The immune cell transcriptome is modulated by vitamin D3 supplementation in people with a first demyelinating event participating in a randomized placebo-controlled trial.

Vitamin D deficiency is a risk factor for developing multiple sclerosis. The PrevANZ trial was conducted to determine if vitamin D3 supplementation can prevent recurrent disease activity in people with a first demyelinating event. As a sub-study of this trial, we investigated the effect of supplementation on peripheral immune cell gene expression. Participants were randomized to 1000, 5000 or 10,000 international units daily of vitamin D3 or placebo. Peripheral blood was collected at baseline and 12 weeks and sent for ribonucleic acid sequencing. Datasets from 55 participants were included. Gene expression was modulated by high dose supplementation. Antigen presentation and viral response pathways were upregulated. Oxidative phosphorylation and immune signaling pathways, including tumor necrosis factor-alpha and interleukin-17 signaling, were downregulated. Overall, vitamin D3 supplementation for 12 weeks modulated the peripheral immune cell transcriptome with induction of anti-inflammatory gene expression profiles. Our results support a dose-dependent effect of vitamin D3 supplementation on immune gene expression.

Vitamin D3 promotes fish oocyte development by directly regulating gonadal steroid hormone synthesis†.

Vitamin D receptors and vitamin D3-metabolizing enzymes have been found to be highly expressed in the ovaries and spermatophores of fish. However, the role of vitamin D3 on fish gonadal development has rarely been reported. In this study, 2-month-old female zebrafish were fed with different concentrations of vitamin D3 diets (0, 700, 1400, and 11 200 IU/kg) to investigate the effects of vitamin D3 on ovarian development. The diet with 0 IU/kg vitamin D3 resulted in elevated interstitial spaces, follicular atresia, and reproductive toxicity in zebrafish ovaries. Supplementation with 700 and 1400 IU/kg of vitamin D3 significantly increased the oocyte maturation rate; upregulated ovarian gonadal steroid hormone synthesis capacity; and elevated plasma estradiol, testosterone, and ovarian vitellogenin levels. Furthermore, the current study identified a vitamin D response element in the cyp19a1a promoter and demonstrated that 1.25(OH)2D3-vitamin D response directly activated cyp19a1a production through activating the vitamin D response element. In conclusion, this study shows that an appropriate concentration of vitamin D3 can promote zebrafish ovarian development and affect vitellogenin synthesis through the vdr/cyp19a1a/er/vtg gene axis.

Amitriptyline and cholecalciferol amend hippocampal histological structure and myelination during stress in Wistar rats via regulating miR200/BMP4/Olig-2 signaling.

Chronic stress is a universal condition commonly associated with many psychiatric diseases. An extensive body of evidence discussed hippocampal affection upon chronic stress exposure, however, the underlying molecular pathways still need to be identified. We investigated the impact of chronic stress on miR200/BMP/Olig-2 signaling and hippocampal myelination. We also compared the effects of chronic administration of amitriptyline and cholecalciferol on chronically stressed hippocampi. Both amitriptyline and cholecalciferol significantly decreased serum cortisol levels, reduced immobility time in the forced swim test, increased the number of crossed squares in open field test, decreased the hippocampal expression of bone morphogenetic protein 4 (BMP4) and its messenger RNA (mRNA) levels, reduced miR200 expression as compared to untreated chronically stressed rats. Also, both drugs amended the hippocampal neuronal damage, enhanced the surviving cell count, and increased the pyramidal layer thickness of Cornu Ammonis subregion 1 (CA1) and granule cell layer of the dentate gyrus. Cholecalciferol was more effective in increasing the area percentage of myelin basic protein (MBP) and Olig-2 positive cells count in hippocampi of chronic stress-exposed rats than amitriptyline, thus enhancing myelination. We also found a negative correlation between the expression of BMP4, its mRNA, miR200, and the immunoexpression of MBP and Olig-2 proteins. This work underscores the amelioration of the stress-induced behavioral changes, inhibition of miR200/BMP4 signaling, and enhancement of hippocampal myelination following chronic administration of either amitriptyline or cholecalciferol, though cholecalciferol seemed more effective in brain remyelination.

