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Vascular calcification is frequently seen in patients with chronic kidney disease (CKD), and significantly increases cardiovascular mortality and morbidity. Sirt7 , a NAD+-dependent histone deacetylases, plays a crucial role in cardiovascular disease. However, the role of Sirt7 in vascular calcification remains largely unknown. Using in vitro and in vivo models of vascular calcification, this study showed that Sirt7 expression was significantly reduced in calcified arteries from mice administered with high dose of vitamin D 3 (vD 3). We found that knockdown or inhibition of Sirt7 promoted vascular smooth muscle cell (VSMC), aortic ring and vascular calcification in mice, whereas overexpression of Sirt7 had opposite effects. Intriguingly, this protective effect of Sirt7 on vascular calcification is dependent on its deacetylase activity. Unexpectedly, Sirt7 did not alter the osteogenic transition of VSMCs. However, our RNA-seq and subsequent studies demonstrated that knockdown of Sirt7 in VSMCs resulted in increased intracellular reactive oxygen species (ROS) accumulation, and induced an Nrf-2 mediated oxidative stress response. Treatment with the ROS inhibitor N-acetylcysteine (NAC) significantly attenuated the inhibitory effect of Sirt7 on VSMC calcification. Furthermore, we found that knockdown of Sirt7 delayed cell cycle progression and accelerated cellular senescence of VSMCs. Taken together, our results indicate that Sirt7 regulates vascular calcification at least in part through modulation of ROS and cellular senescence of VSMCs. Sirt7 may be a potential therapeutic target for vascular calcification. [Display omitted] • Sirt7 expression is decreased in vascular calcification. • Sirt7 attenuates vascular calcification depending on its histodeacetylase activity. • Knockdown of Sirt7 promotes ROS production and cellular senescence in VSMCs. [ABSTRACT FROM AUTHOR]

There is limited randomized controlled trial evidence to support the association between vitamin D deficiency and anemia risk, highlighting the necessity for further investigations into the role of vitamin D in influencing iron status. The aim of this study was to determine the effect of vitamin D3–fortified fruit drink consumption (4,000 IU) on vitamin D and iron status biomarkers among iron-deficient women (serum ferritin of <20 μg/L [to convert μg/L ferritin to ng/mL, multiply by 1]). An 8-week double-blind randomized controlled trial was conducted. A total of 45 healthy, nonpregnant, nonlactating subjects aged 18 through 40 years (mean [SD] 25.3 [4.6] years) were included in the study, excluding those who donated blood 6 months prior, regularly consumed nutritional supplements, or had gastrointestinal or iron metabolic disorders. Subjects were randomly assigned to receive either vitamin D3–fortified fruit drink or a placebo. Measurements of 25-hydroxyvitamin D (25[OH]D), serum ferritin, high-sensitivity C-reactive protein, and full blood count concentrations were obtained at baseline, interim, and post intervention. A mixed model, repeated measures analysis of variance was used to analyze the intervention effect. Attrition rate for the study was 13%, with 6 dropouts, and 39 subjects completed the study. Daily consumption of vitamin D3–fortified fruit drink in the intervention group resulted in significant increases in 25(OH)D and serum ferritin concentrations compared with the placebo group. The intervention group showed significantly higher mean (SD) changes (Δ) in both 25(OH)D (Δ 76.4 [30.2] nmol/L [to convert nmol/L 25(OH)D to ng/mL, multiply by.4] vs Δ –1.3 [10.7] nmol/L; P =.001) and serum ferritin concentrations (Δ 2.2 [4.2] μg/L vs Δ –0.3 [3.4] μg/L; P =.048) between baseline and post intervention. The other iron status biomarkers were not affected by the intervention. Our study found that daily vitamin D3–fortified fruit drink supplementation for 8 weeks effectively improved 25(OH)D and iron stores, indicated by increased serum ferritin concentrations, in iron-deficient women. Further research is needed to evaluate its safety, efficacy, feasibility, and optimal food fortification in diverse populations. [ABSTRACT FROM AUTHOR]

• Natural killer (NK) cell activity is low and NK cell maturation is suppressed in diabetic mice. • Interferon-γ production of splenocyte is low in diabetic mice. • Transforming growth factor-β expression in spleen is high in diabetic mice. • Enhanced NK cell activity may be associated with changes in proportion of mature NK cells. • Vitamin D supplementation enhanced interleukin-12 production. • Vitamin D supplementation enhanced Bcl2 and Tbx21 expression in NK cells. Type 2 diabetes mellitus negatively affects the immune system, resulting in reduced natural killer (NK) cell activity. Vitamin D has been shown to regulate innate and adaptive immune cells. However, the effects of vitamin D on NK cells remain inconclusive, especially in the context of diabetes. We hypothesized that dietary vitamin D 3 supplementation can enhance NK cell activity in diabetic mice. Therefore, we investigated the effects of dietary vitamin D 3 on NK cell activity in control and diabetic mice and explored the mechanisms of NK cell activity modulation by vitamin D 3. Control (CON) and diabetic mice (db/db) were randomly divided into 2 groups, then fed either a control diet (948 IU vitamin D 3 /kg diet, vDC) or a diet supplemented with vitamin D 3 (9,477 IU vitamin D 3 /kg diet, vDS) for 8 weeks. Diabetic mice exhibited lower NK cell activity than control mice. The vDS group had significantly higher NK cell activity than the vDC group in both control and diabetic mice. The vDS group had a higher percentage of CD11b single-positive NK cells than the vDC group (CON-vDS 34%; db/db-vDS 30%; CON-vDC 27%; db/db-vDC 22%). The intracellular expression of splenic TGF-β was significantly higher in the db/db group than in the CON group. Overall, vDS group had higher Bcl2 and Tbx21 mRNA expressions than the vDC group. In conclusion, the present study shows that NK cell activity is impaired under diabetic conditions, possibly due to the reduced percentage of mature NK cells. Moreover, NK activity is enhanced by dietary supplementation in both control and diabetic mice that may be associated with changes in the proportion of mature NK cells. The purpose of the study is to investigate the effects of vitamin D on NK cell activity in diabetic conditions. The results showed that diabetic mice showed impaired NK cell activity with lower percentage of mature NK cells and NKG2D expression. However, dietary vitamin D 3 -supplementated group showed enhanced NK cell activity in diabetic mice, along with increased production of NK-stimulating cytokines and increased levels of mRNAs associated with NK cell maturation.Abbreviations: Bcl-2, B-cell lymphoma/leukemia-2; CD, cluster of differentiation; IFN-γ, Interferon gamma; IL, interleukin; NK cells, Natural killer cells; NKG2D, Natural killer group 2D; Tbx21, T-box transcription factor 21; TGF-β, Transforming growth factor beta. [Display omitted] [ABSTRACT FROM AUTHOR]

• Vitamin D is one of the most widely used drugs. • Large use of vitamin D in prevention leads to therapeutic inappropriateness. • Governments must adopt policies without wasting public resources. At the Asl Napoli 3 SUD a local, regional and national level analysis of prescription and spending related to the prescription and dispensing of drugs intended to increase vitamin D levels in the human body was carried out. The Italian Pharmacy Regulatory Agency (AIFA) in late 2019 introduced a prescriptive note of appropriateness (note 96) to regulate the prescribing activity of a drug that is widely used on the Italian national population, significantly affecting spending by the National Health System (NHS). Despite this action there has been an increase in prescription and expenditure of calcifediol at all levels of analysis (national, regional and local) while regarding the remaining Anatomical Therapeutic Chemical (ATC) referring to drugs used as vitamin D supplement in the Campania Region and at the Asl Napoli 3 SUD there is a slower decrease in expenditure and prescription, sometimes even increasing and in countertendency to the Italian national average. For these reasons, the Campania Region instituted two executive decrees (DD 405/2021 and 91/2022) that led to a marked reduction in spending and prescription in 2022 even higher than in other Italian regional realities. This analysis aims to show how vitamin D prescription is widespread and often inappropriate, attested by wide regional variability. In addition, the main recommendations for the use of these drugs are highlighted in order to raise awareness among all healthcare professionals of the informed use of these molecules ensuring sustainability and governance. [ABSTRACT FROM AUTHOR]

The spontaneous healing of critical-sized bone defects is often limited, posing an increased risk of complications and suboptimal outcomes. Osteogenesis, a complex process central to bone formation, relies significantly on the pivotal role of osteoblasts. Despite the well-established osteogenic properties of vitamin D 3 (VD 3), its lipophilic nature confines administration to oral or muscle injection routes. Therefore, a strategic therapeutic approach involves designing a multifunctional carrier to enhance efficacy, potentially incorporating it into the delivery system. Here, we introduce an innovative sterosome-based delivery system, utilizing palmitic acid (PA) and VD 3 , aimed at promoting osteogenic differentiation and facilitating post-defect bone regeneration. The delivery system exhibited robust physical characteristics, including excellent stability, loading efficiency, sustained drug release and high cellular uptake efficiency. Furthermore, comprehensive investigations demonstrated outstanding biocompatibility and osteogenic potential in both 2D and 3D in vitro settings. A critical-sized calvarial defect model in mice recapitulated the notable osteogenic effects of the sterosomes in vivo. Collectively, our research proposes a clinically applicable strategy for bone healing, leveraging PA/VD 3 sterosomes as an efficient carrier to deliver VD 3 and enhance bone regenerative effects. [Display omitted] [ABSTRACT FROM AUTHOR]

Depression and anxiety disorders are among the most common mental health disorders that affect US adults today, frequently related to vitamin D (VD) insufficiency. Along with VD, growing evidence suggests gut microbiota likely play a role in neuropsychiatric disorders. Here, we investigated if modulation of gut microbiota would disrupt host VD status and promote behaviors related to depression and anxiety in adult mice. Six-week-old male and female C57BL/6J mice (n = 10/mice/group) were randomly assigned to receive (1) control diet (CTR), control diet treated with antibiotics (AB), control diet with total 5000 IU of VD (VD), VD treated with antibiotics (VD + AB), VD supplemented with 5% w/w fructooligosaccharides (FOS; VF), and VF diet treated with antibiotics (VF + AB), respectively, for 8 weeks. Our study demonstrated that VD status was not affected by antibiotic regimen. VD alone ameliorates anxiety-related behavior in female mice, and that combination with FOS (i.e., VF) did not further improve the outcome. Male mice, in contrast, exhibit greater anxiety with VF, but not VD, when compared with CTR mice. Colonic VD receptor was elevated in VF-treated mice in both sexes, compared with CTR, which was positively correlated to colonic TPH1, a rate-limiting enzyme for serotonin synthesis. Taken together, our data indicate that the effect of VF on anxiety-related behavior is sex-specific, which may partially be attributed to the activation of colonic VD signaling and subsequent serotonin synthesis. The synergistic or additive effect of VD and FOS on mood disorders remained to be investigated. The combination of Vitamin D 3 and fructooligosaccharides affects anxiety-related behavior in a sex-specific manner, in which the intervention reduces anxiety in female mice but promotes anxiety in male mice. These phenotype changes are aligned with the circulating serotonin concentrations. In addition, colonic VDR mRNA expression is elevated in mice receiving VD + FOS, suggesting a regulatory role of FOS in colonic Vitamin D signaling and subsequent mood disorders. Abbreviations: FOS, fructooligosaccharides; VD, Vitamin D 3 ; VDR, Vitamin D receptor. [Display omitted] [ABSTRACT FROM AUTHOR]

