Electrochemical nanosensors offer remarkable capabilities for precise and selective vitamin detection, with transformative implications for healthcare, nutrition, and food industry quality control. Nanotechnology advancements have facilitated the creation of nanoscale sensors with customized properties, enhancing the efficacy of detecting vitamins. Materials such as gold nanoparticles, carbon nanotubes, and quantum dots have been modified to display remarkable sensitivity and specificity for distinct vitamins. Integrating these materials with electrochemical techniques enables the translation of biochemical interactions into measurable electrical signals, achieving accurate and swift detection. Real-time monitoring of vitamin levels enables health optimization and improves quality control, nutritional label accuracy and supply chain monitoring in the food industry. This review comprehensively examines the electrochemical properties of sensors for vitamin analysis, highlighting modernization in the design of sensors, restyling nanomaterial-based sensor technologies and exploring their applications in food quality control while simultaneously addressing current challenges and future directions in the development of sensors.

An LC-MS/MS method was developed and validated for simultaneously quantifying 25-hydroxyvitamin D2, D3, and 1α,25-dihydroxyvitamin D3 in human serum. Protein in 200 μL serum was precipitated with acetonitrile. After centrifugation, the metabolites were derivatized using (diacetoxyiodo)benzene (PIA) and 4-(4-dimethylaminophenyl)-1,2,4-triazolidine-3,5-dione (DMAT) and then quantified by the LC-MS/MS system. The limits of detection (LODs) for the three substances were 10, 10, and 5 pg/mL, and the limits of quantification (LOQs) were 20, 20, and 10 pg/mL. The standard curves for these compounds showed linear regression coefficients (R2)>0.998 over specific concentration ranges. Recoveries were 94.36 %-102.34 % for 25(OH)D2, 92.43 %-103.41 % for 25(OH)D3, and 88.98 %-94.36 % for 1α,25(OH)2D3. The mean serum levels in 109 subjects (consisting of 61 healthy adult males and 59 healthy adult females) were 2.0 ± 1.5 ng/ml (25(OH)D2), 16.4 ± 6.1 ng/ml (25(OH)D3) and 36.6 ± 15.1 pg/ml (1α, 25(OH)2D3).Derivatization of vitamin D metabolites using PIA and DMAT is useful for rapidly determining the serum 25(OH) D2, 25(OH) D3 and 1α,25(OH)2D3 concentrations simultaneously in human serum.

The prevalence of cardiometabolic multimorbidity (CMM) has increased substantially in recent years. Previous studies have established the associations between vitamin D, vitamin D receptor (VDR) polymorphisms, and the risk of individual cardiometabolic disease (CMD). However, the role of these factors in the progression of CMD to CMM or mortality remains unclear. This study aimed to investigate the associations between vitamin D, VDR polymorphisms, and the dynamic progression of CMM, as well as to explore the potential modification effect of VDR polymorphisms.

Data for this cohort study were extracted from the UK Biobank. CMM was defined as the coexistence of at least two CMDs, including type 2 diabetes (T2D), coronary heart disease (CHD), and stroke. A multi-state model was used to analyze associations between serum 25(OH)D, VDR polymorphisms and the dynamic progression of CMM.

The sample included 396,192 participants. Over a median follow-up of 13.8 years, 55,772 individuals experienced at least one CMD and 28,624 died. Compared to participants with 25(OH)D < 25 nmol/L, those with 25(OH)D ≥ 75 nmol/L had HRs of 0.70 (95% CI, 0.67, 0.72) for baseline to first CMD (FCMD), 0.74 (95% CI, 0.67, 0.82) for FCMD to CMM, 0.66 (95% CI, 0.62, 0.70) for baseline to death, 0.84 (95% CI, 0.77, 0.92) for FCMD to death, and 0.85 (95% CI, 0.70, 1.03) for CMM to death. L-shaped relationships of these associations were noted, with a threshold around 45 nmol/L. The rs1544410 (BsmI) T alleles may have a detrimental effect, while the rs11568820 (Cdx2) T alleles may exert a protective effect in the early stages of CMM progression. Additionally, VDR polymorphisms significantly modified the association between serum 25(OH)D and certain stages of CMM progression.

