Effects Of VitD Research Articles

Cocoa flavonoids: a promising ingredient that potentiates vitamin d action in skeletal muscle cells

Rationale: Vitamin D (VitD) effects take place by binding to its receptor (VDR) which is a classical nuclear receptor responsible for genomic effects, but there is also a fraction of the VDR located in the muscle plasma membrane that is responsible for its non-genomic effects. In addition to the established effect of VitD in bone and mineral homeostasis, VitD insufficiency/deficiency is linked to a range of muscle disorders including frailty and muscle loss/dysfunction. Flavonoids decrease insulin resistance and have antioxidant and anti-inflammatory properties by activating Akt signaling pathways. Our study has aimed to evaluate, in VitD deficient conditions, if cocoa flavonoids (CF) are able to mediate the interacction between VitD and skeletal muscle glucose uptake by triggerring the modulation of its genomic and non-genomic signaling pathways. This could be useful in pathological deficient VitD situations, such as diabetes or sarcopenia where muscle function is compromised due to the onset of insulin resistance.

Mendelian Randomization Focused Analysis of Vitamin D on the Secondary Prevention of Ischemic Stroke.

Experimental studies showed vitamin D (Vit-D) could promote vascular regeneration and repair. Prior randomized studies had focused mainly on primary prevention. Whether Vit-D protects against ischemic stroke and myocardial infarction recurrence among subjects with prior ischemic insults was unknown. Here, we dissected through Mendelian randomization any effect of Vit-D on the secondary prevention of recurrent ischemic stroke and myocardial infarction. Based on a genetic risk score for Vit-D constructed from a derivation cohort sample (n=5331, 45% Vit-D deficient, 89% genotyped) via high-throughput exome-chip screening of 12 prior genome-wide association study-identified genetic variants of Vit-D mechanistic pathways (rs2060793, rs4588, and rs7041; F statistic, 73; P<0.001), we performed a focused analysis on prospective recurrence of myocardial infarction (MI) and ischemic stroke in an independent subsample with established ischemic disease (n=441, all with prior first ischemic event; follow-up duration, 41.6±14.3 years) under a 2-sample, individual-data, prospective Mendelian randomization approach. In the ischemic disease subsample, 11.1% (n=49/441) had developed recurrent ischemic stroke or MI and 13.3% (n=58/441) had developed recurrent or de novo ischemic stroke/MI. Kaplan-Meier analyses showed that genetic risk score predicted improved event-free survival from recurrent ischemic stroke or MI (log-rank, 13.0; P=0.001). Cox regression revealed that genetic risk score independently predicted reduced risk of recurrent ischemic stroke or MI combined (hazards ratio, 0.62 [95% CI, 0.48-0.81]; P<0.001), after adjusted for potential confounders. Mendelian randomization supported that Vit-D is causally protective against the primary end points of recurrent ischemic stroke or MI (Wald estimate: odds ratio, 0.55 [95% CI, 0.35-0.81]) and any recurrent or de novo ischemic stroke/MI (odds ratio, 0.64 [95% CI, 0.42-0.91]) and recurrent MI alone (odds ratio, 0.52 [95% CI, 0.30-0.81]). Genetically predicted lowering in Vit-D level is causal for the recurrence of ischemic vascular events in persons with prior ischemic stroke or MI.

Autophagy Prevents Osteocyte Cell Death under Hypoxic Conditions

Hypoxia occurs under important clinical conditions such as cancers, heart disease, and ischemia. However, the relationship between hypoxia and autophagy in osteocytes is still unclear. The objective of the present study was to uncover the regulatory mechanisms that prevent regulated cell death, such as apoptosis, necrosis, and autophagy, under hypoxia. MLO-Y4 cells, a mouse osteocyte cell line, were exposed to various O₂ partial pressures (PO₂). Subsequently, the cells underwent apoptosis, autophagy, autophagic cell death, and/or necrosis, and thereby we designated PO₂ = 2% as a representative hypoxic condition. Immunofluorescence staining showed an increase of LC3 and a decrease of p62 in MLO-Y4 cells exposed to hypoxia, indicating the induction of autophagy. We then hypothesized that β-estradiol (E2) and vitamin D play an important role in apoptosis and autophagy of osteocytes under hypoxia. 1,25α-dihydroxyvitamin D3 (VitD) protected MLO-Y4 cells from cell death and induced autophagy. However, E2 showed little effect. Finally, Western blotting for phosphorylated mTOR and Akt was carried out in order to investigate the altered autophagy signaling pathways affected by the addition of VitD and E2. However, neither E2 nor VitD were capable of recovering the decreased phosphorylation of those factors. Our results indicated that the effects of VitD on autophagy under hypoxia were dependent on the Akt and mTOR pathways. Thus, the results of the present study showed that VitD suppresses osteocyte cell death in an mTOR pathway-dependent manner in hypoxic conditions. This suggests the potential of VitD as a therapeutic intervention for diseases in which the cell death of osteocytes mainly occurs via hypoxia.

