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Background: Chicken may be enriched with 25-hydroxy D 3 [25(OH)D 3 ] and docosahexaenoic acid (DHA) to enhance the dietary intake of the public., Objectives: Two experiments (Expt.) were conducted to determine the potential and metabolic impacts of enriching both DHA and 25(OH)D 3 in the tissues of broiler chickens., Methods: In Expt. 1, 144 chicks (6 cages/treatment and 6 birds/cage) were fed a corn-soybean meal basal diet (BD), BD + 10,000 IU 25(OH)D 3 /kg [BD + 25(OH)D 3 ], BD + 1% DHA-rich Aurantiochytrium (1.2 g DHA/kg; BD + DHA), or BD + 25(OH)D 3 +DHA for 6 wk. In Expt. 2, 180 chicks were fed the BD, BD + DHA-rich microalgal oil (1.5-3.0 g DHA/kg, BD + DHA), BD + DHA + eicosapentaenoic acid (EPA)-rich microalgae (0.3-0.6 g EPA/kg, BD + DHA + EPA), BD + DHA + 25(OH)D 3 [6000 to 12,000 IU/kg diet; BD + DHA + 25(OH)D 3 ], and BD + DHA + EPA + 25(OH)D 3 for 6 wk., Results: Supranutrition of these 2 nutrients resulted in 57-62 mg DHA and 1.9-3.3 μg of 25(OH)D 3 /100 g of breast or thigh muscles. The DHA enrichment was independent of dietary EPA or 25(OH)D 3 , but that of 25(OH)D 3 in the liver was decreased (68%, P < 0.05) by dietary DHA in Expt. 1. Compared with BD, BD + 25(OH)D 3 enhanced (P < 0.05) gene expression related to D 3 absorption (scavenger receptor class B type 1 and Niemann-pick c1 like 1) in the liver and D 3 degradation (cytochrome P450 24A1) in the breast, and decreased mRNA or protein concentrations of vitamin D binding protein in the adipose tissue or thigh muscle. Supranutrition of DHA decreased mRNA concentrations of lipid metabolism-related genes (fatty acid desaturase 1,2, ELOVL fatty acid elongase 5, fatty acid desaturase 2, fatty acid synthase, and sterol regulatory element-binding protein 1)., Conclusions: Both DHA and 25(OH)D 3 were enriched in the muscles up to meeting 50%-100% of the suggested intakes of these nutrients by consuming 2 servings of 100 g of fortified chicken. The enrichments altered gene expression related to lipid biosynthesis and vitamin D transport or storage., Competing Interests: Conflict of interest XGL is the Editor of the Journal of Nutrition and played no role in the evaluation of the manuscript. All other authors have no conflicts of interest., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

VD 3 is a crucial vitamin for human health, as it enhances calcium absorption in the intestines and prevent rickets. Calcifediol (25(OH)VD 3 ) and calcitriol (1α,25(OH) 2 VD 3 ) are two derivatives of vitamin D 3 that play an important role in preventing and treating osteoporosis, as well as regulating human physiological functions. Currently, the production of calcifediol, and calcitriol primarily relies on chemical synthesis, which has disadvantages such as low product yield, numerous by-products, and environmental unfriendliness. Therefore, developing a green, safe, and environmentally friendly biocatalytic synthesis pathway is of utmost importance. This article mainly reviews the biocatalytic synthesis pathways of calcifediol, and calcitriol. The P450 enzymes, including P450 monooxygenases (cytochrome P450 monooxygenases, CYPs) and P450 peroxygenases (unspecific peroxygenases, UPOs), are crucial for the production of calcifediol and calcitriol. The catalytic mechanism of the extensively studied P450 monooxygenases, the selection of suitable redox partners, and the key residues involved in the enzyme's catalytic activity are analyzed. In addition, the review explores H 2 O 2 -driven UPOs, including their catalytic mechanism, strategies for high heterologous expression, and in situ regeneration of H 2 O 2 . UPOs are regarded as highly promising biocatalysts because they can facilitate reactions without the need for expensive cofactors and redox partners. This review offers insights into the engineering of P450 for the efficient production of vitamin D 3 derivatives.

A role for vitamin D in immune modulation and in cancer has been suggested. In this work, we report that mice with increased availability of vitamin D display greater immune-dependent resistance to transplantable cancers and augmented responses to checkpoint blockade immunotherapies. Similarly, in humans, vitamin D-induced genes correlate with improved responses to immune checkpoint inhibitor treatment as well as with immunity to cancer and increased overall survival. In mice, resistance is attributable to the activity of vitamin D on intestinal epithelial cells, which alters microbiome composition in favor of Bacteroides fragilis , which positively regulates cancer immunity. Our findings indicate a previously unappreciated connection between vitamin D, microbial commensal communities, and immune responses to cancer. Collectively, they highlight vitamin D levels as a potential determinant of cancer immunity and immunotherapy success.

The short-chain dehydrogenase/reductase (SDR) superfamily encompasses enzymes that play essential roles in the metabolism of steroid hormones and lipids. Despite an enigmatic function, recent genetic studies have linked the novel SDR 42 extended-1 (SDR42E1) gene to 25-hydroxyvitamin D levels. This study investigated the potential SDR42E1 functions and interactions with vitamin D using bioinformatics and molecular docking studies. Phylogenetic analysis unveiled that the nucleotide sequences of human SDR42E1 exhibit high evolutionary conservation across nematodes and fruit flies. Molecular docking analysis identified strong binding affinities between SDR42E1 and its orthologs with vitamin D 3 and essential precursors, 8-dehydrocholesterol, followed by 7-dehydrocholesterol and 25-hydroxyvitamin D. The hydrophobic interactions observed between the protein residues and vitamin D compounds supported the predicted transmembrane localization of SDR42E1. Our investigation provides valuable insights into the potential role of SDR42E1 in skin vitamin D biosynthesis throughout species. This provides the foundation for future research and development of targeted therapies for vitamin D deficiency and related health conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Vitamin D (VD) possesses immunomodulatory properties, but its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains poorly studied. Herein, we aim to explore the regulation and function of VD3 in CRSwNP., Methods: 25-hydroxyvitamin D3 (25VD3) levels in serum and tissue lysates were detected by ELISA. The expression of VD receptor (VDR) and cytochrome P450 family 27 subfamily B member 1 (CYP27B1), the enzyme that converts 25VD3 to the active 1,25-hydroxyvitamin D3 (1,25VD3), and their expression regulation in human nasal epithelial cells (HNECs) were studied by RT-PCR, western blotting, immunofluorescence, and flow cytometry. RNA sequencing was performed to identify genes regulated by 1,25VD3 in HNECs. HNECs and polyp tissue explants were treated with 1,25VD3, 25VD3, and dexamethasone., Results: 25VD3 levels in serum and nasal tissue lysates were decreased in patients with eosinophilic and noneosinophilic CRSwNP than control subjects. The expression of VDR and CYP27B1 were reduced in eosinophilic and noneosinophilic CRSwNP, particularly in nasal epithelial cells. VDR and CYP27B1 expression in HNECs were downregulated by interferon y and poly (I:C). Polyp-derived epithelial cells demonstrated an impaired ability to convert 25VD3 to 1,25VD3 than control tissues. 1,25VD3 and 25VD3 suppressed IL-36y production in HNECs and polyp tissues, and the effect of 25VD3 was abolished by siCYP27B1 treatment. Tissue 25VD3 levels negatively correlated with IL-36y expression and neutrophilic inflammation in CRSwNP., Conclusion: Reduced systemic 25VD3 level, local 1,25VD3 generation and VDR expression result in impaired VD3 signaling activation in nasal epithelial cells, thereby exaggerating IL-36y production and neutrophilic inflammation in CRSwNP.

Vitamin D is neccessary for regulation of calcium and phosphorus metabolism in bones, affects imunity, the cardiovascular system, muscles, skin, epithelium, extracellular matrix, the central nervous system, and plays arole in prevention of aging-associated diseases. Vitamin D receptor is expressed in almost all types of cells and its activation leads to modulation of different signaling pathways. In this review, we have analysed the current knowledge of 1,25-dihydroxyvitamin D 3 or 25-hydroxyvitamin D 3 effects on metabolism of cells important for the function of the cardiovascular system (endothelial cells, vascular smooth muscle cells, cardiac cells and pericytes), tissue healing (fibroblasts), epithelium (various types of epithelial cells) and the central nervous system (neurons, astrocytes and microglia). The goal of this review was to compare the effects of vitamin D on the above mentioned cells in in vitro conditions and to summarize what is known in this field of research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Vitamin D is an immunomodulator, and its effects have been linked to many diseases, including the pathogenesis of cancer. However, the effect of vitamin D supplementation on the regulation of gene expression of the lungs is not fully understood. This study aims to determine the effect of the increased dose of cholecalciferol and a combination of cholecalciferol + calcidiol, as well as the replacement of cholecalciferol with calcidiol, on the miRNA profile of healthy swine lungs., Methods and Results: The swine were long-term (88 days) supplemented with a standard dose (2000IU/kg) of cholecalciferol and calcidiol, the increased dose (3000 IU/kg) of cholecalciferol, and the cholecalciferol + calcidiol combination: grower: 3000 IU/Kg of vitamin D (67% of cholecalciferol and 33% of calcidiol), finisher 2500 IU/Kg of vitamin D (60% of cholecalciferol and 40% of calcidiol). Swine lung tissue was used for Next Generation Sequencing (NGS) of miRNA. Long-term supplementation with the cholecalciferol + calcidiol combination caused significant changes in the miRNA profile. They embraced altered levels of the expression of miR-150, miR-193, miR-145, miR-574, miR-340, miR-381, miR-148 and miR-96 (q-value < 0.05). In contrast, raising the dose of cholecalciferol only changed the expression of miR-215, and the total replacement of cholecalciferol with calcidiol did not significantly affect the miRNAome profile., Conclusions: The functional analysis of differentially expressed miRNAs suggests that the use of the increased dose of the cholecalciferol + calcidiol combination may affect tumorigenesis processes through, inter alia, modulation of gene regulation of the TGF- β pathway and pathways related to metabolism and synthesis of glycan., (© 2023. The Author(s).)