Maintaining adequate vitamin D levels, as a readily implementable intervention strategy, not only reduces the risk of initial CMD but also delays the progression to CMM or death. Risk stratification based on VDR polymorphisms provides further insights for developing personalized prevention strategies.

To determine if microRNAs that are altered in the circulation of women with endometriosis affect metabolic gene expression in hepatic cells.

In vitro study.

Deidentified tissue from women with endometriosis.

MicroRNAs were used to induce or suppress target genes in hepatic cells.

Effect of the microRNAs that are aberrantly expressed in endometriosis on hepatic cell gene expression using quantitative polymerase chain reaction.

Prior microarray studies on the serum of women with endometriosis showed differential expression of microRNAs miR-Let-7b, miR-125b-5p, miR-150-5p, and miR-3613-5p. Bioinformatic analyses revealed that these microRNAs have predicted binding sites in multiple genes involved in liver metabolism. Transfection of these miRs in HepG2 cells followed by real-time quantitative polymerase chain reaction showed that miR-Let-7b mimic increased the expression of Igfbp1 by 8-fold and reduced the expression of Mrc1 by 3.2-fold, whereas its inhibitor reduced Igfbp1 by 2.8-fold and increased Mrc1 by 5.2-fold. MiR-3613-5p mimic reduced the expression of Cyp2r1 by 2.2-fold and Mrc1 by 4-fold. MiR-125b-5p mimic increased the expression of Fabp4 by 4.1-fold, whereas miR-150-5p mimic increased the expression of Mrc1 by 1.8-fold and Cyp2r1 by 2.5-fold. Inhibitors of both miR-125b-5p and miR-150-5p did not show any effect on any of the genes.

Circulating microRNAs, known to be aberrant in endometriosis-regulated hepatic gene expression, likely contribute to the metabolic defects seen in this disease. Treatment with miR-Let-7b and miR-3613-5p, which are downregulated in endometriosis, reversed the effect of endometriosis on the expression of IGFBP1, MRC1, and CYP2r1 genes. Therefore, miR-Let-7b and miR-3613-5p may be novel candidate therapies for endometriosis, potentially correcting the metabolic changes seen in patients with endometriosis.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a subtype of chronic rhinosinusitis (CRS) characterized by bilateral nasal polyps, primarily affecting adults. It is often associated with hyposmia and asthma and driven by persistent Th2 inflammation, particularly in Caucasian patients. The disease is recurrent and significantly impacts quality of life, yet its pathophysiology remains poorly understood. Management includes intranasal steroids, short courses of systemic corticosteroids, surgery for refractory cases, and biologics. However, despite these treatment options, disease control remains challenging. Low vitamin D levels have been associated with worse clinical outcomes, while supplementation studies show promise in improving symptoms in deficient patients. Emerging research suggests that vitamin D modulates immunity, fibroblast activity, and epithelial integrity, potentially contributing to CRSwNP pathogenesis, though the exact mechanisms remain unclear. This review synthesizes current research on vitamin D's role in systemic and local inflammation in CRSwNP. By highlighting its potential therapeutic implications, this work aims to guide future research and inform clinical practice. Additionally, it may serve as a foundation for understanding the broader impact of vitamin D deficiency in sinonasal diseases and other atopic conditions.

Vitamin D is essential for children's growth and for the prevention of rickets; moreover, it has an essential role in phosphocalcic homeostasis. In 2022, new recommendations for vitamin D supplementation were established in France. In this study, we sought to evaluate the modalities of supplementation in children up to the age of 16 years and to determine the factors that might be related to compliance with the recommendations.

This was an observational descriptive study. Over two distinct periods, questionnaires were distributed at three pediatric emergency departments in Basse-Normandie (Lower Normandy) to children up to 16 years of age.