Thirty-three long-term care residents (mean age 76.5 years), who were participating in a study in which they were randomized to receive either oral daily standard dose (400–1000 IU/day) 25-hydroxy vitamin D (vitamin D3) (SD) or high dose (3000–4000 IU/day) (HD) vitamin D3, were vaccinated with the live, attenuated herpes zoster vaccine. Blood was drawn at vaccination and three weeks later to determine varicella-zoster virus (VZV) antibody and T-cell mediated immune responses. ELISA and neutralizing antibodies increased significantly, but to the same extent, in both groups. The antibody avidity significantly increased from pre- to post-vaccination only in the HD group. VZV-CMI, as measured by FLUOROSPOT significantly increased post-vaccination in both groups, but the difference in interferon-γ spot-forming cells (SFC) and interleukin-2 SFC was lower in the HD than SD group. The increase in VZV-CMI correlated inversely with circulating regulatory T cells in the HD group. We conclude that pre-treatment with HD vitamin D3 does not appreciably enhance the antibody response to a live vaccine and that VZV-CMI responses were diminished in HD vitamin D3 recipients. [ABSTRACT FROM AUTHOR]

Increase in the number of adipocytes and fat load in adipocytes cause stress in adipose tissue leading to pro-inflammatory signalling and insulin resistance. Previously, aqueous extract of Catharanthus roseus (L.) G. Don leaf (CRACE) was shown to be effective in inhibiting adipocyte differentiation and reduction of lipid load in mature adipocytes. Further, bioactivity-guided fractionation of the phytoextract following reverse phase HPLC and HR-LCMS analysis revealed that 1α, 25-dihydroxy vitamin D3 is the bioactive moiety in CRACE. The current study investigated the effect of 1α, 25-dihydroxy vitamin D3 containing phytoextract, CRACE, on inflammatory signalling in adipocytes-macrophage co-culture. CRACE treatment increased the secreted levels of key pro-inflammatory and pro-lipolytic cytokines TNFα and IL6 but reduced the secreted levels of other adipose-related pro-inflammatory cytokines- resistin, lipocalin2, and serpin E1. CRACE increased the secretion of important anti-inflammatory adipokines IGFBP3 and LIF1 while reducing the secreted levels of chemo-attractants MCP1, MCSF, VEGF, and IGFBP6. A significant reduction in RAW 264.7 macrophage migration towards mature 3T3-L1 adipocytes was observed in the presence of CRACE. While fatty acid uptake was increased in adipocytes and decreased in muscle cells in the presence of CRACE, glucose uptake was increased in both cells. In conclusion, 1α, 25-dihydroxy vitamin D3 containing phytoextract, CRACE, is a potent inhibitor of pro-inflammatory signaling in adipocytes-macrophage cross talk. It also promotes glucose homeostasis in adipocytes and muscle cells. Thus, it has the potential to improve two conditions simultaneously: obesity and obesity-associated type-2 diabetes. [Display omitted] • 1α, 25-dihydroxy vitamin D3 is the bioactive molecule in CRACE. • CRACE reduces inflammatory issues in mature adipocyte-macrophage co-cultures. • CRACE lowers macrophage migration towards mature adipocytes packed with intracellular lipids. • CRACE increases both fatty acid and glucose uptake activity in adipocytes. • CRACE inhibits fatty acid uptake in differentiating myoblasts while improving glucose uptake. [ABSTRACT FROM AUTHOR]

The objective of the present study was to evaluate the effect of 2 dosages of prepartum cholecalciferol injection on blood minerals, vitamin D metabolites, and milk production. Cows entering their second or greater lactation (n = 158) were randomly assigned to a control group (CON) or one of 2 treatment groups receiving either 6 × 106 IU (6VitD) or 12 × 106 IU (12VitD) cholecalciferol intramuscularly on d 275 ± 1.2 (SD) of gestation. Concentrations of serum total Ca (tCa), phosphate, and Mg were determined on 1, 2, 3, 5, 7, and 10 d in milk (DIM). For a subsample of 30 cows entering the third lactation (n = 10/group), these samples were analyzed for cholecalciferol, 25-hydroxycholecalciferol (25-OHD 3), and 24,25-dihydroxycholecalciferol (24,25-[OH] 2 D 3). In these cows, we also determined 1,25-dihydroxycholecalciferol (1,25-[OH] 2 D 3), the biologically most active metabolite, on 1, 2, 3, and 5 DIM. Repeated measures ANOVA was performed to evaluate the effect of different dosages of cholecalciferol on blood minerals, vitamin D metabolites, and milk yield over the first 5 test days after calving. Binary outcomes such as retained placenta and metritis were analyzed using a chi-squared test. Although the 12VitD treatment increased tCa concentrations on 1, 2, and 3 DIM compared with CON, administration of 6VitD increased tCa concentrations only on 1 DIM. Compared with CON cows and 6VitD cows, 12VitD cows had greater serum phosphate concentration during the first 10 DIM. Furthermore, 6VitD cows had greater serum phosphate concentrations compared with CON cows. On the contrary, 12VitD cows had lower serum Mg concentrations during the first 10 DIM compared with CON and 6VitD cows. Cholecalciferol was increased by the treatment and decreased quickly until 10 DIM. In respect to 25-OHD 3 , the 6VitD treatment resulted in a 4.1-fold increase in comparison to the CON group, while a 6.5-fold increase was observed in 12VitD animals. The vitamin D metabolite 24,25-(OH) 2 D 3 increased linearly with 25-OHD 3 serum levels, resulting in the highest concentrations in the 12VitD group. An increase of 1,25-(OH) 2 D 3 until 3 DIM was observed in all cows. However, this rise was most pronounced in the CON group. The incidence of retained placenta was 1.9%, 11.5%, and 29.6%, and that of metritis was 11.5%, 15.4%, and 31.5% for CON, 6VitD, and 12VitD cows, respectively. Although none of the treated cows exerted clinical signs of hypocalcemia, one cow in CON incurred clinical hypocalcemia. Cows of the 12VitD group had a lower milk yield over the first 5 monthly test days compared with the control and 6VitD group (42.2 ± 0.5, 42.0, ± 0.5 and 40.7 ± 0.5 kg for control cows, 6VitD cows and 12VitD cows, respectively). Although no negative side effects were observed in 6VitD cows, we do not recommend the general application of 6 × 106 IU cholecalciferol before calving as positive effects on calcium homeostasis were marginal and restricted to the first DIM. The present findings confirm that the application of 12 × 106 IU cholecalciferol negatively affected milk production on this farm. [ABSTRACT FROM AUTHOR]

Henoch Schönlein purpura (HSP) and Kawasaki disease (KD) are two main inflammatory diseases among childhood vasculitis. Considering the anti-inflammatory effects of 25-hydroxyvitamin D3, we decided to investigate the association of serum 25-hydroxy vitamin D3 level with the type and severity of these conditions. The present study was performed as a historical cohort of 254 affected children with KD and HSP vasculitis. The required data were extracted, using a researcher-made questionnaire from patients' electronic file, and then they were analyzed after collecting information of the patients. In HSP group, 54% of participants were boys. Similarly, in KD group, boys were more affected than girls. The comparative 25-hydroxyvitamin vitamin D3 level in HSP patients with and without renal involvement (P = 0.02), hematuria (P = 0.14), and in two groups with and without heart disease, and also with and without coronary artery dilatation in KD patients (P < 0.001) were significant. The findings showed that insufficient level of vitamin D3 were significantly associated with the exacerbation of complications of both diseases, and therefore it seems that vitamin D deficiency can be an effective predictive factor of severity in HSP and KD patients. [ABSTRACT FROM AUTHOR]

• Vitamin D status in a group of South Asian Renal Transplant patients is evaluated here, which is one of several papers of this type. • Vitamin D level is correlated with cardio-metabolic risk factors and found no relationship. • A unique group of patients who are young and non-diabetic. • All are living–related transplants. Vitamin D is the main hormone that plays a critical role in controlling mineral homeostasis. Transplant recipients frequently have altered levels of 25-hydroxyvitamin D (25[OH] D) and 1, 25-hydroxyvitamin (1, 25[OH] D). To explore the status of vitamin D level in renal allograft recipients and its association with renal function and cardio-metabolic risk markers. One hundred two adult kidney transplant recipients (KTRs) were included. Clinical history and information about transplantation and immunosuppression were recorded. Blood and urine samples were collected for relevant laboratory tests, including chronic kidney disease (CKD)–mineral and bone disorder markers (Ca, PO4, and 25[OH] D). The mean age was 35 ± 8 years, with a male/female ratio of 89/11%. The transplant duration was 34 ± 26 (4.5-112) months. All donors involved were living–related: fathers comprised 44%, wives 16%, sisters 13%, mothers 11%, and the others 16% (ie, brothers, sons, daughters, uncles, aunts). The immunosuppression regimen included prednisolone and tacrolimus in all, with mycophenolate mofetil in 96%. The estimated glomerular filtration rate showed CKD distribution from stage 1 to 5 in 6%, 29%, 44%, 15%, and 6%, respectively. Vitamin D level was lower in 22% (<20 ng/mL), insufficient (20-30 ng/mL) in 48%, and adequate (>30 ng/mL) in 30%. We compared different clinical and laboratory variables in 3 different vitamin D groups but found no difference in cardio-renal risk factors (P = Not Significant). Similarly, no correlation was seen between vitamin D levels and other clinical and metabolic factors. According to conventional cutoffs, the vitamin D (25[OH] D) level is inadequate in 70% of renal allograft recipients. The hormone level has no apparent association with renal function and major cardio-metabolic risk factors. [ABSTRACT FROM AUTHOR]