Background: The 25-hydroxyvitamin D3 (25 (OH) D3) is crucial for follicular development. This study aimed to investigate the relationship between the level of 25 (OH) D3 in endometriosis patients, pregnancy outcomes of in vitro fertilization (IVF), and the underlying mechanism., Methods: The 25 (OH) D3 levels in serum and follicular Fluid (FF) samples were detected using enzyme-linked immunosorbent assay (ELISA). Clinical features and pregnancy outcomes of endometriosis patients were also compared between the deficient group (< 20 ug/ml) and the adequate group (≥ 20 ug/ml). The effects of 25 (OH) D3 on the proliferation and cell cycle of human ovarian granulosa cells were respectively detected by CCK-8 assay and flow cytometry (FCM). The differentially expressed genes (DEGs) in granulosa cells of endometriosis and tubal infertility patients were screened from GEO database. The effects of 25 (OH) D3 on the expressions of CDKN2D, PPARA, TGFB2 and THBD were determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot., Results: The levels of 25 (OH) D3 in serum and FF samples were decreased in endometriosis patients. The deficient group had fewer embryos that can be transferred, lower quality embryos and lower clinical pregnancy rates. Adequate 25 (OH) D3 levels in FF samples was a protective factor for live birth outcome in endometriosis patients. 25 (OH) D3 enhanced the proliferation capacity of granulosa cells (the concentration of 10 nM was the most significant) and increased the proportion of G2M + S phase cells. The expression of CDKN2D was decreased and TGFB2 and THBD were significantly upregulated., Conclusions: 25 (OH) D3 deficiency may be associated with poor IVF pregnancy outcomes in endometriosis patients. 25 (OH) D3 promotes ovarian granulosa cell proliferation by promoting the ability of cells to divide, and may accelerate cell cycle progression by up-regulating THBD and down-regulating CDKN2D expression., (© 2023. The Author(s).)

Vitamin D is found in two forms in humans, D3 produced in the skin and D2 solely from the diet. Both 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH) 2 D) are oxidised and inactivated by CYP24A1, a tightly regulated mitochondrial enzyme that controls serum levels of these secosteroids. The pathways of oxidation of 25(OH)D2 and 1,25(OH) 2 D2, particularly 25(OH)D2, by human CYP24A1 are not well characterized. The aim of this study was to further elucidate these pathways, and to compare the kinetics of metabolism of 25(OH)D2 and 1,25(OH) 2 D2 with their vitamin D3 counterparts. We used expressed and partially purified human CYP24A1 with substrates dissolved in the membrane of phospholipid vesicles, to mimic the inner mitochondrial membrane. We found that the major pathways for side chain oxidation of 25(OH)D2 and 1,25(OH) 2 D2 were identical and that predominant intermediates of 25(OH)D2 metabolism could be converted to the corresponding intermediates in the pathway of 1,25(OH) 2 D2 oxidation by 1α-hydroxylation by CYP27B1. The initial steps in the CYP24A1-mediated oxidation involved hydroxylation at the C24R position, and another unknown position where the alcohol was oxidised to an aldehyde. The 24R-hydroxylation was followed by hydroxylation at C26 or C28, or cleavage between C24 and C25 to produce the 24-oxo-25,26,27-trinor derivative. All of these products were further oxidised, with 24-oxo-25,26,27-trinor-1(OH)D2 giving a product tentatively identified as 24-oxo-25,26,27-trinor-1,28(OH) 2 D2. The catalytic efficiency (k cat /K m ) of CYP24A1 for initial 25(OH)D2 hydroxylation was similar to that for 25(OH)D3, indicating that they have similar rates of inactivation at low substrate concentrations, supporting that vitamins D2 and D3 are equally effective in maintaining serum 25(OH)D concentrations. In contrast, the k cat /K m value for 1,25(OH) 2 D3 was almost double that for 1,25(OH) 2 D2 indicating a lower rate of inactivation of 1,25(OH) 2 D2 at a low substrate concentration, suggesting that it has increased metabolic stability in vivo., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The incidence of male fertility disorders has increased greatly due to various genetic and lifestyle factors. Recently, it has been hypothesized that vitamin D may be involved with idiopathic infertility. The goal of the study was to determine the effect and relationship between blood vitamin D metabolites, intracellular sperm vitamin D levels, and gene expression of 1-α-hydroxylase and VDR, with regard to semen quality. Seventy volunteers aged 25-45 were involved in the study. According to spermogram analysis, participants were stratified into normozoospermic control group, non-normozoospermic target group, and oligoasthenoteratozoospermic group. Vitamin D metabolites (total 25-hydroxycholecalciferol, 1,25-dihydroxycholecalciferol) in blood and spermatozoa were determined by ELISA. Free and bioavailable 25-hydroxycholecalciferol were calculated using the Vermeulen equation. mRNA expression of VDR and 1-α hydroxylase was evaluated by qPCR. Free and bioavailable 25-hydroxycholecalciferol were significantly higher in the control group compared to the target group and compared to the oligoasthenoteratozoospermic group . Intracellular sperm 1,25-dihydroxycholecalciferol was higher in the control group compared to the target group. The mRNA levels of 1- α-hydroxylase were significantly higher in the control samples, while VDR expression was significantly higher in the target group. Significant positive correlations were established between free and bioavailable 25-hydroxycholecalciferol with sperm motility and morphology. Vitamin D metabolites in blood and intracellular sperm 1,25-dihydroxycholecalciferol seem to exert beneficial effects on sperm motility and morphology. Regarding sperm quality, these effects are more pronounced in the free and bioavailable 25OHD compared to the total 25OHD in blood. Higher expression of 1-α-hydroxylase likely leads to higher intracellular levels of 1,25-dihydroxycholecalciferol, which could contribute to sperm motility and morphology. Higher VDR expression may be a compensatory mechanism related to lower intracellular sperm 1,25-dihydroxycholecalciferol., (© 2023 The Authors. Reproduction in Domestic Animals published by Wiley-VCH GmbH.)

Vitamin D 3 is hydroxylated by cytochrome P450 (CYP) before exerting biological effects. The chicken CYP involved in vitamin D 3 25-hydroxylation has yet to be cloned, and little is known about its functional characteristics, tissue distribution, and cellular expression. We identified a novel, full-length CYP27A1 gene cloned from chicken hepatocyte cDNA that encodes a putative protein of 518 amino acids. Swiss modeling revealed that chicken CYP27A1 has a classic open-fold form. Multisequence homology alignment determined that CYP27A1 contains conserved motifs for substrate recognition and binding. Quantitative real-time PCR analysis in 2-mo-old Partridge Shank broilers demonstrated that CYP27A1 mRNA levels were highest in the liver, followed by the thigh muscles, the breast muscles, and kidneys. The transcripts of CYP27A1 in breast muscles were significantly higher in males than in females. A subcellular localization analysis demonstrated that CYP27A1 was mainly expressed in the mitochondria. In vitro enzyme assays suggested that recombinant CYP27A1 hydroxylates vitamin D 3 at the C-25 position to form 25-hydroxyvitamin D 3 (25(OH)D 3 ). The K m and V max values for CYP27A1-dependent vitamin D 3 25-hydroxylation were estimated to be 4.929 μM and 0.389 mol min -1 mg -1 protein, respectively. In summary, these results suggest that CYP27A1 encodes a mitochondrial CYP that plays an important physiologic role in the 25-hydroxylation of vitamin D 3 in chickens, providing novel insights into vitamin D 3 metabolism in this species., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Little is known regarding factors associated with calcitriol and a relative measure of calcitriol, the calcitriol-24,25-dihydroxyvitamin D3-calcifediol proportion ratio (C24CPR)., Methods: Using a cross-sectional study design, healthy young adults of African and European descent, matched (1:1) on age (±5 years) provided a blood sample in non-summer months (N = 376). Vitamin D metabolites were measured in plasma with HPLC/MS-MS. West African genetic ancestry proportion (WGA) was estimated using STRUCTURE modeling of genetic ancestry-informative markers. Multivariable regression models were used to estimate the association of WGA and vitamin D-pathway gene variants with calcitriol and C24CPR, controlling for days from summer solstice, age, sex, blood pressure, body mass index, dietary vitamin D intake, oral contraceptive/medroxyprogesterone acetate use, smoking, tanning bed use, and time of day., Results: Calcitriol and C24CPR were not highly correlated (rho = 0.14), although both were significantly, positively, and monotonically associated with WGA (Ptrend 0.025 and <0.001, respectively). In fully adjusted models, genetic factors explained a greater proportion of variability in C24CPR (R2 = 0.121 and 0.310, respectively). Variants in genes with associated with calcitriol (CALB1, CYP27B1, GC, and PPARGC1A) differed from those associated with C24CPR (CYP3A43, FGF23, KL, and VDR)., Conclusions: Both absolute and relative measures of calcitriol were significantly higher among African Americans. Otherwise, these biomarkers appear to be genetically distinct., Impact: C24CPR may be better suited to personalized medicine, due to a higher proportion of population variability explained by genetic variation and a less skewed distribution., (©2023 American Association for Cancer Research.)