Serum 25-Hydroxyvitamin D Concentrations and Atopic Dermatitis in Early Childhood: Findings from the Japan Environment and Children’s Study

Vitamin D (VitD) may affect immune system modulation and result in the development of atopic dermatitis (AD). However, published findings have remained controversial. We investigated the association between early-life 25-hydroxyvitamin D (25(OH)D) levels and AD risk at childhood with a birth cohort. The data were obtained from “the Japan Environment and Children’s Study (JECS)” and “the Sub-Cohort study of JECS” performed with children aged 2 years. “Liquid chromatography-tandem mass spectrometry” was used to measure VitD. The information on AD was obtained from parents’ answers to a questionnaire when their children were aged 3 years. In order to explain the seasonal effects on VitD levels, a deseasonalized continuous variable was further calculated. The logistic regression models were fitted to evaluate the effect of VitD on childhood AD. The study included 4378 children with complete data on VitD and AD. The results from models indicated that low VitD at 2 years was not a risk factor for the development of AD at 3 years, after adjusting for potential confounders. Moreover, there was no U-shape relationship between deseasonalized VitD and childhood AD. Overall, early-life 25(OH)D levels were not link to the increased risk of developing childhood AD.

Vitamin D Regulates the Expression of Glucocorticoid Receptors in Blood of Severe Asthmatic Patients.

Purpose Vitamin D (VitD) deficiency is a significant public health concern in many areas around the globe and has been associated with many immune-mediated diseases, including asthma. Severe asthma has been linked to a decreased glucocorticoid receptor (GR) ratio (GR-α/GR-β ratio), indicating steroid hyporesponsiveness. Using a combination of in silico and in vivo approaches, we aimed to explore the immunomodulatory effect of VitD on asthmatic patients diagnosed with hypovitaminosis D. MethodsIn silico tools were used to identify the regulatory effect of VitD supplementation on GR genes. We measured the expression levels of GR-α and the inactive isoform, GR-β, in the blood of adult asthmatics diagnosed with hypovitaminosis D before and after VitD supplementation. Moreover, the blood levels of inflammatory cytokines associated with asthma severity were determined. Results Using an in silico approach, we identified specific genes commonly targeted by VitD as well as corticosteroids, the mainstay of asthma therapy. NR3C1 gene encoding GR was found to be significantly upregulated on Th2 CD4 cells and NK cells. Interestingly, blood expression level of NR3C1 was lower in severe asthmatics compared to nonsevere asthmatics and healthy controls, while the blood level of VitD receptor (VDR) was higher. Upon VitD supplementation of severe asthmatic patients, there was a significant increase in the blood levels of GR-α with no change in GR-β mRNA expression. VitD supplementation also suppressed the blood levels of IL-17F and IL-4. Conclusion VitD may enhance steroid responsiveness by upregulating the expression of steroid receptor GR-α.