Heat stress (HS) impedes cattle behavior and performance and is an animal comfort and welfare issue. The objective of this study was to characterize the time budget and circadian rhythm of lying behavior in dairy cows during HS and to assess the effect of dietary supplementation of vitamin D 3 and Ca. Twelve multiparous Holstein cows (42.2 ± 5.6 kg milk/d; 83 ± 27 d in milk) housed in tiestalls were used in a split-plot design with the concentration of dietary vitamin E and Se as main plots (LESe: 11.1 IU/kg and 0.55 mg/kg, and HESe: 223 IU/kg and 1.8 mg/kg, respectively). Within each plot cows were randomly assigned to (1) HS with low concentrations of vitamin D 3 and Ca (HS, 1,012 IU/kg and 0.73%, respectively), (2) HS with high concentrations of vitamin D 3 and Ca (HS+D 3 /Ca; 3,764 IU/kg and 0.97%, respectively), or (3) thermoneutral pair-fed (TNPF) with low concentrations of vitamin D 3 and Ca (1,012 IU/kg and 0.73%, respectively) in a Latin square design with 14-d periods and 7-d washouts. Lying behavior was measured with HOBO Loggers in 15-min intervals. Overall, cows in HS spent less time lying per day relative to TNPF from d 7 to 14. Daily lying time was positively correlated with milk yield, energy-corrected milk yield, and feed efficiency, and was negatively correlated with rectal temperature, respiratory rate, fecal calprotectin, tumor necrosis factor-α, and C-reactive protein. A treatment by time interaction was observed for lying behavior: the time spent lying was lesser for cows in HS than in TNPF in the early morning (0000–0600 h) and in the night (1800–2400 h). The circadian rhythm of lying behavior was characterized by fitting a cosine function of time into linear mixed model. Daily rhythmicity of lying was detected for cows in TNPF and HS+D 3 /Ca, whereas only a tendency in HS cows was observed. Cows in TNPF had the highest mesor (the average level of diurnal fluctuations; 34.2 min/h) and amplitude (the distance between the peak and mesor; 17.9 min/h). Both the mesor and amplitude were higher in HS+D 3 /Ca relative to HS (26.6 vs. 25.2 min/h and 3.91 min/h vs. 2.18 min/h, respectively). The acrophase (time of the peak) of lying time in TNPF, HS, and HS+D 3 /Ca were 0028, 0152, and 0054 h, respectively. Lastly, a continuous increase in daily lying time in TNPF was observed during the first 4 d of the experimental period in which DMI was gradually restricted, suggesting that intake restrictions may shift feeding behavior and introduce biases in the behavior of animals. In conclusion, lying behavior was compromised in dairy cows under HS, characterizing reduced daily lying time and disrupted circadian rhythms, and the compromised lying behavior can be partially restored by supplementation of vitamin D 3 and Ca. Further research may be required for a more suitable model to study behavior of cows under HS. [ABSTRACT FROM AUTHOR]

Deregulation of mitochondria activity is one of the hallmarks of cancerogenesis and an important target for cancer therapy. Therefore, we compared the impact of an active form of vitamin D 3 (1,25(OH) 2 D 3) on mitochondrial morphology and bioenergetics in human squamous cell carcinoma (A431) and immortalized HaCaT keratinocytes. It was shown that mitochondria of cancerous A431 cells differ from that observed in HaCaT keratinocytes in terms of network, morphology, bioenergetics, glycolysis, and mitochondrial DNA copy number, while treatment of A431 with 1,25(OH) 2 D 3 partially eliminates these differences. Furthermore, mitochondrial membrane potential, basal respiration, and mitochondrial reactive oxygen species production were decreased in A431 cells treated with 1,25(OH) 2 D 3. Additionally, the expression and protein level of mitophagy marker PINK1 was significantly increased in A431 1,25(OH) 2 D 3 treated cells, but not observed in treated HaCaT cells. Knockout of VDR (vitamin D receptor) or RXRA (binding partner retinoid X receptor) partially altered mitochondrial morphology and function as well as mitochondrial response to 1,25(OH) 2 D 3. Transcriptomic analysis on A431 cells treated with 1,25(OH) 2 D 3 revealed modulation of expression of several mitochondrial-related genes involved in mitochondrial depolarization, mitochondrial protein translation (i.e. LYRM9 , MARS2), and fusion-fission (OPA1 , FIS1 , MFN1 and 2), however, none of the genes coded by mitochondrial DNA was affected. Interestingly, in silico analyses of nuclear-encoded mitochondrial genes revealed that they are rather activated by the secondary genomic response to 1,25(OH) 2 D 3. Taken together, 1,25(OH) 2 D 3 remodels mitochondrial architecture and bioenergetics through VDR-dependent and only partially RXRA-dependent activation of the genomic pathway, thus outlining a new perspective for anticancer properties of vitamin D 3 in relation to mitochondria in squamous cell carcinoma. [Display omitted] • Mitochondrial morphology and bioenergetics is disrupted after VDR deletion. • Mitochondrial morphology and bioenergetics is partially disrupted after RXRA deletion. • VDR was not detected in mitochondria of SCC cell line A431 or HaCaT keratinocytes. • VDR knockout affects expression of genes related to mitochondrial function. • VDR knockout affects mitochondrial genome copy number but not mitochondrial gene expression. [ABSTRACT FROM AUTHOR]

Background: In hematopoietic stem cell transplant (HSCT), vitamin D deficiency has been variably associated with increased complications, primarily graft versus host disease (GvHD), with a potential impact on survival. Results from various studies however, have not been consistent. This analysis was conducted to study the impact of peri-transplant vitamin D levels on transplant outcomes in patients with acute leukemia (AL) who underwent HLA matched (related/unrelated) HSCT. Methods: This was a single center retrospective study. Patients of AL including Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML) or Mixed Phenotypic Acute Leukemia (MPAL) who underwent fully matched or 9/10 transplants (related/unrelated) between 2008 and 2019 were included. Vitamin D deficiency was defined as serum 25-hydroxy vitamin D3 levels <20 ng/ml. Those with deficiency received replacement with oral vitamin D at a dose of 60,000 IU weekly for 8 weeks followed by maintenance with daily vitamin D (800 IU/day). Vitamin D levels were repeated at 4 months from start of replacement For patients who received correction, repeat levels >20 ng/ml were considered replete. Based on vitamin D levels in the peri-transplant period (within 120 days of transplant), patients were categorised as either vitamin D replete (> 20 ng/ml) or deplete (< 20 ng/ml). Peri-transplant vitamin D status was correlated with transplant outcomes. Results: Of the 133 patients included. 31 were deplete (median vitamin D 15.0 ng/ml) and 102 were replete (median vitamin D 34 ng/ml) at time of transplant. Both groups were matched for age, diagnosis, EBMT score and disease risk index (DRI). There were no differences in time to neutrophil or platelet engraftment, CMV reactivation, acute GvHD (aGvllD) or chronic GvHD (cGvHD) between the two groups. Relapse rate. Progression Free Survival (PFS) and Overall Survival (OS) were also comparable between the 2 groups. Conclusion: The incidence of vitamin D deficiency was high in our patient cohort. Patients who were vitamin D deficient at the time of transplant did not have inferior outcomes, suggesting a limited role of vitamin D in influencing transplant outcomes. [ABSTRACT FROM AUTHOR]

We investigated the effects of environment calcium challenge and 1α,25(OH) 2 vitamin D 3 (1,25-D 3) on 45Ca2+ influx in the intestine of zebrafish (ZF). In vitro 45Ca2+ influx was analyzed using intestines from fed and fasted fish. ZF were held in water containing Ca2+ (0.02, 0.7, 2.0 mM) to analyze the ex vivo 45Ca2+ influx in the intestine and for histology. Intestines from fish held in water with Ca2+ were incubated ex vivo to characterize ion channels, receptors, ATPases and ion exchangers that orchestrate 45Ca2+ influx. For in vitro studies, intestines were incubated with antagonists/agonist or inhibitors to study the mechanism of 1,25-D 3 on 45Ca2+ influx. Fasted ZF reached a plateau for 45Ca2+ influx at 30 min. In vivo fish at high Ca2+ stimulated ex vivo 45Ca2+ influx and increased the height of intestinal villi in low calcium. In the normal calcium, 45Ca2+ influx was maintained by the reverse-mode Na+/Ca2+ (NCX) activation, Na+/K+-ATPase pump and sarco/endoplasmic reticulum calcium ATPase (SERCA) pump. However, Ca2+ hyperosmolarity is supported by L-type voltage-dependent calcium channels (L-VDCC), transient receptor potential vanilloid subfamily 1 (TRPV1) and Na+/K+-ATPase activity. The calcium challenge causes morphological alteration and changes the ion type-channels involved in the intestine to maintain hyperosmolarity. 1,25-D 3 stimulates Ca2+ influx in normal osmolarity coordinated by L-VDCC activation and SERCA inhibition to keeps high intracellular calcium in intestine. Our data showed that the adult ZF regulates the calcium challenge (per se osmolarity), independently of the hormonal regulation to maintain the calcium balance through the intestine to support ionic adaptation. • In vivo fish exposure to high Ca2+ stimulates ex vivo 45Ca2+ influx. • Calcium challenge alter ion channel types for homeostasis on intestine. • 1,25-D 3 coordinates Ca2+ influx and from stores to keeps intestinal hyperosmolarity. • In vivo exposure to low Ca2+ increase the height of intestinal villi. [ABSTRACT FROM AUTHOR]

Background: Calcimimetic therapy with etelcalcetide (ETEL) has been shown to attenuate the advancement of left ventricular (LV) hypertrophy in hemodialysis patients measured by cardiac magnetic resonance (CMR). The aim of the study was to evaluate whether this effect is accompanied by alterations in LV function and myocardial composition. Methods: This was a post-hoc analysis of a randomized-controlled trial of ETEL versus Alfacalcidol (ALFA) in 62 hemodialysis patients. LV function was assessed using LV ejection fraction (LVEF) and LV global longitudinal strain (GLS) on feature-tracking (FT) CMR. Myocardial tissue characteristics were analyzed using parametric T1 and T2 mapping. Results: Of the total study cohort (n = 62), 48 subjects completed both CMR scans with sufficient quality for FT analysis. In the one-year follow-up, LV GLS deteriorated in the ALFA group, whereas the ETEL group remained stable (LV GLS change: + 2.6 ± 4.6 versus + 0.3 ± 3.8; p = 0.045 when adjusting for randomization factors and baseline LV GLS). We did not observe a difference in the change of LVEF between the two groups (p = 0.513). The impact of ETEL treatment on LV GLS over time remained significant after additional adjustment for the change in LV mass during the study period. ETEL treatment did not significantly affect other CMR parameters. There were no changes in myocardial composition between treatment groups (T1 time change: + 15 ± 42 versus + 10 ± 50; p = 0.411; T2 time change: − 0.13 ± 2.45 versus − 0.70 ± 2.43; p = 0.652). Conclusions: In patients undergoing hemodialysis, treatment with ETEL was protective against deterioration of LV longitudinal function, as evaluated through FT CMR, when compared to the control therapy of ALFA. This effect was not mediated by the change in LV mass. Trial registration URL: https://clinicaltrials.gov/ct2/show/NCT03182699. Unique identifier: NCT03182699. [ABSTRACT FROM AUTHOR]

