Vitamin D3 attenuates autoimmune thyroiditis by regulating Th17/Treg cell differentiation via YAP/JAK1/STAT1 axis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Vitamin D3 attenuates AITD by modulating Th17/Treg cell balance via regulating the YAP/JAK1/STAT1 axis.

Selective Oxidation of Vitamin D3 Enhanced by Long-Range Effects of a Substrate Channel Mutation in Cytochrome P450BM3 (CYP102A1).

Vitamin D deficiency affects nearly half the population, with many requiring or opting for supplements with vitamin D3(VD3), the precursor of vitamin D (1α,25-dihydroxyVD3). 25-HydroxyVD3, the circulating form of vitamin D, is a more effective supplement than VD3 but its synthesis is complex. We report here the engineering of cytochrome P450BM3(CYP102A1) for the selective oxidation of VD3 to 25-hydroxyVD3. Long-range effects of the substrate-channel mutation Glu435Ile promoted binding of the VD3 side chain close to the heme, enhancing VD3 oxidation activity that reached 6.62 g of 25-hydroxyVD3 isolated from a 1-litre scale reaction (69.1% yield; space-time-yield 331 mg/L/h).

Electrolytes, Zinc and Vitamin D3 in COVID-19 Patients with Cardiovascular Complications.

INTRODUCTION: COVID-19 is strongly linked to cardiovascular disease, with direct myocardial injury and systemic inflammation as common mechanisms. Pre-existing or infection-induced cardiovascular disease worsens the outcomes for COVID-19 patients. MATERIALS AND METHODS: To estimate the serum electrolytes (Na+, K+, Ca++, Zn) and vitamin D3, the study depended on ichroma ii device for Vitamin D3 and Chemistry Analyzer for electrolytes in patient samples. RESULTS: A study was conducted on 192 individuals diagnosed with COVID-19, including 35 critical cases, 53 severe cases, 54 moderate cases, and 50 individuals in a control group. The age group with the highest prevalence of infection was between 50‒69 years, while the lowest prevalence was observed in those under 30 years. The study found significant decreases in calcium, potassium, sodium, zinc, and vitamin D3 levels among COVID-19 patients compared to the control group. Zinc and vitamin D3 levels showed a significant correlation with sex, with males experiencing a decline in zinc levels and females having lower vitamin D3 levels. The concentration of calcium, sodium, and zinc showed a negative correlation with age, with older patients having the lowest levels. COVID-19 patients with chronic cardiac issues and high blood pressure exhibited the lowest levels of these markers. The severity of the disease also had a detrimental impact on electrolyte levels, zinc, and vitamin D3, with critical cases showing the lowest levels. The complications such as heart failure were associated with lower levels of potassium, sodium, and zinc. CONCLUSION: In conclusion, the study revealed significant associations between COVID-19 and decreased electrolyte levels, zinc, and vitamin D3. Sex and age were found to be correlated with these markers. Patients with chronic cardiac issues and high blood pressure exhibited the lowest levels of these markers. The severity of the disease was also linked to lower electrolyte levels, zinc, and vitamin D3. Complications such as heart failure were associated with decreased levels of potassium, sodium, and zinc.

Vitamin D, the Sunshine Molecule That Makes Us Strong: What Does Its Current Global Deficiency Imply?

Vitamin D3 deficiency and insufficiency are becoming a common global issue for us, especially in the most industrially developed countries. The only acknowledged activity of vitamin D3 in vertebrates is to promote the absorption of calcium and, therefore, allow for the mineralization of bones. Accordingly, its deficiency is associated with diseases such as rickets. Other numerous vital functions associated with vitamin D3 are yet to be considered, and the function of vitamin D2 in plants is unknown. Thus, 100 years after its discovery, the importance of vitamin D still seems to be unacknowledged (except for rickets), with little attention given to its decrease throughout the world. In this review, I suggest that vitamin D deficiency and insufficiency may be linked to the westernized lifestyle in more developed countries. Furthermore, I suggest that, rather than the calcemic activity, the main function of vitamin D is, in general, that of strengthening living organisms. I conclude with the hypothesis that vitamin D deficiency may represent a marker for a greater risk of chronic inflammatory diseases and a shorter life expectancy.