The interaction between lipid and vitamin D3 impacts lipid metabolism and innate immunity in Chinese mitten crabs Eriocheir sinensis.

As a fat-soluble vitamin, vitamin D3 relies on fat to perform its biological function, affecting lipid metabolism and innate immunity. This study used different percentages of lipid and vitamin D3 diets to evaluate the synergistic effects on the growth, lipid metabolism and immunity of juvenile Eriocheir sinensis (5.83 ± 0.01 g) for 56 days, including low lipid (LL, 1.5%) and normal lipid (NL, 7.5%) and three levels of vitamin D3: low (LVD, 0 IU/kg), medium (MVD, 9000 IU/kg) and high (HVD, 27,000, IU/kg). The synergistic effect of lipid and vitamin D3 was not significant on growth but significant on ash content, total protein, hepatopancreas lipid content, hemolymph 1α,25-hydroxy vitamin D3 [1α,25(OH)2D3] content, hepatopancreas lipolysis and synthesis genes. Crabs fed normal lipid (7.5%) and medium vitamin D3 (9000 IU/kg) had the highest hepatopancreas index, hemolymph 1α,25(OH)2D3 content, antibacterial ability, immune-related genes and hepatopancreatic lipid synthesis genes expression, but down-regulated the lipolysis genes expression. In contrast, crabs fed diets with low lipid percentage (1.5%) had low growth performance, hemolymph 1α,25(OH)2D3, mRNA levels of lipid synthesis genes, antibacterial ability and immune-related gene expression. At the 1.5% lipid level, excessive or insufficient vitamin D3 supplementation led to the obstruction of ash and protein deposition, reduced growth and molting, aggravated the reduction in antioxidant capacity, hindered antimicrobial peptide gene expression and reduced innate immunity, and resulted in abnormal lipid accumulation and the risk of oxidative stress. This study suggests that diets' lipid and vitamin D3 percentage can enhance antioxidant capacity, lipid metabolism and innate immunity in E. sinensis. A low lipid diet can cause growth retardation, reduce antioxidant capacity and innate immunity, and enhance lipid metabolism disorder.

Effect of vitamin D3 supplementation on blood parameters and liver gene expression in female rats.

BACKGROUND: To better understand the molecular mechanism responsible for the therapeutic potential of vitamin D, we conducted an analysis of the liver transcriptomes of adult female rats. METHODS: Adult female rats (n = 18) were divided into three groups, receiving different doses of vitamin D: group I, 0; group II, 1000 U/kg; and group III, 5000 U/kg. Growth, body weight, the weight of main organs, blood haematological and biochemical parameters were evaluated. Gene expression in the liver were analyzed using RNA-seq and qPCR techniques. RESULTS: We observed a lower platelet count (p < 0,008) and a significantly greater (p < 0.02) number of WBCs in rats supplemented with 1000 U/kg than in rats from group III (5000 U/kg). Moreover, we noted a trend (p < 0.06) in total cholesterol concentration, suggesting a linear decrease with increasing doses of vitamin D. RNA-seq analysis did not reveal any differentially expressed genes with FDR < 0.05. However, GSEA revealed significant activation of a number of processes and pathways, including: "metallothionein, and TspO/MBR family", and "negative regulation of tumor necrosis factor production". qPCR analysis revealed significant upregulation of the Mt1, Mt2 and Orm1 genes in animals receiving high doses of vitamin D (p < 0.025, p < 0.025, and p < 0009, respectively). Moreover, Srebp2 and Insig2 were significantly lower in both experimental groups than in the control group (p < 0.003 and p < 0.036, respectively). CONCLUSIONS: Our results support the anti-inflammatory, anitioxidant and anticholesterologenic potential of vitamin D but suggest that high doses of vitamin D are needed to obtain significant results in this regard.

A study on the effects of vitamin D supplementation on hematological parameters and serum 25-hydroxy vitamin D in healthy dogs.