MO081THE INFLUENCE OF VITAMIN D3 ON PODOCYTE DIFFERENTIATION IN SITU AND IN VITRO

Abstract Background and Aims Dedifferentiation of podocytes affects their complex 3 D morphology and is the main initiator for the development of chronic kidney disease (CKD). Unfortunately, there is no causal therapy for CKD until today. Thus, inadequate and late treatment lead to end-stage renal disease which subsequently makes renal replacement therapy inevitable. To address this, new treatment options are of high significance for CKD patients. Recently, vitamin D3 (VitD) became a promising candidate, but it is controversially discussed. In the present study, we investigated the influence of VitD on podocyte differentiation and the related pathways in situ and in vitro. Method We combined a podocyte dedifferentiation model (GlomAssay) with an automated imaging procedure (Aquifer Imaging Machine). We analyzed cultured glomeruli from transgenic mice expressing cyan-fluorescent protein (CFP) under the control of the nephrin promoter which were treated with VitD and its` analogue (calcipotriol). In this model, the decreasing CFP fluorescence is as a read out for podocyte (de)differentiation. Additionally, VitD-, calcipotriol- and VitD receptor (VDR) inhibitor (PS121912)-treated glomeruli were investigated by RNA-Seq and LC-MS/MS to reveal the molecular effects of VitD on podocyte differentiation. Furthermore, we treated cultured murine podocytes with VitD, calcipotriol and PS121912 to elucidate the morphological and molecular changes by immunofluorescence staining, RT-qPCR and Western blot. Results VitD- and calcipotriol-treated glomeruli showed a significantly higher intensity of CFP fluorescence after 9 days, indicating higher level of nephrin compared to the control. This was verified by RT-qPCR and Western blot for nephrin and CFP. Additionally, we found an upregulation of VDR in VitD- and calcipotriol-treated glomeruli compared to controls. By transcriptomic and proteomic analysis, we identified molecular patterns that are specific for the different treated groups. Thus, we observed differential gene expression in VitD- and Wnt-signaling pathway as well as regulated genes that are essential for the actin cytoskeleton, focal adhesion formation and the slit membrane. Beside this, cultured podocytes showed a significant upregulation of the slit membrane protein nephrin, VDR and CYP24A1 by VitD. This is accompanied by an altered morphology of the podocytes due to a reorganization of the actin cytoskeleton. Conclusion Our results show that VitD influences podocyte differentiation in situ and in vitro by the regulation of specific signaling pathways.

Immunomodulation of T Helper Cells by Tumor Microenvironment in Oral Cancer Is Associated With CCR8 Expression and Rapid Membrane Vitamin D Signaling Pathway.

The immune system plays a key role in the protective response against oral cancer; however, the tumor microenvironment (TME) impairs this anti-cancer response by modulating T helper (Th) responses and promoting an anti-inflammatory environment. Regulatory T cells (Tregs) and Th2 effector cells (Teff) are associated with poor prognosis in oral squamous cell carcinoma (OSCC). However, the main immunomodulatory mechanisms associated with the enrichment of these subsets in OSCC remain unknown. We characterized Th-like lineages in Tregs and Teff and evaluated immunomodulatory changes induced by the TME in OSCC. Our phenotypic data revealed a higher distribution of tumour-infiltrating CCR8+ and Th2-like Treg in OSCC compared with non-malignant samples, whereas the percentages of Th1 cells were reduced in cancer. We then analyzed the direct effect of the TME by exposing T cell subsets to cancer secretomes and observed the OSCC secretome induced CCR8 expression and reduced cytokine production from both subsets. Transcriptomic analysis showed that the co-culture with OSCC secretome induced several gene changes associated with the vitamin D (VitD) signaling pathway in T cells. In addition, proteomic analysis identified the presence of several proteins associated with prostaglandin E2 (PGE2) production by rapid membrane VitD signaling and a reduced presence of the VitD binding protein. Thus, we analyzed the effect of VitD and PGE2 and observed that VitD promotes a regulatory Th2-like response with CCR8 expression whilst PGE2 also modulated CCR8 but inhibited cytokine production in combination with VitD. Finally, we evaluated the presence of CCR8 ligand in OSCC and observed increased chemokine CCL18, which was also able to upregulate CCR8 in activated Th cells. Overall, our data showed the immunomodulatory changes induced by the TME involving CCR8 expression and regulatory Th2 phenotypes, which are associated with PGE2 mediated VitD signaling pathway and CCL18 expression in OSCC.

The Influence of Vitamin D Status on the Severity of SARS-CoV-2 Respiratory Infection

