Search

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by painful sinus tracts and significant scarring. Recent evidence suggests that vitamin D deficiency may play a role in the pathogenesis and outcomes of HS. This systematic review aims to evaluate the relationship between vitamin D levels and HS, exploring potential therapeutic benefits of vitamin D supplementation. This systematic review followed PRISMA guidelines and was registered with PROSPERO (ID:CRD42024566092). A comprehensive literature search was conducted in PubMed, Medline (OVID), and Web of Science using the keywords "hidradenitis suppurativa" and "vitamin D." Studies were screened for relevance, and non-randomized studies were assessed for quality using the MINORS score. Due to the heterogeneity of clinical outcome measures, a qualitative analysis was performed. A total of 77 records were identified, with 38 articles remaining after duplicates were removed. After full-text screening, 8 studies met the inclusion criteria. These studies, published between 2014 and 2024, included case-control, cross-sectional, and cohort studies. High prevalence rates of vitamin D deficiency (75–100%) were consistently observed among HS patients. Improved clinical outcomes with vitamin D supplementation were noted in several studies. There were significant correlations between vitamin D deficiency and higher clinical severity, and genetic alterations in vitamin D metabolism and keratinization pathways were identified in HS patients. This systematic review demonstrates a significant association between vitamin D deficiency and HS. Vitamin D's role in immune regulation and anti-inflammatory processes suggests its potential as a therapeutic agent for HS. However, further research is needed to determine optimal dosing and assess the protective effects of vitamin D supplementation in HS management. [ABSTRACT FROM AUTHOR]

Our comprehensive genomic investigation employing tree shrew calcium oxalate stone models unveils intricate links between kidney stone formation and diverse physiological systems. We identify a constellation of genes whose expression patterns point to multifaceted interactions among cardiovascular health, renal fibrosis, and bone homeostasis in the pathogenesis of renal calculi. Key players include CHIT1, TNFRSF18, CLEC4E, RGS1, DCSTAMP, and SLC37A2, which emerge as pivotal actors in arteriosclerosis, renal fibrosis, and osteoclastogenesis respectively, showcasing the complexity of stone disease. The downregulation of ADRA1D, LVRN, and ABCG8 underscores roles in urodynamics, epithelial-mesenchymal transition, and vitamin D metabolism, linking these to nephrolithiasis. Comparative genomics across tree shrew, human (Randall's plaque), rat, and mouse identifies shared KEGG pathways including Calcium signaling, Actin cytoskeleton regulation, Neuroactive ligand-receptor interactions, Complement and coagulation cascades, TRP channel regulation by inflammatory mediators, p53 signaling, and Fc gamma R-mediated phagocytosis. These pathways underscore the interconnectedness of immune, inflammatory, and metabolic processes in stone development. Our findings suggest novel targets for future therapeutics and prevention strategies against nephrolithiasis, highlighting the need for a holistic view of the disease encompassing multiple pathogenic factors. [ABSTRACT FROM AUTHOR]

Objective: This study aims to explore the association between the triglyceride-glucose (TyG) index and vitamin D status to enhance our understanding of how vitamin D status relates to metabolic health and to provide evidence for the early diagnosis of vitamin D deficiency (VDD) using the TyG index. Methods: We conducted a comprehensive search in various databases, including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology Medicine disc, China Science and Technology Journal Database, and Wanfang Data to gather articles published from the inception of these databases until February 19, 2024. We assessed the quality of included studies using the Newcastle-Ottawa Scale (NOS) for case-control studies and the Agency for Healthcare Research and Quality (AHRQ) methodology checklist for cross-sectional studies. Statistical analyses in this study were conducted using conversion methods for non-standard data formats and consolidation techniques for combining multiple groups. The Fisher transformation method was used for correlation coefficients. We used a random-effects model considering the inherent clinical heterogeneity among the studies, and assessed statistical heterogeneity with the Cochrane Q test and I2 statistic, complemented by subgroup analyses and sensitivity analysis. Results: Our meta-analysis selected a total of nine studies. The analysis revealed that patients with vitamin D deficiency (VDD group) exhibited a significantly higher TyG index than those without deficiency (no-VDD group), with a mean difference (MD) of 0.16 (95% CI: 0.10 to 0.23, I2 = 93%). This association was particularly pronounced among patients with type 2 diabetes (T2DM), showing an MD of 0.15 (95% CI: 0.05 to 0.26, I2 = 55%). Additionally, a negative correlation was observed between the TyG index and vitamin D levels, with a correlation coefficient (r) of -0.236 (95% CI: -0.310 to -0.159, I2 = 91%). Excluding each study sequentially in the sensitivity analyses did not significantly alter the outcomes. Conclusions: Our findings demonstrate a significant association between the TyG index and vitamin D status across diverse populations, including those with T2DM, subclinical hypothyroidism (SCH), and metabolic associated fatty liver disease (NAFLD). Our results reveal a notable disparity in the TyG index between vitamin D deficient and non-deficient groups, suggesting that vitamin D may play a critical role in metabolic health. These findings highlight the need for further research to explore the underlying mechanisms and clinical implications of vitamin D in the context of various metabolic disorders. [ABSTRACT FROM AUTHOR]

Patients with coronavirus disease 2019 (COVID-19) often experience acute kidney injury, linked to disease severity or mortality, along with renal tubular dysfunction and megalin loss in proximal tubules. Megalin plays a crucial role in kidney vitamin D metabolism. However, the impact of megalin loss on vitamin D metabolism during COVID-19 is unclear. This study investigated whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection reduces megalin expression in proximal tubules and its subsequent effect on vitamin D metabolism in mice expressing human angiotensin converting enzyme 2 (K18-hACE2 mice). Histological and immunohistochemical staining analyses revealed glomerular and capillary congestion, and elevated renal neutrophil gelatinase-associated lipocalin levels, indicative of acute kidney injury in K18-hACE2 mice. In SARS-CoV-2-infected mice, immunohistochemical staining revealed suppressed megalin protein levels. Decreased vitamin D receptor (VDR) localization in the nucleus and increased mRNA expression of VDR, CYP27B1, and CYP24A1 were observed by quantitative PCR in SARS-CoV-2-infected mice. Serum vitamin D levels remained similar in infected and vehicle-treated mice, but an increase in tumor necrosis factor-alpha and a decrease in IL-4 mRNA expression were observed in the kidneys of the SARS-CoV-2 group. These findings suggest that megalin loss in SARS-CoV-2 infection may impact the local role of vitamin D in kidney immunomodulation, even when blood vitamin D levels remain unchanged. [ABSTRACT FROM AUTHOR]

In a previous study performed by our group, pregnant women with Gestational Diabetes (GDM) showed higher vitamin D (VitD) levels in the last trimester, particularly in those requiring insulin. This phenomenon was not linked to factors like season or supplementation. This study aimed to investigate if insulin treatment in GDM affects DNA methylation in VitD metabolism genes. Thirty-two pregnant women were selected, half of whom had GDM, and were divided into insulin-treated and lifestyle groups. The DNA methylation levels in CpGs from 47 VitD metabolism-related genes were analyzed at the diagnostic visit (24–28 weeks) and before delivery. At week 36–38 of pregnancy, twenty-six CpG sites were differentially methylated (DMPs) in the insulin-treated group compared with the control group and the lifestyle group. Twenty-two of these DMPs were not different at the diagnostic visit. Six CpGs (cg18276810 (CTNNB1), cg03919554 (FGFR3), cg03984919 (NCOA1), cg19218509 (ASIP), cg09922639 (SMAD3), and cg25356935 (PDZD3)) showed significant correlations with VitD levels, not only before childbirth, but also in the postpartum period and at one year later. This suggests that insulin treatment in GDM could influence DNA methylation in genes involved in vitamin D metabolism, affecting VitD levels during and after pregnancy. Further research is warranted to elucidate these findings' clinical implications. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency is widespread and poses a significant health concern, as emerging research links it to allergic diseases owing to its immunomodulatory functions. The optimal functioning of vitamin D and its activation depend on its nuclear receptor, vitamin D receptor (VDR). Genetic variants of VDR have been explored as potential factors in autoimmune and allergic diseases, with limited studies on their association with allergic rhinitis (AR). The present investigation aims to analyse the role of three VDR genetic variants – TaqI, FokI and BsmI – in AR susceptibility and their impact on VDR mRNA and serum vitamin D levels. A total of 550 subjects, consisting of 250 AR cases and 300 age‐ and gender‐matched controls, underwent genotyping by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP). VDR mRNA and vitamin D levels were determined by quantitative real‐time PCR and chemiluminescence, respectively. Although TaqI did not exhibit significant differences, FokI demonstrated a noteworthy association with AR, particularly with the CC genotype (odds ratio [OR]: 3.34; confidence interval [CI]: 1.79–6.23). Similarly, BsmI revealed an increased risk for AR, with the GA + AA genotypes showing a 2.2‐fold elevated risk (OR: 2.20; CI: 1.53–3.16). VDR mRNA expression was threefold lower in AR patients (p <.0001), accompanied by reduced serum vitamin D levels (p <.0001). In addition, CC (p =.01) and AA (p =.02) genotypes of FokI and BsmI were associated with reduced VDR mRNA levels, whereas TaqI showed no such association. Similarly, heterozygous genotypes of TaqI and FokI, as well as homozygous AA of BsmI, correlated with lower serum vitamin D levels (p <.001). This study emphasizes the intricate relationship among VDR genetic variations, altered VDR activity, immune modulation and vitamin D metabolism in AR. Further research involving diverse populations is crucial for confirming and generalizing these findings, paving the way for personalized therapeutic interventions in vitamin D–related disorders. [ABSTRACT FROM AUTHOR]

