effect and the expression of genes related to VitD pathway. The results show that VitD in canine leishmaniasis is neither seasonal nor a risk factor for developing clinical disease. However, its role in reducing parasite load suggests that VitD could be an adjuvant in leishmaniasis therapy. [ABSTRACT FROM AUTHOR]

Background: Vitamin D is an essential micronutrient for the overall health and well-being of individuals. For strong musculoskeletal and neurological development of human body, vitamin D levels during childhood and adolescence have key importance. This is the first national-level study that analyzes the deficiency and concentration of serum 25-Hydroxyvitamin D [25(OH)D)] among Indian children and adolescents with respect to various demographic and socioeconomic characteristics.Methods: Data of Comprehensive National Nutrition Survey (CNNS, 2016-18) was utilized for the present study. Vitamin D levels were assessed based on serum 25-hydroxyvitamin D concentration. Prevalence of vitamin D deficiency has been shown for the three age groups: 0-4 years (n = 12,764), 5-9 years (n = 13,482), 10-19 years (n = 13,065). Vitamin D deficiency was defined as: serum 25(OH)D < 12 ng/mL; and insufficiency as: 12 ng/ml ≤ 25(OH) < 20 ng/ml. 25(OH) D level higher than 20 ng/mL was accepted as adequate. Random slope multilevel logistic regression models were employed to assess the demographic and socioeconomic correlates of vitamin D deficiency.Results: Mean serum 25(OH)D concentration level was found to be 19.51 ± 8.76, 17.73 ± 7.91, and 17.07 ± 8.16 ng/ml in age group 0-4 years, 5-9 years and 10-19 years respectively. 49.12% of the children aged 0-4 years were having insufficient level of vitamin D. Prevalence of vitamin D deficiency was comparatively higher among female adolescents (76.16%), adolescents living in rural region (67.48), Sikh individuals (0-4 years: 76.28%; 5-9 years: 90.26%; 10-19 years: 89.56%), and adolescents coming from rich households. North-Indian individuals were having substantially higher odds of vitamin D deficiency in all the three age groups.Conclusion: The present study demonstrated that the prevalence of vitamin D deficiency is considerably high among children and adolescents of India. The study highlights high-risk group which require prompt policy interventions. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) were identified rapidly due to their important role in many biological processes and human diseases including cancer. 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] and its analogues are widely applied as preventative and therapeutic anticancer agents. However, the expression profile of lncRNAs regulated by 1α,25(OH)2D3 in ovarian cancer remains to be clarified. In the present study, we found 606 lncRNAs and 102 mRNAs that showed differential expression (DE) based on microarray data. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the DE genes were mainly enriched in TGF-β, MAPK, Ras, PI3K-Akt, and Hippo signaling pathways, as well as the vitamin D-related pathway. We further assessed the potential lncRNAs that linked vitamin D signaling with EMT, and lncBCAS1-4_1 was identified in the first time. Moreover, we found that the most upregulated lncBCAS1-4_1 showed 75% same transcripts with CYP24A1 (metabolic enzyme of 1α,25(OH)2D3). Finally, the lncBCAS1-4_1 gain-of-function cell model was established, which demonstrated that the knockdown of lncBCAS1-4_1 inhibited the proliferation and migration of ovarian cancer cells. Furthermore, lncBCAS1-4_1 could resist the antitumor effect of 1α,25(OH)2D3, which was associated with upregulated ZEB1. These data provide new evidences that lncRNAs served as a target for the antitumor effect of 1α,25(OH)2D3. [ABSTRACT FROM AUTHOR]

Th22 cells constitute a recently described CD4+ T cell subset defined by its production of interleukin (IL)-22. The action of IL-22 is mainly restricted to epithelial cells. IL-22 enhances keratinocyte proliferation but inhibits their differentiation and maturation. Dysregulated IL-22 production has been associated to some inflammatory skin diseases such as atopic dermatitis and psoriasis. How IL-22 production is regulated in human T cells is not fully known. In the present study, we identified conditions to generate Th22 cells that do not co-produce IL-17 from naïve human CD4+ T cells. We show that in addition to the transcription factors AhR and RORγt, the active form of vitamin D3 (1,25(OH)2D3) regulates IL-22 production in these cells. By studying T cells with a mutated vitamin D receptor (VDR), we demonstrate that the 1,25(OH)2D3-induced inhibition of il22 gene transcription is dependent on the transcriptional activity of the VDR in the T cells. Finally, we identified a vitamin D response element (VDRE) in the il22 promoter and demonstrate that 1,25(OH)2D3-VDR directly inhibits IL-22 production via this repressive VDRE. [ABSTRACT FROM AUTHOR]