Women who experience antenatal depression may be at increased risk of adverse birth outcomes. Few studies have examined this association among women living with HIV (WHIV). We conducted a prospective cohort study of 2298 pregnant WHIV on antiretroviral therapy (ART) in Dar es Salaam, Tanzania, who were participants in a randomized trial of vitamin D 3 supplementation. Depressive symptoms were assessed at 12–27 weeks gestation using the Hopkins Symptoms Checklist (HSCL-25). Generalized estimating equations to account for twins were used to assess the relative risks of adverse birth outcomes. Approximately 67 % of the women in our study population reported symptoms consistent with depression. We observed a 4.0 % prevalence of stillbirth and a 25.1 % prevalence of preterm birth. We found that low social support, higher education, and more recent initiation of ART were associated with a greater risk of antenatal depression. There was no association of antenatal depression with risk of fetal loss, stillbirth, low birth weight, birth weight, preterm birth, gestational age at delivery, or small-for-gestational age. Depression was self-reported and only collected at one timepoint in pregnancy. Our findings may not be generalizable to all WHIV. Our findings illustrate the high risk of both depression and adverse birth outcomes among WHIV and underscore the need for interventions to improve their mental health and the health of their infants; however, the relationship between depression and birth outcomes remains unclear. Further research on this topic is merited, particularly examining the chronicity and timing of depression in pregnancy. • Two out of three women had symptoms consistent with major depressive disorder. • More recent initiation of ART associated with greater risk of antenatal depression • No association of antenatal depression with adverse birth outcomes • Magnitude of the association not modified by the timing of ART initiation [ABSTRACT FROM AUTHOR]

• We did a phase 3 randomized placebo-controlled trial of vitamin D to prevent tuberculosis (TB) infection in 1682 QuantiFERON-TB Plus-negative children in Cape Town, South Africa. • In total, 63.2% of participants had serum 25-hydroxyvitamin D (25[OH]D) concentrations <75 nmol/l at baseline. • The intervention was weekly oral administration of 10,000 IU vitamin D 3 for 3 years. • This was effective in elevating serum 25(OH)D concentrations in participants randomized to the intervention arm of the trial. • The intervention did not influence the risk of QuantiFERON-TB Plus conversion. To determine whether weekly oral supplementation with 10,000 IU vitamin D 3 for 3 years reduces the risk of sensitization to M. tuberculosis in South African schoolchildren aged 6-11 years with negative QuantiFERON-tuberculosis (TB) Gold Plus (QFT-Plus) assay results at baseline. We conducted a phase 3 randomized placebo-controlled trial in 1682 children attending 23 primary schools in Cape Town. The primary outcome was a positive end-trial QFT-Plus result, analyzed using a mixed effects logistic regression model with the school of attendance included as a random effect. 829 vs. 853 QFT-Plus-negative children were randomized to receive vitamin D 3 vs. placebo, respectively. Mean end-study 25(OH)D concentrations in participants randomized to vitamin D vs. placebo were 104.3 vs 64.7 nmol/l, respectively (95% confidence interval for difference, 37.6 to 41.9 nmol/l). A total of 76/667 (11.4%) participants allocated to vitamin D vs. 89/687 (13.0%) participants allocated to placebo tested QFT-Plus positive at 3-year follow-up (adjusted odds ratio 0.86, 95% confidence interval 0.62-1.19, P = 0.35). Weekly oral supplementation with 10,000 IU vitamin D 3 for 3 years elevated serum 25(OH)D concentrations among QFT-Plus-negative Cape Town schoolchildren but did not reduce their risk of QFT-Plus conversion. [ABSTRACT FROM AUTHOR]

• Vitamin D3 partially ameliorates behavioral abnormalities of LPS-stimulated mice. • Vitamin D3 inhibits LPS-induced microglial activation and neuroinflammation. • Vitamin D3 upregulates microglial Sirt6 and reduce H3K9ac in vivo and in vitro. • Vitamin D3 promotes Sirt6 and attenuates inflammatory microglial changes. Vitamin D3 may suppress microglial activation and neuroinflammation, which play a central role in the pathophysiology of many neurological disorders. Sirt6 can remove histone 3 lysine 9 acetylation (H3K9ac) to repress expression of pathological genes and produce anti-inflammatory effects. However, whether vitamin D3 upregulates microglial Sirt6 to exert its protective effects against microglial activation and neuroinflammation is unclear. The effects of lower, normal, and higher dosages (1, 10 and 100 μg/kg/day) of vitamin D3 on behavioral and neuromorphological changes, brain inflammatory factors, Sirt6 and H3K9ac levels, and microglial Sirt6 distribution in hippocampus were evaluated in lipopolysaccharide (LPS)-stimulated mice. In addition, the effects of vitamin D3 on inflammatory factors, reactive oxygen species, Sirt6, and H3K9ac were confirmed in LPS-stimulated BV-2 cells. We verified that vitamin D3 ameliorated the impaired sociability of LPS-stimulated mice by three-chamber test. In addition, vitamin D3 upregulated brain Sirt6 generation, reduced H3K9ac levels and inhibited generation of brain inflammatory factors. Moreover, vitamin D3 promoted microglial Sirt6 distribution and attenuated microglia displaying an activated morphology in the hippocampus of LPS-stimulated mice. Similarly, vitamin D3 upregulated Sirt6 generation and intensity, reduced H3K9ac levels, and inhibited the inflammatory activation of LPS-stimulated BV-2 cells. In conclusion, vitamin D3 may upregulate microglial Sirt6 to reduce H3K9ac and inhibit microglial activation, thereby antagonizing neuroinflammation. [ABSTRACT FROM AUTHOR]

This study: 1) examined cross-sectional and longitudinal relations of serum brain-derived neurotrophic factor (BDNF) to late-life depression (LLD); 2) tested effects of vitamin D3 and omega-3s on change in BDNF; 3) explored modifying or mediating roles of BDNF on effects of vitamin D3 and omega-3s for LLD. We selected 400 adults from a completed trial of vitamin D3 and omega-3 supplements for LLD prevention. BDNF was measured using an enzyme-linked immunosorbent assay. We administered semi-structured diagnostic interviews and Patient Health Questionnaire [PHQ]-9 to ascertain outcomes at baseline (depression caseness vs. non-caseness; PHQ-9) and at 2-year follow-up among baseline non-depressed individuals (incident vs. no incident MDD; change in PHQ-9). At baseline, while there were no significant differences in mean serum BDNF comparing depression cases and non-cases, being in the lowest vs. highest serum BDNF quartile was significantly associated with worse depressive symptoms. There were no significant longitudinal associations between serum BDNF and LLD. Neither supplement significantly affected change in BDNF; serum BDNF did not appear to modify or mediate treatment effects on LLD. In conclusion, we observed significant cross-sectional but not longitudinal associations between serum BDNF levels and LLD. Vitamin D3 or omega-3s did not alter serum BDNF over 2 years. • There is an urgent need to identify biomarkers for major depressive disorder. • Low serum BDNF has promise as a biomarker for major depressive disorder. • Low serum BDNF was associated with worse depressive symptoms at baseline. • Serum BDNF did not predict the new onset of major depressive disorder. • Vitamin D and omega-3 supplements did not alter serum BDNF levels over 2 years. [ABSTRACT FROM AUTHOR]

Twelve multiparous Holstein cows (42.2 ± 5.6 kg of milk/d; 83 ± 27 d in milk) were used in a split-plot design testing the effects of mineral and vitamin supplementation on the time course of animal performance, metabolism, and inflammation markers during heat stress. The main plot was the average concentrations of dietary vitamin E and Se (adequate: 11.1 IU/kg of vitamin E and 0.55 mg/kg of Se, and high: 223 IU/kg of vitamin E and 1.8 mg/kg of Se, respectively). Within each plot, cows were randomly assigned to (1) heat stress (HS) with adequate concentrations of vitamin D 3 and Ca (1,012 IU/kg and 0.73%, respectively), (2) HS with high concentrations of vitamin D 3 and Ca (HS+D 3 /Ca; 3,764 IU/kg and 0.97%, respectively), or (3) pair-feeding (PF) in thermoneutrality with adequate concentrations of vitamin D 3 and Ca (1,012 IU/kg and 0.73% Ca) in a Latin square design with 14-d periods and 7-d washouts. The highest rectal temperature was recorded at 1700 h for HS (39.4°C; mean of d 1 to 14), being 1.2 and 0.8°C greater than for PF and HS+D 3 /Ca, respectively. Respiratory rate and water intake were higher in HS (73 breaths/min and 115 L/d, respectively) relative to PF (28 breaths/min and 76 L/d). Heat stress decreased dry matter intake progressively, reaching a nadir on d 5 to 7 (33% reduction) and was not different between treatments. Milk yield decreased progressively in all treatments, but remained greater in PF relative to HS from d 3 to 14 (10%), whereas HS and HS+D 3 /Ca were not different. Milk fat, protein, and lactose concentrations and yields were lower in HS relative to PF from d 3 to 14, but not different between HS and HS+D 3 /Ca. Relative to PF, preprandial insulin concentrations were increased in HS, whereas plasma nonesterified fatty acids were decreased on d 7 and 14. Plasma lipopolysaccharide-binding protein concentrations increased in HS cows on d 7 and 14, respectively, relative to PF, whereas they were reduced in HS + D 3 /Ca on d 14. Plasma C-reactive protein, tumor necrosis factor-α, and fecal calprotectin were increased in HS relative to both PF and HS+D 3 /Ca on d 7 and 14. Rectal temperature was positively associated with plasma lipopolysaccharide-binding protein (r = 0.72), tumor necrosis factor-α (r = 0.74), C-reactive protein (r = 0.87), and with milk somatic cells (r = 0.75). Plasma 8-hydroxy-2-deoxyguanosine concentrations presented a 3-way interaction, where 8-hydroxy-2-deoxyguanosine was lower in HS than in PF on d 7 and 14, and lower in HS+D 3 /Ca relative to HS on d 14 in the adequate vitamin E and Se treatment, but no effects were observed in the high vitamin E and Se group. Plasma superoxide dismutase concentrations increased over time, and were higher in HS relative to PF on d 14, whereas HS+D 3 /Ca was similar to HS. Heat stress markedly reduced milk production and milk components while increasing markers of leaky gut and inflammation. In contrast, vitamin D 3 and Ca supplementation reduced hyperthermia (d 7–14), markers of leaky gut, and inflammation independent of dietary concentrations of vitamin E and Se. [ABSTRACT FROM AUTHOR]

Parathyroid gland lesions in anurans are infrequently reported and most often occur secondary to experimental interventions. Husbandry-related parathyroid changes have not been documented in this order of Amphibia. Three American bullfrogs (Lithobates catesbeianus) living in a captive colony were euthanized due to clinical concern for metabolic bone disease secondary to lack of consistent dietary supplementation with vitamin D 3. Necropsy revealed cystic dilation and variable proliferation of unidentified structures within the cranial coelom corresponding to the anatomical location of anuran parathyroid glands. Histologically, the structures consisted of sheets and whorls of elongated cells. Immunohistochemistry for pan-cytokeratin revealed strong cytoplasmic staining and Grimelius staining identified neuroendocrine granules in the elongated cells of these structures, supportive of a parathyroid origin. [ABSTRACT FROM AUTHOR]