Renal αKlotho along with fibroblast growth factor 23 regulates phosphate and vitamin D metabolism. Its cleavage yields soluble Klotho controlling intracellular processes. αKlotho has anti‐inflammatory and antioxidant effects and is nephro‐ and cardioprotective. AMP‐dependent kinase (AMPK) is a nephro‐ and cardioprotective energy sensor. Given that both αKlotho and AMPK have beneficial effects in similar organs, we studied whether AMPK regulates αKlotho gene expression in Madin–Darby canine kidney, normal rat kidney 52E, and human kidney 2 cells. Using quantitative real‐time PCR and western blotting, we measured αKlotho expression upon pharmacological manipulation or siRNA‐mediated knockdown of AMPKα. AMPK activator 5‐aminoimidazole‐4‐carboxamide ribonucleoside (AICAR) enhanced αKlotho expression, an effect reduced in the presence of AMPK inhibitor compound C or siRNA targeting AMPK catalytic α‐subunits (α1 and α2). Similarly, AMPK activators metformin and phenformin upregulated αKlotho transcripts. Taken together, our results suggest that AMPK is a powerful inducer of αKlotho and could thereby contribute to the development of future therapeutic interventions. [ABSTRACT FROM AUTHOR]

The 6th International Conference, "Controversies in Vitamin D," was convened to discuss controversial topics, such as vitamin D metabolism, assessment, actions, and supplementation. Novel insights into vitamin D mechanisms of action suggest links with conditions that do not depend only on reduced solar exposure or diet intake and that can be detected with distinctive noncanonical vitamin D metabolites. Optimal 25-hydroxyvitamin D (25(OH)D) levels remain debated. Varying recommendations from different societies arise from evaluating different clinical or public health approaches. The lack of assay standardization also poses challenges in interpreting data from available studies, hindering rational data pooling and meta-analyses. Beyond the well-known skeletal features, interest in vitamin D's extraskeletal effects has led to clinical trials on cancer, cardiovascular risk, respiratory effects, autoimmune diseases, diabetes, and mortality. The initial negative results are likely due to enrollment of vitamin D-replete individuals. Subsequent post hoc analyses have suggested, nevertheless, potential benefits in reducing cancer incidence, autoimmune diseases, cardiovascular events, and diabetes. Oral administration of vitamin D is the preferred route. Parenteral administration is reserved for specific clinical situations. Cholecalciferol is favored due to safety and minimal monitoring requirements. Calcifediol may be used in certain conditions, while calcitriol should be limited to specific disorders in which the active metabolite is not readily produced in vivo. Further studies are needed to investigate vitamin D effects in relation to the different recommended 25(OH)D levels and the efficacy of the different supplementary formulations in achieving biochemical and clinical outcomes within the multifaced skeletal and extraskeletal potential effects of vitamin D. [ABSTRACT FROM AUTHOR]

High-dose vitamin D supplementation is common in the general population, but unsupervised high-dose supplementation in vitamin D-replete individuals poses a risk of severe toxicity. Susceptibility to vitamin D toxicity shows a significant inter-individual variability that may in part be explained by genetic predispositions (i.e., CYP24A1 polymorphism). The classic manifestation of vitamin D toxicity is hypercalcemia, which may be refractory to conventional therapy. Its causes include the endogenous overaction of 1α-hydroxylase, monogenic alterations affecting vitamin D metabolizing enzymes and exogenous vitamin D intoxication. In this manuscript, we include a literature review of potential pharmacological interventions targeting calcitriol metabolism to treat vitamin D intoxication and present a case of severe, exogenous vitamin D intoxication responding to systemic corticosteroids after the failure of conventional therapy. Systemic glucocorticoids alleviate acute hypercalcemia by inhibiting enteric calcium absorption and increasing the degradation of vitamin D metabolites but may cause adverse effects. Inhibitors of 1α-hydroxylase (keto/fluconazole) and inducers of CYP3A4 (rifampicin) may be considered steroid-sparing alternatives for the treatment of vitamin D intoxication. [ABSTRACT FROM AUTHOR]

Backgroud: The relationship between serum uric acid (SUA) and 25-hydroxyvitamin D (25(OH)D) has been variably characterized in existing literature, with inconsistent results regarding its nature and implications in the Chinese population. This study aims to clarify this association, considering the potential impact of vitamin D levels on SUA. Methods: This cross-sectional study involved 7,086 individuals from the Second Affiliated Hospital of Zhejiang University School of Medicine, screened throughout 2020. We collected data on 25(OH)D, SUA, and other metabolic markers. Logistic regression models adjusted for confounding factors were utilized to analyze the relationships. Results: Our findings illustrate a statistically significant inverted U-shaped relationship between 25(OH)D and SUA. The identified threshold effect at 28.82 ng/ml is pivotal; with 25(OH)D levels below this point associated with an increased risk of hyperuricemia (odds ratio: 1.0146, p = 0.0148), and levels above it offering protective benefits (odds ratio: 0.9616, p = 0.0164). Conclusions: Our findings confirm a nonlinear, inverted U-shaped correlation between 25(OH)D and SUA, emphasizing the importance of maintaining vitamin D levels within a specific range to effectively manage hyperuricemia. These results support the implementation of personalized vitamin D supplementation strategies to optimize metabolic health outcomes, highlighting the complex interplay between vitamin D status and uric acid levels. [ABSTRACT FROM AUTHOR]

Aging and obesity are associated with a decrease in plasma 25‐hydroxyvitamin D (25(OH)D) levels. In the context of a growing aging population and the rising incidence of obesity, we hypothesized that aging process, either independently or in combination with obesity, could influence vitamin D (VD) metabolism, consequently resulting in the reduced 25(OH)D plasma concentrations. C57BL/6JRJ young (6 months) and old (23 months) mice fed with control (CD) or high fat diet (HF) were compared. Plasma and adipose concentration of cholecalciferol and 25(OH)D and mRNA expression of genes coding for the main VD actors were analyzed. Aging was associated with a decrease in plasma 25(OH)D levels, whereas combined effect of obesity and aging did not generate a cumulative effect on plasma 25(OH)D levels. The mRNA expression of Cyp27a1, Cyp3a11, and Cyp2j6 were decreased in the liver during aging. Together, these regulations could explain the reduced 25‐hydroxylation. Interestingly, the lack of cumulative reduction of 25(OH)D in aged and obese mice could be related to the strong induction of Cyp2j6. In kidneys, a complex modulation of Cyp27b1 and Cyp24a1 could contribute to the reduced 25‐hydroxylation in the liver. In white adipose tissue, an induction of Cyp2r1 was observed during aging and obesity, together with an increase of 25(OH)D quantity, suggesting an exacerbated storage that may participated to the reduced plasma 25(OH)D levels. These findings support the notion that aging alone or combined with obesity, induces regulation of VD metabolism in the organs, beyond the classical reduction of epidermal VD precursor, which may contribute to the decrease in 25(OH)D levels. [ABSTRACT FROM AUTHOR]