Background: Our previous studies showed that vitamin D receptor (VDR) depletion promotes lipopolysaccharide (LPS)‐induced acute kidney injury (AKI) in mice, and renal VDR is down‐regulated in AKI, but the mechanism of VDR down‐regulation is unclear. Methods: Nutritional vitamin D deficiency was induced by feeding mice a vitamin D‐deficient (VD‐D) diet. Mice were injected intraperitoneally with LPS (20 mg/kg) to establish LPS‐induced AKI. Levels of VDR and miR‐122 were measured both in vivo and in vitro. The associations between VDR and miR‐122 were analysed by dual‐luciferase reporter assays. Results: Compared with vitamin D‐sufficient (VD‐S) mice, VD‐D mice developed more severe renal injury following LPS challenge. LPS induced a dramatic decrease in VDR expression and marked induction of miR‐122 both in vivo and in vitro. Furthermore, miR‐122 hairpin inhibitor alleviated LPS‐induced VDR down‐regulation whereas miR‐122 mimic directly suppressed VDR expression in HK‐2 cells. In luciferase reporter assays, miR‐122 mimic was able to suppress luciferase activity in 293T cells co‐transfected with a luciferase reporter that contains a putative miR‐122 target site from 3′UTR of the VDR transcript, but not when this site was mutated. Moreover, miR‐122 mimic significantly blocked paricalcitol‐induced luciferase activity in 293T cells co‐transfected with a VDRE‐driven luciferase reporter, whereas miR‐122 hairpin inhibitor enhanced paricalcitol's activity to suppress PUMA and caspase 3 activation induced by LPS in HK‐2 cells. Conclusions: Collectively, these studies provide evidence that miR‐122 directly targets VDR in renal tubular cells, which strongly suggest that miR‐122 up‐regulation in the kidney under LPS challenge contributes to kidney injury by down‐regulating VDR expression. [ABSTRACT FROM AUTHOR]

Vitamin D2 (vit. D2) is a nutraceutical essentially needed for good health. However, it is susceptible to oxygen and high temperature. The use of natural products such as bioflavonoids possessing anti-degradative effect of vit. D2 degradation has not been described before. A combinational effect of vit. D2 with quercetin showed a positive effect and inhibited vit. D2 degradation when exposed to high temperature (50 °C and 75 °C) at different time points. The results obtained revealed vit. D2 degradation was drastically increased with longer incubation under thermal treatment. However, quercetin and vit. D2 groups were able to significantly inhibit the degradation of vit. D2 and stabilize it, evaluated through the retention percentage. We also exposed vit. D2 at solutions with different pH values (1, 4, 5, 7, 10). Quercetin exerted vit. D2 anti-degradation at different pH values as well as under thermal pressure at different time points. Conclusively, quercetin can be an effective way to reduce temperature and pH induced degradation of vit. D2. [ABSTRACT FROM AUTHOR]

Vitamin D2 is an essential constituent of human nutrition, bone health, and its deficiency can cause various chronic diseases in humans. To meet the daily requirement of vitamin D2, vitamin D2 enrichment in mushrooms like Agaricus bisporus (abundant with pre-vitamin D2) is essential. Once the mushrooms are fortified, their quantification is required to validate the process. So, an analytical method was developed and validated using UPLC-MS/MS. Zorbax Eclipse C18 column was used for vitamin D2 liquid chromatographic separation with mobile phases of methanol, ammonium acetate, and formic acid by gradient elution method. Multiple Reaction Monitoring (MRM) transitions using Electrospray Ionization (ESI) interface was used, and fragmented ion detected was m/z 397/121. The developed method has a Lower Limit of Detection (LOD) of 0.40 ng/mL and covers a wide range of concentrations (0.80–100 ng/mL). UVC light was used to fortify A. bisporus with vitamin D2; optimization was carried out for exposure time and distance. Vitamin D2 from mushrooms was extracted by the Liquid-Liquid extraction method. The maximum increase of 3.2-fold in Vitamin D2 concentration was observed of UV exposure for 1 min and at a distance of 0.35 m. The present study has successfully developed and demonstrated the UPLC-MS/MS method for the quantification of vitamin D2. [ABSTRACT FROM AUTHOR]