Lignin nanoparticles from Ayurvedic industry spent materials: Applications in Pickering emulsions for curcumin and vitamin D3 encapsulation.

Lignin nanoparticles (LNP), extracted from spent materials of Dashamoola Arishta (Ayurvedic formulation), shared a molecular weight of 14.42 kDa with commercial lignin. Processed into LNPs (496.43 ± 0.54 nm) via planetary ball milling, they demonstrated stability at pH 8.0 with a zeta potential of -32 ± 0.27 mV. Operating as Pickering particles, LNP encapsulated curcumin and vitamin D3 in sunflower oil, forming LnE + Cu + vD3 nanoemulsions (particle size: 347.40 ± 0.71 nm, zeta potential: -42.27 ± 0.72 mV) with high encapsulation efficiencies (curcumin: 87.95 ± 0.21%, vitamin D3: 72.66 ± 0.11%). The LnE + Cu + vD3 emulsion exhibited stability without phase separation over 90 days at room (27 ± 2 °C) and refrigeration (4 ± 1 °C) temperatures. Remarkably, LnE + Cu + vD3 exhibited reduced toxicity, causing 29.32% and 34.99% cell death in L6 and RAW264.7 cells respectively, at the highest concentration (50 µg/mL). This underscores the potential valorization of Ayurvedic industry spent materials for diverse industrial applications.

The role of vitamin D3 in follicle development.

Vitamin D3 plays a crucial role in female reproduction. As research progresses, the mechanisms of action of vitamin D3 on follicular development have been widely discussed. Firstly, key enzymes involved in the synthesis and metabolism of vitamin D3 have been discovered in the ovary, suggesting that vitamin D3 can be synthesized and metabolized locally within the ovary. Additionally, the detection of vitamin D3 receptors (VDR) in follicles suggests that vitamin D3 may exert its effects by binding specifically to these receptors during follicular development. Further research indicates that vitamin D3 promotes follicular growth by enhancing the development of granulosa cells (GCs) and oocytes. Currently, the mechanism of action of vitamin D3 in follicular development is becoming increasingly clear. Vitamin D3 promotes oocyte development by regulating molecules involved in meiotic arrest in oocytes. It also enhances granulosa cell proliferation by stimulating steroid hormone synthesis and cell cycle regulation. Additionally, vitamin D3 exerts anti-inflammatory effects by reducing oxidative stress and advanced glycation end-products (AGEs), mitigating the detrimental effects of inflammation on follicular development. These functions of vitamin D3 have clinical applications, such as in treating polycystic ovary syndrome (PCOS), improving female fertility, and enhancing outcomes in in vitro fertilization (IVF). This review summarizes the research progress on the role and mechanisms of vitamin D3 in follicular development and briefly summarizes its clinical applications.

High-Dose Vitamin D3 and Tonsillectomy as Therapeutic Management in Henoch-Schönlein Purpura Following Hepatitis B Vaccination: A Rare Case Report.

Henoch-Schönlein purpura (HSP) is an immunoglobulin A (IgA)-mediated systemic vasculitis, which is one of the rare adverse reactions to hepatitis B vaccination. Low vitamin D levels were found to be present in the majority of HSP patients.A 19-year-old woman was admitted with a purpuric rash on bilateral lower limbs and joint pain on her left index finger in January 2020. A previous history of rash occurred one week after the patient received her first dose of recombinant hepatitis-B vaccination. Routine hematological examination, creatinine, urinalysis, C3, and C4 showed normal results. HBsAg, Anti-HCV, and ANA tests were negative, and anti-HBs were elevated. Vitamin D is very low. The patient was diagnosed with HSP and given mycophenolate mofetil, methylprednisolone, vitamin D3, and folic acid. Within 1 month of therapy, the rash still occurred frequently, so mycophenolate mofetil was changed to mycophenolic acid, the dose of methylprednisolone was increased and fexofenadine was administered. In the next 3 months, the rash has improved. However, patients reported knee joint pain and hair loss. In May 2021, the patient underwent tonsillectomy due to acute exacerbation of chronic tonsillitis. Thereafter, the patient reported that the rash had completely resolved and never worsened, and the vitamin D assay was normal.Hepatitis B vaccination is one of the etiologies of HSP, although it is rare, so it is important to ask about the vaccination history in patients with suspected HSP. Correction of vitamin D and performing tonsillectomy provide better treatment results in HSP cases in this patient.