Background: Our aim is to investigate cardiovascular risk factors, chronic graft-versus-host disease (CGvHD), and vitamin D metabolism in very long-term survivors of adult allogeneic stem cell transplantation (alloSCT). Methods: This study is a prospective unicentric, non-interventional trial. The detailed study protocol is available via the WHO Clinical Trial Registry. Results: We were able to include 33 patients with a mean age of 60.5 years (SD 11.1). Acute myeloid leukemia (AML) was the most frequent underlying disease (n = 12; 36.4%). The median survival time was 9.0 years (IQR 8.5–13.0). Relevant cardiovascular risk factors in the study population are the body mass index, cholesterol, LDL cholesterol, and lipoprotein(a). Cardiovascular risk factors have no significant impact on HRQoL. CGvHD of the skin as a limited disease was present in six patients (18.2%), and it has no impact on HRQoL. CGvHD was significantly associated with eosinophilia in peripheral blood (p = 0.003). Three patients (9.1%) had a shortage of calcitriol, and one patient (3.0%) took calcium substitution. The shortage is significantly associated with increased infection rates (p = 0.038). Conclusions: Cardiovascular risk factors and CGvHD need to be closely monitored. Eosinophilia might be a good and convenient monitoring parameter for CGvHD. [ABSTRACT FROM AUTHOR]

Calcium is a fundamental and integrative element and helps to ensure optimal health by regulating various physiological and pathological processes. While there is substantiated evidence confirming the beneficial effects of calcium in the treatment, management, and prevention of various health conditions, including cancer, conflicting studies are imperative to acknowledge the potential negative role of calcium supplementation. The studies on calcium supplementation showed that a specific dose can help in the maintenance of good human health, and in the control of different types of diseases, including cancer. Calcium alone and when combined with vitamin D, emerges as a promising therapeutic option for efficiently managing cancer growth, when used with chemotherapy. Combination therapy is considered a more effective approach for treating advanced types of colorectal cancer. Nevertheless, several challenges drastically influence the treatment of cancer, such as individual discrepancy, drug resistance, and stage of cancer, among others. Henceforth, novel preventive, reliable therapeutic modalities are essential to control and reduce the incidence and mortality of colorectal cancer (CRC). The calcium-sensing receptor (CaSR) plays a pivotal role in calcium homeostasis, metabolism, and regulation of oncogenesis. Numerous studies have underscored the potential of CaSR, a G protein-coupled receptor, as a potential biomarker and target for colorectal cancer prevention and treatment. The multifaceted involvement of CaSR in anti-inflammatory and anti-carcinogenic processes paves the way for its utilization in the diagnosis and management of colorectal cancer. The current review highlights the important role of supplemental calcium in overall health and disease, along with the exploration of intricate mechanisms of CaSR pathways in the management and prevention of colorectal cancer. [ABSTRACT FROM AUTHOR]

An editorial is presented the Scientific Advisory Committee on Nutrition's (SACN) 2016 report, which determined that blood vitamin D levels below 25nmol/L increase the risk of poor musculoskeletal health. Topics include the recommended daily intake of vitamin D, historical changes in UK fortification practices, and current government advice on vitamin D supplementation.

This document is an editorial for a special issue of the journal Biomedicines, focusing on the molecular and cellular mechanisms of cardiovascular disease (CVD), specifically atherosclerosis. The editorial highlights the various theories and research findings related to atherogenesis, including the role of lipid accumulation, LDL modifications, endothelial dysfunction, and changes in immune cell function. The authors discuss the potential causes and mechanisms behind these processes, such as the impact of high-fat diets on lipid metabolism and the pro-inflammatory properties of certain fatty acids. The editorial emphasizes the interconnected nature of these factors and the need for further research to develop a comprehensive understanding of atherosclerosis. Additionally, the document provides a comprehensive list of sources for library patrons conducting research on atherosclerosis and related topics, covering areas such as oxidized LDL, palmitic acid, macrophages, and monocyte subsets. [Extracted from the article]

Background and Objectives: Polycystic ovary syndrome (PCOS) is a frequent and complex multidisciplinary disorder. Data regarding the role of genes involved in vitamin D metabolism in PCOS are as-yet elusive but suggest an association of VDR (vitamin D receptor) and vitamin D levels with metabolic, endocrine and cutaneous manifestations. The aim of this study was to evaluate the association between VDR gene polymorphisms and cutaneous manifestations, to find a correlation between hormonal parameters, oxidative stress and skin manifestations in women with PCOS, and to determine the impact of VDR gene polymorphisms on these parameters. Materials and Methods: This case–control study included 39 controls and 46 women with PCOS, matched by age and BMI distribution. Acne, hirsutism, seborrhea, androgenetic alopecia, oxidative stress and androgen hormones were recorded. VDR gene polymorphisms ApaI, FokI and TaqI were examined by polymerase chain reaction restriction fragment length polymorphism, and the androgen hormone (total testosterone, DHEAS), SHBG and malondialdehyde levels were assessed. Results: The most frequent skin manifestations in PCOS cases were acne followed by seborrhea, hirsutism and androgenic alopecia. The VDR-FokI polymorphism CC genotype had a significant protective role in the odds of acne (OR = 0.11, 95% CI: [0.02, 0.70], p = 0.015, p-corrected = 0.040) and seborrhea (OR = 0.15, 95% CI: [0.03, 0.75], p = 0.019, p-corrected = 0.039). The results demonstrated a significant protective effect of the C allele on the odds of acne and seborrhea in PCOS cases. Moreover, the dominant genotype of VDR-TaqI could have a protective role against oxidative stress (lower MDA levels) compared to patients carrying the TT genotype. Conclusions: In summary, this is the first study to demonstrate that the FokI CC genotype may have a protective role against both acne and seborrhea in women with PCOS, while the VDR-TaqI dominant genotype is associated with diminished oxidative stress in PCOS patients. [ABSTRACT FROM AUTHOR]

Phosphate is essential for numerous biological processes, and serum levels are tightly regulated to accomplish these functions. The regulation of serum phosphate in a narrow physiological range is a well-orchestrated process and involves the gastrointestinal (GI) tract, bone, kidneys, and several hormones, namely, parathyroid hormone, fibroblast growth factor 23 (FGF23), and 1,25-dihydroxyvitamin D (1,25 Vitamin D). Although primarily synthesized in the bone, FGF23, an endocrine FGF, acts on the kidney to regulate phosphate and Vitamin D homeostasis by causing phosphaturia and reduced levels of 1,25 Vitamin D. Recent studies have highlighted the complex regulation of FGF23 including transcriptional and post-translational modification and kidney-bone cross talk. Understanding FGF23 biology has led to the identification of novel therapeutic agents to treat diseases that disrupt phosphate metabolism secondary to FGF23. The focus of this review is to provide an overview of phosphate homeostasis, FGF23 biology, and the role of FGF23 in phosphate balance. [ABSTRACT FROM AUTHOR]

Background: Our aim is to investigate cardiovascular risk factors, chronic graft-versus-host disease (CGvHD), and vitamin D metabolism in very long-term survivors of adult allogeneic stem cell transplantation (alloSCT). Methods: This study is a prospective unicentric, non-interventional trial. The detailed study protocol is available via the WHO Clinical Trial Registry. Results: We were able to include 33 patients with a mean age of 60.5 years (SD 11.1). Acute myeloid leukemia (AML) was the most frequent underlying disease (n = 12; 36.4%). The median survival time was 9.0 years (IQR 8.5–13.0). Relevant cardiovascular risk factors in the study population are the body mass index, cholesterol, LDL cholesterol, and lipoprotein(a). Cardiovascular risk factors have no significant impact on HRQoL. CGvHD of the skin as a limited disease was present in six patients (18.2%), and it has no impact on HRQoL. CGvHD was significantly associated with eosinophilia in peripheral blood (p = 0.003). Three patients (9.1%) had a shortage of calcitriol, and one patient (3.0%) took calcium substitution. The shortage is significantly associated with increased infection rates (p = 0.038). Conclusions: Cardiovascular risk factors and CGvHD need to be closely monitored. Eosinophilia might be a good and convenient monitoring parameter for CGvHD.