The identification of factors associated with 25-hydroxycholecalciferol (25(OH)D) concentration can help suggest more specific interventions for older adults. In this cross-sectional study of older adults from southern Brazil, we hypothesized that some sociodemographic, behavioral, and health factors positively or negatively influence the 25(OH)D concentration in this population. This analysis was performed using data from the second wave of the EpiFloripa Aging Cohort Study (2013-2015). Serum 25(OH)D levels were classified according to the guidelines of the Endocrine Society. Multinomial logistic regression was performed to evaluate the relative risks of sociodemographic, behavioral, and health factors in each 25(OH)D category. A total of 574 older adults (aged 63-93 years) participated in this study. The prevalence of insufficiency (21-29 ng/mL) was 43.7% and that of deficiency (≤20 ng/mL) was 23.5%. In the adjusted analysis, female sex, higher levels of low-density lipoprotein cholesterol (LDL-C ≥160 mg/dL), obesity by adiposity (body fat percentage [%fat], male ≥31%; female ≥43%), and body mass index (BMI, >30 kg/m2) presented higher relative risks for insufficiency than for sufficiency. For those with deficiency, the associated factors were female sex, disability in 4 or more activities of daily living (ADLs), LDL-C ≥100 mg/dL, and obesity by %fat and BMI. A protective factor against insufficiency and deficiency was active leisure-time physical activity (PA, ≥150 min/week). Our results demonstrated that being female and having modifiable factors, such as high levels of LDL-C, obesity, and disability on ADLs, were negatively associated with hypovitaminosis D. On the other hand, leisure-time PA was positively associated with adequate serum vitamin D concentration. Multinomial analysis revealed the determinants of vitamin D. The risk factors for insufficiency (21-29 ng/mL) were being female, obesity by both adiposity (body fat percentage [%Fat]: male ≥ 31%; female ≥ 43%) and BMI (>30 kg/m2), and high levels of LDL-C (≥160 mg/dL). Risk factors for deficiency (≤20 ng/mL) were being female, obesity by both adiposity (%Fat) and BMI, LDL-C (>100 mg/dL), and disability in ADLs (≥4 activities). Regarding the protective factor, being active in leisure-time physical activity (≥150 minutes/wk) presented less risk of both insufficiency and deficiency. Abbreviations: 25(OH)D, 25-hydroxyvitamin D; ADL, activities of daily life; BMI, body mass index; F, female; LDL-C, low-density lipoprotein cholesterol; M, male. [Display omitted] [ABSTRACT FROM AUTHOR]

What is the effect of vitamin D3 (1,25(OH) 2 D 3) on proliferation, cell cycle and apoptosis of endometrial stromal cells (ESC) in endometriotic patients? ESC isolated from 10 women with endometriosis and 10 healthy controls were treated with 1,25(OH) 2 D 3. The proliferation of control endometrial stromal cells (CESC), eutopic endometrial stromal cells (EuESC) and ectopic endometrial stromal cells (EESC) was analysed 72 h after the treatment using methyl thiazolyl tetrazolium assay. Propidium iodide staining and flow cytometry were used to determine the cell cycle distribution in ESC. Annexin V/propidium iodide double staining was used to evaluate apoptosis in ESC. In the presence of oestrogen, 1,25(OH) 2 D 3 treatment inhibited the proliferation of ESC from all three origins (P = 0.009 for CESC, P = 0.005 for EuESC and P < 0.001 for EESC). The percentage of S phase cells in EESC was higher than in EuESC and CESC (P = 0.002 and P = 0.001, respectively). The percentage of S phase cells in EuESC was higher than in CESC (P = 0.005). The percentage of G1 phase cells in EESC was lower than that of EuESC and CESC (P = 0.003 and P = 0.002, respectively) and the percentage of G1 phase cells in EuESC was lower than that of CESC (P = 0.007). Moreover, 1,25(OH) 2 D 3 inhibited cell cycle regardless of cell type (P = 0.002 in EESC, P = 0.001 in EuESC and P = 0.014 in CESC), but in the absence of oestrogen, inhibited cell cycle only in EuESC (P = 0.012). Although 1,25(OH) 2 D 3 increased apoptotic and necrotic cells and decreased live cells in the EuESC and EESC, it did not affect apoptosis in CESC and only increased necrotic cells. These findings indicate that 1,25(OH) 2 D 3 potentially has a growth-inhibiting and pro-apoptotic effect on ESC from endometriotic patients. [ABSTRACT FROM AUTHOR]

Observational studies suggest that higher serum 25-hydroxy vitamin D (25(OH)D) concentration may be associated with lower risk of cataract. However, no randomized controlled trials have assessed the effect of vitamin D supplementation on the incidence of cataract. We aimed to assess whether vitamin D supplementation reduces the incidence of cataract surgery. We conducted an ancillary study of the D-Health Trial, a randomized, double-masked, placebo-controlled trial of monthly vitamin D conducted from 2014 through 2020 within the Australian general population. We invited 421 207 men and women 60 to 84 years of age to participate; including an additional 1896 volunteers, 40 824 expressed interest. Those with hypercalcemia, hyperparathyroidism, kidney stones, osteomalacia, or sarcoidosis or those who were taking more than 500 international units (IU) supplemental vitamin D per day were excluded. A total of 21 315 were randomized, and 1390 participants did not fulfil the eligibility criteria for this analysis (linked data available, no cataract within first 6 months), leaving 19 925 included. The median follow-up was 5 years. Participants took 60 000 IU of vitamin D 3 (n = 10 662) or placebo (n = 10 653) orally once per month for a maximum of 5 years. The primary outcome for this analysis was the first surgical treatment for cataract, ascertained through linkage to universal health insurance records and hospital data. Among 19 925 participants eligible for this analysis (mean age, 69.3 years; 46% women) 3668 participants (18.4%) underwent cataract surgery during follow-up (vitamin D: n = 1841 [18.5%]; placebo: n = 1827 [18.3%]). The incidence of cataract surgery was similar between the two groups (incidence rate, 41.6 and 41.1 per 1000 person-years in the vitamin D and placebo groups, respectively; hazard ratio, 1.02; 95% confidence interval, 0.95–1.09). In prespecified subgroup analyses, the effect of vitamin D supplementation on the incidence of cataract surgery was not modified by age, sex, body mass index, predicted serum 25(OH)D concentration, or ambient ultraviolet radiation. Routinely supplementing older adults who live in an area with a low prevalence of vitamin D deficiency with high-dose vitamin D is unlikely to reduce the need for cataract surgery. Proprietary or commercial disclosure may be found after the references. [ABSTRACT FROM AUTHOR]

Osteoporosis may result from risk factors such as smoking, alcohol, low body mass index, less physical exercise, and dietary calcium deficiency. The risk of osteoporosis fractures can be reduced with lifestyle changes, which include diet, exercise, and preventing falls. The present study is an effort to measure the burden of risk factors of osteoporosis in adult male soldiers in the Armed Forces. The present study was a cross-sectional study among serving soldiers in South-Western part of India, and 400 participants consented to be included in the study. After obtaining informed consent, the questionnaire was distributed. Venous blood samples were collected to measure serum calcium, phosphorus, vitamin D, and parathyroid hormone (PTH). The prevalence of vitamin D3 severe deficiency (<10 ng/mL) was 38.5%, and the prevalence of vitamin D3 deficiency (10–19 ng/mL) was 33%. Low serum calcium (<8.4 mg/dL) and serum phosphorus (<2.5 mg/dL) were found among 19.5% and 11.5%, respectively, whereas a raised serum PTH level (>66.5 pg/mL) was seen in 5.5% of the participants. A statistically significant association was found between consumption of milk and milk products and levels of calcium. With a cutoff value of 20 ng/mL for vitamin D3 deficiency, a statistically significant association was found for consumption of fish, physical activity, and sun exposure. A remarkably large percentage of otherwise normal healthy soldiers have deficiency or insufficiency of vitamin D and might be prone to osteoporosis. Despite significant advances in our understanding and management options for male osteoporosis, there still remain important gaps in knowledge which needs to be looked into. [ABSTRACT FROM AUTHOR]

In spite of bone's healing capacity, critical-size bone defect regeneration and peri -implant osseointegration are challenging. Tissue engineering provides better outcomes, but requires expensive adjuncts like stem cells, growth factors and bone morphogenic proteins. Vitamin D (Vit.D) regulates calcium and phosphorus metabolism, and helps maintain bone health. Vit.D supplements in deficient patients, accentuates bone healing and regeneration. Therefore the aim of this systematic review was to evaluate the role of adjunctive Vit.D on bone defect regeneration. Comprehensive database search of indexed literature, published between January 1990 and June 2022, was carried out. English language articles fulfilling inclusion criteria (clinical/in vivo studies evaluating bone regeneration including osseointegration and in vitro studies assessing osteogenic differentiation, with adjunct Vit.D) were identified and screened. Database search identified 384 titles. After sequential title, abstract and full-text screening, 23 studies (in vitro – 9/in vivo – 14) were selected for review. Vit.D as an adjunct with stem cells and osteoblasts resulted in enhanced osteogenic differentiation and upregulation of genes coding for bone matrix proteins and alkaline phosphatase. When used in vivo, Vit.D resulted in early and increased new bone formation and mineralization within osseous defects, and better bone implant contact and osseointegration, around implants. Adjunct Vit.D in animals with induced systemic illnesses resulted in bone defect regeneration and osseointegration comparable to healthy animals. While systemic and local administration of Vit.D resulted in enhanced bone defect healing, outcomes were superior with systemic route. Based on this review, adjunct Vit.D enhances bone defect regeneration and osseointegration. In vitro application of Vit.D to stem cells and osteoblasts enhances osteogenic differentiation. Vit.D is a potentially non-invasive and inexpensive adjunct for clinical bone regeneration and osseointegration. Long term clinical trials are recommended to establish protocols relating to type, dosage, frequency, duration and route of administration. [ABSTRACT FROM AUTHOR]

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 m M), 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 m M serum Ca; CHOL = 1.70 vs. CAL = 1.78 ± 0.02 m M 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. [ABSTRACT FROM AUTHOR]