Explorative case control study on the associations of serum vitamin D3, folic acid and vitamin B12 levels on Kawasaki disease and coronary artery lesions.

Background: Kawasaki Disease (KD) is a pediatric vasculitic disorder characterized by systemic small vasculitis, notably coronary arteritis, with unclear pathogenesis. This explorative case-control study investigated the association between folic acid (FA), vitamin D3 (VD3), and vitamin B12 (VB12) levels and the different types of Kawasaki Disease, as well as the incidence of coronary artery lesions (CALs). Methods: In this explorative case control study, 365 KD children admitted to our hospital from January 1, 2022 to June 30, 2023 were included as the KD group. Simultaneously, 365 healthy children who received physical examination during the same period were included as the control group. The KD group was divided into typical KD group and incomplete KD group (IKD group), CALs group and non-CALS group, and IVIG sensitive group and IVIG resistant group. The children with CALs were divided into small tumor group, medium tumor group and large tumor group. Serum levels of FA, VB12, and VD3 were compared across all groups. Results: Serum levels of FA and VD3 were significantly decreased in both the KD and CALs groups (p < 0.05), and both factors were identified as independent risk factors for KD and CALs. Similarly, reduced serum VD3 levels were observed in the IKD and IVIG-resistant groups (p < 0.05), with VD3 also being an independent risk factor for both IKD and IVIG resistance. Additionally, lower serum FA levels were noted in the group with large aneurysms (p < 0.05), establishing FA as an independent risk factor for aneurysm size. Conclusion: Serum levels of folic FA and vitamin VD3 were significantly reduced in children with KD. Furthermore, these reductions were more pronounced in children with IKD and CALs. This pattern suggests that lower FA and VD3 levels may increase the risk of more severe coronary lesions in KD patients. Therefore, monitoring these biomarkers could provide valuable insights for early clinical diagnosis and intervention.

A Comprehensive Investigation of Stimulatory Agents on MAIT and Vα7.2+/CD161- T Cell Response and Effects of Immunomodulatory Drugs.

Mucosal-associated invariant T (MAIT) cells, a subset of Vα7.2+ T cells, are a crucial link between innate and adaptive immunity, responding to various stimuli through TCR-dependent and independent pathways. We investigated the responses of MAIT cells and Vα7.2+/CD161- T cells to different stimuli and evaluated the effects of Cyclosporin A (CsA) and Vitamin D3 (VitD). Peripheral blood mononuclear cells (PBMCs) from healthy donors were stimulated with various agents (PMA/Ionomycin, 5-OP-RU, 5-OP-RU/IL-12/IL-33) with or without CsA and VitD. Flow cytometric analysis assessed surface markers and intracellular cytokine production. Under steady-state conditions, MAIT cells displayed elevated expression of CCR6 and IL-13. They showed upregulated activation and exhaustion markers after activation, producing IFNγ, TNFα, and TNFα/GzB. CsA significantly inhibited MAIT cell activation and cytokine production. Conversely, Vα7.2+/CD161- T cells exhibited distinct responses, showing negligible responses to 5-OP-RU ligand but increased cytokine production upon PMA stimulation. Our study underscores the distinct nature of MAIT cells compared to Vα7.2+/CD161- T cells, which resemble conventional T cells. CsA emerges as a potent immunosuppressive agent, inhibiting proinflammatory cytokine production in MAIT cells. At the same time, VitD supports MAIT cell activation and IL-13 production, shedding light on potential therapeutic avenues for immune modulation.

