Search Results (12)

PEIG-1/GPRC5A (phorbol ester induced gene-1/G-protein Coupled Receptor Class C Group 5 Member A) was the first identified member of the orphan G protein-coupled receptor family GPRC5. Deregulation of its expression is associated with the development and progression of various types of tumours, particularly colon carcinoma. In this work, we study the effects of vitamin D (VD, cholecalciferol) and retinoic acid (RA) on GPRC5A mRNA expression in the colorectal cancer cell lines Caco-2 and T84. Both VD (10 µM) and all-trans retinoic acid (ATRA, atRA, RA) (10 µM) increased GPRC5A mRNA levels. Protein kinase C (PKC) inhibition with Gö6983 (10 µM) completely abolished the effects of VD and RA on GPRC5A expression. In parallel, VD and RA increased cytosolic and mitochondrial ROS levels (cROS and mtROS). However, the antioxidants NAC (10 mM) and MitoTEMPO (10 µM) raised GPRC5A gene expression levels in the presence of VD or RA, suggesting that elevated ROS may inhibit GPRC5A expression. In conclusion, both VD and RA stimulate GPRC5A expression. The mechanisms involve a common and essential PKC signalling pathway, as Gö6983 inhibited both VD- and RA-induced signalling. Full article

Despite numerous scientific reports on the negative impact of vitamin D3 deficiency on many respiratory diseases, little is known about the influence of this phenomenon on the development and progression of hypersensitivity pneumonitis (HP). The presented study is an attempt to shed light on this occurrence. The research was performed on mouse strain C57BL/6J exposed to the antigen of Pantoea agglomerans (etiological factor of HP). To induce vitamin D3 deficiency, mice received a diet with a 10 times lower amount of cholecalciferol than the main control group. VD3-deficient mice inhaled 25(OH)-VD3 or 1,25(OH)2-VD3 used separately or with SE-PA. At the beginning of the experiment and after 14 and 28 days of inhalation, respiratory function was examined using whole-body plethysmography. Moreover, at indicated time points, mice were sacrificed and samples collected for histological examination, flow cytometry, and ELISA. The performed study revealed that inhalations with 25(OH)-VD3 and 1,25(OH)2-VD3 effectively eliminated most of the negative changes in the respiratory system caused by vitamin D3 deficiency by restoring the physiological concentration of 1,25(OH)₂-VD3 in the body. VD3-deficient mice which inhaled P. agglomerans antigen and vitamin D3 metabolites also demonstrated the ability of the tested compounds to eliminate, or at least weaken, the negative effects of the HP causative factor and desired effect, including improvement of respiratory functions and attenuation of inflammation and signs of fibrosis. The obtained results suggested that the beneficial influence of inhaled vitamin D3 metabolites on HP development was associated with the restoration of the physiological concentration of 1,25(OH)2-VD3 in the pulmonary compartments in VD3-deficient mice. Full article

Vitamin D (VD) deficiency (serum 25(OH)D < 50 nmol/L) affects 27.3% of preschool children in Mexico. The purpose of this study was to assess the effect of vitamin D supplementation at different doses on serum 25(OH)D concentrations in preschool children. In a randomized control trial, 222 children 12–30 months old were randomly assigned to one of four treatment groups: (1) Vitamin D2 (Ergocalciferol) 400 IU/day (n = 56); (2) Vitamin D2 (Ergocalciferol) 800 IU/day (n = 55); (3) Vitamin D3 (Cholecalciferol) 1000 IU/day (n = 56); or (4) multiple micronutrients (MM) non-VD (n = 55). Supplements were given five days/wk for three months. Serum 25(OH)D was measured at baseline and after three months. At baseline, mean serum 25(OH)D was 58.9 ± 12.6 nmol/L and 23.4% were VD-deficient. There was a statistically significant increase in serum concentrations of 25(OH)D (range across groups: +8.2 to +17.3 nmol/L). Additionally, the prevalence of vitamin D deficiency decreased after three months: for D2 400 IU, −9.0%; for D2 800 IU, −11.0%; for D3 1000 IU, −18.0%; and for MM non-VD, −2.8% (p < 0.05). No adverse effects were observed. VD supplementation for three months was effective for increasing serum 25(OH)D concentrations and for reducing VD deficiency in preschool children. The highest efficacy was observed by giving 1000 IU D3/d. Full article