The objectives were to test the effects of dietary vitamin D 3 [cholecalciferol (CHOL)] compared with 25-hydroxyvitamin D 3 [calcidiol (CAL)] on vitamin D status and response to an endotoxin challenge. Forty-five Holstein bull calves (5 ± 2 d of age) were blocked into weekly cohorts, fed a basal diet that provided 0.25 µg/kg body weight (BW) CHOL, and assigned randomly to 1 of 5 treatments: control [(CON) no additional vitamin D], 1.5 µg/kg BW CHOL (CHOL1.5), 3 µg/kg BW CHOL (CHOL3), 1.5 µg/kg BW CAL (CAL1.5), or 3 µg/kg BW CAL (CAL3). Calves were fed milk replacer until weaning at 56 d of age and had ad libitum access to water and starter grain throughout the experiment. Treatments were added daily to the diet of milk replacer until weaning and starter grain after weaning. Measures of growth, dry matter intake, and serum concentrations of vitamin D, Ca, Mg, and P were collected from 0 to 91 d of the experiment. At 91 d of the experiment, calves received an intravenous injection of 0.1 µg/kg BW lipopolysaccharide (LPS). Clinical and physiological responses were measured from 0 to 72 h relative to LPS injection. Data were analyzed with mixed models that included fixed effects of treatment and time, and random effect of block. Orthogonal contrasts evaluated the effects of (1) source (CAL vs. CHOL), (2) dose (1.5 vs. 3.0 µg/kg BW), (3) interaction between source and dose, and (4) supplementation (CON vs. all other treatments) of vitamin D. From 21 to 91 d of the experiment, mean BW of supplemented calves was less compared with CON calves, but the effect was predominantly a result of the CHOL calves, which tended to weigh less than the CAL calves. Supplementing vitamin D increased concentrations of 25-hydroxyvitamin D in serum compared with CON, but the increment from increasing the dose from 1.5 to 3.0 µg/kg BW was greater for CAL compared with CHOL (CON = 18.9, CHOL = 24.7 and 29.6, CAL = 35.6 and 65.7 ± 3.2 ng/mL, respectively). Feeding CAL also increased serum Ca and P compared with CHOL. An interaction between source and dose of treatment was observed for rectal temperature and derivatives of reactive metabolites after LPS challenge because calves receiving CHOL3 and CAL1.5 had lower rectal temperatures and plasma derivatives of reactive metabolites compared with calves receiving CHOL1.5 and CAL3. Supplementing vitamin D increased plasma P concentrations post-LPS challenge compared with CON, but plasma concentrations of Ca, Mg, fatty acids, glucose, β-hydroxybutyrate, haptoglobin, tumor necrosis factor-α, and antioxidant potential did not differ among treatments post-LPS challenge. Last, supplementing vitamin D increased granulocytes as a percentage of blood leukocytes post-LPS challenge compared with CON. Supplementing CAL as a source of vitamin D to dairy calves was more effective at increasing serum 25-hydroxyvitamin D, Ca, and P concentrations compared with feeding CHOL. Supplemental source and dose of vitamin D also influenced responses to the LPS challenge. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In this study, a recombinant E. coli strain with the multienzyme system of the vitamin D 3 hydroxylase CYP105A1, the electron transport respiratory chain Fdx-FdR and the key enzymes (Glk-Zwf) in the cyclic regeneration of the coenzyme NADPH was constructed for the efficient hydroxylation of VD 3 to prepare physiologically active 25(OH)VD 3 and 1α, 25(OH) 2 VD 3. The constructed recombinant E. coli strain with a multienzyme system was demonstrated to possess hydroxylation capability for VD 3. The hydroxylation reaction of VD 3 was carried out under optimal conditions. The highest concentration of the intermediate product 25(OH)VD 3 was 58.92 mg/L with a yield of 11.31 %. The highest concentration of the final product 1α, 25(OH) 2 VD 3 was 90.23 mg/L with a yield of 16.7 %. Ultimately, 395.92 mg/L 25(OH)VD 3 and 272.21 mg/L 1α, 25(OH) 2 VD 3 were produced by further substrate fed-batch experiments. This study contributes to the preparation of physiologically active 25(OH)VD 3 and 1α, 25(OH) 2 VD 3 by whole-cell biocatalysis of VD 3 via the constructed recombinant strain. [Display omitted] • The coenzyme NADPH regeneration system in E. coli was established. • The recombinant E. coli with a multienzyme system was constructed. • The constructed E. coli could catalyze vitamin D 3 to its active forms. • Fermentation conditions of the recombinant E. coli were explored. • This study contributes to the preparation of physiologically active vitamin D 3. [ABSTRACT FROM AUTHOR]

The role of gut microbiota and their sex-specific differences in colorectal cancer remain to be explored. In the current issue of Cancer Cell , Li et al. discovered that estrogen facilitates the colonization of Carnobacterium maltaromaticum in the mouse gut and exerts its anti-colorectal cancer effects by increasing the production of vitamin D3. [ABSTRACT FROM AUTHOR]

• In hemodialysis patients, measuring 25-hydroxyvitamin D levels is recommended. • 25-hydroxyvitamin D levels increased with native vitamin D therapy. • 1,25-dihydroxyvitamin D concentrations are not associated with active vitamin D. In hemodialysis patients, monitoring 25-hydroxyvitamin D (25(OH)D) levels is recommended. It is however unclear if monitoring 1,25-dihydroxyvitamin D (1,25(OH) 2 D) levels is interesting. We repeatedly measured 1,25(OH) 2 D (DiaSorin Liaison analyser) and 25(OH)D (LCMS/MS) concentrations in patients newly treated by active or native vitamin D to study the impact of such treatments on serum concentrations. Ten patients were included in the native and 12 in the active vitamin D group. In the native group, a significant increase was observed between the baseline and the last 25(OH)D concentrations available (21.65[17.39;25.26] versus 33.49[28.60;40.30] ng/mL, p = 0.0059). The baseline and last available 1,25(OH) 2 D concentrations were not different (12.15[4.25;15.40] versus 11.35[9.72;21.85] pg/mL, p = 0.5566). In the active group, no difference was observed between the baseline and the last 25(OH)D concentrations (51.70[42.97;63.95] versus 50.89[42.02;64.49] ng/mL, p = 0.5186). The same observation was made for 1,25 (OH) 2 D concentrations (25.65[17.05;41.85] versus 28.70[23.36;43.73] pg/mL, p = 0.6221). Using a linear mixed model, a significant change over time was only observed in 25(OH)D serum levels for patients treated by with native vitamin D. Measuring 1,25(OH)2D levels in patients newly treated by active vitamin D does not seem useful in monitoring active vitamin D therapy. [ABSTRACT FROM AUTHOR]

Despite substantial evidence that vitamin D deficiency is highly prevalent among infants born extremely preterm (≤28 weeks' of gestation), several consensus statements do not recommend vitamin D doses >400 IU/day for these infants. Safety remains a concern. The study aim was to determine safety and efficacy profiles of enteral vitamin D in Black and White infants randomized to three different vitamin D doses soon after birth. Ancillary study of a masked randomized clinical trial. Seventy-three infants born extremely preterm between 2012 and 2015 at a southern US academic neonatal unit (33' latitude) who had >90% compliance with the assigned intervention were included. Infants were randomized to receive placebo (placebo group), 200 IU/day vitamin D (200 IU group), or 800 IU/day vitamin D (800 IU group) during the first 28 days after birth. Safety outcomes included serum 25-hydroxy vitamin D (25[OH]D) and calcium concentrations. Efficacy outcomes included the predictive risk of bronchopulmonary dysplasia. Per-protocol analysis using unadjusted, repeated-measures mixed models. Mean birth weight was 815 ± 199 g. Half were male and 56% were Black. Of 58 infants with 25(OH)D measurements at birth, 40 (69%) had vitamin D deficiency (<20 ng/mL). The mean difference in 25(OH)D in nanograms per milliliter between Postnatal Day 28 and Postnatal Day 1 was +9 in the placebo group, +23 in the 200 IU group, and +62 in the 800 IU group (P < 0.0001). The increase observed in 25(OH)D was more significant among Black infants. The predictive risk of severe bronchopulmonary dysplasia in the 200 IU and 800 IU groups was lower, but this difference did not reach statistical significance. No vitamin D or calcium toxicity was observed. A vitamin D dose of 800 IU/day safely corrected vitamin D deficiency by Postnatal Day 14. [ABSTRACT FROM AUTHOR]

Background: Vitamin D status and requirements of infants of women with gestational diabetes mellitus (GDM) are unclear.Objectives: The objectives were to assess vitamin D status in infants of mothers with GDM and compare vitamin D status in response to 400 vs. 1000 IU/d vitamin D supplementation in infants born with serum 25-hydroxyvitamin D [25(OH)D] <50 nmol/L.Methods: Women with GDM delivering full-term infants (n = 98; March 2017-2019, Montreal, Canada) were surveyed for demographic and lifestyle factors. Pregnancy history was obtained from medical records. Newborn serum 25(OH)D was measured (immunoassay) and categorized as <30 (deficient) or ≥40 nmol/L (adequate). Breastfed neonates (n = 16) with serum 25(OH)D <50 nmol/L at birth were randomly assigned to 400 or 1000 IU/d of supplemental cholecalciferol (vitamin D3), and serum 25(OH)D was measured at baseline (≤1 mo) and 3, 6, and 12 mo of age. Groups were compared using a linear mixed-effects model and Tukey-Kramer post hoc tests.Results: Mean newborn serum 25(OH)D was 46.4 (95% CI: 43.9, 49.9) nmol/L, with 15.3% (95% CI: 8.2%, 22.4%) <30 nmol/L and 61.2% (95% CI: 51.6%, 70.9%) ≥40 nmol/L. During the trial, most infants were breastfed to 3 mo (400 IU/d: 87.5%; 1000 IU/d: 75.0%). Mean (± SEM) infant serum 25(OH)D was higher in the 1000-IU/d group at 3 mo (79.9 ± 5.9 vs. 111.5 ± 15.2 nmol/L; P = 0.0263), and although not different at 6-12 mo, was maintained at >50 nmol/L.Conclusions: Most infants of women with GDM had adequate vitamin D status in this study. In those born with serum 25(OH)D <50 nmol/L, vitamin D status was corrected by 3 mo of age in response to 400 or 1000 IU/d of supplemental vitamin D. Dietary guidance should continue to recommend that all women who could become pregnant take a multivitamin supplement and that breastfed infants receive 400 IU/d of supplemental vitamin D. This study and ancillary trial were registered at clinicaltrials.gov (https://www.clinicaltrials.gov/ct2/show/NCT02563015) as NCT02563015. [ABSTRACT FROM AUTHOR]