Vitamin D3 supplementation in COVID-19 patients with cardiovascular disease and gut dysbiosis.

BACKGROUND: The COVID-19 pandemic has highlighted the vulnerability of particular patient groups to SARS-CoV-2 infection, including those with cardiovascular diseases, hypertension, and intestinal dysbiosis. COVID-19 affects the gut, suggesting diet and vitamin D3 supplementation may affect disease progression. AIMS: To evaluate levels of Ang II and Ang-(1-7), cytokine profile, and gut microbiota status in patients hospitalized for mild COVID-19 with a history of cardiovascular disease and treated with daily doses of vitamin D3. METHODS: We recruited 50 adult patients. We screened 50 adult patients and accessed pathophysiology study 22, randomized to daily oral doses of 10,000IU vitamin D3 (n=11) or placebo (n=11). Plasma levels of Ang II and Ang-(1-7) were determined by radioimmunoassay, TMA and TMAO were measured by liquid chromatography and interleukins (ILs) 6, 8, 10 and TNF-α by ELISA. RESULTS: The Ang-(1-7)/Ang II ratio, as an indirect measure of ACE2 enzymatic activity, increased in the vitamin D3 group (24±5pg/mL vs. 4.66±2pg/mL, p<0.01). Also, in the vitamin D3-treated, there was a significant decline in inflammatory ILs and an increase in protective markers, such as a substantial reduction in TMAO (5±2µmoles/dL vs. 60±10µmoles/dL, p<0.01). In addition, treated patients experienced less severity of infection, required less intensive care, had fewer days of hospitalization, and a reduced mortality rate. Additionally, improvements in markers of cardiovascular function were seen in the vitamin D3 group, including a tendency for reductions in blood pressure in hypertensive patients. CONCLUSIONS: Vitamin D3 supplementation in patients with COVID-19 and specific conditions is associated with a more favourable prognosis, suggesting therapeutic potential in patients with comorbidities such as cardiovascular disease and gut dysbiosis.

3D printed scaffolds with quercetin and vitamin D3 nanocarriers: In vitro cellular evaluation.

Increasing bone diseases and anomalies significantly challenge bone regeneration, necessitating the development of innovative implantable devices for effective healing. This study explores the potential of 3D-printed calcium phosphate (CaP) scaffolds functionalized with natural medicine to address this issue. Specifically, quercetin and vitamin D3 (QVD) encapsulated solid lipid nanoparticles (QVD-SLNs) are incorporated into the scaffold to enhance bone regeneration. The melt emulsification method is utilized to achieve high drug encapsulation efficiency (~98%) and controlled biphasic release kinetics. The process-structure-property performance of these systems allows more controlled release while maintaining healthy cell-material interactions. The functionalized scaffolds show ~1.3- and ~-1.6-fold increase in osteoblast cell proliferation and differentiation, respectively, as compared with the control. The treated scaffold demonstrates a reduction in osteoclastic activity as compared with the control. The QVD-SLN-loaded scaffolds show ~4.2-fold in vitro chemopreventive potential against osteosarcoma cells. Bacterial assessment with both Staphylococcus aureus and Pseudomonas aeruginosa shows a significant reduction in bacterial colony growth over the treated scaffold. These findings summarize that the release of QVD-SLNs through a 3D-printed CaP scaffold can treat various bone-related disorders for low or non-load-bearing applications.

The therapeutic effects of vitamin D3 administration on the embryo implantation.