Overall, 710 questionnaires were analyzed. Adherence to vitamin D supplementation among children aged 0-16 years was low, with only 17 % of children following the supplementation recommendations, but it increased to 38 % in children under 2 years old. The main factors associated with adherence to the recommendations were younger age (odds ratio [OR]: 0.35, 95 % confidence interval [CI] [0.19-0.62], p < 0.001), medical follow-up by a pediatrician (OR: 0.34, 95 % CI [0.21-0.55], p < 0.001), and a higher socioeconomic status of the parents (OR: 2.43, 95 % CI [1.23-5.16], p = 0.014).

Adherence to the 2022 vitamin D supplementation recommendations was low, with only 17 % of children complying. However, these data need to be verified by conducting further large-scale research to confirm the findings and identify the most effective strategies for improving long-term adherence to the recommendations.

Hyperhomocysteinemia and vitamin D deficiency are known to promote cardiac hypertrophy, however, whether vitamin D signaling is involved in hyperhomocysteinemia-induced cardiac hypertrophy remains unexplored. This study aimed to address this question by clarifying the effect of homocysteine on vitamin D and vitamin D receptor (VDR), with further elucidation of the regulatory mechanisms. Methionine diet-induced hyperhomocysteinemic (HHcy) rats and homocysteine-incubated cardiomyocytes were used as in vivo and in vitro models of cardiac hypertrophy. Gain-and-loss-of function of VDR and miR-125b-5p were achieved by plasmid transfection and AAV9-mediated delivery. HHcy rats showed lowered serum and cardiac 1,25(OH)2D3 levels and increased 24-hydroxylase (CYP24A1) expression in kidney and myocardium. VDR expression was downregulated and miR-125b-5p was upregulated in the myocardium of HHcy rats and in homocysteine-incubated cardiomyocytes as well. Knockdown of VDR facilitated while overexpression mitigated homocysteine-induced cardiomyocyte hypertrophy, accompanied by activation and inhibition of calcineurin/nuclear factor of activated T cells 4 (NFATc4) respectively. Dual-luciferase reporter gene assay and gain-and-loss-of function of miR-125b-5p in cardiomyocytes indicated the targeting and repressing of VDR by miR-125b-5p and its pro-hypertrophic effect. The role of miR-125b-5p-mediated VDR downregulation in homocysteine-induced cardiac hypertrophy was further demonstrated in vivo. Treatment with VDR agonist inhibited hypertrophic growth both in vivo and in vitro, resulting from VDR upregulation and consequent calcineurin/NFATc4 inhibition. These findings demonstrated that homocysteine reduces 1,25(OH)2D3 level in both plasma and myocardium via upregulating CYP24A1 and represses myocardial VDR expression via the mediation of miR-125b-5p. Vitamin D/VDR deficiency contributes to hyperhomocysteinemia-induced cardiac hypertrophy via activating calcineurin/NFATc4 pathway.

Irritable Bowel Syndrome (IBS) is a chronic functional gastrointestinal disorder. Despite its common occurrence, the pathophysiology of IBS remains not fully understood. Emerging evidence suggests that IBS is a multifactorial condition characterized by low-grade inflammation, immune system activation, impaired gut permeability, intestinal hypersensitivity, and alterations in intestinal microbiota. Recent data have highlighted the potential role of vitamin D in modulating these underlying mechanisms. Vitamin D is known to influence various cellular processes, including the regulation of the gut microbiome, immune response modulation, and anti-inflammatory effects, which may alleviate the altered gut function observed in IBS. Research indicates that individuals with IBS often have lower levels of vitamin D compared to healthy controls, suggesting a possible link between vitamin D deficiency and IBS. Vitamin D supplementation has been associated with improvements in IBS symptoms, such as bloating, flatulence, abdominal pain, constipation, and overall quality of life. The mechanisms by which vitamin D exerts these effects may involve direct or indirect modulation of immune responses, the production of antimicrobial peptides, and the regulation of gene expression related to serotonergic metabolism. Despite these promising findings, the exact pathways through which vitamin D affects IBS pathophysiology remain unclear. The aim of this review is to outline the current knowledge and evidence regarding these mechanisms, as well as the therapeutic potential of vitamin D supplementation in IBS patients. Exploring the connection between vitamin D and IBS may pave the way for innovative interventions, enhancing both management strategies and the quality of life for those affected by the disorder.