Vitamin D 3 's role in mineral homeostasis through its endocrine function, associated with the main circulating metabolite 25-hydroxyvitamin D 3 , is well characterized. However, the increasing recognition of vitamin D 3 's paracrine and autocrine functions—such as cell growth, immune function, and hormone regulation—necessitates examining vitamin D 3 levels across different tissues post-supplementation. Hence, this review explores the biodistribution of vitamin D 3 in blood and key tissues following oral supplementation in humans and animal models, highlighting the biologically active metabolite, 1,25-dihydroxyvitamin D 3 , and the primary clearance metabolite, 24,25-dihydroxyvitamin D 3. While our findings indicate significant progress in understanding how circulating metabolite levels respond to supplementation, comprehensive insight into their tissue concentrations remains limited. The gap is particularly significant during pregnancy, a period of drastically increased vitamin D 3 needs and metabolic alterations, where data remains sparse. Within the examined dosage ranges, both human and animal studies indicate that vitamin D 3 and its metabolites are retained in tissues selectively. Notably, vitamin D 3 concentrations in tissues show greater variability in response to administered doses. In contrast, its metabolites maintain a more consistent concentration range, albeit different among tissues, reflecting their tighter regulatory mechanisms following supplementation. These observations suggest that serum 25-hydroxyvitamin D 3 levels may not adequately reflect vitamin D 3 and its metabolite concentrations in different tissues. Therefore, future research should aim to generate robust human data on the tissue distribution of vitamin D 3 and its principal metabolites post-supplementation. Relating this data to clinically appropriate exposure metrics will enhance our understanding of vitamin D 3 's cellular effects and guide refinement of clinical trial methodologies. [Display omitted] • Vitamin D 3 and its key metabolites mediate a variety of important autocrine and paracrine mechanisms. • These non-endocrine functions highlight the importance of vitamin D 3 tissue stores. • Data on human tissue distribution of vitamin D 3 metabolites is lacking, particularly in the context of pregnancy. • Human and animal studies indicate dose-dependent and tissue-specific retention of vitamin D 3 and metabolites. • The blood-tissue kinetics of vitamin D 3 metabolites should be further investigated to inform supplementation strategies. [ABSTRACT FROM AUTHOR]

Investigations were performed to determine the systemic immune and small intestine (SI) morphological responses of Ross 708 broilers to the Marek's Disease vaccine (MDV) administered alone or in conjunction with the in ovo and dietary administration of calcifediol (25OHD 3). Live embryonated hatching eggs were assigned at random to 3 in ovo treatments at 18 d of incubation. Pre-specified in ovo treatments were: commercial MDV-alone-injected (50 µL) or commercial MDV containing 1.2 (MDV+25OHD 3 -1.2) or 2.4 (MDV+25OHD 3 -2.4) μg of 25OHD 3. A noninjected control treatment was also included. For the growing phase, broilers received a commercial diet containing 250 IU of vitamin D 3 /kg (control) or a commercial diet supplemented with 2,760 IU of 25OHD 3 /kg (Hy-D diet). For determination of serum IgG, nitric oxide, and α-1-acid glycoprotein (AGP) at 14 and 40 d of age (doa), blood was collected from 1 bird per pen (48 total). In the duodenum, jejunum, and ileum of the same bird, villus length (VL), crypt depth (CD), VL to CD ratio (VCR), and villus surface area were also determined. There were no significant dietary x in ovo treatment interactions for any of the variables examined. However, birds fed Hy-D diets had lower serum AGP levels at 14 doa when compared to those fed un-supplemented commercial diets. Additionally, at 40 doa, birds in the MDV+25OHD 3 -1.2 and MDV+25OHD 3 -2.4 treatments experienced a decrease in serum AGP in comparison to those belonging to the noninjected and MDV-alone treatment groups. A higher jejunal VCR was observed at 14 and 40 doa in birds that belonged to the MDV+25OHD 3 -1.2 treatment when compared to those in the noninjected and MDV-alone treatment groups, and dietary Hy-D increased the VL of the duodenum and jejunum in birds at 14 and 40 doa when compared to those fed the commercial diet. In conclusion, both dietary or in ovo administration of 25OHD 3 lowered inflammatory reactions and improved the SI morphology of broilers that were in ovo - injected with the MDV. [ABSTRACT FROM AUTHOR]

• Vitamin D administration significantly decreased thyroid follicle destruction, lymphocyte infiltration, and lowered serum levels of thyroid hormones and autoantibodies. • Vitamin D treatment effectively reduced Th17 cell frequencies while promoting the Treg cell subsets both in vivo and in vitro. • Vitamin D suppressed pro-inflammatory while facilitating anti-inflammatory cytokines production. • Vitamin D enhanced YAP expression and activated the JAK/STAT pathway. Autoimmune thyroiditis (AITD) is an organ-specific autoimmune disease. Substantial evidence suggests that Vitamin D (VitD) deficiency is closely associated with an increased risk of AITD. However, the effects of VitD3 on immune cells, especially Th17/Treg cell subsets, and the underlying molecular mechanism in AITD have not yet been investigated. An experimental autoimmune thyroiditis (EAT) mouse model was established with a high-iodine diet. After 8 weeks, thyroid injury was assessed using hematoxylin and eosin (H&E) staining. ELISA was employed to measure serum levels of thyroxine (T3 and T4), thyroid autoimmune antibodies (Tg-Ab and TPO-Ab), and inflammatory cytokines. Flow cytometry and multiplex fluorescence immunohistochemical (mIHC) assays were used to analyze Th17/Treg cell subsets. The CCK-8 and flow cytometry assays were used to determine cell viability and apoptosis. Administration of VitD3 reduced thyroid follicle destruction, decreased lymphocyte infiltration, and lowered T3, T4, Tg-Ab, and TPO-Ab serum levels in EAT mice. VitD3 treatment also reduced the frequency of Th17 cells while promoting the Treg cell subset both in the thyroid tissue and in the splenocytes cultured in vitro. Furthermore, VitD3 administration suppressed the production of inflammatory cytokines in EAT mice. VitD3 was also found to regulate Treg cells' differentiation, viability, and apoptosis. Mechanistically, we discovered that VitD3 treatment upregulated YAP expression and activated the JAK/STAT pathway. Rescue assays confirmed that depletion of YAP counteracted the effects of VitD3 on Treg cell differentiation and function. Vitamin D3 attenuates AITD by modulating Th17/Treg cell balance via regulating the YAP/JAK1/STAT1 axis. [ABSTRACT FROM AUTHOR]

Fatty acid (FA), carotenoid and vitamin contents of UK eggs were assessed for four production systems (caged (CA), free-range (FR), organic (OR) and extensive organic (EO)) as well as season. The impact of enforced housing, due to avian influenza, was also investigated. Production system did not alter vitamin D 3 , B 2 or B 9 content, but significantly influenced nutritionally desirable FA, carotenoid and vitamins A and E - concentrations decreased as production intensity increased, although for most, CA and FR did not differ significantly. Vitamin E and FA profiles for OR and EO were also similar, although carotenoids were higher in EO eggs. In contrast, FA, carotenoids, vitamins E and B 9 were consistent throughout the year, unlike vitamins A, D 3 and B 2 , which fluctuated with season; D and B 2 were higher in July than January and lower vitamin A was the only detected implication from enforced housing of FR and OR birds. • Fatty acid, carotenoid and vitamins in eggs from caged, free range and organic hens • Eggs from free range and caged systems were very similar • Nutrients in organic eggs were higher than free range and cage eggs • Vitamins A, E, B 9 , carotenoids and fatty acids were consistent throughout the year • Vitamin D and B 2 were higher in summer than winter [ABSTRACT FROM AUTHOR]

Vitamin D is a critical fat-soluble vitamin for the nervous system. Research suggests a potential link between vitamin D deficiency and attention-deficit hyperactivity disorder (ADHD), particularly in children and adolescents. The core symptoms of ADHD are associated with deficits in striatal functions, and maintaining sufficient levels of vitamin D may help prevent or alleviate ADHD symptoms. However, the molecular changes in the striatum caused by vitamin D supplementation that may contribute to the brain processes linked to ADHD symptoms remain unclear. In this study, we established a mouse model fed diets with three different dose gradients of vitamin D3 (0, 500, and 2000 IU/kg·day) from postnatal day 21 (P21) to 14 weeks of age. Striatal tissues from mice with gradient vitamin D3 intake were subjected to reduced representation bisulfite sequencing (RRBS), RNA-sequencing, and neurotransmitter profiling by liquid chromatography-mass spectrometry (LC-MS). Our findings indicate that vitamin D supplementation since childhood influenced the overall landscape of DNA methylations and the expression of many genes involved in critical neurological functions in a dose-dependent manner. Additionally, our data demonstrate how vitamin D modulated neuropeptide signaling pathways, as well as cholinergic and dopaminergic synapses in the striatum, through an orchestrated mechanism involving epigenetic and transcriptional regulations. Furthermore, we observed a synergistic effect of vitamin D on dopamine release following acute methylphenidate injection into our mouse model. In summary, this study provides mechanistic insights into how dietary vitamin D supplementation since childhood can modulate specific signal transductions among striatal cells, underscoring the importance of vitamin D supplementation for ADHD management. [Display omitted] • Establishing a mouse model by controlling daily vitamin D3 intake since childhood. • Vitamin D influences striatal DNA methylations and gene expression dose-specifically. • Vitamin D regulates striatal signal-transduction at DNA methylation and mRNA levels. • Vitamin D has a synergistic effect on dopamine release with methylphenidate. [ABSTRACT FROM AUTHOR]

In the domain of infant nutrition, optimizing the absorption of crucial nutrients such as vitamin D 3 (VD 3) is paramount. This study harnessed dynamic-high-pressure microfluidization (DHPM) on soybean protein isolate (SPI) to engineer SPI-VD 3 nanoparticles for fortifying yogurt. Characterized by notable binding affinity (K a = 0.166 × 105 L·mol−1) at 80 MPa and significant surface hydrophobicity (H 0 = 3494), these nanoparticles demonstrated promising attributes through molecular simulations. During simulated infant digestion, the 80 MPa DHPM-treated nanoparticles showcased an impressive 74.4% VD 3 bioaccessibility, delineating the pivotal roles of hydrophobicity, bioaccessibility, and micellization dynamics. Noteworthy was their traversal through the gastrointestinal tract, illuminating bile salts' crucial function in facilitating VD 3 re-encapsulation, thereby mitigating crystallization and augmenting absorption. Moreover, DHPM treatment imparted enhancements in nanoparticle integrity and hydrophobic properties, consequently amplifying VD 3 bioavailability. This investigation underscores the potential of SPI-VD 3 nanoparticles in bolstering VD 3 absorption, thereby furnishing invaluable insights for tailored infant nutrition formulations. [Display omitted] • Microfluidization enhanced SPI hydrophobicity, promoting bioactive interaction. • SPI's binding with VD 3 regulated its release and transfer to bile salt micelles. • Improved VD 3 mobility during digestion boosted its bioaccessibility. • Developed SPI-VD 3 nanoparticles broaden applications in infant foods. [ABSTRACT FROM AUTHOR]