Aim: To explore the protective effects and related mech-anisms of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) on en-dothelial dysfunction under hyperglycemic conditions. Methods: Cultured human umbilical vein endothelial cells (HUVECs) were treated with normal glucose (glucose concentration of 5.5 mmol/L), high glucose (glucose concentration of 33 mmol/L), and high glucose plus 1,25(OH)2D3, respectively. Cell viability and apoptosis, intracellular reactive oxygen species (ROS) and nitric oxide (NO) contents, antioxidant enzyme activities, proinflammatory cytokine mRNA levels, and expression levels of proteins involved were measured. Results: High glucose decreased HUVEC viability, promoted ROS production and apoptosis, and reduced NO generation, which was associated with decreased activities of antioxidant enzymes and increased levels of proinflam-matory cytokines. 1,25(OH)2D3 treatment enhanced HUVEC viability, attenuated ROS generation and apoptosis, and -increased NO production, which was accompanied by -enhanced antioxidant enzyme activities and reduced -proinflammatory factors. Mechanically, 1,25(OH)2D3 promoted nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) in a vitamin D receptor (VDR)-dependent manner, and Nrf2 siRNA abolished the antioxidative and -anti-inflammatory effects of 1,25(OH)2D3. Conclusions: 1,25(OH)2D3 attenuates high-glucose-induced endothelial oxidative injury through upregulation of the Nrf2 antioxidant pathway in a VDR-dependent manner. [ABSTRACT FROM AUTHOR]

There is an astounding amount of conversation and research about vitamin D. It carries many claims, and there is controversy as to what adequate levels should be, how to ensure reaching appropriate serum levels, and what the consequences are of vitamin D insufficiency. This article describes the role of vitamin D, reviews some of the evidence, and provides the current recommendations for vitamin D supplementation, including if a daily walk in the sun is the most appropriate prescription or do we need something more? [ABSTRACT FROM AUTHOR]

Introduction: Vitamin-D has very important role in calcium metabolism and optimum bone health. Vitamin-D is derived from endogenous UVB (Ultraviolet-B) which induces vitamin D synthesis in the skin. Currently very high prevalence of vitamin D deficiency in India can be attributed to the lifestyle changes and low sunlight exposure. Identification of the vitamin-D receptor (VDR) in almost every human cells, suggest a role in extra skeletal diseases. Various studies have shown that vitamin D deficiency is an independent risk factor for essential hypertension. Aim: To evaluate the association between vitamin D and essential hypertension among people coming for out patient department at a tertiary care centre of Udaipur. Materials and Methods: Study was carried out as a cross sectional study at a tertiary care hospital of Udaipur. Participants (259) were both males and females (134 males and 125 females), between the age group of 20-60 years attending the OPD clinic of our tertiary care hospital. Statistical Analysis: Appropriate Statistical test was done using latest version of SPSS. Results: It is found that severe vitamin D deficiency is highly prevalent in people with hypertension as compare to people without hypertension (P value <0.001). Conclusion: Since India is a tropical country, it was assumed that vitamin D deficiency and its ill effects are less common. But it is found that, vitamin D deficiency is highly prevalent in people with hypertension at Udaipur, attributed to the need of early vitamin D supplementation. Therefore, to reduce cardio-vascular events early identification of vitamin D deficiency and appropriate vitamin D supplement may be of very important in population with high prevalence. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency is associated with poor cancer outcome in humans, and administration of vitamin D or its analogs decreases tumor progression and metastasis in animal models. Using the mouse mammary tumor virus-polyoma middle T antigen (MMTV-PyMT) model of mammary cancer, we previously demonstrated a significant acceleration of carcinogenesis in animals on a low vitamin D diet and a reduction in spontaneous lung metastases when mice received vitamin D through perfusion. We investigate here the action mechanism for vitamin D in lung metastasis in the same non-immunodeficient model and demonstrate that it involves the control of epithelial to mesenchymal transition as well as interactions between chemokine C-X-C motif chemokine 12 (CXCL12) and its receptor C-X-C chemokine receptor type 4 (CXCR4). In vitro, 10−9M vitamin D treatment modifies the phenotype of MMTV-PyMT primary mammary tumor cells and significantly decreases their invasiveness and mammosphere formation capacity by 40% and 50%, respectively. Vitamin D treatment also inhibits phospho-signal transducer and activator of transcription 3 (p-STAT3), zinc finger E-box-binding homeobox 1 (Zeb1), and vimentin by 52%, 75%, and 77%, respectively, and increases E-cadherin by 87%. In vivo, dietary vitamin D deficiency maintains high levels of Zeb1 and p-STAT3 in cells from primary mammary tumors and increases CXCL12 expression in lung stroma by 64%. In lung metastases, vitamin D deficiency increases CXCL12/CXCR4 co-localization by a factor of 2.5. These findings indicate an involvement of vitamin D in mammary cancer "seed" (primary tumor cell) and "soil" (metastatic site) and link vitamin D deficiency to epithelial-to-mesenchymal transition (EMT), CXCL12/CXCR4 signaling, and accelerated metastasis, suggesting vitamin D repleteness in breast cancer patients could enhance the efficacy of co-administered therapies in preventing spread to distant organs. [ABSTRACT FROM AUTHOR]