25-Hydroxyvitamin D3 (25(OH)D3) is present in the human circulation esterified to sulfate with some studies showing that 25(OH)D3 3-sulfate levels are almost as high as unconjugated 25(OH)D3. Vitamin D3 is also present in human serum in the sulfated form as are other metabolites. Our aim was to determine whether sulfated forms of vitamin D3 and vitamin D3 metabolites can be acted on by vitamin D-metabolizing cytochromes P450 (CYPs), one of which (CYP11A1) is known to act on cholesterol sulfate. We used purified, bacterially expressed CYPs to test if they could act on the sulfated forms of their natural substrates. Purified CYP27A1 converted vitamin D3 sulfate to 25(OH)D3 3-sulfate with a catalytic efficiency (k cat /K m ) approximately half that for the conversion of vitamin D3 to 25(OH)D3. Similarly, the rate of metabolism of vitamin D3 sulfate was half that of vitamin D3 for CYP27A1 in rat liver mitochondria. CYP2R1 which is also a vitamin D 25-hydroxylase did not act on vitamin D3 sulfate. CYP11A1 was able to convert vitamin D3 sulfate to 20(OH)D3 3-sulfate but at a considerably lower rate than for conversion of vitamin D3 to 20(OH)D3. 25(OH)D3 3-sulfate was not metabolized by the activating enzyme, CYP27B1, nor by the inactivating enzyme, CYP24A1. Thus, we conclude that 25(OH)D3 3-sulfate in the circulation may act as a pool of metabolically inactive vitamin D3 to be released by hydrolysis at times of need whereas vitamin D3 sulfate can be metabolized in a similar manner to free vitamin D3 by CYP27A1 and to a lesser degree by CYP11A1., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The objectives of this experiment were to determine the effects of supplementing 25-hydroxyvitamin D 3 (calcidiol, CAL) compared with vitamin D 3 (cholecalciferol, CHOL) at 1 or 3 mg/d in late gestation on production outcomes of dairy cows. One hundred thirty-three parous and 44 nulliparous pregnant Holstein cows were enrolled in the experiment. Cows were blocked by parity and previous lactation milk yield (parous) or genetic merit (nulliparous) and assigned randomly to receive 1 or 3 mg/d of CAL or CHOL in a 2 × 2 factorial arrangement of treatments (CAL1, CAL3, CHOL1, and CHOL3). Treatments were provided to individual cows as a top-dress to the prepartum diet from 250 d in gestation until parturition. The prepartum diet had a dietary cation-anion difference of -128 mEq/kg of dry matter. Production and disease were evaluated for the first 42 d in milk, and reproduction was evaluated to 300 d in milk. Incidence of postpartum diseases did not differ among treatments. Feeding CAL compared with CHOL increased yields of colostrum and colostrum fat, protein, and total solids, resulting in an increased amount of net energy for lactation secreted as colostrum (CHOL = 7.0 vs. CAL = 9.0 ± 0.7 Mcal). An interaction between source and amount was observed for milk yield: CAL3 increased milk yield compared with CHOL3 (CHOL3 = 34.1 vs. CAL3 = 38.7 ± 1.4 kg/d) but milk yield did not differ between CAL1 and CHOL1 (CHOL1 = 36.9 vs. CAL1 = 36.4 ± 1.4 kg/d). Concentrations of serum calcidiol on day of calving and average serum Ca from d 2 to 11 postpartum were positively associated with milk yield in the first 42 d in milk. Interactions between source and amount of vitamin D were also observed for pregnancy after first AI: the percentage of cows receiving CHOL1 and CAL3 that became pregnant was smaller than that of cows receiving CHOL3 and CAL1. However, pregnancy per AI and pregnancy by 300 d in milk did not differ among treatments. Overall, CAL3 increased milk yield compared with CHOL3, whereas in cows fed 1 mg/d (CAL1 and CHOL1), the source of vitamin D generally had no effect. The effect of CAL3 may be explained in part by serum CAL concentrations and postpartum serum Ca, which were associated with milk yield., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

The objectives of the experiment were to determine the effects of supplementing 2 amounts of 25-hydroxyvitamin D 3 (calcidiol; CAL) compared with equal amounts of vitamin D 3 (cholecalciferol; CHOL) on serum concentrations, absorptions, and retentions of Ca, Mg, and P in periparturient dairy cows. One hundred seventy-seven (133 parous and 44 nulliparous) pregnant Holstein cows were enrolled in the experiment. Cows were blocked by parity and previous lactation milk yield (parous) or genetic merit for energy-corrected milk yield (nulliparous) and assigned randomly to receive 1 or 3 mg/d of CAL or CHOL in a 2 × 2 factorial arrangement of treatments. Treatments were provided to individual cows as a top-dress to the prepartum diet from 250 d gestation until parturition. The prepartum diet had a dietary cation-anion difference of -128 mEq/kg of dry matter. All cows were fed a common postpartum diet containing 46 μg of vitamin D 3 /kg of dry matter without further supplementation of treatments. Concentrations of vitamin D metabolites, Ca, Mg, and P in serum were measured pre- and postpartum, in addition to total-tract digestibility and urinary excretion of Ca, Mg, and P in the prepartum period. Feeding 3 mg compared with 1 mg of CAL increased serum 25-hydroxyvitamin D 3 (CAL1 = 94 vs. CAL3 = 173 ± 3 ng/mL). In comparison, the increment in serum 25-hydroxyvitamin D 3 from feeding 3 mg compared with 1 mg of CHOL was small (CHOL1 = 58 vs. CHOL3 = 64 ± 3 ng/mL). Feeding CAL increased prepartum concentration of P in serum compared with CHOL (CHOL = 1.87 vs. CAL = 2.01 ± 0.02 mM), regardless of the amount fed, but neither source nor amount affected prepartum Ca or Mg in serum. Feeding CAL increased serum Ca and P for the first 11 d postpartum compared with CHOL (CHOL = 2.12 vs. CAL = 2.16 ± 0.01 mM serum Ca; CHOL = 1.70 vs. CAL = 1.78 ± 0.02 mM serum P) but the amount of vitamin D did not affect postpartum concentrations of Ca, Mg, and P in serum. Feeding CAL increased prepartum apparent digestibility of Ca compared with CHOL (CHOL = 26.6 vs. CAL = 33.5 ± 2.8%) but treatments did not affect Ca retention prepartum. Neither source nor amount of vitamin D affected Mg and P apparent digestibility, but CAL decreased the concentration of P excreted in urine during the prepartum period (CHOL = 1.8 vs. CAL = 0.8 ± 0.3 g/d). Calcidiol tended to increase the amount of Ca secreted in colostrum (CHOL = 9.1 vs. CAL = 11.2 ± 0.9 g/d) and Ca excreted in urine postpartum (CHOL = 0.4 vs. CAL = 0.6 ± 0.1 g/d) compared with CHOL. Collectively, feeding CAL at 1 or 3 mg/d compared with CHOL in the last 24 d of gestation is an effective way to increase periparturient serum P concentration and postpartum serum Ca of dairy cows fed a prepartum diet with negative DCAD., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Vitamin D has a well-established role in regulating the intestinal absorption of minerals but its association with immunity has not been extensively explored in livestock. Although an optimal circulating concentration of 30 ng/ml 25-hydroxycholecalciferol (25(OH)D) is proposed for immune function, it is unknown if this vitamin D concentration is sufficient, particularly for cows under a pasture-based, spring-calving dairy production system. The objectives of this retrospective analysis were to assess circulating vitamin D concentrations in a total of 843 bio-banked serum samples from Holstein-Friesian dairy cows enrolled from 12 spring-calving, pasture-based dairy farms in Ireland. Mean 25(OH)D concentrations were 36.3 ng/ml at calving, 30.7 ng/ml at 7 days post-partum (DPP), and 38.3 ng/ml at 21 DPP. However, mean concentrations masked significant inter-farm and inter-individual variation (P < 0.05). In fact, the proportion of cows with vitamin D insufficiency of < 30 ng/ml was found to be 33.8%, 55.5% and 19.5% at each time point, respectively. In addition, 25(OH)D concentrations correlated positively with immune cell populations (monocytes and lymphocytes) and negatively with blood urea and non-esterified fatty acids (NEFA) at 7 DPP. This is the first report of 25(OH)D concentrations in pasture-based peripartum dairy cows and we show a high degree of variation across farms and between individual animals. Sub-optimal concentrations of vitamin D in some post-partum cows may predispose cattle to multiple metabolic or infectious diseases, and therefore further work is now warranted., (© 2022. The Author(s).)

In this paper, we report an efficient synthetic route for the 23,23-difluoro-25-hydroxyvitamin D 3 ( 5 ) and its 24-hydroxylated analogues ( 7 , 8 ), which are candidates for the CYP24A1 main metabolites of 5 . The key fragments, 23,23-difluoro-CD-ring precursors ( 9 - 11 ), were synthesized starting from Inhoffen-Lythgoe diol ( 12 ), and introduction of the C23 difluoro unit to α-ketoester ( 19 ) was achieved using N , N -diethylaminosulfur trifluoride (DAST). Preliminary biological evaluation revealed that 23,23-F 2 -25(OH)D 3 ( 5 ) showed approximately eight times higher resistance to CYP24A1 metabolism and 12 times lower VDR-binding affinity than its nonfluorinated counterpart 25(OH)D 3 ( 1 ).

1,25-dihydroxyvitamin D3 (1,25(OH) 2 D 3 ), the active metabolite of vitamin D3 has a strong impact on the differentiation and function of immune cells. Here we analysed the influence of its precursor 25-hydroxyvitamin D3 (25(OH)D 3 ) on the differentiation of human CD4 + T cells applying physiological concentrations in vitro. Our data show that 25(OH)D 3 is converted to its active form 1,25(OH) 2 D 3 by T cells, which in turn supports FOXP3, CD25 and CTLA-4 expression and inhibits IFN-γ production. These changes were not reflected in the demethylation of the respective promoters. Furthermore, we investigated the impact of vitamin D3 metabolites under induced Treg (iTreg) polarization conditions using TGF-β. Surprisingly, no additive effect but a decreased percentage of FOXP3 expressing cells was observed. However, the combination of 25(OH)D 3 or 1,25(OH) 2 D 3 together with TGF-β further upregulated CD25 and CTLA-4 and significantly increased soluble CTLA-4 and IL-10 secretion whereas IFN-γ expression of iTreg was decreased. Our data suggest that physiological levels of 25(OH)D 3 act as potent modulator of human CD4 + T cells and autocrine or paracrine production of 1,25(OH) 2 D 3 by T cells might be crucial for the local regulation of an adaptive immune response. However, since no epigenetic changes are detected by 25(OH)D 3 a rather transient phenotype is induced., (© 2022 The Authors. Scandinavian Journal of Immunology published by John Wiley & Sons Ltd on behalf of The Scandinavian Foundation for Immunology.)