The aim of this study was to assess the relationship between serum 25-hydroxyvitamin levels and all-cause mortality in patients with chronic diarrhea.

We carried out a cross-sectional study using information drawn from the National Health and Nutrition Examination Survey (NHANES). To assess mortality outcomes, we compared our data with records from the National Death Index as of December 31, 2011. The NHANES data were used to determine mortality outcome. We used a Cox regression model-based approach to analyze the relationship between serum 25-hydroxyvitamin concentrations and mortality in chronic diarrhea patients.

A total of 2,972 participants with chronic diarrhea were included in our study, 488 cases of all-cause mortality were recorded. The study showed an L-shaped relationship between 25-hydroxyvitamin concentrations and all-cause mortality with a threshold of 73.40 nmol/L. On the left side of the threshold, each 1-unit increase in 25-hydroxyvitamin concentrations was associated with a 2.2% reduction in the risk of all-cause mortality (HR 0.978; 95% CI: 0.969, 0.987); however, on the right side of the threshold, there was no significant correlation between 25(OH)D concentrations and all-cause mortality.

Serum 25-hydroxyvitamin D levels showed an L-shaped association with all-cause mortality in patients with chronic diarrhea, with 73.40 nmol/L as the potential threshold. However, because this was a cross-sectional study, only an association, not a causal relationship, can be inferred. Further prospective studies are needed to confirm these findings and explore the potential impact of vitamin D supplementation on mortality outcomes.

Vitamin D is crucial for maintaining bone health and development, and bone mineral accumulation during childhood and adolescence affects long-term bone health. Vitamin D deficiency has been widely recognized as one of the main causes of osteoporosis and fractures, especially during the growth and development stage of children. Recent studies have shown that vitamin D deficiency may affect the deviation of bone development in children by mediating lipid metabolism disorders, but its specific mechanism of action has not been fully elucidated. In this study, through clinical correlation analysis, it was found that vitamin D deficiency was negatively correlated with lipid metabolism levels. Subsequently, lipidomic analysis of vitamin D-deficient mice and children showed that triglycerides were the main lipid metabolites. It was found that the triglyceride synthesis pathway plays a key role in bone development in vitamin D-deficient obese children. Our study found that vitamin D deficiency mediates bone dysplasia by affecting triglyceride synthesis. These findings provide new insights into the mechanisms by which vitamin D deficiency affects bone development in children, which may guide more precise clinical interventions and support the development of new clinical treatments.

How will the scientific community and authoritative bodies define future nutritional requirements for vitamin D? At the International Symposium on Nutritional Aspects of Musculoskeletal Health, the authors debated the strength of current evidence for setting vitamin D intake recommendations from diet: the positive side of the strength of the evidence (PRO) suggests there is a physiological requirement for vitamin D and the opposing view (CON) that in light of negative results from large, recent trials, particularly those with fractures and bone health outcomes, we are left rudderless. Should we provide recommendations based on empiric treatment of vitamin D for most groups and conditions? It is becoming increasingly evident that vitamin D plays a role in many physiological functions and processes associated with long-term human health; however, to what extent are these benefits apparent beyond what is needed for adequate nutritional status, measured as serum 25-hydroxyvitamin D levels, for active calcium absorption? The meeting attendees voted for the PRO vs. CON position at the end of the session.

The purpose of this study was to investigate the effect of folic acid (FA) and vitamin D supplementation on increasing maternal serum folate and 25-hydroxyvitamin D [25(OH)D] concentrations during pregnancy and further reveal its role in reducing the risk of fetal growth restriction (FGR) in patients with preeclampsia (PE).

A total of 300 preeclamptic patients (treatment group 204 and control group 96) who had undergone routine obstetric examinations were retrospectively analyzed in this study. Data that include maternal serum levels of folate and 25(OH)D detected during early, middle, and late gestational periods from the medical records were analyzed. Multifactorial logistic regression analysis was performed to investigate the correlation of serum folate and 25(OH)D concentrations with the incidence of FGR.