This research aimed to evaluate the effects of high-dose cholecalciferol (VD₃) supplements (50,000 IU/week) on selected circulating cytokines associated with cytokine storms in adults with vitamin D deficiency. This clinical trial, based in Jordan, included 50 participants receiving vitamin D₃ supplements (50,000 IU/week) for 8 weeks; the exact number was assigned to the control group. Interleukin-6 (IL-6), interleukin-1β (IL-1β), interleukin-10 (IL-10), tumor necrotic factor-α (TNF-α), and leptin were measured in serum at baseline and 10 weeks (wash out: 2 weeks). Our results revealed that vitamin D₃ supplementation significantly increased the serum levels of 25OHD, IL-6, IL-10, IL-1β, and leptin compared with baseline. In contrast, the serum level of TNF-α insignificantly increased in the group receiving vitamin D₃ supplementation. Although the observations of this trial may refer to a potential negative effect of VD₃ supplementation during cytokine storms, further trials are required to clarify the potential benefits of VD₃ supplement during cytokine storms. Full article

Vitamin D (calciferol) is a fat-soluble vitamin that has a significant role in phospho-calcium metabolism, maintaining normal calcium levels and bone health development. The most important compounds of vitamin D are cholecalciferol (vitamin D3, or VD3) and ergocalciferol (vitamin D2, or VD2). Besides its major role in maintaining an adequate level of calcium and phosphate concentrations, vitamin D is involved in cell growth and differentiation and immune function. Recently, the association between vitamin D deficiency and the progression of fibrosis in chronic liver disease (CLD) was confirmed, given the hepatic activation process and high prevalence of vitamin D deficiency in these diseases. There are reports of vitamin D deficiency in CLD regardless of the etiology (chronic viral hepatitis, alcoholic cirrhosis, non-alcoholic fatty liver disease, primary biliary cirrhosis, or autoimmune hepatitis). Vitamin D binding protein (VDBP) is synthesized by the liver and has the role of binding and transporting vitamin D and its metabolites to the target organs. VDBP also plays an important role in inflammatory response secondary to tissue damage, being involved in the degradation of actin. As intense research during the last decades revealed the possible role of vitamin D in liver diseases, a deeper understanding of the vitamin D, vitamin D receptors (VDRs), and VDBP involvement in liver inflammation and fibrogenesis could represent the basis for the development of new strategies for diagnosis, prognosis, and treatment of liver diseases. This narrative review presents an overview of the evidence of the role of vitamin D and VDBP in CLD, both at the experimental and clinical levels. Full article

This study compared the efficacies of enteral cholecalciferol and/or intravenous (IV) calcitriol administration on mesenteric lymph node (MLN) cluster-of-differentiation-4-positive (CD4+) T cell distribution and intestinal barrier damage in obese mice complicated with sepsis. Mice were fed a high-fat diet for 16 weeks and then sepsis was induced by cecal ligation and puncture (CLP). Mice were divided into the following sepsis groups: without vitamin D (VD) (S); with oral cholecalciferol 1 day before CLP (G); with IV calcitriol 1 h after CLP (V); and with both cholecalciferol before and IV calcitriol after CLP (GV). All mice were sacrificed at 12 or 24 h after CLP. The findings show that the S group had a higher T helper (Th)17 percentage than the VD-treated groups at 12 h after CLP. The V group exhibited a higher Th1 percentage and Th1/Th2 ratio than the other groups at 24 h, whereas the V and GV groups had a lower Th17/regulatory T (Treg) ratio 12 h post-CLP in MLNs. In ileum tissues, the VD-treated groups had higher tight junction protein and cathelicidin levels, and higher mucin gene expression than the S group at 24 h post-CLP. Also, aryl hydrocarbon receptor (AhR) and its associated cytochrome P450 1A1 and interleukin 22 gene expressions were upregulated. In contrast, levels of lipid peroxides and inflammatory mediators in ileum tissues were lower in the groups with VD treatment after CLP. These results suggest that IV calcitriol seemed to have a more-pronounced effect on modulating the homeostasis of Th/Treg subsets in MLNs. Both oral cholecalciferol before and IV calcitriol after CLP promoted cathelicidin secretion, alleviated intestinal inflammation, and ameliorated the epithelial integrity in obese mice complicated with sepsis possibly via VD receptor and AhR signaling pathways. Full article