Pregnancy 25-hydroxyvitamin D [25(OH)D] concentrations are associated with maternal and fetal health outcomes. Using physiological human placental perfusion and villous explants, we investigate the role of the placenta in regulating the relationships between maternal 25(OH)D and fetal physiology. We demonstrate active placental uptake of 25(OH)D 3 by endocytosis, placental metabolism of 25(OH)D 3 into 24,25-dihydroxyvitamin D 3 and active 1,25-dihydroxyvitamin D [1,25(OH) 2 D 3 ], with subsequent release of these metabolites into both the maternal and fetal circulations. Active placental transport of 25(OH)D 3 and synthesis of 1,25(OH) 2 D 3 demonstrate that fetal supply is dependent on placental function rather than simply the availability of maternal 25(OH)D 3 . We demonstrate that 25(OH)D 3 exposure induces rapid effects on the placental transcriptome and proteome. These map to multiple pathways central to placental function and thereby fetal development, independent of vitamin D transfer. Our data suggest that the underlying epigenetic landscape helps dictate the transcriptional response to vitamin D treatment. This is the first quantitative study demonstrating vitamin D transfer and metabolism by the human placenta, with widespread effects on the placenta itself. These data demonstrate a complex interplay between vitamin D and the placenta and will inform future interventions using vitamin D to support fetal development and maternal adaptations to pregnancy., Competing Interests: BA, CS, CJ, FH, JF, FR, EL, EH, LC, PM, RM, SC, HI, JH, KJ, RL, MB, JC No competing interests declared, AM AM is CSO of Proteas Bioanalytics Inc, BioLabs at the Lundquist Institute, CW Cory H White is affiliated with Merck Exploratory Science Centre, Merck Research Laboratories. The author has no financial interests to declare, SB SB part of an academic consortium that has received research funding from Abbott Nutrition, Nestec and Danone, EC EC reports honoraria/travel support from Eli Lilly, UCB, Pfizer and Amgen outside the submitted work, KG KMG has received reimbursement for speaking at conferences sponsored by companies selling nutritional products, and is part of an academic consortium that has received research funding from Abbott Nutrition, Nestec, BenevolentAI Bio Ltd. and Danone, CC CC has received lecture fees and honoraria from Amgen, Danone, Eli Lilly, GSK, Kyowa Kirin, Medtronic, Merck, Nestle, Novartis, Pfizer, Roche, Servier, Shire, Takeda and UCB outside of the submitted work, MH MH has received an honorarium for presenting to Thornton and Ross, SG SG is President and CEO/CTO of Proteas Bioanalytics Inc, BioLabs at the Lundquist Institute, NH NCH reports personal fees, consultancy, lecture fees and honoraria from Alliance for Better Bone Health, AMGEN, MSD, Eli Lilly, Servier, Shire, UCB, Consilient Healthcare, Kyowa Kirin and Internis Pharma, outside the submitted work, (© 2022, Ashley et al.)

Background: The beneficial function of phytase and 25-hydroxyvitamin D3 (HyD) on the feed utilization rate has been widely investigated. However, studies concerning its influence on weaned piglets largely lag behind. The aim of this study was to investigate the effects of phytase and HyD supplementation on the growth performance and bone development in weaned piglets under dietary Ca and P deficiency., Results: The results showed that dietary Ca and P deficiency decreased (P < 0.05) the content of serum P in 6-10 kg piglets, as well as reducing (P < 0.05) the contents of serum Ca and P, average daily gain (ADG), bone mineral density (BMD), breaking force (BF), bone ash and femur Ca in 10-20 kg piglets. Compared with the control group, the feed-to-gain ratio (F/G) of 6-10 kg piglets in the Phy group was decreased (P < 0.05), whereas the ADG, blood Ca and P, BMD, BF, bone ash, P apparent digestibility, Ca and P retention rate of 10-20 kg piglets were increased (P < 0.05). The contents of serum osteocalcin and HyD in 6-10 kg piglets and ADG were higher than in the control group (P < 0.05), as well as the contents of serum Ca and HyD in 10-20 kg piglets in the HyD treatment group. Supplementation with both Phy and HyD decreased the F/D (P < 0.05) and increased the contents of serum Ca, P and HyD in 6-10 kg piglets as well as enhancing the ADG, BMD, BF, bone ash, femur Ca and P, serum Ca and P, HyD, and the apparent digestibility and retention of Ca and P (P < 0.05) in 10-20 kg piglets. Supplementation with Phy and HyD in Ca- and P-deficient dietary decreased bone resorption, and improved tight arrangement of collagen fibers and oblique fibers in weaned piglets., Conclusion: These data indicated that supplementation with both 1500 U kg -1 Phy and 50 μg kg -1 HyD could enhance dietary Ca and P utilization and promote bone development in low Ca and P dietary, and supplementation with both Phy and HyD had a significant synergy effect compared to single supplement. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

Background: With the development of intensive farming, long-term exposure of pigs to poor light conditions is not conducive to the production of vitamin D 3 , and vitamin D 3 deficiency could affect absorption and metabolism of calcium (Ca) and phosphorus (P). 25-Hydroxyvitamin D 3 (25OHD 3 ) has higher bioactivity than regular vitamin D 3 . This study investigated the effects of 25OHD 3 on performance, serum parameters, fecal microbiota, and metabolites in weaned piglets fed with low Ca-P diet., Results: It was found that a low Ca-P diet supplemented with 50 μg/kg 25OHD 3 (NC + 25-D) improved (P < 0.05) average daily gain (ADG) in phase 2 and in the overall period of the experiment, and increased (P < 0.05) the immunoglobulin G (IgG), immunoglobulin A (IgA), catalase (CAT), bone-specific alkaline phosphatase (BALP), and osteocalcin (OC) serum content on day 28 compared with a low Ca-P diet (NC), but no differences were observed between a normal Ca-P diet (PC) and the NC + 25-D diet. Compared with NC, the abundance of Firmicutes was higher (P < 0.05) in PC and NC + 25-D. NC + 25-D decreased (P < 0.05) the abundance of Streptococcaceae compared with PC and NC, and increased (P < 0.05) the abundance of Lachnospiraceae compared with NC. Serum 25OHD 3 was negatively correlated with the abundance of fecal Streptococcaceae (P < 0.05), and positively correlated with the abundance of fecal Lachnospiraceae (P < 0.05)., Conclusion: Supplementation of 25OHD 3 in a low Ca-P diet improved serum immunity, bone biochemical parameters, and fecal microbiota such as decreased Streptococcaceae abundance and increased Lachnospiraceae abundance, which could subsequently promote growth of piglets. The effects were similar to that of a normal Ca-P diet. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

An 82-year-old man was transferred to our hospital due to impaired consciousness. His albumin-corrected calcium level was 14.2 mg/dL, intact parathyroid hormone (PTH) and PTH-related protein levels were reduced, and his 1,25-dihydroxyvitamin D [1,25 (OH) 2 VitD] level was elevated at 71.5 pg/mL. Computed tomography revealed masses on the bilateral ribs. The mass on the rib was biopsied and diagnosed as diffuse large B-cell lymphoma (DLBCL). Immunostaining of the biopsy sample with the anti-CYP27B1 antibody revealed the ectopic expression of 1α-hydroxylase in the lesion. We herein report a rare case of hypercalcemia induced by the overproduction of 1,25 (OH) 2 VitD in DLBCL ectopically expressing 1α-hydroxylase.

The parathyroid hormone 1 receptor (PTHR1) plays a crucial role in calcium homeostasis and bone metabolism. However, its genetic role in regulating bone turnover markers (BTMs) in postmenopausal osteoporosis (PMO) remains unclear. Herein, we explored parathyroid hormone (PTH) and PTHR gene variant susceptibility to osteoporosis and their association with various circulating BTM and inflammatory markers in postmenopausal women of Arab ethnicity. In total, 600 postmenopausal Arab women (300-PMO and 300-control) were genotyped for selected SNPs in PTH (rs1459015, rs307253, rs6054, rs307247, rs10500783 and rs10500784), PTHR1 (rs6442037, rs1138518, and rs724449 SNPs) and PTHR2 (rs9288393, rs10497900, and rs897083). Anthropometrics, BTMs, and inflammatory markers were measured. Bone mineral density (BMD) was measured at the lumbar spine L1-L4 and the femoral neck using dual-energy X-ray absorptiometry (DXA). PTHR1 rs1138518 genotype C/T was found to be a significant risk factor for PMO (OR = 1.49, 95% CI 1.0-2.1, P = 0.03). The genotypes C/T and T/T of PTHR1 rs1138518 were associated with 25-hydroxy-vitamin D (25(OH)D) regulation. In the PMO group, carriers of the C/T genotype had significantly lower 25(OH)D levels than carriers of the same genotypes in the control group (59.9 (36.7-92.4) nmol/l and 66.4 (43.5-87.8) nmol/l, respectively; P = 0.048]. Our study concludes that the PTHR1 rs1138518 genotype could be a potential risk factor for osteoporosis and 25(OH)D regulation in Arab women with PMO., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Saba Abdi et al.)

Objectives: Our aim was to investigate the prevalence and predictive variables of sarcopenia., Methods: We recruited participants from the Peking Union Medical College Hospital Multicenter Prospective Longitudinal Sarcopenia Study (PPLSS). Muscle mass was quantified using bioimpedance, and muscle function was quantified using grip strength and gait speed. Logistic regression revealed the relationships between sarcopenia and nutritional, lifestyle, disease, psychosocial and physical variables., Results: The prevalence of sarcopenia and sarcopenic obesity was 9.2%-16.2% and 0.26%-9.1%, respectively. Old age, single status, undernourishment, higher income, smoking, low physical activity, poor appetite and low protein diets were significantly associated with sarcopenia. Multiple logistic regression analysis showed that age was a risk factor for all stages of sarcopenia, and participants above 80 years were greater than fivefold more susceptible to sarcopenia, while lower physical activity was an independent risk factor. The optimal cut-off value for age was 71 years, which departs from the commonly accepted cut-off of 60 years. Female participants were greater than twofold less susceptible to sarcopenia than male participants. The sterol derivative 25-hydroxyvitamin D was associated with fourfold lower odds of sarcopenia in male participants. Several protein intake variables were also correlated with sarcopenia. Based on these parameters, we defined a highly predictive index for sarcopenia., Conclusions: Our findings support a predictive index of sarcopenia, which agglomerates the complex influences that sterol metabolism and nutrition exert on male vs female participants., (© 2021 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.)

It is well known that cell can response to various chemical and mechanical stimuli. Therefore, flow pressure variation induced by sample loading and elution should be small enough to ignore the physical impact on cells when we use a Chip-SPE-MS system for cells. However, most existent Chip-SPE-MS systems ignored the pressure alternation because it is extremely difficult to develop a homogeneous-flow-pressure hyphenated module. Herein, we developed an interesting fluidic isolation-assisted homogeneous-flow-pressure Chip-SPE-MS system and demonstrated that it is adequate for online high-throughput determination and quantification of the 25-hydroxyvitamin D 3 (25(OH)D 3 ) biotransformation in different cells. Briefly, the homogeneous ambient flow pressure is achieved by fluidic isolation between the cell culture channel and the SPE column, and an automatic sampling probe could accomplish the sample loading and dispensing to fulfill online pretreatment of the sample. Through this new system, the expression levels of 24,25-dihydroxyvitamin D 3 (24,25(OH) 2 D 3 ) can be determined in real time with a detection limit of 2.54 nM. In addition, the results revealed that 25(OH)D 3 metabolic activity differed significantly between normal L-02 cells and cancerous HepG2 cells. Treatment of L-02 cells with a high dose of 25(OH)D 3 was found to increase significant formation of 24,25(OH) 2 D 3 , but this change was not apparent in HepG2 cells. The presented system promises to be a versatile tool for online accurate molecule biotransformation investigation and drug screening processes.