BACKGROUND: Limited studies are available on vitamin D supplementation in dogs. This study evaluates the effect of a commercial vitamin D3 supplement on serum 25-hydroxy vitamin D as well as selected biochemical and hematological parameters in healthy dogs. Eight intact male adult dogs with a mean body weight of 20 kg from mixed breeds were included in the study. After adaptation period, dogs received vitamin D3 supplement at the dose of 50 IU/kg body weight per day. Blood samples were collected on days 0, 14, 28 and 42 of supplementation. Food was used for analysis of vitamin D3 content. RESULTS: Significant increase in serum level of 25-hydroxy vitamin D3 was detected since day 14 of supplementation. Changes in serum 25-hydroxy vitamin D3 concentration during time showed an upward significance (p < 0.05). Vitamin D3 content of the food was 2900 IU/kg dry matter. Changes in serum phosphorus levels were upward significant. No dog showed calcium or phosphorus levels above the highest reference level. Liver and kidney parameters remained in the reference range during the experiment. A gradual significant increase was observed in hemoglobin and hematocrit which was started from day 14. Vitamin D3 supplementation had no significant effect on neutrophils, monocytes and lymphocytes percent during the study. CONCLUSIONS: Vitamin D3 supplementation at 50 IU/kg BW daily, increases serum levels of 25-hydroxy vitamin D in healthy dogs fed with a diet containing proper amount of this vitamin. It also increases hemoglobin and hematocrit levels in a time dependent manner without inducing adverse effects.

Cytokine storm modulation using cholecalciferol and low dose gamma radiation in Escherichia coli infected mice.

This work investigates the efficiency of cholecalciferol and low dose gamma radiation in modulating cytokine storm through their impact on inflammatory and anti-inflammatory cytokine and protecting against lung and liver injuries. Male Swiss albino mice were exposed to 0.2 Gy gamma radiation/week for four consecutive weeks then injected intraperitoneally (i.p) with a single dose of 8.3 × 106 CFU Escherichia coli/g b.w. then injected i.p. with 1.0 mg/kg cholecalciferol (Vit D3) for 7 days starting 4 h after E. coli injection. The results revealed that Cholecalciferol and low dose gamma radiation caused significant depletion in the severity of E. coli infection (colony forming unit per milliliter), log10 of E. coli, Tumor necrosis factor alpha, Interleukin 6, VEGF, alanine aminotransferase, and aspartate aminotransferase levels and significant elevation in IL-10, IL-4, and HO-1. Immunohistochemical analysis of caspase-3 expression in lung tissue section showed low caspase-3 expression in cholecalciferol and low dose gamma radiation treated group. Histopathological examinations were performed in both lung and liver tissues which also emphasis the biochemical findings. Our results exhibit the importance of cholecalciferol and low dose gamma radiation in improving liver function and providing anti-inflammatory response in diseases causing cytokine storm.

Vitamin D3 improved hypoxia-induced lung injury by inhibiting the complement and coagulation cascade and autophagy pathway.

BACKGROUND: Pulmonary metabolic dysfunction can cause lung tissue injury. There is still no ideal drug to protect against hypoxia-induced lung injury, therefore, the development of new drugs to prevent and treat hypoxia-induced lung injury is urgently needed. We aimed to explore the ameliorative effects and molecular mechanisms of vitamin D3 (VD3) on hypoxia-induced lung tissue injury. METHODS: Sprague-Dawley (SD) rats were randomly divided into three groups: normoxia, hypoxia, and hypoxia + VD3. The rat model of hypoxia was established by placing the rats in a hypobaric chamber. The degree of lung injury was determined using hematoxylin and eosin (H&E) staining, lung water content, and lung permeability index. Transcriptome data were subjected to differential gene expression and pathway analyses. In vitro, type II alveolar epithelial cells were co-cultured with hepatocytes and then exposed to hypoxic conditions for 24 h. For VD3 treatment, the cells were treated with low and high concentrations of VD3. RESULTS: Transcriptome and KEGG analyses revealed that VD3 affects the complement and coagulation cascade pathways in hypoxia-induced rats, and the genes enriched in this pathway were Fgb/Fga/LOC100910418. Hypoxia can cause increases in lung edema, inflammation, and lung permeability disruption, which are attenuated by VD3 treatment. VD3 weakened the complement and coagulation cascade in the lung and liver of hypoxia-induced rats, characterized by lower expression of fibrinogen alpha chain (Fga), fibrinogen beta chain (Fgb), protease-activated receptor 1 (PAR1), protease-activated receptor 3 (PAR3), protease-activated receptor 4 (PAR4), complement (C) 3, C3a, and C5. In addition, VD3 improved hypoxic-induced type II alveolar epithelial cell damage and inflammation by inhibiting the complement and coagulation cascades. Furthermore, VD3 inhibited hypoxia-induced autophagy in vivo and in vitro, which was abolished by the mitophagy inducer, carbonyl cyanide-m-chlorophenylhydrazone (CCCP). CONCLUSION: VD3 alleviated hypoxia-induced pulmonary edema by inhibiting the complement and coagulation cascades and autophagy pathways.