The biology of vitamin D3 is well defined, as are the effects of its active metabolites on various cells, including mesenchymal stromal/stem cells (MSCs). However, the biological potential of its precursor, cholecalciferol (VD3), has not been sufficiently investigated, although its significance in regenerative medicine—mainly in combination with various biomaterial matrices—has been recognized. Given that VD3 preconditioning might also contribute to the improvement of cellular regenerative potential, the aim of this study was to investigate its effects on bone marrow (BM) MSC functions and the signaling pathways involved. For that purpose, the influence of VD3 on BM-MSCs obtained from young human donors was determined via MTT test, flow cytometric analysis, immunocytochemistry, and qRT-PCR. Our results revealed that VD3, following a 5-day treatment, stimulated proliferation, expression of pluripotency markers (NANOG, SOX2, and Oct4), and osteogenic differentiation potential in BM-MSCs, while it reduced their senescence. Moreover, increased sirtuin 1 (SIRT1) expression was detected upon treatment with VD3, which mediated VD3-promoted osteogenesis and, partially, the stemness features through NANOG and SOX2 upregulation. In contrast, the effects of VD3 on proliferation, Oct4 expression, and senescence were SIRT1-independent. Altogether, these data indicate that VD3 has strong potential to modulate BM-MSCs’ features, partially through SIRT1 signaling, although the precise mechanisms merit further investigation. Full article

Vitamin D (VD) is a calcium- and phosphate-controlling hormone used to treat bone disorders; yet, several other effects are progressively emerging. VD deficiency is highly prevalent worldwide, with suboptimal exposure to sunlight listed among the leading causes: oral supplementation with either cholecalciferol or calcitriol is used. However, there is a scarcity of clinical studies investigating how quickly VD concentrations can increase after supplementation. In this pilot study, the commercial supplement ImmuD3 (by Erboristeria Magentina^®) was chosen as the source of VD and 2000 IU/day was administered for one month to 21 healthy volunteers that had not taken any other VD supplements in the previous 30 days. Plasma VD levels were measured through liquid chromatography coupled to tandem mass spectrometry after 7, 14, and 28 days of supplementation. We found that 95% of the participants had insufficient VD levels at baseline (<30 ng/mL; median 23.72 ng/mL; IQR 18.10–26.15), but after 28 days of supplementation, this percentage dropped to 62% (median 28.35 ng/mL; IQR 25.78–35.20). The median increase in VD level was 3.09 ng/mL (IQR 1.60–5.68) after 7 days and 8.85 ng/mL (IQR 2.85–13.97F) after 28 days. This study suggests the need for continuing VD supplementation and for measuring target level attainment. Full article

Dysfunctional mitochondrial metabolism has been linked to skeletal muscle loss in several physio-pathological states. Although it has been reported that vitamin D (VD) supports cellular redox homeostasis by maintaining normal mitochondrial functions, and VD deficiency often occurs in conditions associated with skeletal muscle loss, the efficacy of VD supplementation to overcome muscle wasting is debated. Investigations on the direct effects of VD metabolites on skeletal muscle using C2C12 myotubes have revealed an unexpected pro-atrophic activity of calcitriol (1,25VD), while its upstream metabolites cholecalciferol (VD3) and calcidiol (25VD) have anti-atrophic effects. Here, we investigated if the atrophic effects of 1,25VD on myotubes depend on its activity on mitochondrial metabolism. The impact of 1,25VD and its upstream metabolites VD3 and 25VD on mitochondria dynamics and the activity of C2C12 myotubes was evaluated by measuring mitochondrial content, architecture, metabolism, and reactive oxygen species (ROS) production. We found that 1,25VD induces atrophy through protein kinase C (PKC)-mediated ROS production, mainly of extramitochondrial origin. Consistent with this, cotreatment with the antioxidant N-acetylcysteine (NAC), but not with the mitochondria-specific antioxidant mitoTEMPO, was sufficient to blunt the atrophic activity of 1,25VD. In contrast, VD3 and 25VD have antioxidant properties, suggesting that the efficacy of VD supplementation might result from the balance between atrophic pro-oxidant (1,25VD) and protective antioxidant (VD3 and 25VD) metabolites. Full article