CYP24A1-deficient (Cyp24a1 KO) rats were generated using the CRISPER/Cas9 system to investigate CYP24A1-dependent or -independent metabolism of 25(OH)D3, the prohormone of calcitriol. Plasma 25(OH)D3 concentrations in Cyp24a1 KO rats were approximately twofold higher than in wild-type rats. Wild-type rats showed five metabolites of 25(OH)D3 in plasma following oral administration of 25(OH)D3, and these metabolites were not detected in Cyp24a1 KO rats. Among these metabolites, 25(OH)D3-26,23-lactone was identified as the second major metabolite with a significantly higher T max value than others. When 23S,25(OH) 2 D3 was administered to Cyp24a1 KO rats, neither 23,25,26(OH) 3 D3 nor 25(OH)D3-26,23-lactone was observed. However, when 23S,25R,26(OH) 3 D3 was administered to Cyp24a1 KO rats, plasma 25(OH)D3-26,23-lactone was detected. These results suggested that CYP24A1 is responsible for the conversion of 25(OH)D3 to 23,25,26(OH) 3 D3 via 23,25(OH) 2 D3, but enzyme(s) other than CYP24A1 may be involved in the conversion of 23,25,26(OH) 3 D3 to 25(OH)D3-26,23-lactone. Enzymatic studies using recombinant human CYP species and the inhibitory effects of ketoconazole suggested that CYP3A plays an essential role in the conversion of 23,25,26(OH) 3 D3 into 25(OH)D3-26,23-lactone in both rats and humans. Taken together, our data indicate that Cyp24a1 KO rats are valuable for metabolic studies of vitamin D and its analogs. In addition, long-term administration of 25(OH)D3 to Cyp24a1 KO rats at 110 μg/kg body weight/day resulted in significant weight loss and ectopic calcification. Thus, Cyp24a1 KO rats could represent an important model for studying renal diseases originating from CYP24A1 dysfunction., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Dry eye disease (DED) is a common ocular surface condition across age groups. Recently, vitamin D deficiency has gained importance as a causative factor, and its supplementation alleviates symptoms of DED. Resveratrol (RES) regulates vitamin D receptors (VDRs) and Notch signaling. We investigated the role of RES on vitamin D levels and Notch signaling under hyperosmolar conditions., Methods: Human corneal epithelial (HCE-T) cells were treated with RES in hyperosmolar and normal conditions. Quantitative real-time polymerase chain reaction (PCR), immunofluorescence, enzyme-linked immunosorbent assay, and western blot analysis were performed for estimating reactive oxygen species, VDR, secreted 25-hydroxyvitamin D3, and Notch signaling pathway molecules in treated and control cells., Results: HCE-T cells in hyperosmolar conditions had increased reactive oxygen species levels and decreased vitamin D levels that got restored in the presence of RES. Hyperosmolarity also reduced VDR expression and Notch activity that normalized to original levels with RES. In the presence of Notch blocker LY-411575, RES could not restore VDR expression or secreted vitamin D levels in HCE-T cells exposed to hyperosmolar conditions, whereas recombinant Jagged1 restored vitamin D and VDR levels., Conclusions: RES restores vitamin D levels in hyperosmolar conditions most likely through activation of Notch signaling. Hence, RES can be a potential adjuvant in DED for patients considered for vitamin D treatment.

This study was conducted to test the effects of maternal 25-hydroxycholecalciferol (25OHD 3 ) supplementation on serum parameters, intestinal morphology and microbiota in suckling piglets. The experiment started on day 107 of gestation and lasted until piglets were weaned on day 21 of lactation. Thirty-two sows were allocated randomly to two treatments (ND diet, basal diet with 2000 IU/kg of vitamin D 3 ; 25-D diet, basal diet with 50 μg/kg 25OHD 3 ). Results showed that maternal 25-D treatment increased ( p < 0.05) serum 25OHD 3 concentration in the umbilical cords, which led to higher ( p < 0.05) serum 25OHD 3 concentration of suckling piglets from 25-D sows. The GSH-Px activity in colostrum was higher ( p < 0.05), as well as SOD and GSH-Px activities in milk, were higher ( p < 0.05) in 25-D sows than ND sows. Compared with piglets suckling ND sows, piglets suckling 25-D sows had higher ( p < 0.05) serum SOD activity on day 7, 14 and 21 of lactation. On day 21 of lactation, piglets form 25-D sows had greater ( p < 0.05) serum levels of GH and IGF-I and lower ( p < 0.05) serum DAO activity than those from ND sows. Piglets from 25-D sows had higher ( p < 0.05) jejunal villus height than those from ND sows. Feeding 25OHD 3 to sows tended to increase ( p < 0.10) the species richness in the colonic digesta of suckling piglets, as reflected by the α-diversity index of Chao-1. In the caecal digesta, the α-diversity for bacterial community analysis of Simpson and Shannon was lower ( p < 0.05) in 25-D piglets than ND piglets. The relative abundances of colonic Alloprevotella and caecal Lactobacillus were significantly higher, while the population of caecal [Eubacterium]&#95;coprostanoligenes&#95;group was lower ( p < 0.05) in 25-D piglets than ND piglets. In conclusion, maternal 25OHD 3 supplementation partly improved antioxidant status in sows and suckling piglets and altered gut microbiota in the hindgut of piglets.

The vitamin D receptor is highly expressed in the gastrointestinal tract where it transacts gene expression. With current limited understanding of the interactions between the gut microbiome and vitamin D, we conduct a cross-sectional analysis of 567 older men quantifying serum vitamin D metabolites using LC-MSMS and defining stool sub-Operational Taxonomic Units from16S ribosomal RNA gene sequencing data. Faith's Phylogenetic Diversity and non-redundant covariate analyses reveal that the serum 1,25(OH) 2 D level explains 5% of variance in α-diversity. In β-diversity analyses using unweighted UniFrac, 1,25(OH) 2 D is the strongest factor assessed, explaining 2% of variance. Random forest analyses identify 12 taxa, 11 in the phylum Firmicutes, eight of which are positively associated with either 1,25(OH) 2 D and/or the hormone-to-prohormone [1,25(OH) 2 D/25(OH)D] "activation ratio." Men with higher levels of 1,25(OH) 2 D and higher activation ratios, but not 25(OH)D itself, are more likely to possess butyrate producing bacteria that are associated with better gut microbial health.

Neonatal mortality rates in Indonesia are still at an alarming rate, with preterm birth as one of the causes. Nutritional deficiencies such as low level of vitamin D is suspected to be the risk factors of preterm birth but still a little knowledge about it. Vitamin D metabolism includes 25-hydroxyvitamin D 3 (25(OH)D 3 ) and 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ), as the inactive and active form, with the help of 1α-hydroxylase (CYP27B1) enzyme. Our study aims to determine the differences of 25(OH)D 3 , 1,25(OH) 2 D 3 and CYP27B1 enzyme in term and preterm birth. A cross-sectional study was performed in Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia, in January-June 2017. The blood sample was taken soon after delivery, to examine maternal 25(OH)D 3 and 1,25(OH) 2 D 3 in serum and tissue placenta, as well as placental CYP27B1 enzyme. Statistical analysis using SPPS version 20 was used to find significances. There were a total of sixty subjects in this study, with term-preterm birth group ratio 1:1. We found that placental 25(OH)D 3 was significantly low ( P = 0⋅001), and CYP27B1/25(OH)D 3 ratio was high in preterm birth. Also, there were significant negative correlations found in CYP27B1 level and both placental 25(OH)D 3 ( r 0⋅481, P < 0⋅001) and 1,25(OH) 2 D 3 ( r -0⋅365, P = 0⋅004) levels. Our study concludes that preterm birth showed lower placental 25(OH)D 3 status, and higher CYP27B1/25(OH)D 3 ratio compared to term pregnancy., (© The Author(s) 2020.)

A variety of metabolites derived from 25-hydroxyvitamin D 3 [25(OH)D 3 ], including its 3-epimer [Epi-25(OH)D 3 ] and 3-O-sulfate [25(OH)D 3 -3S], is found in human plasma/serum. We hypothesized that the 3-O-sulfate of Epi-25(OH)D 3 [Epi-25(OH)D 3 -3S] might be present in plasma/serum. Clarifying this point could improve our understanding of the metabolism of vitamin D 3 . In this study, we first carefully analyzed the cord plasma samples by derivatization-assisted liquid chromatography/electrospray ionization-tandem mass spectrometry and demonstrated the occurrence of Epi-25(OH)D 3 -3S in the plasma. However, the concentration ratio of Epi-25(OH)D 3 -3S to 25(OH)D 3 -3S (sulfated form) was infinitely lower than the ratio of Epi-25(OH)D 3 to 25(OH)D 3 (unconjugated form). To determine what caused this result, we next performed an in vitro experiment of the 3-O-sulfation for 25(OH)D 3 and Epi-25(OH)D 3 using the recombinant human sulfotransferase (SULT) 2A1. This in vitro experiment revealed that Epi-25(OH)D 3 is a poor substrate for the 3-O-sulfation catalyzed by SULT2A1 as compared to 25(OH)D 3 . This substrate specificity of SULT2A1 would be the main cause for the result obtained from the analysis of the cord plasma samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Scope: Vitamin D 3 is a critical molecule for the properly controlled activity of the immune system. In myeloid-derived cells, vitamin D 3 induces the production of the antimicrobial and antitumor peptide cathelicidin. In this study, the mechanism of the entry of 25-hydroxycholecalciferol (25(OH)D) in myeloid-derived cells is explored., Methods and Results: Here, a novel regulatory pathway of vitamin D 3 biology is described. Using a polyclonal antibody, two different chemical inhibitors, and a high-density lipoprotein as a competing ligand, it is demonstrated here that the 25(OH)D signaling pathway in myeloid cells depends on scavenger receptor class B type I (SR-B1). This effect is observed in the THP-1 monocytic cell line and in human primary monocytes. SR-B1 blockade abrogates the cellular uptake of 25(OH)D leading to a general shut down of the gene transcription program modulated by 25(OH)D. The results obtained at the transcriptional level are confirmed at the protein and functional level for CD14 in the THP-1 cell line., Conclusion: In conclusion, SR-B1 plays a critical role in vitamin D 3 biology, paving the way for novel therapeutic interventions., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Rationale: Vitamin D deficiency is common in patients with asthma and chronic obstructive pulmonary disease (COPD). Low 25-hydroxyvitamin D (25[OH]D) levels may represent a cause or a consequence of these conditions. Objectives: To determine whether vitamin D metabolism is altered in asthma or COPD. Methods: We conducted a longitudinal study in 186 adults to determine whether the 25(OH)D response to six oral doses of 3 mg vitamin D 3 , administered over 1 year, differed between those with asthma or COPD versus control subjects. Serum concentrations of vitamin D 3 , 25(OH)D 3 , and 1α,25-dihydroxyvitamin D 3 (1α,25[OH] 2 D 3 ) were determined presupplementation and postsupplementation in 93 adults with asthma, COPD, or neither condition, and metabolite-to-parent compound molar ratios were compared between groups to estimate hydroxylase activity. Additionally, we analyzed 14 datasets to compare expression of 1α,25(OH) 2 D 3 -inducible gene expression signatures in clinical samples taken from adults with asthma or COPD versus control subjects. Measurements and Main Results: The mean postsupplementation 25(OH)D increase in participants with asthma (20.9 nmol/L) and COPD (21.5 nmol/L) was lower than in control subjects (39.8 nmol/L; P  = 0.001). Compared with control subjects, patients with asthma and COPD had lower molar ratios of 25(OH)D 3 -to-vitamin D 3 and higher molar ratios of 1α,25(OH) 2 D 3 -to-25(OH)D 3 both presupplementation and postsupplementation ( P  ≤ 0.005). Intergroup differences in 1α,25(OH) 2 D 3 -inducible gene expression signatures were modest and variable if statistically significant. Conclusions: Attenuation of the 25(OH)D response to vitamin D supplementation in asthma and COPD associated with reduced molar ratios of 25(OH)D 3 -to-vitamin D 3 and increased molar ratios of 1α,25(OH) 2 D 3 -to-25(OH)D 3 in serum, suggesting that vitamin D metabolism is dysregulated in these conditions.