Background: Kidney transplantation is followed by immunosuppressive therapy involving calcineurin inhibitors (CNIs) such as cyclosporin A. However, long-term high CNIs doses can lead to vitamin D deficiency, and genetic variations influencing vitamin D levels can indirectly impact the necessary CNIs dosage. This study investigates the impact of genetic variations of vitamin D binding protein (DBP) rs2282679 and CYP2R1 hydroxylase rs10741657 polymorphisms on the cyclosporin A dosage in kidney transplant recipients. Additional polymorphisims of genes that are predicted to influence the pharmacogenetic profile were included. Methods: Gene polymorphisms in 177 kidney transplant recipients were analyzed using data mining techniques, including the Random Forest algorithm and Classification and Regression Trees (C&RT). The relationship between the concentration/dose (C/D) ratio of cyclosporin A and genetic profiles was assessed to determine the predictive value of DBP rs2282679 and CYP2R1 rs10741657 polymorphisms. Results: Polymorphic variants of the DBP (rs2282679) demonstrated a strong predictive value for the cyclosporin A C/D ratio in post-kidney transplantation patients. By contrast, the CYP2R1 polymorphism (rs10741657) did not show predictive significance. Additionally, the immune response genes rs231775 CTLA4 and rs1800896 IL10 were identified as predictors of cyclosporin A response, though these did not result in statistically significant differences. Conclusions:DBP rs2282679 polymorphisms can significantly predict the cyclosporin A C/D ratio, potentially enhancing the accuracy of CNI dosing. This can help identify patient groups at risk of vitamin D deficiency, ultimately improving the management of kidney transplant recipients. Understanding these genetic influences allows for more personalized and effective treatment strategies, contributing to better long-term outcomes for patients. [ABSTRACT FROM AUTHOR]

Approximately five million children die each year from preventable causes, including respiratory infections, diarrhea, and malaria. Roughly half of those deaths are attributable to undernutrition, including micronutrient deficiencies (MNDs). The influence of infection on micronutrient status is well established: The inflammatory response to pathogens triggers anorexia, while pathogens and the immune response can both alter nutrient absorption and cause nutrient losses. We review the roles of vitamin A, vitamin D, iron, zinc, and selenium in the immune system, which act in the regulation of molecular- or cellular-level host defenses, directly affecting pathogens or protecting against oxidative stress or inflammation. We further summarize high-quality evidence regarding the synergistic or antagonistic interactions between MNDs, pathogens, and morbidity or mortality relevant to child health in low- and middle-income countries. We conclude with a discussion of gaps in the literature and future directions for multidisciplinary research on the interactions of MNDs, infection, and inflammation. [ABSTRACT FROM AUTHOR]

Background: Glaucoma is the second leading cause of blindness worldwide, with intraocular pressure as the only known modifiable risk factor. Vitamin D has been proposed to influence intraocular pressure and decrease retinal ganglion cell degeneration. Based on these findings, vitamin D has been suggested to prevent or reduce the severity of primary open-angle glaucoma (POAG), which is the most common form. Methods: We applied two-sample Mendelian randomisation (MR) analyses to data from the SUNLIGHT consortium and the UK Biobank to assess the causal effect of vitamin D levels and vitamin D deficiency on primary open-angle glaucoma (POAG). MR analysis, including sensitivity tests using other GWAS summary statistics from FinnGen, was also performed. We also investigated the association between single nucleotide polymorphisms (SNPs) on genes involved in vitamin D metabolic pathways and POAG. Results: We found no statistical evidence that vitamin D levels (OR = 1.146, 95% CI 0.873 to 1.504, p = 0.326) or vitamin D deficiency (OR = 0.980 (95% CI 0.928 to 1.036, p = 0.471) causally affect the risk of developing POAG. Sensitivity analyses, including the use of a more relaxed p-value threshold, and use of winter-measured samples only, replication in the FinnGen dataset, and exploration of specific genetic markers also showed no evidence of association between SNPs for genes involved in key steps of vitamin D metabolism and POAG. Conclusions: These results indicate that vitamin D may not be a significant factor in modifying POAG risk, challenging the hypothesis that vitamin D supplementation could be effective in reducing POAG risk. Further research should focus on identifying other potential risk factors for POAG prevention strategies. [ABSTRACT FROM AUTHOR]

Vitamin D status has been involved with coronavirus disease 19 (COVID‐19) severity. This may be mediated by vitamin D metabolism regulatory genes. Of interest is the vitamin D receptor (VDR) gene, which has been previously associated with other inflammatory and respiratory diseases. In order to investigate the role of VDR gene polymorphisms in COVID‐19 severity and outcome, a total of 292 COVID‐19 patients were classified according to severity in moderate (n = 56), severe (n = 89) and critical (n = 147) and, according to outcome in survivor (n = 163) and deceased (n = 129), and analysed for FokI and TaqI VDR gene polymorphisms by polymerase chain reaction‐based restriction enzyme digestion. The FokI and TaqI single nucleotide polymorphisms (SNPs) were not associated with COVID‐19 severity or mortality individually but when analysed by haplotype, TC was associated with an increased risk of presenting critical COVID‐19. Additionally, FokI CT genotype was more frequent in COVID‐19 patients with hypertension, and T allele carriers presented higher aspartate aminotransferase levels. Our results suggest a relationship between VDR FokI and TaqI SNPs and COVID‐19 severity in Mexican population. Although there are some previous reports of VDR polymorphisms in COVID‐19, this represents the first report in Latin American population. Further studies on other populations are encouraged. [ABSTRACT FROM AUTHOR]

The microgravity environment aboard the International Space Station (ISS) provides a unique stressor that can help understand underlying cellular and molecular drivers of pathological changes observed in astronauts with the ultimate goals of developing strategies to enable long- term spaceflight and better treatment of diseases on Earth. We used this unique environment to evaluate the effects of microgravity on kidney proximal tubule epithelial cell (PTEC) response to serum exposure and vitamin D biotransformation capacity. To test if microgravity alters the pathologic response of the proximal tubule to serum exposure, we treated PTECs cultured in a microphysiological system (PT-MPS) with human serum and measured biomarkers of toxicity and inflammation (KIM-1 and IL-6) and conducted global transcriptomics via RNAseq on cells undergoing flight (microgravity) and respective controls (ground). Given the profound bone loss observed in microgravity and PTECs produce the active form of vitamin D, we treated 3D cultured PTECs with 25(OH)D3 (vitamin D) and monitored vitamin D metabolite formation, conducted global transcriptomics via RNAseq, and evaluated transcript expression of CYP27B1, CYP24A1, or CYP3A5 in PTECs undergoing flight (microgravity) and respective ground controls. We demonstrated that microgravity neither altered PTEC metabolism of vitamin D nor did it induce a unique response of PTECs to human serum, suggesting that these fundamental biochemical pathways in the kidney proximal tubule are not significantly altered by short-term exposure to microgravity. Given the prospect of extended spaceflight, more study is needed to determine if these responses are consistent with extended (>6 months) exposure to microgravity. [ABSTRACT FROM AUTHOR]

• suboptimal response to vitamin D supplementation is common in cystic fibrosis. • whole genome sequencing can reveal genetic variants in vitamin D metabolism. • genetic variants partially explain low vitamin D levels in cystic fibrosis adults. Vitamin D sufficiency has been difficult to achieve consistently in patients with cystic fibrosis (CF), even with robust oral supplements. To assess vitamin D status and resistance to supplementation, we studied 80 adults using 25-hydroxyvitamin D (25OHD) determinations and whole genome sequencing to construct polygenic risk scores (PRS) that aggregate variants associated with vitamin D status. The results revealed that 30 % of patients were below the threshold of 30 ng/mL and thus should be regarded as insufficient despite normal vitamin E status, a reflection of adherence to fat soluble vitamin supplementation. The PRS values were significantly correlated with 25OHD concentrations, confirming our results in children with CF, and indicating that genetic factors play a role and have implications for therapy. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated the relationship between vitamin D deficiency, infection severity and mortality from COVID-19. This study aimed to analyze the vitamin D metabolites and cytokine expression levels of COVID-19 patients who were hospitalized with bolus cholecalciferol supplementation. Materials and methods: This study represents the next stage of the open-label randomized pilot conducted by the Almazov National Medical Research Centre. A total of 44 hospitalized patients, comparable in demographic, clinical, laboratory and instrumental baseline characteristics, with moderate/severe COVID-19 were included. All patients had similar doses of concomitant corticosteroid therapy. Twenty-two patients received 50,000 IU cholecalciferol on the first and eighth days of hospitalization. The serum 25(OH)D, 1,25(OH)2D and 28 plasma cytokines were estimated for each group initially and on the ninth day of hospitalization. Results: Initially, there were no differences in the 1,25(OH)2D and cytokine levels in patients with vitamin D deficiency and normal 25(OH)D. Bolus cholecalciferol therapy at a total dose of 100,000 IU led to an increase in 25(OH)D levels in hospitalized patients with COVID-19, while the levels of the active metabolite (1,25(OH)2D) did not show significant differences between the groups or in its increased level over time, regardless of cholecalciferol supplementation. Furthermore, cholecalciferol supplementation at a total dose of 100,000 IU did not affect the majority of the cytokines estimated on the ninth day of hospitalization, except for the pro-inflammatory marker IL-1b, the concentration of which was lower in the group of patients without vitamin D supplementation. Conclusions: The 25(OH)D level was positively associated with an anti-inflammatory immune response, but cholecalciferol supplementation at a total dose of 100,000 IU did not affect the active-form vitamin D or cytokine expression levels. This fact may be explained by the impact of corticosteroid therapy, and it requires further investigation in a post-COVID-19 context. [ABSTRACT FROM AUTHOR]