Various adjuvants have been tested clinically for patients with problems with embryo implantation during in vitro fertilization (IVF)-embryo transfer (ET). Vitamin D3, an essential modulator of various physiological processes, has received attention as an important adjuvant for successful pregnancy, as many studies have shown a strong association between vitamin D deficiency and implantation failure and fetal growth restriction. However, vitamin D has been widely utilized in different protocols, resulting in non-reproducible and debatable outcomes. In the present study, we demonstrated that cyclic intrauterine administration of vitamin D3 increased endometrial receptivity and angiogenesis, which could be attributed to increased recruitment of uterus-resident natural killer cells. In particular, cyclic treatment of vitamin D3 promoted stable attachment of the embryo onto endometrial cells in vitro, suggesting its merit during the early stage of embryo implantation to support the initial maternal-fetal interactions. Our findings suggest that women with repeated implantation failure may benefit from the use of vitamin D3 as a risk-free adjuvant prior to IVF-ET procedures to improve the uterine environment, and make it favorable for embryo implantation.

Lipocalin-2 as a marker of inflammation, bone density, and triglyceride-glucose index for new-onset arthritis patients in Mosul, Iraq.

OBJECTIVE: Lipocalin-2 is an acute phase-associated adipokine that can serve as an inflammatory and biomarker indicator of cartilage deterioration in osteoarthritis. However, its role in the musculoskeletal system remains not fully understood. Hence, this study aimed to evaluate lipocalin-2 and its relationship with markers of inflammation (Interferon-gamma, ESR, and CRP), bone density (vitamin D3 and calcium), and the triglyceride-glucose index in new-onset arthritis patients in Mosul, Iraq. METHODS: This study included 125 participants aged 20 to 65, divided into two groups. The Arthritis Patient Group comprised 70 participants (37 females and 33 males) attending the Bone Diseases Consultation Unit at the Ibn Sina Teaching Hospital in Mosul, Iraq. The Control Group comprised 31 females and 24 males. Ethical approval was obtained from the Iraqi Ministry of Health - Nineveh Health (No. 2022095). Commercial ELISA kits were used to measure serum lipocalin-2, Interferon-gamma, ESR, and CRP as inflammation markers, vitamin D3, and calcium as bone density markers. Moreover, the Triglyceride Glucose (TYG) Index was evaluated. RESULTS: The findings revealed a significant increase in lipocalin-2 levels in males compared to females, with LCN-2 increasing with age. Arthritis patients showed a significant increase (72%) in lipocalin-2 levels. Inflammatory indicators (erythrocyte sedimentation rate, C-reactive protein, interferon-gamma) displayed significant increases (46%, 1200%, and 581%, respectively). Glucose (23%), triglycerides (71%), and TYG index (21%) also exhibited significant increases. Meanwhile, bone density indicators (vitamin D3 and calcium) found a significant decrease (53% and 20%, respectively) in arthritis patients. Linear correlation coefficient (R) analysis revealed a significant positive relationship between lipocalin-2 and indicators of inflammation, glucose, TG, and TYG index. CONCLUSION: This study's findings suggest that LCN-2 serum levels were higher in patients with new-onset arthritis than in controls in Mosul, and LCN-2 serum increased in males compared with females and getting older serum LCN-2 increased for the patients and control groups. Furthermore, a significant correlation was found between the Triglyceride Glucose Index, which measures metabolic disorders, and serum LCN-2 levels and inflammatory indicators in new-onset arthritis patients in Mosul, Iraq.

Effect of Vitamin D3 Supplementation on Severe COVID-19: A Meta-Analysis of Randomized Clinical Trials.