Vitamin D 3 (25-hydroxyvitamin D 3 (VD)) and vitamin E (VE) have proven to have immunomodulatory and antioxidant functions along with capacities to improve the reproductive function in chickens. Coccidiosis in laying hens at different stages of growth has been shown to negatively affect performance, immune response, and oxidative status, thus increasing the cost of production. A study was conducted to evaluate the influence of dietary VD or VE on performance, gut health, immune response, and oxidative status of laying hens at peak production. Laying hens (23 wk-of-age, n = 225) were randomly allocated into 5 treatment groups (n = 9 hens/replicate) with 5 replicate groups each: 1) unchallenged control (UC), 2) pair-fed control (PF), 3) challenged control (CC), 4) challenged control top-dressed with 5,000 IU of 25-hydroxyvitamin D 3 (VD) per kg of diet, and 5) challenged control top-dressed with 100 IU of DL-α-tocopherol (VE). At 25 wk-of-age, hens grouped in CC, VD, and VE were challenged with mixed Eimeria spp. to induce coccidiosis. VD or VE supplemented hens did not impact bird body weight; however, egg production increased by 10.36% and 13.77%, respectively (P < 0.0001). Furthermore, the gut health of the hens was improved with either VD or VE supplementation, as indicated by lowered gut permeability and intestinal lesion scores (P < 0.05). VE significantly reduced the heterophil count (P = 0.0490) alongside numerically increasing the peripheral CD4+ and CD8+ T cells and monocyte counts (P > 0.05). Both VD or VE increased the TAC at 14 DPI compared to UC (P< 0.05). Preliminary findings suggest that dietary VD or VE supplementation has the potential to improve gut health, modulate the immune response, and increase egg production in coccidiosis-infected laying hens. [ABSTRACT FROM AUTHOR]

[Display omitted] • Particles enriched with cholecalciferol were produced. • Plasmolysis treatment increased impregnation efficiency. • S. pastorianus waste is a low-cost option for micronutrient biosorption. • Spray drying after plasmolysis provided effective vitamin D 3 protection and retention. Vitamin D 3 (cholecalciferol) plays a crucial role in various physiological processes. However, vitamin D 3 deficiency is a major public health problem affecting millions of people. Therefore, it is important to develop effective strategies that ensure the protection and stability of this important vitamin for food supplementation and fortification. This work aimed to impregnate intact and plasmolyzed Saccharomyces pastorianus brewer's yeast biomass with cholecalciferol using a biosorption process followed by spray drying to characterize the obtained material in terms of morphology, average particle size, zeta potential, moisture, water activity, FT-IR, and the stability of the encapsulated vitamin during the drying and storage process. Plasmolysis proved to be an effective method for improving the biosorption efficiency, retention during spray drying, and stability of vitamin D 3. In addition, this process promoted an increase in cell size, which favored the dispersion stability of the system, as evidenced by the zeta potential values. These results contribute to the understanding of a new method for delivering this vitamin that conforms to environmentally conscious practices. [ABSTRACT FROM AUTHOR]

Bacterial chondronecrosis with osteomyelitis (BCO) lameness is a leg disorder in broilers leading to huge economic losses, food safety concerns, and animal welfare issues in the poultry industry. The active metabolite of vitamin D 3 , 1,25-dihydroxyvitamin D 3, plays pivotal roles in mineral homeostasis, bone health, and immune systems which are essential for protection against BCO. Thus, we hypothesized that supplementation with a Solanum glaucophyllum -derived source of 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 -glycosides) would be an effective measure to control lameness. Here, we report the optimum concentration of 1,25(OH) 2 D 3 -glycosides supplementation in reducing BCO by comparing the inclusions of 0 µg/kg, 0.5 µg/kg, 1.0 µg/kg, and 2.0 µg/kg of 1,25(OH) 2 D 3 -glycosides. The application of 1.0 µg/kg of 1,25(OH) 2 D 3 -glycosides reduced lameness by 53.7%, which reciprocally differed (P < 0.05) from 0 µg/kg and 0.5 µg/kg but was similar (P > 0.05) to 2.0 µg/kg. The second aim was to assess the timing for 1,25(OH) 2 D 3 -glycosides feeding by comparing the applications of 1.0 µg/kg of 1,25(OH) 2 D 3 -glycosides for the entire 56 d, the first 28 d, and the last 28 d. Feeding the broilers with 1.0 µg/kg of 1,25(OH) 2 D 3 -glycosides for the first 28 d alleviated BCO incidence by 53%, which significantly differed (P < 0.05) from the application for the last 28 d but was without significant difference (P > 0.05) from the supplementation for the entire 56 d. Therefore, feeding 1.0 µg/kg 1,25(OH) 2 D 3 -glycosides in the first 28 d is the optimum 1,25(OH) 2 D 3 -glycosides administration and provides equal protection to the supplementation for the entire production cycle. This early feeding strategy would minimize feed additive costs without compromising bone health while promoting protection against BCO lameness. [ABSTRACT FROM AUTHOR]

[Display omitted] • Microalgae exhibit rapid growth, CO2 capture, and high Vitamin D content. • Vitamin D is synthesized via many pathways involving sterol precursors. • Genetic engineering and environmental optimization enhance Vitamin D production in microalage. • The Vitamin D market is expanding, with significant interest in algae-based sources. • Patent trends indicate increased protection of microalgae-derived Vitamin D technologies. Vitamin D (VD) production-based microalgae biosynthesis presents various benefits including sustainability, fast expansion, and the capacity to generate substantial quantities. However, this approach suffers from serious challenges that require effective cultivation methods and extraction processes. Indeed, further researches are of significant interest to understand the biosynthesis pathways, enhance the processes, and ensure its viability. In this context, the present review focuses on an in-depth understanding of the chemistry of VD and its analogues and provides a comprehensive explanation of the biosynthesis pathways, precursors, and production methods. In addition, this work discusses the state of the art reflecting the recent advances researches and the global market of microalgae as a potential source of VD. In sum, this paper demonstrates that microalgae can efficiently biosynthesize various forms of VD, presenting a sustainable alternative for VD production. [ABSTRACT FROM AUTHOR]

Dan-shen Yin (DSY), a traditional prescription, has been demonstrated to be effective in decreasing hyperlipidemia and preventing atherosclerosis (AS), but its mechanism remains unknown. We hypothesized that DSY activates farnesoid X receptor (FXR) to promote bile acid metabolism and excretion, thereby alleviating AS. This study was designed to explore whether DSY reduces liver lipid accumulation and prevents AS by activating FXR and increasing cholesterol metabolism and bile acid excretion. The comprehensive chemical characterization of DSY was analyzed by UHPLC-MS/MS. The AS models of ApoE−/− mice and SD rats was established by high-fat diet and high-fat diet combined with intraperitoneal injection of vitamin D3, respectively. The aortic plaque and pathological changes were used to evaluate AS. Lipid levels, H&E staining and oil red O staining were used to evaluate liver lipid accumulation. The cholesterol metabolism and bile acid excretion were evaluated by enzyme-linked immunosorbent assay, UPLC-QQQ/MS. In vitro, the lipid and FXR/bile salt export pump (BSEP) levels were evaluated by oil red O staining, real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. A total of 36 ingredients in DSY were identified by UPLC-MS/MS analysis. In vivo, high-dose DSY significantly inhibited aortic intimal thickening, improved arrangement disorder, tortuosity, and rupture of elastic fibers, decreased lipid levels, and reduced the number of fat vacuoles and lipid droplets in liver tissue in SD rats and ApoE−/− mice. Further studies found that high-dose DSY significantly reduced liver lipid and total bile acids levels, increased liver ursodeoxycholic acid (UDCA) and other non-conjugated bile acids levels, increased fecal total cholesterol (TC) levels, and augmented FXR, BSEP, cholesterol 7-alpha hydroxylase (CYP7A1), ATP binding cassette subfamily G5/G8 (ABCG5/8) expression levels, while decreasing ASBT expression levels. In vitro studies showed that DSY significantly reduced TC and TG levels, as well as lipid droplets, while also increasing the expression of ABCG5/8, FXR, and BSEP in both HepG2 and Nr1h4 knockdown HepG2 cells. This study demonstrated that DSY promotes bile acid metabolism and excretion to prevent AS by activating FXR. For the prevent of AS and drug discovery provided experimental basis. [Display omitted] [ABSTRACT FROM AUTHOR]

Prediabetes is a crucial stage for prevention and treatment of diabetes, and vitamin D (VD) has been found to be linked to the development of prediabetes and diabetes. Thus, we aimed to identify the effect of VD supplementation on glucose metabolism in prediabetic participants and mice. A 1:1 paired design of randomized, placebo-controlled trial with 1600 IU/day VD 3 or placebo was administered to individuals with prediabetes, two-way repeated-measures ANCOVA was used to analyze glycolipid and inflammatory factors. A high-fat diet induced prediabetic KKay mice were utilized to evaluate the effects of VD 3 with 16 weeks supplementation. Generalized estimation equation, one way ANOVA were used to analyze continuous monitoring indexes and terminal indexes, respectively. Exercise capacity, skeletal muscle pathological features and relevant proteins were examined. The clinical results showed that VD 3 could improve insulin secretion and decrease inflammation. Results of KKay mice exhibited that VD 3 not only ameliorate glycolipid metabolism and inflammatory indicators, but also regulated pathological changes of skeletal muscle and exercise capacity. Mechanistically, our results demonstrated that VD 3 could inhibit the TLR4/NFκB and activate PI3K/AKT signaling pathway. Collectively, the study indicated that VD 3 exerts its beneficial effects by inhibiting TLR4/NFκB to decrease inflammatory response, and activating PI3K/AKT signaling pathway to regulate glucose homeostasis. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency is common in patients with chronic liver disease and is associated with increased risk of infection and mortality. This study evaluated the effects of preoperative vitamin D levels on clinical outcomes after liver transplant. This single-center retrospective study included liver transplant recipients from June to November 2017 who had preoperative 25-OH-vitamin D3 (25-OH-D3) data. Severe vitamin D deficiency, insufficiency, and normal levels were defined as serum 25-OH-D3 concentrations of < 10 ng/mL, 10 to 20 ng/mL, and ≥ 20 ng/mL, respectively. The primary outcome was length of hospital stay; secondary outcomes included the duration of normalization of inflammatory markers after liver transplant, new infection rates, rejection rates, length of intensive care unit stay, and mortality according to preoperative 25-OH-D3 levels. Among 219 liver transplant recipients, 67.6% were vitamin D-deficient. The mean (standard deviation) 25-OH-D3 concentration was 17.8 (13.2) ng/mL, and 65 (29.7%) patients had levels < 10 ng/mL. Patients with lower mean 25-OH-D3 levels had significantly longer intensive care unit (13.8 [21.9] days vs 5.9 [12.3] days vs 2.7 [4.6] days, P <.001) and hospital (59.0 [66.0] days vs 42.0 [67.4] days vs 27.2 [17.1] days, P =.001) stays. The incidence of new infections was higher in the vitamin D deficiency group. (46.2% vs 28.9% vs 14.1%, P <.001). A higher Nutritional Risk Screening 2002 score (adjusted odds ratio, 1.77; 95% confidence interval [CI], 1.24-2.56; P =.002) and severe vitamin D deficiency (adjusted odds ratio, 3.43; 95% CI, 1.57-7.57; P =.002) were significant risk factors for poor outcome among patients who had been in the hospital for more than 43 days. Vitamin D deficiency before liver transplant was associated with increased intensive care unit and hospital lengths of stay. Although several factors may influence the clinical outcomes of patients with liver transplant, low vitamin D3 was an independent risk factor. [ABSTRACT FROM AUTHOR]