Background: Head and neck cancer encompasses neoplasms affecting the oral cavity, pharynx, larynx, and thyroid. Identifying factors that modulate the carcinogenesis process can aid in identifying subgroups at higher risk of developing the disease, enabling implementation of prevention programs. Vitamin D receptor polymorphisms can affect the carcinogenesis of various tumors by altering vitamin D metabolism and cellular response. Methods: To elucidate the role of vitamin D receptor polymorphisms in head and neck cancer, a systematic review was performed, searching the Embase, PubMed, Scopus, and Lilacs databases. A total of 19 articles met the inclusion criteria. The frequency of vitamin D receptors polymorphism alleles (FokI, ApaI, BsmI, TaqI, Cdx2, rs2107301, rs2238135) was recorded and pooled to calculate the odds ratio in a meta‐analysis using the Review Manager software. Results: Subgroup analysis demonstrated significant associations in the anatomical site of cancer (oral cancer in ApaI and BsmI, and unspecified subsites of head and neck cancer in TaqI), genotyping method (FokI and BsmI), and continent of the study (ApaI, FokI, and BsmI). Conclusion: Our findings were heterogeneous, as with other evidence available in the literature. Therefore, more clinical studies with larger sample sizes are needed to obtain more accurate results on the relationship between vitamin D receptor polymorphism and head and neck cancer. [ABSTRACT FROM AUTHOR]

Vitamin D (vitD) deficiency (25-hydroxy-vitamin D < 50 nmol/L) is common in pregnancy and associated with an increased risk of adverse pregnancy outcomes. High-dose vitD supplementation is suggested to improve pregnancy health, but there is limited knowledge about the effects on placental vitD transport and metabolism and the vitD status of newborns. Comparing the current standard maternal supplementation, 10 µg/day to a 90 µg vitD supplement, we investigated placental gene expression, maternal vitD transport and neonatal vitD status. Biological material was obtained from pregnant women randomized to 10 µg or 90 µg vitD supplements from week 11–16 onwards. Possible associations between maternal exposure, neonatal vitD status and placental expression of the vitD receptor (VDR), the transporters (Cubilin, CUBN and Megalin, LRP2) and the vitD-activating and -degrading enzymes (CYP24A1, CYP27B1) were investigated. Maternal vitD-binding protein (VDBP) was determined before and after supplementation. Overall, 51% of neonates in the 10 µg vitD group were vitD-deficient in contrast to 11% in the 90 µg group. High-dose vitD supplementation did not significantly affect VDBP or placental gene expression. However, the descriptive analyses indicate that maternal obesity may lead to the differential expression of CUBN, CYP24A1 and CYP27B1 and a changed VDBP response. High-dose vitD improves neonatal vitD status without affecting placental vitD regulation. [ABSTRACT FROM AUTHOR]

Cytochrome P450 (CYP450) is a group of enzymes that play an essential role in Phase I metabolism, with 57 functional genes classified into 18 families in the human genome, of which the CYP1, CYP2, and CYP3 families are prominent. Beyond drug metabolism, CYP enzymes metabolize endogenous compounds such as lipids, proteins, and hormones to maintain physiological homeostasis. Thus, dysregulation of CYP450 enzymes can lead to different endocrine disorders. Moreover, CYP450 enzymes significantly contribute to fatty acid metabolism, cholesterol synthesis, and bile acid biosynthesis, impacting cellular physiology and disease pathogenesis. Their diverse functions emphasize their therapeutic potential in managing hypercholesterolemia and neurodegenerative diseases. Additionally, CYP450 enzymes are implicated in the onset and development of illnesses such as cancer, influencing chemotherapy outcomes. Assessment of CYP450 enzyme expression and activity aids in evaluating liver health state and differentiating between liver diseases, guiding therapeutic decisions, and optimizing drug efficacy. Understanding the roles of CYP450 enzymes and the clinical effect of their genetic polymorphisms is crucial for developing personalized therapeutic strategies and enhancing drug responses in diverse patient populations. [ABSTRACT FROM AUTHOR]

Background: Children with sickle cell disease (SCD) are more likely to have deficient serum levels of vitamin D for bone metabolism. However, appropriate interventions are essential to prevent its progression and alleviate symptoms. Purpose: The aim of this study is to determine interventions for managing bone disease in children with SCD. Methods: This study uses a scoping review. A literature review was conducted using PubMed, CINAHL, ScienceDirect, Scopus, and Google Scholar search engines. The study was eligible for inclusion if it included articles published from 2013 to 2023, full-text, and original study design. Study quality was assessed using the Joanna Briggs Institute (JBI) appraisal tool. Results: This review identified six studies and 114 children with SCD, including 57 boys (50%) and 57 girls (50%). The majority of SCD types experienced were HbSS (86.84%), HbS-B0 Thal (7.01%), HbSC (5.27%), and the HbSS Arab-Indian haplotype (0.88%). Bone disease problems that often arise in children with SCD include Avascular Necrosis (AVN) (78.08%), Osteonecrosis of the Femoral Head (ONFH) (18.42%), and other bone problems (3.50%). Meanwhile, four types of intervention findings were used in managing bone disease among children with SCD: 1). Surgical procedures 53 (41.09%) included total hip arthroplasty (THA), Osteotomy, and Multiple epiphyseal drilling with Autologous Bone Marrow Implantation (AMBI); 2). Invasive procedures 67 (51.93%) included intravenous bisphosphonates, hydroxyurea (HU), and core decompression (CD) with bone marrow aspirate concentrate injection: 3). Oral pharmacological or Vitamin D3 (cholecalciferol) 4 (3.10%); 4). Non-pharmacology or physical therapy 5 (3.88%). Conclusion: Our findings highlight that surgical, invasive, pharmacological, and physical therapy interventions positively impact increasing bone mineral density (BMD) and functional improvement of bone disease among children with SCD. The interventions provided excellent functional outcomes with minimal complications and no life-threatening side effects. [ABSTRACT FROM AUTHOR]

Researchers have studied the effects of exercise on serum methyl-arginine and vitamin D metabolites; however, the effects of exercise combined with antioxidants are not well documented. Since oxidative stress affects the metabolism of vitamin D and methyl-arginine, we hypothesised that the antioxidant coenzyme Q10 (CoQ10) might modulate exercise-induced changes. A group of twenty-eight healthy men participated in this study and were divided into two groups: an experimental group and a control group. The exercise test was performed until exhaustion, with gradually increasing intensity, before and after the 21-day CoQ10 supplementation. Blood samples were collected before, immediately after, and 3 and 24 h after exercise. CoQ10, vitamin D metabolites, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine, methylarginine, dimethylamine, arginine, citrulline, and ornithine were analysed in serum samples. CoQ10 supplementation caused a 2.76-fold increase in the concentration of serum CoQ10. Conversely, the 25(OH)D3 concentration increased after exercise only in the placebo group. ADMA increased after exercise before supplementation, but a decrease was observed in the CoQ10 supplementation group 24 h after exercise. In conclusion, our data indicate that CoQ10 supplementation modifies the effects of exercise on vitamin D and methyl-arginine metabolism, suggesting its beneficial effects. These findings contribute to the understanding of how antioxidants like CoQ10 can modulate biochemical responses to exercise, potentially offering new insights for enhancing athletic performance and recovery. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite recent advances in diagnosis and therapy, malignant melanoma poses a significant problem both to clinicians and cancer researchers due to its resistance to therapy and unpredictable behavior. In this review, we discuss etiology, risk factors, diagnosis, prognosis, and therapy of melanoma, with a focus on new developments in these areas including bioinformatics. These are analyzed in the context of its unique metabolic characteristics and of recent advances in vitamin D biology with implications for melanoma. Active forms of vitamin D can prevent or inhibit melanoma development and progression, and can be used in therapy of this disease. Knowledge of patient vitamin D status and vitamin D signaling in the tumoral tissue can help in predicting the progression of the disease and in primary or adjuvant therapy. Therefore, vitamin D signaling represents a realistic target for the prevention or therapy of malignant melanoma. Melanoma, originating through malignant transformation of melanin-producing melanocytes, is a formidable malignancy, characterized by local invasiveness, recurrence, early metastasis, resistance to therapy, and a high mortality rate. This review discusses etiologic and risk factors for melanoma, diagnostic and prognostic tools, including recent advances in molecular biology, omics, and bioinformatics, and provides an overview of its therapy. Since the incidence of melanoma is rising and mortality remains unacceptably high, we discuss its inherent properties, including melanogenesis, that make this disease resilient to treatment and propose to use AI to solve the above complex and multidimensional problems. We provide an overview on vitamin D and its anticancerogenic properties, and report recent advances in this field that can provide solutions for the prevention and/or therapy of melanoma. Experimental papers and clinicopathological studies on the role of vitamin D status and signaling pathways initiated by its active metabolites in melanoma prognosis and therapy are reviewed. We conclude that vitamin D signaling, defined by specific nuclear receptors and selective activation by specific vitamin D hydroxyderivatives, can provide a benefit for new or existing therapeutic approaches. We propose to target vitamin D signaling with the use of computational biology and AI tools to provide a solution to the melanoma problem. [ABSTRACT FROM AUTHOR]