Since the beginning of the COVID-19 pandemic, vitamin D has attracted interest due to its immunomodulatory properties. Numerous studies show a correlation between vitamin D levels and COVID-19 cases and mortality. Therefore, we conducted a meta-analysis in order to assess the relationship between vitamin D3 supplementation and COVID-19 severity. We included 13 randomized clinical trials that contained the analyzed endpoints: length of COVID-19 hospitalization, number of intensive care unit (ICU) admissions, length of stay in the ICU, number of cases requiring any supplemental oxygenation, duration of any supplemental oxygenation, number of overall mortality and number of deaths associated with COVID-19. The relative risk with 95% confidence interval (CI) and the mean difference with 95% CI were calculated to compare the effect. A random effects model was used to calculate effect sizes. Our meta-analysis showed a positive effect of vitamin D3 supplementation on ICU admission (RR = 0.73; 95% CI [0.57; 0.95], p = 0.02, I2 = 19.6%) and mortality associated with COVID-19 among patients (RR = 0.56; 95% CI [0.34; 0.91]; p = 0.02; I2 = 0%). Vitamin D3 supplementation may potentially reduce the risk of ICU admission and death associated with COVID-19.

Association between CTX-1 and Fibulin-1 Serum Levels with Pathogenesis of Multiple Myeloma Cancer.

BACKGROUND: Multiple myeloma (MM) is the second most prevalent blood cancer after non-Hodgkin lymphoma. It is identified by the excessive production of abnormal monoclonal immunoglobulins, which can result in various clinical symptoms such as destructive bone lesions, renal dysfunction, anemia, and immunodeficiency. The current study aims to evaluate the serum levels of carboxy-terminal collagen crosslinks 1 (CTX-1), Fibulin-1, vitamin D3, LDH, and albumin in MM patients and their significance for early diagnosis. MATERIALS AND METHODS: This study included 30 healthy controls (11 males, 19 females) and 60 patients with multiple myeloma (37 males and 23 females), aged between 40-60 years. Five-milliliter blood samples were collected and stored at -20°C. Afterward, enzyme-linked immunosorbent assay (ELISA) kits were used to estimate the concentrations of CTX-1, Fibulin-1, and vitamin D3. Additionally, LDH and albumin levels were determined using the automated biochemistry analyzer. RESULTS: This study revealed that the majority of patients with multiple myeloma are between the ages of 51 and 60 years. The serum concentrations of CTX-1, Fibulin-1, and LDH were significantly increased in the multiple myeloma patients compared to the healthy control group. In contrast, the serum level of vitamin D3 was significantly decreased in patients with MM. CONCLUSION: Our results indicate that the incidence of multiple myeloma is higher in males than in females. Additionally, the serum concentrations of CTX-1 and Fibulin-1 were significantly higher in the multiple myeloma patients compared to the healthy control group, indicating their potential for early detection and as therapeutic targets.

Associations of Gut and Circulating Microbiota with Circulating Vitamin D3, Type I Interferon, and Systemic Inflammation in Chronic Spontaneous Urticaria Patients.

Objective: To analyze the associations of the gut and circulating microbiota with circulating vitamin D3 (VD3), type I interferon (IFNI), systemic inflammation, and clinical profiles in chronic spontaneous urticaria (CSU) patients. Methods: A total of 36 CSU patients with VD3 insufficiency (VDI; serum 25(OH)VD3 <30 ng/mL) and 36 sex-, age-, and body mass index-matched CSU patients with non-VDI were enrolled. Fecal and serum bacteria were identified through 16S rRNA sequencing, and serum 25(OH)VD3 and inflammation biomarkers were assessed using ELISA kits. IFNI response was determined by measuring the stimulatory activity of serum on IFNI-stimulated response element in HEK293 cells in vitro with luciferase assays. Results: Higher urticarial activity score over 7 days (UAS7), higher frequency of levocetirizine resistance, and more severe proinflammation but weaker IFNI response were observed in VDI than non-VDI patients (all P<0.05). IFNI response was strongly positively associated with serum 25(OH)VD3 level in both groups (P<0.001). Compared to non-VDI patients, abundance of the fecal genera Prevotella 9, Escherichia-Shigella, and Klebsiella was significantly increased, while Bacteroides, Faecalibacterium, and Agathobacter were remarkably reduced in VDI patients (all P<0.05). Burkholderia-Caballeronia-Paraburkholderia (40.95%), Acinetobacter (3.05%), and Aquabacterium (2.37%) were the top three bacteria in sera from VDI patients. Both serum 25(OH)VD3 level and IFNI response were positively associated with fecal Bacteroides in the two groups (P<0.05). In non-VDI patients, there were moderately positive associations between IFNI response and fecal Lachnoclostridium, unclassified_f__Lachnospiraceae, and Phascolarctobacterium and between serum 25(OH)VD3 level and fecal Lachnoclostridium (all P<0.01). Circulating microbiota in VDI patients was closely related only to proinflammation and UAS7 (both P<0.05). Conclusion: Changes in gut but not circulating microbiota composition are associated with serum 25(OH)VD3 insufficiency and impaired IFNI homeostasis, which points to greater disease severity (UAS7) and systemic proinflammation in CSU patients.