Introduction: The high prevalence of vitamin D (vitD) deficiency in the general population is well recognized. Evidence suggests an immunomodulatory role for vitD in pro-inflammatory conditions, but doubt remains on its association with the severity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) respiratory infection (RI). Aim: To assess the impact of vitD status on the severity of SARS-CoV-2 RI in adults. Material and Methods: A cross-sectional study that included adults infected with SARS-CoV-2 until 1/14/2020 was performed. Patients taking calcium, vitD supplementation or antiepileptics, with malabsorptive and/or calcium and phosphate metabolic disorders or stage 4 or 5 chronic kidney disease were excluded. Levels of 25-hydroxyvitamin D (25(OH)D) were obtained at the time of RI diagnosis. The participants were divided into 2 groups, depending on the vitD status (sufficiency and insufficiency [≥20 ng/mL]; deficiency [<20 ng/mL]), and in 3 groups of clinical severity of RI (adapted from the update [14/10/2020] of the standard 004/2020 of the Portuguese Directorate-General for Health): mild/moderate disease (g1); severe disease without bacterial coinfection (g2); severe disease with bacterial coinfection/critical disease (g3). Other factors associated with RI severity were analyzed. A multiple logistic regression model was developed to predict the severity of SARS-CoV-2 RI, considering vitD status as a categorical variable and other variables with statistical significance after univariate analysis. Results: This study encompassed 71 infected patients with a median age of 68 (p25;p75 = 58;77) years, 40 (56.3%) of which were women. 32 (45.1%) patients integrated g1, 14 (19.7%) g2 and 25 (35.2%) g3. 39 (54.9%) presented vitD deficiency and 32 (45.1%) vitD sufficiency or insufficiency. In the univariate analysis, vitD deficiency, age (>60 years old), male gender, Arterial Hypertension, Diabetes Mellitus, use of angiotensin-II receptor antagonist and reduced levels of ionized serum calcium correlated with the severity of RI. In the multivariate regression model that included these variables, vitD deficiency remained independently correlated with critical/severe disease with bacterial coinfection (g3 vs. g1: OR=9.7; CI95%=[1.7; 56.4]; p=0.011; g3 vs. g2: OR=6.3; CI95%=[1.1–37.0]; p=0.044), with a tendency, albeit not statistically significant, for severe RI without bacterial coinfection (g2 vs g1: OR=1.6; CI95%=[0.3; 7.4]; p=0.581). Conclusions: An independent association of vitD deficiency with the severity of SARS-CoV-2 RI was found, supporting the anti-inflammatory effects of vitD. It is essential to identify and treat its deficiency in patients prone to adverse outcomes of SARS-CoV-2 RI.

The relationship between vitamin D status, intake and exercise performance in UK University-level athletes and healthy inactive controls.

The potential ergogenic effects of vitamin D (vitD) in high performing athletes has received considerable attention in the literature and media. However, little is known about non-supplemented university athletes and students residing at a higher latitude. This study aimed to investigate the effects of vitD (biochemical status and dietary intake) on exercise performance in UK university athletes and sedentary students. A total of 34 athletes and 16 sedentary controls were studied during the spring and summer months. Serum vitD status and sunlight exposure were assessed using LC-MS/MS and dosimetry, respectively. Muscular strength of the upper and lower body was assessed using handgrip and knee extensor dynamometry (KE). Countermovement jump (CMJ) and aerobic fitness were measured using an Optojump and VO2max test, respectively. Statistical analysis was performed using paired/ independent t-tests, ANCOVA and Pearson/ Spearman correlations, depending on normality. VitD status increased significantly over the seasons, with athletes measuring higher status both in spring (51.7±20.5 vs. 37.2±18.9 nmol/L, p = 0.03) and summer (66.7±15.8 vs 55.6±18.8 nmol/L, p = 0.04) when compared to controls, respectively. Notably, 22% of the subjects recruited were vitD deficient during the spring term only (<25nmol/L, n 9). Subjects with ‘insufficient’ vitD status (<50nmol/L) elicited significantly lower CMJ when contrasted to the vitD ‘sufficient’ (>50nmol/l) group (p = 0.055) and a lower VO2 max (p = 0.05) in the spring and summer term (p = 0.05 and p = 0.01, respectively). However, an ANCOVA test showed no significant difference detected for either CMJ or VO2max following adjustments for co-variates. In conclusion, we provide novel information on the vitD status, dietary intake, physical fitness and sunlight exposure of UK young adults across two separate seasons, for which there is limited data at present.

Vitamin D Supplementation and Impact on Skeletal Muscle Function in Cell and Animal Models and an Aging Population: What Do We Know So Far?