Sclerostin (SOST) is produced by osteocytes and is known as a negative regulator of bone homeostasis. Parathyroid hormone (PTH) regulates calcium, phosphate as well as vitamin D metabolism, and is a strong inhibitor of SOST synthesis in vitro and in vivo. PTH has two methionine amino acids (positions 8 and 18) which can be oxidized. PTH oxidized at Met18 (Met18(ox)-PTH) continues to be bioactive, whereas PTH oxidized at Met8 (Met8(ox)-PTH) or PTH oxidized at Met8 and Met18 (Met8, Met18(di-ox)-PTH) has minor bioactivity. How non-oxidized PTH (n-oxPTH) and oxidized forms of PTH act on sclerostin synthesis is unknown. The effects of n-oxPTH and oxidized forms of PTH on SOST gene expression were evaluated in UMR106 osteoblast-like cells. Moreover, we analyzed the relationship of SOST with n-oxPTH and all forms of oxPTH in 516 stable kidney transplant recipients using an assay system that can distinguish in clinical samples between n-oxPTH and the sum of all oxidized PTH forms (Met8(ox)-PTH, Met18(ox)-PTH, and Met8, Met18(di-ox)-PTH). We found that both n-oxPTH and Met18(ox)-PTH at doses of 1, 3, 20, and 30 nmol/L significantly inhibit SOST gene expression in vitro, whereas Met8(ox)-PTH and Met8, Met18(di-ox)-PTH only have a weak inhibitory effect on SOST gene expression. In the clinical cohort, multivariate linear regression showed that only n-oxPTH, but not intact PTH (iPTH) nor oxPTH, is independently associated with circulating SOST after adjusting for known confounding factors. In conclusion, only bioactive PTH forms such as n-oxPTH and Met18(ox)-PTH, inhibit SOST synthesis. [ABSTRACT FROM AUTHOR]

OBJECTIVE The research aimed to determine the importance of vitamin D and markers of bone metabolism in the overall assessment of bone mineralization during a child's first year of life. METHODS The 198 children were selected by screening all infants seen at our pediatric clinic over a 2-year period from 2020-2022 and including those who met the eligibility criteria of being aged 0 to 1 year, healthy with no chronic conditions, and not on vitamin D supplementation. Children were divided into 3 groups depending on the content of vitamin D in the blood serum: sufficient, insufficient, and deficient. The markers of bone tissue status included: markers of mineral metabolism (calcium, phosphorus, parathyroid hormone, calcitonin), a marker of bone formation (osteocalcin), resorption marker (deoxypyridinoline). Laboratory values were obtained at the time of study enrollment during the initial study visit. Labs were not repeated during the course of the study. RESULTS A quarter of the infants exhibited vitamin D deficiency at enrollment with serum 25OHD concentrations below 20 ng/mL, which showed a positive correlation with serum calcium and phosphorus concentrations and a negative correlation with PTH, while osteocalcin and deoxypyridinoline concentrations remained consistent regardless of vitamin D status. CONCLUSIONS The study's practical significance allows for the recommendation of using vitamin D concentrations as a marker to detect bone formation and mineral metabolism disorders in children during their first year of life. By identifying and addressing these issues early on, the health care system aims to ensure better musculoskeletal health for children. [ABSTRACT FROM AUTHOR]

Vitamin D hydroxylation in the liver/kidney results in conversion to its physiologically active form of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. 1,25(OH)2D3 controls gene expression through the nuclear vitamin D receptor (VDR) mainly expressed in intestinal epithelial cells. Cytochrome P450 (CYP) 24A1 is a catabolic enzyme expressed in the kidneys. Interestingly, a recently identified mutation in another CYP enzyme, CYP3A4 (gain-of-function), caused type III vitamin D-dependent rickets. CYP3A are also expressed in the intestine, but their hydroxylation activities towards vitamin D substrates are unknown. We evaluated CYP3A or CYP24A1 activities on vitamin D action in cultured cells. In addition, we examined the expression level and regulation of CYP enzymes in intestines from mice. The expression of CYP3A or CYP24A1 significantly reduced 1,25(OH)2D3-VDRE activity. Moreover, in mice, Cyp24a1 mRNA was significantly induced by 1,25(OH)2D3 in the intestine, but a mature form (approximately 55 kDa protein) was also expressed in mitochondria and induced by 1,25(OH)2D3, and this mitochondrial enzyme appears to hydroxylate 25OHD3 to 24,25(OH)2D3. Thus, CYP3A or CYP24A1 could locally attenuate 25OHD3 or 1,25(OH)2D3 action, and we suggest the small intestine is both a vitamin D target tissue, as well as a newly recognized vitamin D-metabolizing tissue. [ABSTRACT FROM AUTHOR]

Chronic pancreatitis (CP) is a progressive inflammatory disease with an increasing global prevalence. In recent years, a strong association between CP and metabolic bone diseases (MBDs), especially osteoporosis, has been identified, attracting significant attention in the research field. Epidemiological data suggest a rising trend in the incidence of MBDs among CP patients. Notably, recent studies have highlighted a profound interplay between CP and altered nutritional and immune profiles, offering insights into its linkage with MBDs. At the molecular level, CP introduces a series of biochemical disturbances that compromise bone homeostasis. One critical observation is the disrupted metabolism of vitamin D and vitamin K, both essential micronutrients for maintaining bone integrity, in CP patients. In this review, we provide physio-pathological perspectives on the development and mechanisms of CP-related MBDs. We also outline some of the latest therapeutic strategies for treating patients with CP-associated MBDs, including stem cell transplantation, monoclonal antibodies, and probiotic therapy. In summary, CP-associated MBDs represent a rising medical challenge, involving multiple tissues and organs, complex disease mechanisms, and diverse treatment approaches. More in-depth studies are required to understand the complex interplay between CP and MBDs to facilitate the development of more specific and effective therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background: Iron deficiency is known to impair muscle function and reduce athletic performance, while vitamin D has been reported to induce iron deficiency. However, the mechanism underlying exercise-induced changes in iron metabolism and the involvement of vitamins in this mechanism are unclear. The present study examined changes in biological iron metabolism induced by continuous training and the effects of vitamin D on these changes. Methods: Diet, physical characteristics, and blood test data were collected from 23 female high school students in a dance club on the last day of each of a 2-month continuous training period and a 2-week complete rest periods. Results: Serum hepcidin-25 levels were significantly lower during the training period than the rest period (p = 0.013), as were the red blood cell count, hemoglobin, and hematocrit (all p < 0.001). Serum erythropoietin was significantly higher (p = 0.001) during the training period. Significant positive correlations were observed between 25(OH)D levels and serum iron, serum ferritin, and transferrin saturation during the training period. Multiple regression analysis with serum 25(OH)D level as the dependent variable and serum ferritin and iron levels as independent variables during the training period revealed a significant association with serum ferritin. Conclusion: Continuous training may promote hemolysis and erythropoiesis, contributing to the suppression of hepcidin expression. The relationship between serum 25(OH)D and iron in vivo may be closely related to metabolic changes induced by the exercise load. [ABSTRACT FROM AUTHOR]