Effects of supplementation of grazing Nellore cows with ß-carotene and vitamins A + D3 + E + biotin on follicle diameter, oestrus, establishment of pregnancy, and foetal morphometry.

The objectives of this experiment were to evaluate the effects of supplementation of Nellore (Bos indicus) cows with ß-carotene + vitamins A + D3 + E + biotin on body condition score (BCS), oestrus, pregnancy, and foetal morphometry. Lactating cows (n = 497) from two herds were balanced for BCS and calving period [early calving (EC); late calving (LC)] and were assigned randomly to: Control (n = 251)-supplementation with a mineral supplement; and SUP (n = 246)-supplementation with the mineral supplement fed to control + ß-carotene (150 mg/day) + vitamin A (40,000 IU/day) + vitamin D3 (5000 IU/day) + vitamin E (300 mg/day) + biotin (20 mg/day). Cows were supplemented from Days -30 to 30 (Day 0 = timed artificial insemination; TAI). Pregnancy was diagnosed 30 days after TAI and foetal crown-rump distance and thoracic diameter were measured at 30 and 77 days of gestation. Cows in the SUP treatment were more likely to have BCS ≥3.0 on Day 0 (63.0 ± 3.1 vs. 60.2 ± 3.1; p < .01) and were more likely to gain BCS from Days -30 to 30 (57.7 ± 3.3 vs. 44.1 ± 3.3%; p < .01). Fewer LC cows in the SUP treatment were detected in oestrus at the time of the first TAI (Control: LC: 75.4 ± 4.4 vs. SUP: LC: 64.0 ± 5.2 vs. Control: EC: 65.3 ± 4.0 vs. SUP: EC: 71.8 ± 3.7; p = .04). There was a tendency for the SUP treatment to increase pregnancy to the first TAI (64.2 ± 3.0 vs. 56.6 ± 3.1%; p = .08). A greater percentage of SUP cows was detected in oestrus at the time of the second TAI (70.1 ± 5.0 vs. 52.3 ± 4.8%; p = .01). The SUP treatment increased pregnancy to the second TAI among LC cows (SUP: LC: 75.9 ± 8.0% vs. Control: LC: 50.0 ± 8.3% vs. Control: EC: 52.0 ± 5.9% vs. SUP: EC: 41.4 ± 6.5%; p = .02). The SUP treatment increased foetal size (crown-rump; p = .04 and thoracic diameter; p < .01) at 30 days of gestation and, despite decreasing crow-rump length at 77 days after the first TAI among EC cows (p < .01), it increased the thoracic diameter at 77 days after the first TAI independent of calving season. Our results support that pregnancy establishment and foetal growth can be improved when grazing Nellore cows are supplemented with ß-carotene and vitamins A + D3 + E + biotin.

The utility of Hibiscus sabdariffa L. to prepare metal oxides NPs for clinical application on osteoporosis supported by theoretical study.