Aging is associated with impairment in skeletal muscle mass and contractile function, predisposing to fat mass gain, insulin resistance and diabetes. The impact of Vitamin D (VitD) supplementation on skeletal muscle mass and function in older adults is still controversial. The aim of this review was to summarize data from randomized clinical trials, animal dietary intervention and cell studies in order to clarify current knowledge on the effects of VitD on skeletal muscle as reported for these three types of experiments. A structured research of the literature in Medline via PubMed was conducted and a total of 43 articles were analysed (cells n = 18, animals n = 13 and humans n = 13). The results as described by these key studies demonstrate, overall, at cell and animal levels, that VitD treatments had positive effects on the development of muscle fibres in cells in culture, skeletal muscle force and hypertrophy. Vitamin D supplementation appears to regulate not only lipid and mitochondrial muscle metabolism but also to have a direct effect on glucose metabolism and insulin driven signalling. However, considering the human perspective, results revealed a predominance of null effects of the vitamin on muscle in the ageing population, but experimental design may have influenced the study outcome in humans. Well-designed long duration double-blinded trials, standardised VitD dosing regimen, larger sample sized studies and standardised measurements may be helpful tools to accurately determine results and compare to those observed in cells and animal dietary intervention models.

Immunomodulatory Agents Combat Multidrug-Resistant Tuberculosis by Improving Antimicrobial Immunity.

BackgroundMultidrug-resistant (MDR) tuberculosis has low treatment success rates, and new treatment strategies are needed. We explored whether treatment with active vitamin D3 (vitD) and phenylbutyrate (PBA) could improve conventional chemotherapy by enhancing immune-mediated eradication of Mycobacterium tuberculosis.MethodsA clinically relevant model was used consisting of human macrophages infected with M. tuberculosis isolates (n = 15) with different antibiotic resistance profiles. The antimicrobial effect of vitD+PBA, was tested together with rifampicin or isoniazid. Methods included colony-forming units (intracellular bacterial growth), messenger RNA expression analyses (LL-37, β-defensin, nitric oxide synthase, and dual oxidase 2), RNA interference (LL-37-silencing in primary macrophages), and Western blot analysis and confocal microscopy (LL-37 and LC3 protein expression).ResultsVitD+PBA inhibited growth of clinical MDR tuberculosis strains in human macrophages and strengthened intracellular growth inhibition of rifampicin and isoniazid via induction of the antimicrobial peptide LL-37 and LC3-dependent autophagy. Gene silencing of LL-37 expression enhanced MDR tuberculosis growth in vitD+PBA–treated macrophages. The combination of vitD+PBA and isoniazid were as effective in reducing intracellular MDR tuberculosis growth as a >125-fold higher dose of isoniazid alone, suggesting potent additive effects of vitD+PBA with isoniazid.ConclusionsImmunomodulatory agents that trigger multiple immune pathways can strengthen standard MDR tuberculosis treatment and contribute to next-generation individualized treatment options for patients with difficult-to-treat pulmonary tuberculosis.

Reveal the Myths about Role of Vitamin D Level on Some Hematological Parameters

Background: Vitamin D (Vit-D) may have effect on hematological parameters. Objective: To measure the effect of Vit-D on blood indices, our study was conducted to assess the relationship between Vit-D levels and hematological parameters. Subjects and Methods: The present study was cross section study conducted on 200 patients. Demographic data including age, sex, disease history and blood samples were withdrawn to measure serum vitamin D levels and hematological parameters. Data were reported as Mean ±SD and as frequency (percentage). ANOVA test was used to compare the mean serum levels of vitamin D in terms of sex, age or disease history. Results: Subjects enrolled into the study were 200 patients; 115(57.5%) females and 85(42.5%) males with mean age± SD of 37.6± 15.5 years. The mean serum vitamin D level in patients was 21.96 ± 14.31. There was non-significant relationship between hematological parameters and serum vitamin D level based on Pearson’s test. Conclusion: According to the findings of this study, it is interesting area of research that vitamin D was not the sole factor that have a role on hematological parameters as other factor may play a role as erythropoietin

A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial of High-Dose, Short-Term Vitamin D Administration in the Prevention of Acute Kidney Injury after Cardiac Surgery