Dietary Super-Doses of Cholecalciferol Fed to Aged Laying Hens Illustrates Limitation of 24,25-Dihydroxycholecalciferol Conversion.

Background: Older humans taking high concentrations of vitamin D3 supplementation for a prolonged time may be at risk of vitamin D toxicity. It is unclear how dietary super-doses (10,000 times greater than the requirement) can affect vitamin D3 status in aged animals. Aged laying hens could be a model to compare vitamin D3 supplementation effects with women in peri- or postmenopausal stages of life. Objectives: We investigated the dietary super-dose impacts of cholecalciferol (vitamin D3) on vitamin D3 status in aged laying hens in production. Methods: Forty-eight 68-wk-old Hy-Line Brown laying hens were individually housed in cages with 8 hens per dietary treatment for 11 wk. Hens were randomly assigned to 1 of 6 treatment groups of dietary vitamin D3 supplementation and consumed ad libitum. Supplementation concentrations were 400, 800, 7400, 14,000, 20,000, and 36,000 IU D3/kg of feed. At the end of the study, all hens were sacrificed, and tissue samples and feces were collected. Plasma and egg yolk vitamin D3 metabolites, calcium and phosphorus composition of eggshells, ileal digesta, and feces were measured. Duodenal, ileal, liver, and kidney gene expression levels were also measured. Results: We observed that increasing dietary vitamin D3 increased plasma vitamin D3 and egg yolk vitamin D3 (P < 0.0001 for both sites). We also observed an increase in plasma 24,25-dihydroxycholecalciferol as dietary vitamin D3 concentrations increased (P < 0.0001). The plasma 25-hydroxycholecalciferol:24,25-dihydroxycholecalciferol ratio exhibited an asymptotic relationship starting at the 14,000 IU/kg D3 treatment. Conclusions: Dietary super-doses of vitamin D3 led to greater plasma and egg yolk vitamin D3 concentrations, which shows that aged laying hens can deposit excess vitamin D3 in egg yolk. We suggest future research should explore how 24-hydroxylation mechanisms are affected by vitamin D3 supplementation. Further understanding of 24-hydroxylation can help ascertain ways to reduce the risk of vitamin D toxicity.

Effects of Zilpaterol Hydrochloride with a Combination of Vitamin D3 on Feedlot Lambs: Growth Performance, Dietary Energetics, Carcass Traits, and Meat Quality.

This study evaluated the impact of supplementing ZH in combination with D3 on the growth performance, energy efficiency, carcass traits, and meat quality of feedlot lambs. Thirty-two Dorper × Katahdin cross lambs (37.3 ± 5.72 kg) were utilized in a 29 d experiment in a completely randomized block design with a 2 × 2 factorial structure consisting of two levels of ZH for 26 d (0 and 0.20 mg/kg PV-1) and two levels of D3 for 7 d (0 and 1.5 × 106 IU/d-1). ZH improved (p ≤ 0.05) the average daily gain (ADG) and feed efficiency by 9.9% and 17.8%, respectively, as well as hot carcass weight (HCW) and dressing carcass by 4.3% and 2.6%, respectively. (p ≤ 0.03). However, ZH increased (p < 0.01) muscle pH and Warner-Bratzler shear force (WBSF) (2.5 and 23.0%, respectively). D3 supplementation negatively affected (p ≤ 0.02) dry matter intake (DMI) (last 7 d) and ADG by 15.7% and 18.1%. On the other hand, D3 improved the pH of the longissimus thoracis muscle by 1.7% (p = 0.03) without affecting WBSF. When D3 was supplemented in combination with ZH, it was observed that meat quality was improved by reducing muscle pH compared to lambs treated only with ZH. However, D3 did not improve the meat tenderness negatively affected by ZH supplementation.