A supplement of 69 μg 25-hydroxycholecalciferol (25-OH-D3)/kg feed suppressed the mortality in feed-restricted broiler breeder hens and in hens allowed ad libitum feed intake (Ad-hens) in a feeding trial from age 26 to 60 wk. Outcomes for the mechanisms found that 25-OH-D3 relieved systemic hypoxia, pathological cardiac remodeling and arrhythmias, and hepatopathology to improve hens' livability. In the study, we further evaluated the effect of 25-OH-D3 on blood pressure and vascular remodeling relative to cardiac pathogenesis of sudden death (SD). Ad libitum feed intake increased mechanical loading and contributed to maladaptive cardiac hypertrophy as evidenced by consistently elevated peripheral arterial blood pressure in Ad-hens before SD (P < 0.05). In planned longitudinal measurements, Ad-hens also showed higher right ventricle systolic pressure and right ventricle diastolic pressure (RVDP) (P < 0.05). Supplemental 25-OH-D3 relieved peripheral hypertension and prevented time-dependent increases of RVDP in Ad-hens through the renin-angiotensin system and circulating nitric oxide availability and by regulating vascular remodeling including elastin/collagen ratio and smooth muscle cell proliferation in the pulmonary artery for improved elasticity/stiffness (P < 0.05). The antihypertensive effect via the renin-angiotensin system and nitric oxide regulation in respect to heart rate and arrhythmias by 25-OH-D3 were further confirmed in 51 week-old feed-restricted broiler breeder hens challenged with salt loading for 5 wk. Despite feed restriction, the most feed-efficient hens of feed-restricted groups also exhibited cardiac pathological hypertrophy, in conjunction with higher right ventricle systolic pressure, RVDP, plasma nitric oxide levels, and more dramatic arterial remodeling (P < 0.05). These results suggest that peripheral and pulmonary hypertension are the key drivers of SD and that 25-OH-D3 is an effective antihypertensive supplement to alleviate cardiac pathogenesis and improve livability in broiler breeder hens., (Copyright © 2020. Published by Elsevier Inc.)

This study investigated the effect of complexation with whey and casein protein, respectively, on post prandial absorption of vitamin D3. For this purpose, Sprague-Dawley rats (n = 78) were administered 840 IU vitamin D3 dissolved in ethanol and either (i) complexed with whey protein isolate (protein : vitamin ration 2 : 1), (ii) complexed with caseinate (protein : vitamin ration 2 : 1), or (iii) provided in a water solution. Serum concentrations of vitamin D3, 25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 were measured before and 2, 3, 4, 5, 6, 7, 8, and 10 hours after administration of vitamin D3. Significant effects of complexation on serum concentrations of vitamin D3, 25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 were demonstrated. Complexation with whey protein isolate resulted in the fastest and highest absorption of vitamin D3 while an effect of complexation with caseinate was evident but more modest and non-significant. In conclusion, the study demonstrates that complexation with milk proteins is an efficient strategy to enhance bioaccessibility of vitamin D3.

This study was conducted to determine the effects of 25-hydroxycholecalciferol (25-OH-D 3 ) on performance, egg quality, tibia quality, and serum hormones concentration in laying hens reared under high stocking density. A total of 800 45-week-old Lohmann laying hens were randomly allotted into a 2 × 2 factorial design with 2 levels of dietary 25-OH-D 3 levels (0 and 69 μg/kg) and 2 rates of stocking densities [506 (low density) and 338 (high density) cm 2 /hen]. Laying hens were monitored for 16 wk. High stocking density decreased laying rate, egg weight, and feed intake compared with low stocking density (P < 0.01) during 1 to 8 wk and 1 to 16 wk. Overall, high stocking density increased eggshell lightness value and decreased shell redness and yellowness value, strength, thickness, and relative weight compared with low stocking density (P < 0.05). Dietary supplementation with 25-OH-D 3 reduced the value of the eggshell lightness and increased its yellowness and eggshells weight (P ≤ 0.05). The increase in eggshell thickness was more pronounced when 25-OH-D 3 was supplemented to layers under high stocking density (interaction, P < 0.05). Layers under high stocking density had lower ash content and calcium content in the tibia than layers under low stocking density (P = 0.04); dietary 25-OH-D 3 increased tibia strength compared with no addition (P = 0.05). Layers under high stocking density had higher serum concentrations of 25-OH-D 3 , corticosterone (CORT), lipopolysaccharide (LPS), and osteocalcin (OC; P < 0.05), lower content of parathyroid hormone (PTH) compared with layers under low stocking density (P < 0.01). Dietary 25-OH-D 3 increased serum concentration of 25-OH-D 3 , carbonic anhydrase (CA), and calcitonin (CT) (P < 0.01) and reduced corticosterone, lipopolysaccharide and osteocalcin concentration (P ≤ 0.05). The increase effect in PTH was more pronounced when 25-OH-D 3 was supplemented to layers under high stocking density (interaction, P = 0.05). Overall, the results gathered in this study indicate that high stocking density result in reducing production performance, shell color and quality, and tibia health, whereas dietary 25-OH-D 3 was able to maintain tibia health and to mitigate the negative impact of high stocking density on productive performance., (Copyright © 2020. Published by Elsevier Inc.)

Vitamin D plays a role in bone and metabolic health in life long, however hypovitaminosis D is common in different settings. The aim of this study was to describe vitamin D status among adolescents from a large sunny country and analyze associated factors. This was a multicenter, cross-sectional, school-based study. A total of 1152 adolescents age 12-17 from four Brazilian cities, Rio de Janeiro, Fortaleza, Brasília, and Porto Alegre, were included. Anthropometric variables, diet, type of school, race and season of data collection were evaluated. Serum concentrations of 25-hydroxyvitamin D [25(OH)D] were measured and categorized into three levels: ≤ 20 ng/mL, 21-29 ng/mL and ≥ 30 ng/mL. Ordered logistic regression models were used to explore the factors associated with hypovitaminosis D. The prevalence of vitamin D levels below 20 ng/mL, between 21 and 29 ng/mL and above 30 ng/mL was 21 % (95 %CI: 19 %-24 %), 42 % (95 %CI: 39 %-46 %) and 37 % (95 %CI: 33 %-40 %), respectively. In the final adjusted model, hypovitaminosis D was positively associated with gender, center (latitudes), data collected in winter or spring, non-whites, and private school students. A higher proportional odds ratio (POR) for hypovitaminosis D was found among obese boys (POR = 2.2, 95 %CI: 1.1-4.5), but not girls. Adequate dietary intake of vitamin D was a protective factor (POR = 0.4, 95 %CI: 0.2-0.6) against hypovitaminosis D. In conclusion, there is a high prevalence of Brazilian adolescents at risk of hypovitaminosis D, independent of region. Due to their potential benefits, lifestyle changes should be stimulated, including healthier food choices and spending more time outdoors (with sun protection)., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Rationale: 25-Hydroxylated vitamin D is the best marker for vitamin D (VD). Due to its low ionization efficiency, a Cookson-type reagent, 1,2,4-triazoline-3,5-dione (TAD), is used to improve the detection/quantification of VD metabolites by liquid chromatography/tandem mass spectrometry (LC/MS/MS). However, the high reactivity of TAD makes its solution stability low and inconvenient for practical use. We here describe the development of a novel caged Cookson-type reagent, and we assess its performances in the quantitative and differential detection of four VD metabolites in serum using LC/MS/MS., Methods: Caged 4-(4'-dimethylaminophenyl)-1,2,4-triazoline-3,5-dione (DAPTAD) analogues were prepared from 4-(4'-dimethylaminophenyl)-1,2,4-triazolidine-3,5-dione. Their stability and reactivity were examined. The optimized caged DAPTAD (14-(4-(dimethylamino)phenyl)-9-phenyl-9,10-dihydro-9,10-[1,2]epitriazoloanthracene-13,15-dione, DAP-PA) was used for LC/MS/MS analyses of VD metabolites., Results: The solution stability of DAP-PA in ethyl acetate dramatically improved compared with that of the non-caged one. We measured the thermal retro-Diels-Alder reaction enabling the release of DAPTAD and found that the derivatization reaction was temperature-dependent. We also determined the detection limit and the lower limit of quantifications for four VD metabolites with DAPTAD derivatization., Conclusions: DAP-PA was stable enough for mid- to long-term storage in solution. This advantage shall contribute to the detection and quantification of VD in clinical laboratories, and as such to the broader use of clinical mass spectrometry., (© 2019 The Authors. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd.)