Background: Acute kidney injury (AKI) after cardiac surgery is a relatively common complication affecting short- and long-term survival. The renoprotective effect of vitamin D (VitD) has been confirmed in several experimental models. This study was conducted to evaluate the effect of high-dose VitD administration in patients with VitD insufficiency on the incidence of postoperative AKI, the urinary level of tubular biomarkers, and serum anti-inflammatory biomarker after coronary artery bypass graft. Design and Method: In this randomized double-blind controlled clinical trial, the patients were randomly allocated to either the VitD group (n = 50), receiving 150,000 IU VitD tablets daily for 3 consecutive days before surgery or the control group (n = 61), receiving placebo tablets. Results: There was no difference in the incidence of postoperative AKI between the groups. Both of the urinary levels of interleukin-18 and kidney injury molecule-1 were significantly increased after the operation (p < 0.001, for both). Also, the serum level of interleukin-10 was increased after 3 days of VitD supplementation (p = 0.001). In comparison with the control group, it remained on a higher level after the operation (p < 0.001) and the next day (p = 0.03). The patients with AKI had more postoperative bleeding and received more blood transfusion. Conclusion: VitD pretreatment was unable to impose any changes in the incidence of AKI and the urinary level of renal biomarkers. However, high-dose administration of VitD may improve the anti-inflammatory state before and after the operation. Further studies are needed to assess the renoprotective effect of VitD on coronary surgery patients.

The possible double-edged sword effects of vitamin D on COVID-19: A hypothesis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gains access to host cells by attaching to angiotensin-converting enzyme 2 (ACE2). Vitamin D (VitD) can upregulate ACE2 and has an antagonistic effect on Renin, which exerts a vasodilatation and anti-inflammatory effect against coronavirus disease (COVID-19). However, it may also facilitate viral entry by increasing ACE2 as the main SARS-CoV-2 receptor and mediates ROS production through NADPH oxidase, as a double-edged sword effect. Lung function and the immune system are also influenced by VitD through several mechanisms, including increased natural antibiotics (Defensin and Cathelicidin) and upregulated transforming growth factor-β. A higher IgA, Th2/Th1 ratio, and T-regulatory cells are attributable to VitD effects on the immune cells, while these changes may also be a double-edged sword in COVID-19. Although VitD supplementation might be highly recommended in COVID-19, the administration's dosage and route could be challenging. Furthermore, this issue has not been mentioned in various studies so far. So, the report aimed to explain the current challenges with the application of VitD in COVID-19.

Arsenic exposure associated T cell proliferation, smoking, and vitamin D in Bangladeshi men and women.

There are limited data examining the consequences of environmental exposure to arsenic on the immune system in adults, particularly among smokers. Smoking has been shown to exacerbate or contribute to impaired immune function in men chronically exposed to arsenic. In contrast, vitamin D (VitD) is known to have a positive influence on innate and adaptive immune responses. The effect of circulating VitD on arsenic-associated immune dysfunction is not known. Here we examine the relationship of arsenic exposure and T cell proliferation (TCP), a measure of immune responsiveness, and circulating VitD among adult men and women in Bangladesh. Arsenic exposure was assessed using total urinary arsenic as well as urinary arsenic metabolites all adjusted for urinary creatinine. TCP was measured ex vivo in cryopreserved peripheral blood mononuclear cells from 614 adult participants enrolled in the Bangladesh Health Effects of Arsenic Longitudinal Study; serum VitD was also evaluated. The influence of cigarette smoking on arsenic-induced TCP modulation was assessed only in males as there was an inadequate number of female smokers. These studies show that arsenic suppressed TCP in males. The association was significantly strong in male smokers and to a lesser extent in male non-smokers. Interestingly, we found a strong protective effect of high/sufficient serum VitD levels on TCP among non-smoking males. Furthermore, among male smokers with low serum VitD (⊔20 ng/ml), we found a strong suppression of TCP by arsenic. On the other hand, high VitD (>20 ng/ml) was found to attenuate effects of arsenic on TCP among male-smokers. Overall, we found a strong protective effect of VitD, when serum levels were >20 ng/ml, on arsenic-induced inhibition of TCP in men, irrespective of smoking status. To our knowledge this is the first large study of immune function in healthy adult males and females with a history of chronic arsenic exposure.