Serum folate and 25(OH)D concentrations were similar between the treatment group and control group in the early gestation. During the middle and late gestation, the serum folate and 25(OH)D levels were both continuously increased in the treatment group, but persistently decreased in the control group, leading to significant differences between the two groups (p < .001). In addition, the incidence of FGR was significantly lower in the treatment group than in the control group (p < .001). Logistic regression analysis showed significant correlations of increased serum folate and 25(OH)D levels with lower risk of FGR.

FA and vitamin D supplementations facilitated to lower the risk of FGR in preeclamptic patients. These results would be the solid foundation for the further investigation of approaches to improve adverse outcomes of pregnancy, and have potential guiding implications for clinical practice.

Vitamin D plays important roles in various physiological processes such as cardiovascular health, calcium balance regulation, bone health, immune system support, neurological function regulation, muscle function maintenance, and anti-inflammatory effects. Therefore, maintaining its adequate levels is essential for overall health. Genetic polymorphisms in vitamin D metabolic pathways have become a key factor affecting the susceptibility and progression of cardiovascular disease (CVD). This article reviews the relationship between gene polymorphisms in vitamin D metabolic pathways and vitamin D levels or CVD. It is emphasized that the polymorphisms of key genes such as GC, VDR, CYP2R1, CYP24A1 and CYP27B1 are related to the pathogenesis of CVD. These polymorphisms can regulate serum levels of vitamin D, thereby affecting the susceptibility, comorbidities and clinical manifestations of CVD. Despite the progress made, there are still inconsistencies and gaps in the literature. Thus, it is necessary to conduct large-scale, multicenter studies to verify these findings and deepen our understanding of the intricate interactions between gene polymorphisms in vitamin D metabolic pathways and CVD.

Chronic obstructive pulmonary disease (COPD) is one of the world's major public health problems. It is characterized by a major inflammatory response, where vitamin D, due to its role in regulating the immune system, and genetic variants involved in its metabolism may play an essential role. The aim of this study is to evaluate the association between 13 polymorphisms related to vitamin D metabolism and the COPD risk.

A retrospective longitudinal study was designed in which 152 cases of COPD diagnosed at the University Hospital Virgen de las Nieves and 456 controls without the pathology, matched by age and sex, were included. The determination of the 13 polymorphisms was carried out using TaqMan™ probes.

Statistical analysis showed that the AA genotype and the A allele of the CYP27B1 rs4646536 polymorphism may be associated with an increased risk of developing COPD according to genotypic models (OR = 2. 6; 95% CI = 1.38-5.22; p = 0.004), dominant (OR = 1.69; 95% CI = 1.15-2.5; p = 0.008), recessive (OR = 2.24; 95% CI = 1.22-4.41; p = 0.013) and additive (OR = 1.56; 95% CI = 1.18-2.08; p = 0.020) models. Likewise, the AA genotype and the A allele of the CYP2R1 rs10741657 polymorphism were also associated with the risk of developing COPD according to the genotypic (OR = 1.9; 95% CI = 1.06-3.36; p = 0.028) and additive (OR = 1.37; 95% CI = 1.04-1.81; p = 0.027) models. Likewise, an association was found between GATG (p = 0.002; OR = 2.05; 95%CI = 1.32-3.20) and AGGT (p < 0.0001; OR = 2.1e46; 95%CI = 2.1e46-2.1e46) haplotypes and an increased risk of COPD.

We can therefore conclude that those variants could be used in the early detection of the disease in the future.

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.

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.

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.

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.