Green synthesis of metal oxides as a treatment for bone diseases is still exploring. Herein, MgO and Fe2O3 NPs were prepared from the extract of Hibiscus sabdariffa L. to study their effect on vit D3, Ca+2, and alkaline phosphatase enzyme ALP associated with osteoporosis. Computational chemistry was utilized to gain insight into the possible interactions. These oxides were characterized by X-ray diffraction, SEM, FTIR, and AFM. Results revealed that green synthesis of MgO and Fe2O3 NPs was successful with abundant. MgO NPs were in vitro applied on osteoporosis patients (n = 35) and showed a significant elevation of vit D3 and Ca+2 (0.0001 > p < 0.001) levels, compared to healthy volunteers (n = 25). Thus, Hibiscus sabdariffa L. is a good candidate to prepare MgO NPs, with a promising enhancing effect on vit D3 and Ca+2 in osteoporosis. In addition, interactions of Fe2O3 and MgO NPs with ALP were determined by molecular docking study.

Enhancing Vitamin D3 Efficacy: Insights from Complexation with Cyclodextrin Nanosponges and Its Impact on Gut-Brain Axes in Physiology and IBS Syndrome.

Vitamin D3 (VitD3) plays a crucial role in various cellular functions through its receptor interaction. The biological activity of Vitamin D3 can vary based on its solubility and stability. Thus, the challenge lies in maximizing its biological effects through its complexation within cyclodextrin (ßNS-CDI 1:4) nanosponges (NS) (defined as VitD3NS). Therefore, its activity has been evaluated on two different gut-brain axes (healthy gut/degenerative brain and inflammatory bowel syndrome gut/degenerative brain axis). At the gut level, VitD3-NS mitigated liposaccharide-induced damage (100 ng/mL; for 48 h), restoring viability, integrity, and activity of tight junctions and reducing ROS production, lipid peroxidation, and cytokines levels. Following intestinal transit, VitD3-NS improved the neurodegenerative condition in the healthy axis and the IBS model, suggesting the ability of VitD3-NS to preserve efficacy and beneficial effects even in IBS conditions. In conclusion, this study demonstrates the ability of this novel form of VitD3, named VitD3-NS, to act on the gut-brain axis in healthy and damaged conditions, emphasizing enhanced biological activity through VitD3 complexation, as such complexation increases the beneficial effect of vitamin D3 in both the gut and brain by about 50%.

The Potential Use of Vitamin D3 and Phytochemicals for Their Anti-Ageing Effects.

Unlike other vitamins, vitamin D3 is synthesised in skin cells in the body. Vitamin D3 has been known as a bone-related hormone. Recently, however, it has been considered as an immune vitamin. Vitamin D3 deficiency influences the onset of a variety of diseases. Vitamin D3 regulates the production of proinflammatory cytokines such as tumour necrosis factor-α (TNF-α) through binding to vitamin D receptors (VDRs) in immune cells. Since blood levels of vitamin D3 (25-OH-D3) were low in coronavirus disease 2019 (COVID-19) patients, there has been growing interest in the importance of vitamin D3 to maintaining a healthy condition. On the other hand, phytochemicals are compounds derived from plants with over 7000 varieties and have various biological activities. They mainly have health-promoting effects and are classified as terpenoids, carotenoids, flavonoids, etc. Flavonoids are known as the anti-inflammatory compounds that control TNF-α production. Chronic inflammation is induced by the continuous production of TNF-α and is the fundamental cause of diseases like obesity, dyslipidaemia, diabetes, heart and brain diseases, autoimmune diseases, Alzheimer's disease, and cancer. In addition, the ageing process is induced by chronic inflammation. This review explains the cooperative effects of vitamin D3 and phytochemicals in the suppression of inflammatory responses, how it balances the natural immune response, and its link to anti-ageing effects. In addition, vitamin D3 and phytochemicals synergistically contribute to anti-ageing by working with ageing-related genes. Furthermore, prevention of ageing processes induced by the chronic inflammation requires the maintenance of healthy gut microbiota, which is related to daily dietary habits. In this regard, supplementation of vitamin D3 and phytochemicals plays an important role. Recently, the association of the prevention of the non-disease condition called "ME-BYO" with the maintenance of a healthy condition has been an attractive regimen, and the anti-ageing effect discussed here is important for a healthy and long life.