Vitamin D plays a crucial role in the human body, influencing a wide range of physiological processes from bone health to immune function. The complex biochemical pathways involved in the synthesis, metabolism, and action of Vitamin D are explored, emphasizing its importance in nutrition and food technology. This review also investigates the regulatory mechanisms that control Vitamin D metabolism and its systemic effects on calcium homeostasis, cell proliferation, differentiation, and immune modulation. The role of Vitamin D3 in regulating blood pressure and atherosclerosis in the onset of cardiovascular disorders is discussed. Given the importance of Vitamin D in food science and technology, the regulatory mechanisms that control Vitamin D metabolism and its systemic effects on calcium homeostasis are also investigated, integrating innovative approaches and advanced technologies to improve human health through nutrition. Additionally, the review assesses the influence of food processing on Vitamin D levels and discusses cutting-edge technologies as innovative strategies to mitigate Vitamin D loss during food processing. This comprehensive exploration aims to improve our understanding of the biochemical pathways of Vitamin D and its relevance to food science, contributing to the development of new strategies for food fortification and the promotion of optimal health through diet. [ABSTRACT FROM AUTHOR]

Introduction: The reduction of nitrogen (N) and phosphorus (P) in ruminant feed is desirable due to costs and negative environmental impact. Ruminants are able to utilize N and P through endogenous recycling, particularly in times of scarcity. When N and/or P were reduced, changes in mineral homeostasis associated with modulation of renal calcitriol metabolism occurred. The aim of this study was to investigate the potential effects of dietary N- and/or P-reduction on the regulatory mechanisms of mineral transport in the kidney and its hormonal regulation in young goats. Results: During N-reduction, calcium (Ca) and magnesium (Mg) concentrations in blood decreased, accompanied by a lower protein expression of cytochrome P450 family 27 subfamily B member 1 (CYP27B1) (p = 0.016). The P-reduced fed goats had low blood phosphate concentrations with simultaneously high Ca and Mg levels. The insulin-like growth factor 1 concentrations decreased significantly with P-reduction. Furthermore, gene expression of CYP27B1 (p < 0.001) and both gene (p = 0.025) and protein (p = 0.016) expression of the fibroblast growth factor receptor 1c isoform in the kidney were also significantly reduced during a P-reduced diet. ERK1/2 activation exhibited a trend toward reduction in P-reduced animals. Interestingly, calcitriol concentrations remained unaffected by either restriction individually, but interacted significantly with N and P (p = 0.014). Additionally, fibroblast growth factor 23 mRNA expression in bone decreased significantly with P-restriction (p < 0.001). Discussion: These results shed light on the complex metabolic and regulatory responses of mineral transport of young goats to dietary N and P restriction. [ABSTRACT FROM AUTHOR]

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

Context There is a high prevalence of vitamin D deficiency and impaired cognitive function in people with type 2 diabetes mellitus (T2DM). Objective To critically and systematically review the literature on the association between vitamin D status and cognitive performance in people with type 2 diabetes. Data Sources This review was conducted according to PRISMA recommendations. MEDLINE, SCOPUS, the Cochrane Library, and Web of Science databases were searched using the terms "Diabetes Mellitus, Type 2", "Cognitive Function", and "Vitamin D". Data Extraction Eight observational and 1 randomized study were included, containing data of 14 648 adult and elderly individuals (19–74 y). All extracted data were compiled, compared, and critically analyzed. Data Analysis There is no strong evidence that lower serum concentrations of vitamin D and vitamin D–binding protein are associated with worsening cognitive function in individuals with T2DM. Vitamin D supplementation (12 wk) improved the scores of some executive functioning tests, although there was no difference between low doses (5000 IU/wk) and high doses (50 000 IU/wk). Conclusions There is no high-quality evidence demonstrating an association between vitamin D status and cognitive function, or clinical benefits on cognition from vitamin D supplementation in individuals with T2DM. Future studies are needed. Systematic Review Registration: PROSPERO registration no. CRD42021261520. [ABSTRACT FROM AUTHOR]

Objective: To investigate pathways from micronutrient intake and serum levels to Chronic Oral Diseases Burden. Methods: We analyzed cross‐sectional data from NHANES III (n = 7936) and NHANES 2011–2014 (n = 4929). The exposure was the intake and serum levels of vitamin D, calcium, and phosphorus. Considering the high correlation of those micronutrients in the diet, they were analyzed as a latent variable dubbed Micronutrient intake. The outcome was the Chronic Oral Diseases Burden, a latent variable formed by probing pocket depth, clinical attachment loss, furcation involvement, caries, and missing teeth. Pathways triggered by gender, age, socioeconomic status, obesity, smoking, and alcohol were also estimated using structural equation modeling. Results: In both NHANES cycles, micronutrient intake (p‐value < 0.05) and vitamin D serum (p‐value < 0.05) were associated with a lower Chronic Oral Diseases Burden. Micronutrient intake reduced the Chronic Oral Diseases Burden via vitamin D serum (p‐value < 0.05). Obesity increased the Chronic Oral Diseases Burden by reducing vitamin D serum (p‐value < 0.05). Conclusion: Higher micronutrient intake and higher vitamin D serum levels seem to reduce Chronic Oral Diseases Burden. Healthy diet policies may jointly tackle caries, periodontitis, obesity, and other non‐communicable diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Vitamin D supplementation's effectiveness in reducing cancer is widely debated. The controversy may be explained by differences in 25(OH)D3 metabolism. Previous studies showed that breast cancer cells produce vitamin D3 metabolites locally, and their ability to regulate tumorigenesis is related to the presence of estrogen receptor alpha 66 (ERα66). The present study examined this process in another estrogen-dependent cancer, laryngeal cancer. This study evaluated the effects of the active vitamin D3 metabolite 24R,25(OH)2D3 on cell growth, whether these cells can produce their own secreted vitamin D3 metabolites, and whether this ability is related to the presence or absence of ERα66. To address these questions, ERα-positive (UM-SCC-12) and ERα-negative (UM-SCC-11A) laryngeal cancer cell lines were examined for the presence of ERα66; the enzymes responsible for metabolizing 25(OH)D3 (CYP24A1 and CYP27B1); the local production of 24,25(OH)2D3 and 1,25(OH)2D3; and the effect of 24R,25(OH)2D3 on cell growth and markers of metastasis. The results showed that laryngeal cancer cells express CYP24A1 and CYP27B1, produce 24,25(OH)2D3, and respond differently to 24R,25(OH)2D3, in correlation with ERα66 levels. These findings suggest that tumor cells locally produce vitamin D metabolites to regulate their growth, which must be considered when recommending vitamin D supplementation. Studies have evaluated vitamin D3's therapeutic potential in estrogen-responsive cancers, with conflicting findings. We have shown that the proliferation of breast cancer cells is regulated by 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3) depending on estrogen receptor alpha 66 (ERα66) expression, suggesting that this could also be the case for estrogen-sensitive laryngeal cancer cells. Accordingly, we examined levels of ERα isoforms in ERα66-positive UM-SCC-12 and ERα66-negative UM-SCC-11A cells and their response to 24R,25(OH)2D3. 24R,25(OH)2D3 stimulated proliferation, increased the expression of metastatic markers, and inhibited apoptosis in UM-SCC-12 cells while having the opposite effect in UM-SCC-11A cells. To evaluate if vitamin metabolites could act via autocrine/paracrine mechanisms, we assessed the expression, protein levels, and activity of vitamin D3 hydroxylases CYP24A1 and CYP27B1. Both cell types expressed both mRNAs; but the levels of the enzymes and their activities were differentially regulated by estrogen. ERα66-negative UM-SCC-11A cells produced more 24,25(OH)2D3 than UM-SCC-12 cells, but comparable levels of 1,25(OH)2D3 when treated with 25(OH)D3 These results suggest that the regulation of vitamin D3 metabolism in laryngeal cancer cells is modulated by ERα66 expression, and support a role for 24R,25(OH)2D3 as an autocrine/paracrine regulator of laryngeal cancer. The local metabolism of 25(OH)D3 should be considered when determining the potential of vitamin D3 in laryngeal cancer. [ABSTRACT FROM AUTHOR]

Tendons are vital components of the musculoskeletal system, facilitating movement and supporting mechanical loads. Emerging evidence suggests that vitamin D, beyond its well-established role in bone health, exerts significant effects on tendon physiology. The aim of this manuscript is to review the impact of vitamin D on tendons, focusing on its mechanisms of action, clinical implications, and therapeutic applications. A comprehensive search of scientific electronic databases was conducted to identify articles on the effects of vitamin D on tendon health. Fourteen studies were included in this review. Five studies were performed in vitro, and nine studies were conducted in vivo. Despite some conflicting results, the included studies showed that vitamin D regulates collagen synthesis, inflammation, and mineralization within tendons through its interaction with vitamin D receptors. Epidemiological studies link vitamin D deficiency with tendon disorders, including tendinopathy and impaired healing. Supplementation with vitamin D shows promise in improving tendon strength and function, particularly in at-risk populations such as athletes and the elderly. Future research should address optimal supplementation strategies and explore the interplay between vitamin D and other factors influencing tendon health. Integrating vitamin D optimization into clinical practice could enhance tendon integrity and reduce the burden of tendon-related pathologies. [ABSTRACT FROM AUTHOR]