Maternal Vitamin D Status Affects Hepatitis B Vaccine Response in Breastfeeding Infants

Abstract Objectives Vitamin D (VitD) affects immune function across the lifespan, which includes pregnancy and lactation. We hypothesized that the response of fully breastfeeding (BrF) infants to HBV would differ as a function of maternal and/or infant's vitD status as measured by circulating 25-hydroxyD (25-D) concentration. Methods Plasma 25-D concentration and HBV titers were measured in a subset of mothers and exclusively BrF infants (n = 56 pairs) participating in a lactation vitD supplementation clinical trial. Mothers were randomized to receive either 400 vs. 6400 IU vitD3/day and infants 400 IU/day or placebo (if mother was in 6400 IU group). An additional 14 infants were exclusively formula-fed (FF). 25-D concentration (RIA) and infant anti-HBV IgG titers (ELISA) after 3 vaccinations (7 months of age) were measured. The associations between maternal vitD treatment group, circulating 25-D, and HBV IgG titers were explored using t-tests, ANOVA and linear correlations. Results After 3 vaccinations, all infants in this study were considered to be highly immune to HBV (plasma anti-HBV surface IgG titer &amp;gt;100 IU/mL). However, we found that mean anti-HBV IgG titers in exclusively BrF infants were significantly lower if mother was vitD sufficient (2200 vs 4500 IU/ml; P = 0.017), with inverse correlation between infant IgG titers and maternal vitD status (r = −0.31; P = 0.02). We also found that these infant anti-HBV titers were not significantly correlated with their own vitD status (P = 0.18). Results also showed that mean titers in exclusively FF infants were not correlated with vitD status and were nearly identical to those of BrF infants of vitD-insufficient mothers. Conclusions Though still considered immune after 3 vaccinations, HBV IgG titers of BrF infants differed at 7 months of age by maternal vitD treatment and not on the basis of infant vitD status. These findings suggest that effects of vitD on breastmilk composition results in regulation of an infant's immune response perhaps by induction of immunotolerance, whether through blunting of a massive immune response to HBV antigens or affecting a more rapid switch from active plasma cells to memory B cells. A currently ongoing lactation pilot study continues to collect samples to confirm and expand these findings. Funding Sources NIH/NCATS, SC Translational Research Institute, MUSC Pediatrics.

Effects of vitamin D on apoptosis and betatrophin in the kidney tissue of experimental diabetic rats.

The aim of this study is to investigate the effects of vitamin D on betatrophin and apoptosis in rats kidney tissue using an experimental diabetes model created with streptozotocin (STZ). 41 male Wistar-albino breed rats were assigned to 5 groups, which included 3 groups consisting of 7 animals each and 2 groups consisting of 10 animals each. The control group received no treatments. Single-dose 0.1 M sodium buffer was administered ip to the Buffer group. The Vitamin D group was orally administered 200 IU/day vitamin D. The Diabetes group was injected ip with single-dose 50 mg/kg STZ by dissolving the material in 0.1 M sodium buffer. Subjects with a glucose level exceeding 250 mg/dl were accepted to be diabetic. The Diabetes + Vitamin D group was injected ip with 50 mg/kg single-dose STZ by dissolving the material in 0.1 M sodium buffer. Once diabetes was established, 200 IU/day vitamin D was administered orally. Rats in all groups were decapitated in the end of the experiment, their kidney tissues were promptly extracted and TUNEL stained with immunohistochemistry. Additionally, serum samples acquired from all groups were evaluated with regard to total antioxidant status (TAS) and total oxidant status (TOS) levels. The histological and biochemical analyses of the Control, Buffer, and Vitamin D groups revealed similar serum TOS and TAS levels, and TUNEL positivity and betatrophin immunoreactivity. While the Diabetes group showed significantly higher TOS levels and TUNEL positivity compared to the Control group, their TAS levels and betatrophin immunoreactivity were significantly reduced. The Diabetes+Vitamin group demonstrated significantly lower TOS levels and TUNEL positivity compared to the Diabetic group, and their TAS levels and betatrophin immunoreactivity increased significantly. In conclusion; experimental diabetes was found to increase TOS and apoptotic cells and decrease TAS and betatrophin levels in kidney tissue in experimental diabetes, and that administering VitD as treatment caused a decrease in TOS and apoptotic cells and an increase in TAS and betatrophin levels. It was concluded that future studies needed to investigate various experimental diabetes times so that the role of diabetes in the pathophysiology of its effect on kidney tissue could be uncovered. (www.actabiomedica.it)

Effects of vitamin D in an animal model of Alzheimer's disease: behavioral assessment with biochemical investigation of Hippocampus and serum.