Background: Low 25-Hydroxy-vitamin-D; "25(OH)-D3" serum and vitamin D receptor (VDR) levels were recently correlated to advanced fibrosis. However, VDR mechanism in liver fibrosis modulations is not well understood. In this study, we aimed to evaluate changes in liver NK cells cytotoxicity due to modulations in VDR in CCl 4 fibrosis model following 25(OH) D3 injections., Methods: Carbon-tetrachloride (CCl 4 ) hepatic-fibrosis was induced in BALB/c mice for 1 and 4 weeks as an acute and chronic fibrosis model, respectively. Along 1th to 4th weeks, vitamin D were i.p injected/2x week. Liver were assessed histologically and for proteins quantification for VDR and αSMA expressions. In vitro, potential killing of NK cells were evaluated following co-culture with primary-hepatic-stellate-cells (pHSCs) obtained from BALB/c WT-mice., Results: Systemic inflammation and hepatic-fibrosis increased along 4 weeks of CCl 4 as indicated by serum ALT and αSMA expressions (P < 0.02) as well as histological assessments, respectively. These results were associated with increased NK1.1 activations and hypercalcemia. While vitamin D administrations delayed fibrosis of early stages, vitamin D worsen hepatic-fibrosis of late stages of CCl 4 . In week 4, no further activations of NK cells were seen following vitamin D injections and were associated with down-expressions of VDR (1.7 Fold, P < 0.004) indicating the inability of vitamin D to ameliorate hepatic fibrosis. In vitro, NK cells from the chronic model of CCl 4 did not affect pHSCs killing and fail to reduce fibrosis., Conclusion: Vitamin D alleviate liver NK cytotoxicity in acute but not in chronic fibrosis model due to modulations in vitamin D receptor and calcium. Hypercalcemia associated with late fibrosis may inhibited VDR levels, however, may not explain the profibrogenic effects of vitamin D.

Recent studies have suggested that vitamin D activities involve vitamin D receptor (VDR)-dependent and VDR-independent effects of 1α,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) and 25-hydroxyvitamin D 3 (25(OH)D 3 ) and ligand-independent effects of the VDR. Here, we describe a novel in vivo system using genetically modified rats deficient in the Cyp27b1 or Vdr genes. Type II rickets model rats with a mutant Vdr (R270L), which recognizes 1,25(OH) 2 D 3 with an affinity equivalent to that for 25(OH)D 3 , were also generated. Although Cyp27b1-knockout (KO), Vdr-KO, and Vdr (R270L) rats each showed rickets symptoms, including abnormal bone formation, they were significantly different from each other. Administration of 25(OH)D 3 reversed rickets symptoms in Cyp27b1-KO and Vdr (R270L) rats. Interestingly, 1,25(OH) 2 D 3 was synthesized in Cyp27b1-KO rats, probably by Cyp27a1. In contrast, the effects of 25(OH)D 3 on Vdr (R270L) rats strongly suggested a direct action of 25(OH)D 3 via VDR-genomic pathways. These results convincingly suggest the usefulness of our in vivo system.

Vitamin D has emerged as a potentially important molecule in ophthalmology. To date, all ophthalmic data pertaining to vitamin D has been restricted primarily to tear and serum analysis in human patients. Considering the isolated nature of the eye, we sought to determine the presence of intraocular vitamin D in ocular disease., Methods: 25-Hydroxyvitamin D 3 (25(OH)D 3 ) concentrations were measured in the eye and blood of 120 participants undergoing ophthalmic procedures. Ocular localization of the 1,25-dihydroxyvitamin D 3 -generating (CYP27B1) and deactivating (CYP24A1) hydroxylases was performed by immunohistochemistry. Gene expression of CYP27B1, CYP24A1 and VEGF-A was measured in eyes from patients with and without disease., Results: 25(OH)D 3 was quantified in 112 ocular samples. In 40 cataract patient samples, the average 25(OH)D 3 concentration was 0.057 ng/mL, compared to 72 retinal disease patient samples, average of 0.502 ng/mL (p < 0.001). Intraocular 25(OH)D 3 did not correlate with serum levels of 25(OH)D 3 . There was no difference between the level of 25(OH)D 3 measured in the aqueous and vitreous humour. The vitamin D-specific CYPs 27B1 and 24A1, strongly localized to complementary regions of the ciliary body, retinal pigment epithelium and neural retina. Gene expression analysis confirmed retinal CYP27B1 correlated strongly with VEGF-A in eyes from diabetic patients (r = 0.92, p < 0.001)., Conclusions: Our data confirms that vitamin D is present in the humours of the human eye and that local synthesis/degradation is possible via the ocular CYP27B1 and CYP24A1. This argues for a functional role for local vitamin D production and signaling in the eye and suggests that vitamin D may be an important intraocular mediator in disease pathogenesis., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Genetic selection and intensive nutrition for increased growth rate in meat-type ducks has resulted in an imbalance between pectorales increment and sternal mass, which is detrimental to productivity and welfare. Reducing body weight and increasing sternal mass probably reverses these adverse effects. Therefore, 2 experiments (Expt.) were conducted to investigate the effects of 25-hydroxycholecalciferol (25-OH-D3), a vitamin D3 metabolites, on sternal mass. In Expt. 1, 512 1-day-old male ducks were randomly assigned to 4 low-nutrient density diets and received following treatments in a 2 × 2 factorial arrangement: (i) NRC or China Agricultural industry standards (NY/T) vitamin premixes and (ii) 0.069 mg/kg 25-HyD in feed or not. At 49 D of age, regardless of 25-OH-D3, NY/T vitamin regimen inhibited bone turnover and consequently increased sternal trabecular bone volume and mineral deposition compared with NRC vitamin premix. Supplementing 25-OH-D3 to NRC but not NY/T vitamin regimen significantly improved sternal microarchitecture and mineral content, which companied by decreased serum bone resorption markers concentration, as well as downregulation of the gene expressions of osteoclast differentiation and activity. In Expt. 2, 256 1-day-old male ducks were fed a standard nutrient density diet contained NRC vitamin premix with 0 or 0.069 mg/kg of 25-OH-D3. Results also showed that 25-OH-D3 treatment significantly improved sternal mineral accumulation and microarchitecture, along with decreasing osteoblast and osteoclast numbers in bone surface, declining serum bone turnover markers levels, and increasing serum Ca concentration. Collectively, these findings indicated that the dietary administration of 25-OH-D3 increased sternal mass in NRC vitamin diet by suppressing bone resorption in 49-day-old meat duck., (Copyright © 2020. Published by Elsevier Inc.)

Aims: Previous evidence has demonstrated an increased fracture risk among the population with type 2 diabetes mellitus (T2DM). This study investigated the prevalence of bone fractures in elderly subjects (with and without type 2 diabetes) and identified any fracture risk factors, especially the risk factors for common known fractures in particular diabetic populations., Methods: This cross-sectional study was conducted with community-dwelling people over 60 years old in nine communities from the city of Shenyang, which is the capital of Northeast China's Liaoning Province. A total of 3430 elderly adults (2201 females, mean ± standard deviation age 68.16 ± 6.1 years; 1229 males, 69.16 ± 6.7 years) were included. Our study measured the heel bone mineral density (BMD) and used the timed "up and go" (TUG) test and other indicators. In addition, we performed logistic regression analysis to explore the risk factors for fractures in the general population and the diabetic population and to analyze the differences., Results: The results revealed that a total of 201 elderly persons (5.8%), with an average age of 70.05 ± 6.54 years, suffered from a history of fragility fractures, which affected more females (74.6%) than males ( p = 0.001). The prevalence of fractures in the T2DM population was 7.3%, which was much higher than the 5.2% in non-T2DM population ( p = 0.001). The prevalence of fractures in the T2DM population was 7.3%, which was much higher than the 5.2% in non-T2DM population ( p = 0.001). The prevalence of fractures in the T2DM population was 7.3%, which was much higher than the 5.2% in non-T2DM population ( p = 0.001). The prevalence of fractures in the T2DM population was 7.3%, which was much higher than the 5.2% in non-T2DM population ( T -score≤-2.5 (OR 1.750) were independent risk factors for fragility fractures in the non-T2DM population, but they were not risk factors in the T2DM population., Conclusions: This study found that low BMD and slow TUG time were independent risk factors for fractures in non-T2DM patients, while no associations were found in the T2DM population. Patients with T2DM have a higher risk for fractures even when they have sufficient BMD and a short TUG time. TUG and BMD underestimated the risk for fractures in the T2DM population., Competing Interests: All the authors declare that there is no conflict of interest., (Copyright © 2020 Yan Guo et al.)

Background: Cognitive decline in older adults is a serious public health problem today. Association between vitamin D supplementation and cognition remains controversial., Objective: To determine whether a 12-month vitamin D supplementation improves cognitive function in elderly subjects with mild cognitive impairment (MCI), and whether it is mediated through the mechanism in which telomere length (TL) regulate oxidative stress., Methods: This was a double-blind, randomized, placebo-controlled trial in Tianjin, China. Participants were all native Chinese speakers aged 65 years and older with MCI. 183 subjects were randomized to an intervention group (vitamin D 800 IU/day, n = 93) or a placebo group (the matching starch granules, n = 90), and followed up for 12 months. Tests of cognitive function and mechanism-related biomarkers were evaluated at baseline, 6 months, and 12 months., Results: Repeated-measures ANOVA showed substantial improvements in the full scale intelligence quotient (FSIQ), information, digit span, vocabulary, block design, and picture arrangement scores in the vitamin D group over the placebo group (p < 0.001). Leukocyte TL was significantly higher, while serum 8-OXO-dG, OGG1mRNA, and P16INK4amRNA revealed greater decreases in the vitamin D group over the placebo group (p < 0.001). According to mixed-model repeated-measures ANOVA analysis, vitamin D group showed a significant enhancement in the FSIQ score for 12 months compared with the control (estimate value = 5.132, p < 0.001)., Conclusion: Vitamin D supplementation for 12 months appears to improve cognitive function through reducing oxidative stress regulated by increased TL in order adults with MCI. Vitamin D may be a promising public health strategy to prevent cognitive decline.