Standard Doses of Cholecalciferol Reduce Glucose and Increase Glutamine in Obesity-Related Hypertension: Results of a Randomized Trial.

In arterial hypertension, the dysregulation of several metabolic pathways is closely associated with chronic immune imbalance and inflammation progression. With time, these disturbances lead to the development of progressive disease and end-organ involvement. However, the influence of cholecalciferol on metabolic pathways as a possible mechanism of its immunomodulatory activity in obesity-related hypertension is not known. In a phase 2, randomized, single-center, 24-week trial, we evaluated, as a secondary outcome, the serum metabolome of 36 age- and gender-matched adults with obesity-related hypertension and vitamin D deficiency, before and after supplementation with cholecalciferol therapy along with routine medication. The defined endpoint was the assessment of circulating metabolites using a nuclear magnetic resonance-based metabolomics approach. Univariate and multivariate analyses were used to evaluate the systemic metabolic alterations caused by cholecalciferol. In comparison with normotensive controls, hypertensive patients presented overall decreased expression of several amino acids (p < 0.05), including amino acids with ketogenic and glucogenic properties as well as aromatic amino acids. Following cholecalciferol supplementation, increases were observed in glutamine (p < 0.001) and histidine levels (p < 0.05), with several other amino acids remaining unaffected. Glucose (p < 0.05) and acetate (p < 0.05) decreased after 24 weeks in the group taking the supplement, and changes in the saturation of fatty acids (p < 0.05) were also observed, suggesting a role of liposoluble vitamin D in lipid metabolism. Long-term cholecalciferol supplementation in chronically obese and overweight hypertensives induced changes in the blood serum metabolome, which reflected systemic metabolism and may have fostered a new microenvironment for cell proliferation and biology. Of note, the increased availability of glutamine may be relevant for the proliferation of different T-cell subsets.

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.

Mitigation of Breast Cancer Cells' Invasiveness via Down Regulation of ETV7, Hippo, and PI3K/mTOR Pathways by Vitamin D3 Gold-Nanoparticles.

Metastasis in breast cancer is the major cause of death in females (about 30%). Based on our earlier observation that Vitamin D3 downregulates mTOR, we hypothesized that Vitamin D3 conjugated to gold nanoparticles (VD3-GNPs) reduces breast cancer aggressiveness by downregulating the key cancer controller PI3K/AKT/mTOR. Western blots, migration/invasion assays, and other cell-based, biophysical, and bioinformatics studies are used to study breast cancer cell aggressiveness and nanoparticle characterization. Our VD3-GNP treatment of breast cancer cells (MCF-7 and MDA-MB-231) significantly reduces the aggressiveness (cancer cell migration and invasion rates > 45%) via the simultaneous downregulation of ETV7 and the Hippo pathway. Consistent with our hypothesis, we, indeed, found a downregulation of the PI3K/AKT/mTOR pathway. It is surprising that the extremely low dose of VD3 in the nano formulation (three orders of magnitude lower than in earlier studies) is quite effective in the alteration of cancer invasiveness and cell signaling pathways. Clearly, VD3-GNPs are a viable candidate for non-toxic, low-cost treatment for reducing breast cancer aggressiveness.

Coated sodium butyrate and vitamin D3 supplementation improve gut health through influencing intestinal immunity, barrier, and microflora in early-stage broilers.