Rickets results from impaired mineralization of growing bone due to alterations in calcium and phosphate homeostasis. Clinical signs of rickets are related to the age of the patient, the duration of the disease, and the underlying disorder. The most common signs of rickets are swelling of the wrists, knees or ankles, bowing of the legs (knock-knees, outward bowing, or both) and inability to walk. However, clinical features alone cannot differentiate between the various forms of rickets. Rickets includes a heterogeneous group of acquired and inherited diseases. Nutritional rickets is due to a deficiency of vitamin D, dietary calcium or phosphate. Mutations in genes responsible for vitamin D metabolism or function, the production or breakdown of fibroblast growth factor 23, renal phosphate regulation, or bone mineralization can lead to the hereditary form of rickets. This position paper reviews the relevant literature and presents the expertise of the Bone and Mineral Metabolism Group of the Italian Society of Pediatric Endocrinology and Diabetology (SIEDP). The aim of this document is to provide practical guidance to specialists and healthcare professionals on the main criteria for diagnosis, treatment, and management of patients with rickets. The various forms of rickets are discussed, and detailed references for the discussion of each form are provided. Algorithms to guide the diagnostic approach and recommendations to manage patients with rare forms of hereditary rickets are proposed. [ABSTRACT FROM AUTHOR]

Background: Previous studies have unequivocally demonstrated that the vitamin D (VD) metabolism pathway significantly influences prognosis and sensitivity to hormone therapy in prostate cancer (PCa). However, the precise underlying mechanism remains unclear. Methods: We performed molecular profiling of 1045 PCa patients, leveraging genes linked to VD synthesis and VD receptors. We then identified highly variable gene modules with substantial associations with patient stratification. Subsequently, we intersected these modules with differentially expressed genes between PCa and adjacent paracancerous tissues. Following a meticulous process involving single-factor regression and LASSO regression to eliminate extraneous variables and construct a prognostic model. Within the high-risk subgroup defined by the calculated risk score, we analyzed their differences in cell infiltration, immune status, mutation landscape, and drug sensitivity. Finally, we selected Apolipoprotein E (APOE), which featured prominently in this model for further experimental exploration to evaluate its potential as a therapeutic target. Results: The prognostic model established in this study had commendable predictive efficacy. We observed diminished infiltration of various T-cell subtypes and reduced expression of co-stimulatory signals from antigen-presenting cells. Mutation analysis revealed that the high-risk cohort harbored a higher frequency of mutations in the TP53 and FOXA genes. Notably, drug sensitivity analysis suggested the heightened responsiveness of high-risk patients to molecular inhibitors targeting the Bcl-2 and MAPK pathways. Finally, our investigation also confirmed that APOE upregulates the proliferative and invasive capacity of PCa cells and concurrently enhances resistance to androgen receptor antagonist therapy. Conclusion: This comprehensive study elucidated the potential mechanisms through which this metabolic pathway orchestrates the biological behavior of PCa and findings hold promise in advancing the development of combination therapies in PCa. [ABSTRACT FROM AUTHOR]

Background: Vitamin D, essential for bone health and overall well-being, plays a pivotal role in reproductive health. This study aimed to assess the prevalence of vitamin D deficiency among infertile women in India, considering regional and demographic factors. Methods: This retrospective study involved 34,844 infertile women seeking treatment at various centers across India. Exclusions were made for women with kidney or liver disorders and those on medications affecting vitamin D metabolism. Serum 25(OH)D levels were measured through immunoassay techniques, and the data were analyzed using statistical software. Results: This study analyzed the vitamin D levels of 34,844 individuals across 21 states in India. The overall prevalence of vitamin D levels revealed that 24.70% had normal levels, while 45.10% had insufficiency, and 21.30% had deficiency. Few individuals (8.80%) had borderline high levels, and only a small fraction (0.10%) showed signs of vitamin D toxicity. Significant regional disparities were observed, with states like Goa exhibiting high normal levels while Delhi had high rates of both deficiency and insufficiency. Conclusion: This study unveils a substantial prevalence of vitamin D deficiency among infertile women in India, potentially affecting their fertility and reproductive health. While evidence suggests that optimizing vitamin D status may enhance reproductive outcomes, further research is required to establish clear guidelines for vitamin D supplementation in infertility treatment. [ABSTRACT FROM AUTHOR]

Background: Epilepsy has a wide-ranging impact on the quality of life in patients of all age groups. Reduced levels of active vitamin D contribute to various bone diseases and may influence seizure control. Nevertheless, the risk factors for low vitamin D levels in patients with epilepsy remain inconclusive and are not well-established. The limited number of studies in Thailand may not be sufficient to provide guideline recommendations for screening vitamin D levels in adults with epilepsy. Objective: To evaluate the prevalence and risk factors of low vitamin D levels in Thai adults with epilepsy taking long-term antiepileptic drugs. To provide supporting recommendations for screening vitamin D levels in patients with epilepsy for early diagnosis and appropriate vitamin supplementation. Materials and Methods: The present study was a cross-sectional study conducted on 87 adults with epilepsy aged 18 to 76 years who were followed up at the Neurological Institute of Thailand between March and October 2023. Patients with comorbidities affecting vitamin D metabolism were excluded from the study. Baseline demographic data, epilepsy-related information, and anti-seizure medication information were analyzed. Blood tests for vitamin D for 25-hydroxyvitamin D [25(OH)D], calcium, phosphorus, and albumin were performed. Results: The prevalence of low vitamin D levels was 85%, including deficiency at 37% and insufficiency at 48%, with the mean (±SD) of serum 25(OH)D being 21.9±7.60 ng/mL. Multivariate analyses revealed that female was significantly associated with low vitamin D levels, adjusted OR 4.97 (95% CI 1.23 to 20.05). There was no significant association among epilepsy-related information, anti-seizure medications, and low vitamin D levels. Conclusion: The prevalence of low vitamin D levels in the present study was significantly higher than that observed in the previous studies, which is consistent with the findings of the recent studies in many countries. The authors strongly recommend screening for vitamin D levels in Thai adults with epilepsy, particularly in females. Early diagnosis and management of this condition are beneficial for patients with epilepsy and can help mitigate the various complications resulting from low vitamin D levels. [ABSTRACT FROM AUTHOR]

Vitamin D is rightly recognized as an essential key factor in the regulation of calcium and phosphate homeostasis, affecting primary adequate bone mineralization. In the last decades, a more complex and wider role of vitamin D has been postulated and demonstrated. Cardiovascular diseases have been found to be strongly related to vitamin D levels, especially to its deficiency. Pre-clinical studies have suggested a direct role of vitamin D in the regulation of several pathophysiological pathways, such as endothelial dysfunction and platelet aggregation; moreover, observational data have confirmed the relationship with different conditions, including coronary artery disease, heart failure, and hypertension. Despite the significant evidence available so far, most clinical trials have failed to prove any positive impact of vitamin D supplements on cardiovascular outcomes. This discrepancy indicates the need for further information and knowledge about vitamin D metabolism and its effect on the cardiovascular system, in order to identify those patients who would benefit from vitamin D supplementation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Skin cancer is a significant health burden being the fourth most common cancer globally and accounts for 6.2% of the total combined cancer cases. However, mortality rates due to skin cancer are less when compared with other cancers, but it is significantly high in the Asian population (43%). DNA mutations and environmental and genetic factors are linked with skin cancer prognosis; however, long-term exposure to ultraviolet (UV) radiation remains one of the leading factors worldwide. Sun exposure is a major environmental risk factor for skin cancers but is also an essential source of vitamin D. On the other hand, studies exploring the relationship between skin cancer risk and vitamin D show mixed, somewhat conflicting results. This study investigates the role of vitamin D and skin carcinogenesis to clarify the associations. Moreover, in addition to suppressing cancer stem cells, it has been observed that vitamin D also regulates tumour initiation and metastasis. In conclusion, the incorporation of well-designed studies on the metabolism of vitamin D from a genotypic and phenotypic perspective is required to understand the intricate mechanisms linking the role of vitamin D in skin carcinogenesis. These new findings will open up new pathways in targeting the disease and lead to novel opportunities for its treatment and cure. [ABSTRACT FROM AUTHOR]