Protective Effects of Dietary Vitamin D3, Turmeric Powder, and Their Combination against Gasoline Intoxication in Rats.

The inhalation of gasoline vapors (GV) is associated with developing various pathologies. Particularly, oil refinery and gas station workers are at a greater risk of developing lung cancer, kidney cancer, bladder cancer, and hematological disorders, including acute myeloid leukemia. Therefore, preventing the harmful effects of GV and alleviating their consequences appear to be important and timely issues. In this study, we investigated the potential of vitamin D3, turmeric powder, and their combination to ameliorate the toxicity of gasoline fumes in rats. Separate groups of animals fed with a standard rodent diet, with or without the supplementation of vitamin D3 (750 IU/kg body weight) and/or turmeric powder (0.5%, w/w, in food), were untreated or treated with GV (11.5 ± 1.3 cm3/h/m3/day) for 30, 60, or 90 days. Changes in the body weight were monitored weekly. Histological, biochemical, and hematological parameters were determined at the end of each treatment period. While the exposure of rats to GV resulted in a time-dependent reduction in body weight, supplementation with vitamin D3, but not with turmeric root powder or their combination, partially prevented weight loss. Macroscopical and histological analyses showed pronounced time-dependent changes in the organs and tissues of GV-treated rats. These included alveolar wall collapse in the lungs, the destruction of the lobular structure and hepatocytolysis in the liver, the shrinkage and fragmentation of glomeruli in the kidneys, and the disorganization of the lymphoid follicles in the spleen. However, co-treatment with the nutritional supplements tested, especially vitamin D3, noticeably alleviated the above conditions. This was accompanied by a significant improvement in the blood chemistry and hematological parameters. Collectively, our results demonstrate that the harmful effects of environmental exposure to GV can be reduced upon supplementation of vitamin D3. The fact that the protective activity of vitamin D3 alone was higher than that of turmeric root powder or the combined treatment suggests that combinations of these supplements may not always be more beneficial than each agent applied separately.

Vitamin D and bone health: What vitamin D can and cannot do.

Historically vitamin D deficiency had devastating consequences for children causing rickets resulting in severe bone deformities often leading to death. The mystery of the cause of rickets finally came to light when it was observed that cod liver oil and sunlight could prevent and cure rickets. The first vitamin D to be discovered was vitamin D2 from ergosterol in ultraviolet irradiated yeast. Vitamin D3 was discovered from UV exposure to the skin. Investigations revealed the two major functions of vitamin D were to increase intestinal calcium and phosphate absorption and mobilize calcium from the skeleton to maintain calcium and phosphorus homeostasis. Later studies demonstrated that vitamin D does not have an active role in bone mineralization. Vitamin D deficiency results in secondary hyperparathyroidism increasing bone resorption. As a result, this decreases bone mineral content and compromises the architectural integrity increasing risk for fracture. Vitamin D deficiency has also been shown to enhance aging of the bone causing cracks and enhancing bone fractures. Vitamin D deficiency also causes osteomalacia. Therefore, vitamin D sufficiency is extremely important to maximize bone health throughout life. It helps to prevent bone loss, but it cannot restore bone loss due to increased bone resorption that can occur under a variety of circumstances including menopause. The Endocrine Society Guidelines recommends for all ages that adequate vitamin D obtained from the sun, foods and supplements is necessary in order to maintain a circulating concentration of 25-hydroxyvitamin D of at least 30 ng/mL for maximum bone health.