25-hydroxyvitamin D 3 has attracted considerable attention due to its great medical value and huge market demand in animal husbandry. Microbial production of 25-hydroxyvitamin D 3 has been recognized as an alternative superior to traditional chemical synthesis. In this study, a Gram-positive bacteria zju 4-2 (CCTCC M 2019385) was isolated from the soil using vitamin D 3 as the sole carbon source and was identified as Bacillus cereus according to its physiological characteristics and 16S rRNA analysis, which also showed a relatively high capacity for 25-hydroxyvitamin D 3 production. Through systematic optimization of different catalytic conditions, the optimal solvent system of vitamin D 3 , vitamin D 3 addition time and concentration, temperature, and pH were shown to be propylene glycol/ethanol (v/v = 9:1), early stationary phase, 2 g/L, 37 °C, and pH 7.2, respectively. With these optimal conditions, 796 mg/L of 25-hydroxyvitamin D 3 was achieved after 48 h bioconversion with zju 4-2 at the shake flask level. Finally, up to 830 mg/L 25-hydroxyvitamin D 3 with a yield of 41.5% was obtained in a 5 L fermentation tank. Our developed biotransformation process with this newly isolated strain provides a platform to produce 25-hydroxyvitamin D 3 efficiently at industrialization scale.

Coccidiosis penalizes calcium (Ca), phosphorus (P), and fat-soluble vitamin status, as well as bone mineralization in broiler chickens. We hypothesized that dietary vitamin D (VitD) supplementation in the form of 25-hydroxycholecalciferol (OHD), compared to cholecalciferol (D3), would improve bone mineralization in broilers receiving marginally deficient Ca/P diets, with more pronounced effects during malabsorptive coccidiosis. In a 2 VitD source × 2 Ca/P levels × 2 levels of infection factorial experiment (n = 6 pens per treatment, 6 birds/pen), Ross 308 broilers were assigned to an Aviagen-specified diet supplemented with 4,000 IU/kg of either OHD or D3 between days 11 and 24 of age. The diet contained adequate (A; 8.7:4.4 g/kg) or marginally deficient (M; 6.1:3.1 g/kg) total Ca and available (av)P levels. At day 12 of age, birds were inoculated with water (C) or 7,000 Eimeria maxima oocysts (I). Pen performance was measured over 12 days post-infection (pi). One bird per pen was assessed for parameters of bone mineralization and intestinal histomorphometric features (day 6 and 12 pi), as well as E. maxima replication and gross lesions of the small intestine (day 6 pi). There was no interaction between infection status and Ca/avP level on bone mineralization. Bone breaking strength (BS), ash weight (AW), and ash percentage (AP) were highest in broilers fed the OHD-supplemented A diets irrespective of infection status. Eimeria maxima infection impaired (P < 0.05) ADG and FCR pi; Ca and P status at day 6 pi; OHD status, BS, AW, and AP at day 12 pi; and intestinal morphology at day 6 and 12 pi. A- compared to M-fed broilers had higher BS, AW, and AP at day 6 pi, and AW at day 12 pi. VitD source affected only OHD status, being higher (P < 0.001) for OHD- than D3-fed broilers at day 6 and 12 pi. In conclusion, offering OHD and adequate levels of Ca and P improved bone mineralization, with no effect on performance. Dietary D3 and OHD supplemented at 4,000 IU/kg had similar effects on coccidiosis-infected and uninfected broilers, which led to the rejection of our hypothesis., (© 2019 Poultry Science Association Inc.)

The study aimed to examine the effects of 25-hydroxycholecalciferol (25-OH-D3) on reproductive performance and livability in broiler breeder hens. Hens at age of 26 wk were continued on restricted rations (R) or allowed ad libitum feeding (Ad) to 60 wk of age. Ad-feed intake greatly impaired egg production and hens' livability. The survival rate in both R- and Ad-hens was improved (86.7 vs.78.9% and 48.2 vs.29.1%, respectively) as was egg production in R-hens (P < 0.05) by inclusion of 69 μg 25-OH-D3/kg feedin the basal diet. Sudden death (SD) was the cause of hen mortality; hens died earlier with heavier BW and greater absolute and relative abdominal fat weights than surviving hens. Interestingly, feed intake of SD hens became less than that of surviving hens after 37 and 42 wk in Ad- and R-groups, respectively, and led to a progressive decline in SD hen BW with a ratio (relative to surviving hens of the same age) equaled 1 around 34 to 38 wk in Ad-groups and 52 to 53 wk in R-groups. Supplementation of 25-OH-D3 ameliorated untoward changes of heart and respiratory rate of Ad-survivors after 29 wk (P < 0.05), but had no significant effects on SD AD-hens. In contrast to the surviving counterparts, all SD hens experienced persistently higher respiratory rates in conjunction with declining heart rates (P < 0.05), suggesting compromised cardiac function as the cause of SD, in which hens increased heart and respiratory rate for more blood and oxygen supply to meet the need for rapid BW gain and/or adiposity in response to Ad-feed intake or due to genetically better feed efficiency even under R-feed intake. As the cardiorespiratory derangements advanced, compromised cardiac function ultimately led to heart failure and sudden death despite spontaneous reductions in feed intake and BW loss in all SD hens. Provision of 69 μg 25-OH-D3/kg feed is an effective and practical method to improve livability in broiler breeder hens., (© 2019 Poultry Science Association Inc.)

Factors that can modify the bioavailability of orally administered vitamin D are not yet widely known. Ergosterol is a common fungal sterol found in food which has a chemical structure comparable to that of vitamin D. This study aimed to investigate the effect of ergosterol on vitamin D metabolism. Therefore, 36 male wild type-mice were randomly subdivided into three groups (n = 12) and received a diet containing 25 μg vitamin D 3 and either 0 mg (control), 2 mg or 7 mg ergosterol per kg diet for 6 weeks. To elucidate the impact of ergosterol on hepatic hydroxylation of vitamin D, human hepatoma cells (HepG2) were treated with different concentrations of ergosterol. Concentrations of vitamin D 3 and 25-hydroxyvitamin D 3 (25(OH)D 3 ) in cells, livers and kidneys of mice and additionally 24,25-dihydroxyvitamin D 3 (24,25(OH) 2 D 3 ) in serum were quantified by LC-MS/MS. The concentration of 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) in serum was analyzed by commercially-available enzyme immuno assay. The concentrations of cholesterol and triglycerides were analyzed in livers of mice by photometric assays. Analyses revealed that mice receiving 7 mg/kg ergosterol with their diet had 1.3-, 1.7- and 1.5-times higher concentrations of vitamin D 3 in serum, liver and kidney, respectively, than control mice (P < 0.05), whereas no significant effects were observed in mice fed 2 mg/kg ergosterol. The hydroxylation of vitamin D remained unaffected by dietary ergosterol, since the concentration of 25-hydroxyvitamin D 3 in serum and tissues and the concentrations of 1,25(OH) 2 D 3 and 24,25(OH) 2 D 3 in serum were not different between the three groups of mice. The lipid concentrations in liver were also not affected by dietary ergosterol. Data from the cell culture studies showed that ergosterol did not influence the conversion of vitamin D 3 to 25(OH)D 3 . To conclude, ergosterol appears to be a modulator of vitamin D 3 concentrations in the body of mice, without modulating the hydroxylation of vitamin D 3 in liver., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Sunlight contains ultraviolet (UV)A and UVB radiation. UVB is essential for vitamin D synthesis but is the main cause of sunburn and skin cancer. Sunscreen use is advocated to reduce the sun's adverse effects but may compromise vitamin D status., Objectives: To assess the ability of two intervention sunscreens to inhibit vitamin D synthesis during a week-long sun holiday., Methods: The impact of sunscreens on vitamin D status was studied during a 1-week sun holiday in Tenerife (28° N). Comparisons were made between two formulations, each with a sun protection factor (SPF) of 15. The UVA-protection factor (PF) was low in one case and high in the other. Healthy Polish volunteers (n = 20 per group) were given the sunscreens and advised on the correct application. Comparisons were also made with discretionary sunscreen use (n = 22) and nonholiday groups (51·8° N, n = 17). Sunscreen use in the intervention groups was measured. Behaviour, UV radiation exposure, clothing cover and sunburn were monitored. Serum 25-hydroxyvitamin D 3 [25(OH)D 3 ] was assessed by high-performance liquid chromatography-tandem mass spectrometry., Results: Use of intervention sunscreens was the same (P = 0·60), and both equally inhibited sunburn, which was present in the discretionary use group. There was an increase (P < 0·001) in mean ± SD 25(OH)D 3 (28·0 ± 16·5 nmol L -1 ) in the discretionary use group. The high and low UVA-PF sunscreen groups showed statistically significant increases (P < 0·001) of 19·0 ± 14·2 and 13·0 ± 11·4 nmol L -1 25(OH)D 3 , respectively with P = 0·022 for difference between the intervention sunscreens. The nonholiday group showed a fall (P = 0·08) of 2·5 ± 5·6 nmol L -1 25(OH)D 3 ., Conclusions: Sunscreens may be used to prevent sunburn yet allow vitamin D synthesis. A high UVA-PF sunscreen enables significantly higher vitamin D synthesis than a low UVA-PF sunscreen because the former, by default, transmits more UVB than the latter. What's already known about this topic? Action spectra (wavelength dependence) for erythema and the cutaneous formation of vitamin D overlap considerably in the ultraviolet (UV)B region. Theoretically, sunscreens that inhibit erythema should also inhibit vitamin D synthesis. To date, studies on the inhibitory effects of sunscreens on vitamin D synthesis have given conflicting results, possibly, in part, because people typically apply sunscreen suboptimally. Many studies have design flaws. What does this study add? Sunscreens (sun protection factor, SPF 15) applied at sufficient thickness to inhibit sunburn during a week-long holiday with a very high UV index still allow a highly significant improvement of serum 25-hydroxyvitamin D 3 concentration. An SPF 15 formulation with high UVA protection enables better vitamin D synthesis than a low UVA protection product. The former allows more UVB transmission., (© 2019 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

For many individuals, in particular during winter, supplementation with the secosteroid vitamin D 3 is essential for the prevention of bone disorders, muscle weakness, autoimmune diseases, and possibly also different types of cancer. Vitamin D 3 acts via its metabolite 1α,25-dihydroxyvitamin D 3 [ 1,25(OH) 2 D 3 ] as potent agonist of the transcription factor vitamin D receptor (VDR). Thus, vitamin D directly affects chromatin structure and gene regulation at thousands of genomic loci, i.e., the epigenome and transcriptome of its target tissues. Modifications of 1,25(OH) 2 D 3 at its side-chain, A-ring, triene system, or C-ring, alone and in combination, as well as nonsteroidal mimics provided numerous potent VDR agonists and some antagonists. The nearly 150 crystal structures of VDR's ligand-binding domain with various vitamin D compounds allow a detailed molecular understanding of their action. This review discusses the most important vitamin D analogs presented during the past 10 years and molecular insight derived from new structural information on the VDR protein.