BACKGROUND: Intestinal development and function are critical to maintaining sustained broiler growth. The present study aimed to evaluate the effects of coated sodium butyrate (CSB) and vitamin D3 (VD3) on the intestinal immunity, barrier, oxidative stress and microflora in early-stage broilers. In total, 192 one-day-old broilers were assigned to a 2 × 2 factorial design including two dietary supplements at two different levels, in which the main effects were VD3 (3000 or 5000 IU kg-1) and CSB (0 or 1 g kg-1). RESULTS: The results showed that CSB supplementation increased ileal goblet cells (GCs) numbers, villus height and decreased crypt depth in broilers. CSB increased ileal proliferating cell nuclear antigen expression and high-level VD3 decreased cluster of differentiation 3 expression. CSB reduced serum d-lactate, endotoxin (ET), adrenocorticotropic hormone, corticosterone and malondialdehyde (MDA) concentrations and increased total antioxidant capacity (T-AOC) level. Meanwhile, high-level VD3 decreased serum ET concentration. Furthermore, CSB increased ileal T-AOC, lysozyme (LYZ) and transforming growth factor (TGF)-ß and decreased MDA, whereas high-level VD3 decreased ileal MDA and increased secretory immunoglobulin A. CSB up-regulated ileal claudin1, superoxide dismutase 1, TGF-ß and LYZ mRNA expression and down-regulated interleukin-1ß mRNA expression. CSB combined with high-level VD3 increased ileal Faecalibaculum abundance. Spearman correlation analysis showed that Faecalibaculum was related to the immune and barrier function. CONCLUSION: Dietary supplementation with CSB and high-level VD3 improved early gut health in broilers by promoting intestinal development, enhancing antioxidant capacity, strengthening barrier function and enhancing the favorable composition of the gut bacterial flora. © 2024 Society of Chemical Industry.

Vitamin D and wound healing: Assessing skin barrier function and implications for chloasma treatment.

Chloasma, which is distinguished by irregularities in the pigmentation of skin, poses substantial challenge in the field of dermatology. The regulatory influence of vitamin D on the functions of skin cells implies that it may have the capacity to effectively treat chloasma and promote wound healing. To assess the efficacy of vitamin D in chloasma treatment and its impact on the function of skin barrier during the process of wound healing. The research spanned from April 2022 to September 2023, in Shanghai, China, examined 480 individuals who had been diagnosed with chloasma. A double-blind, placebo-controlled clinical trial was utilized to evaluate effectiveness of topical vitamin D3 in treatment of chloasma. Concurrently, randomized control trial investigated the effects of ingested vitamin D3 supplements on the process of wound healing. Transepidermal water loss (TEWL), chloasma severity score changes, wound size reduction and skin hydration levels were critical performance indicators. Statistically, the severity scores of chloasma decreased significantly in the vitamin D treatment group at 3 and 6 months compared with the placebo (p < 0.05). The Vitamin D group exhibited superior wound healing outcomes, including more substantial reduction in lesion size and enhanced skin barrier function, as evidenced by increased skin hydration and decreased TEWL (p < 0.05). Vitamin D substantially mitigated the severity of chloasma and has beneficial effect on wound healing and integrity of the skin barrier. Based on the results obtained, vitamin D exhibited promise as a therapeutic intervention in the field of dermatology, specifically in treatment of chloasma and promotion of wound recovery.

Assessment of the Antibacterial Effect of Vitamin D3 against Red Complex Periodontal Pathogens: A Microbiological Assay.

AIM: The study aims is to evaluate the antibacterial effect of vitamin D3 against the red complex bacteria, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia in chronic periodontitis patients. MATERIALS AND METHODS: The study comprised 98 participants with chronic periodontitis. All clinical parameters including plaque index (PI), gingival bleeding index (GBI), probing pocket depth (PPD), clinical attachment level (CAL), and a microbiological assay of P. gingivalis, T. denticola, T. forsythia were assessed at the baseline. All study participants who underwent scaling and root planning were divided into two groups, A and B, each with 49 patients and only group B patients were advised to take vitamin D supplementation of 60,000 IU granules, once daily for 2 months. All the patients of both the groups were recalled at the end of 2nd month and all the clinical and microbiological parameters were reassessed. RESULTS: After two months, there was a reduction in all the clinical markers in both groups, but the group B patients showed more improvement following non-surgical treatment vitamin D intake. There was also a statistical reduction in P. gingivalis, T. denticola, and T. forsythia following administration of vitamin D in group B patients compared to group A. CONCLUSION: These discoveries proposed that vitamin D has a superb antimicrobial impact against red complex periodontal microbes and might be considered a promising compound in the counteraction of periodontal disease. CLINICAL SIGNIFICANCE: Vitamin D is considered to possess anti-inflammatory and antimicrobial activity, which may help to delay the progression of periodontitis. So, vitamin D3 can be used as a potential supplement that could be employed to stop the advancement of periodontal disease. How to cite this article: Govindharajulu R, Syed NK, Sukumaran B, et al. Assessment of the Antibacterial Effect of Vitamin D3 against Red Complex Periodontal Pathogens: A Microbiological Assay. J Contemp Dent Pract 2024;25(2):114-117.