Regulatory role of vitamin D (VitD) in cognitive memory and learning has been proposed. Here, we examine the behavioral and biochemical effects of VitD in Alzheimer's disease (AD), as the most common form of dementia, in male Wistar rats. Animals (n = 48) were randomly divided into six groups: control, sham solvent, sham surgery, VitD (by intraperitoneal injection), AD (receiving intrahippocampal injection of amyloid-beta peptide, Aβ), and combination of VitD and Aβ. Learning and memory functions were investigated through the passive avoidance and the Morris water maze (MWM) tasks. Moreover, oxidative stress biomarkers including total antioxidant capacity (TAC), total thiol groups (TTG), lipid peroxidation (LPO), and DNA damage were assessed in hippocampus and serum. In passive avoidance task, Aβ significantly impaired the step-through latency and time in dark compartment. It also increased escape latency and time spent in the target quadrant in the MWM. VitD administration attenuated the Aβ-induced memory impairment in passive avoidance and MWM tests. Furthermore, VitD reduced deleterious biochemical effect of Aβ by enhancing the levels of TAC and TTG in addition to decreasing LPO and DNA damage levels in both hippocampus and serum. We showed, for the first time, that VitD administration improves the impaired Aβ-induced memory and that, by acting as a strong antioxidant, it can attenuate the stress oxidative biomarkers in hippocampus and serum of rats with AD. Altogether, our results provide evidence for further application of VitD in neurodegenerative disorders such as AD to enlighten the involved mechanisms.

Vitamin D increases remyelination by promoting oligodendrocyte lineage differentiation.

IntroductionSeveral experimental studies have suggested the potential remyelinating effects of vitamin D (VitD) supplements regardless of the presence of VitD deficiency. This study aims to analyze neurogenesis in a model of toxic demyelination in order to evaluate the effects of VitD on demyelination and remyelination.Material and methodsWe used 24 male Wistar rats that had received surgical lesions to the corpus callosum and were injected with lysolecithin. Rats were divided into three groups: Group 1 included eight rats with lesions to the corpus callosum but not lysolecithin injections (sham group), group 2 included eight rats with lesions to the corpus callosum that were injected with lysolecithin (lysolecithin group), and group 3 included eight rats with lesions that were injected with lysolecithin and received VitD (VitD group). We analyzed neurogenesis both in the subventricular zone and at the lesion site.ResultsAdministration of VitD promotes the proliferation and differentiation of neural stem cells in the subventricular zone and the migration of these cells to the lesion site in the corpus callosum; these cells subsequently differentiate into oligodendrocyte lineage cells and produce myelin basic protein. This phenomenon was not caused by microglial activation, which was less marked in rats receiving VitD. Megalin expression did not increase at the lesion site, which suggests that VitD is internalized by other mechanisms.ConclusionOur results support the hypothesis that regardless of the presence of VitD deficiency, treatment with VitD may contribute to remyelination by promoting the proliferation of oligodendrocyte precursor cells.

Effect of high doses of vitamin D supplementation on dengue virus replication, Toll-like receptor expression, and cytokine profiles on dendritic cells.

Dengue, caused by dengue virus (DENV) infection, is a public health problem worldwide. Although DENV pathogenesis has not yet been fully elucidated, the inflammatory response is a hallmark feature in severe DENV infection. Although vitamin D (vitD) can promote the innate immune response against virus infection, no studies have evaluated the effects of vitD on DENV infection, dendritic cells (DCs), and inflammatory response regulation. This study aimed to assess the impact of oral vitD supplementation on DENV-2 infection, Toll-like receptor (TLR) expression, and both pro- and anti-inflammatory cytokine production in monocyte-derived DCs (MDDCs). To accomplish this, 20 healthy donors were randomly divided into two groups and received either 1000 or 4000 international units (IU)/day of vitD for 10days. During pre- and post-vitD supplementation, peripheral blood samples were taken to obtain MDDCs, which were challenged with DENV-2. We found that MDDCs from donors who received 4000IU/day of vitD were less susceptible to DENV-2 infection than MDDCs from donors who received 1000IU/day of vitD. Moreover, these cells showed decreased mRNA expression of TLR3, 7, and 9; downregulation of IL-12/IL-8 production; and increased IL-10 secretion in response to DENV-2 infection. In conclusion, the administration of 4000IU/day of vitD decreased DENV-2 infection. Our findings support a possible role of vitD in improving the innate immune response against DENV. However, further studies are necessary to determine the role of vitD on DENV replication and its innate immune response modulation in MDDCs.