Vitamin D (VD) has been observed to have anti-inflammatory properties. However, the effects of VD supplementation on the serum amyloid P component (SAP) has not been established. This study aimed to investigate the effect of VD supplementation on serum SAP levels in Arab adults. A total of 155 VD-deficient adult Saudis (56 males and 99 females) were recruited in this non-randomized, 6-month, single-arm trial. The intervention was as follows; cholecalciferol 50,000 international units (IU) every week for the first 2 months, followed by 50,000 twice a month for the next two months, and for the last two months, 1000 IU daily. Serum 25(OH)D, SAP, C-reactive protein (CRP), lipid profile, and glucose were assessed at baseline and post-intervention. At post-intervention, VD levels were significantly increased, while SAP levels significantly decreased in all study participants. Remarkably, this reduction in SAP was more significant in males than females after stratification. SAP was inversely correlated with VD overall (r = −0.17, p < 0.05), and only in males (r = −0.27, p < 0.05) after stratification according to sex after 6 months of VD supplementation. Such a relationship was not observed at baseline. VD supplementation can favorably modulate serum SAP concentrations in Arab adults, particularly in males. Full article

There are indications that ultraviolet B (UVB) exposure has beneficial effects on well-being through mechanisms other than vitamin D synthesis alone. We conducted a randomized controlled multicenter trial to compare the effects of UVB light and vitamin D supplementation (VD) in terms of the well-being of nursing home residents with dementia. Participants were randomly assigned to the intervention group (UVB group, n = 41; half-body UVB irradiation, twice weekly over 6 months, with 1 standard erythema dose (SED)) or to the control group (VD group, n = 37; 5600 International units (IU) cholecalciferol supplementation once a week). The main outcome was well-being, measured by the Cohen-Mansfield Agitation Inventory (CMAI) and the Cornell scale for depression in dementia at 0, 3, and 6 months. Secondary outcomes were QUALIDEM quality of life domains and biochemical parameters of bone homeostasis. Intention-to-treat analysis with linear mixed modeling showed no significant between-group differences on agitation (p = 0.431) or depressive symptoms (p = 0.982). At six months, the UVB group showed less restless/tense behavior compared to the VD group (mean difference of the mean change scores 2.2, 95% CI 0.8 to 3.6; p = 0.003 for group x time interaction) and lower serum 25(OH)D3 concentration (estimated mean difference - 21.9, 95% CI −32.6 to −11.2; p = 0.003 for group difference). The exposure of nursing home residents with dementia to UVB light showed no positive benefits in terms of wellbeing. UVB treatment may have a positive effect on the restless/tense behavior characteristic of advanced dementia but more research is needed to confirm this finding. Full article

Obesity predisposes to vitamin D deficiency (VDD) and glucose abnormalities. It is currently debated if vitamin D administration may improve glucose homeostasis by interacting with modulators of insulin sensitivity, such as adiponectin and its oligomers. In a 4-week inpatient study on a metabolic rehabilitation program, consisting of individualized caloric restriction and aerobic physical exercise in obese subjects with VDD, we assessed the acute effects of 600,000 IU cholecalciferol given per os VD group, 12 subjects; body mass index (BMI) 42.7 ± 1.3 kg/m²) or placebo per os (PL group, 12 subjects, BMI 39.8 ± 0.9 kg/m²) on high (HWM-A), medium (MMW-A), and low molecular weight adiponectin (LMW-A), as quantified by western immunoblot (WIB) and ELISA. During the 4-week study, dieting promoted a similar magnitude of weight loss in VD and PL groups. Compared to the PL group, cholecalciferol administration increased 25(OH)Vit D levels (p < 0.001) and promoted a significant increase of HMW-A expression analyzed by WIB (p = 0.02). In parallel, a significant decrease of leptin/HMW-A ratio (p < 0.05), a biomarker of metabolic homeostasis, was observed. During the study, changes of MMW-A and LMW-A occurred independently of cholecalciferol administration, and were likely explained by weight loss. At odds with these findings, the ELISA assessment of adiponectin oligomers showed no modifications in the VD group or PL group. Current findings suggest that acute cholecalciferol administration selectively modifies HMW-A and the leptin/HMW-A ratio. Full article