Electrocardiographic, biochemical, and scintigraphic evidence for the cardioprotective effect of paricalcitol and vitamin D3 on doxorubicin-induced acute cardiotoxicity in rats.

AIM: We aimed to investigate the possible cardioprotective effects of paricalcitol (PR), its vitamin D receptor agonist, and vitamin D3 (VIT-D3) on an experimental model of doxorubicin (DX) cardiotoxicity by 99mTc-PYP scintigraphy, electrocardiographic (ECG) and biochemical methods. METHOD: Forty-two male Wistar/Albino rats (250‒300 g; aged 10‒12 weeks) were randomly separated into six groups, namely into control (CN), doxorubicin (DX), paricalcitol (PR), vitamin D3 (VIT-D3), paricalcitol + doxorubicin (PR+DX), and vitamin D3 + doxorubicin (VIT-D3+DX) groups. Cardiotoxicity was induced by three doses of DX (18 mg/kg, i.p.) at 24-hour intervals on days 18, 19 and 20. PR (0.5 ug/ kg, i.p) and VIT-D3 (5,000 IU/kg, i.p) were injected for 20 days before and after the application of DX (18 mg/kg, i.p.). On day 21 of the experiment, biochemical parameters [tumor necrosis factor TNF-alpha (TNF-α); interleukin-6 (IL-6), nitric oxide (NO), and cardiac troponin T (cTnT)], as well as ECG and scintigraphic (99mTc-PYP) features were assessed. RESULTS: Compared to CN, DX significantly raised TNF-α, IL-6, and NO in heart tissue, cTnT in serum, 99mTc-PYP uptake in the myocardium, and ECG parameters, specifically QRS complex duration, QT interval duration, and ST-segment amplitude, while also reducing heart rate (p<0.001). Pretreatment with PR and VIT-D3 mitigated these abnormalities produced by DX in the heart (p<0.001). CONCLUSION: Results show that vitamin D receptor agonist paricalcitol and vitamin D protect against DX-induced cardiotoxicity through anti-inflammatory and antioxidant effects (Fig. 4, Ref. 59). Text in PDF www.elis.sk Keywords: paricalcitol, doxorubicin, vitamin D, ECG, 99mTc-PYP scintigraphy, cardiotoxicity, inflammation.

Changes in DNA Methylation and mRNA Expression in Lung Tissue after Long-Term Supplementation with an Increased Dose of Cholecalciferol.

Maintaining an appropriate concentration of vitamin D is essential for the proper functioning of the body, regardless of age. Nowadays, there are more and more indications that vitamin D supplementation at higher than standard doses may show protective and therapeutic effects. Our study identified differences in the body's response to long-term supplementation with cholecalciferol at an increased dose. Two groups of pigs were used in the experiment. The first group received a standard dose of cholecalciferol (grower, 2000 IU/kg feed, and finisher, 1500 IU/kg feed), and the second group received an increased dose (grower, 3000 IU/kg feed, and finisher, 2500 IU/kg feed). After slaughter, lung samples were collected and used for RRBS and mRNA sequencing. Analysis of the methylation results showed that 2349 CpG sites had significantly altered methylation patterns and 1116 (47.51%) identified DMSs (Differentially Methylated Sites) were related to genes and their regulatory sites. The mRNA sequencing results showed a significant change in the expression of 195 genes. The integrated analysis identified eleven genes with DNA methylation and mRNA expression differences between the analyzed groups. The results of this study suggested that an increased vitamin D intake may be helpful for the prevention of lung cancer and pulmonary fibrosis. These actions may stem from the influence of vitamin D on the expression of genes associated with collagen production, such as SHMT1, UGT1A6, and ITIH2.The anti-cancer properties of vitamin D are also supported by changes in KLHL3 and TTPA gene expression.