Gut microbiome plays a vital role in the intestinal ecosystem and has close association with metabolites. Due to the development of metabolomics and microbiomics, recent studies have observed that alteration of either the gut microbiome or metabolites may have effects on the progression of pancreatitis. Several new treatments based on the gut microbiome or metabolites have been studied extensively in recent years. Gut microbes, such as Bifidobacterium, Akkermansia, and Lactobacillus, and metabolites, such as short-chain fatty acids, bile acids, vitamin, hydrogen sulfide, and alcohol, have different effects on pancreatitis. Some preliminary studies about new intervention measures were based on the gut microbiome and metabolites such as diet, prebiotic, herbal medicine, and fecal microbiota transplantation. This review aims to summarize the recent advances about the gut microbiome, metabolites, and pancreatitis in order to determine the potential beneficial role of the gut microbiome and metabolites in pancreatitis.

Plasma 25-dihydroxyvitamin D levels appear reduced in patients with obesity or type 2 diabetes, as reported in several observational studies. However, the association between these reduced hormone levels and metabolic parameters is unclear. In any case, vitamin D supplementation in patients with Metabolic Syndrome is standard. Still, the impacts of this supplementation on conditions such as glycemia, blood pressure, and lipidemia are debatable. Based on this question, we carried out a systematic review and meta-analysis of randomized clinical trials in Brazil, Europe, and the United States that analyzed the effects of vitamin D supplementation on Metabolic Syndrome parameters in patients with obesity or type 2 diabetes. Our search yielded 519 articles and included 12 randomized controlled trials in the meta-analysis. Vitamin D supplementation had no effect on any of the outcomes analyzed (fasting blood glucose and insulinemia, glycated hemoglobin, HOMA index, systolic and diastolic blood pressure, weight, waist circumference, total cholesterol, LDL and HDL, and triglycerides). However, subgroup analyses indicated that using vitamin D up to 2000 IU daily reduced participants' fasting blood glucose and glycated hemoglobin. Furthermore, the intervention reduced diastolic blood pressure only in participants with vitamin D deficiency. At least two studies showed a high risk of bias using the Rob2 protocol. According to the GRADE protocol, the evidence quality varied from moderate to very low. These results indicate that vitamin D supplementation does not improve patients' metabolic parameters and that the association between plasma 25-dihydroxyvitamin D levels and Metabolic Syndrome may not be causal but caused by other confounding characteristics. However, in any case, the quality of evidence is still low, and more randomized clinical trials are essential to clarify these relationships.

Introduction Obesity is measured scientifically by calculating body mass index (BMI). Body mass index in men is linked to various hormonal imbalances. This study aims to observe the relationships between BMI, vitamin D, and testosterone levels in patients attending the outpatient clinic at Hayatabad Medical Complex, Peshawar, Pakistan. Methods This observational cross-sectional study involved 272 patients, presenting to the medical outpatient department from January 1st, 2023, to December 31st, 2023. Body mass index, serum vitamin D, and testosterone levels were measured for each participant. Body mass index was categorized into normal, overweight, and obese. Statistical analysis was calculated, including descriptive statistics, logistic regression, and correlation analysis to evaluate associations between these variables. Results The mean BMI of the participants was 25.82 ± 7.88 kg/m². A significant inverse correlation was observed between BMI and vitamin D levels (r = -0.79, p < 0.001) and between BMI and testosterone levels (r = -0.87, p < 0.001). A positive correlation was found between vitamin D and testosterone levels (r = 0.87, p < 0.001). Logistic regression analysis revealed that higher BMI in the range of overweight or above was associated with a 2.5-fold increase in the likelihood of vitamin D deficiency (odds ratio (OR) = 2.50, 95% CI = 1.8-3.5, p < 0.001) and a 3.1-fold increase in the likelihood of low testosterone levels (OR = 3.10, 95% CI = 2.2-4.3, p < 0.001). Conclusion In this study, higher BMI is significantly associated with lower vitamin D and testosterone levels. These findings suggest that addressing obesity could help mitigate hormonal imbalances, such as vitamin D deficiency and low testosterone, which are linked to metabolic health risks. It can also be hypothesized that obesity can be a risk factor for vitamin D and testosterone deficiency.

There has been increasing interest in the role of micronutrient supplementation in critical care. This narrative review summarizes the recent studies on micronutrients in critically ill patients. We searched two databases for primary randomized controlled trials that investigated the effects of micronutrient supplementation in patients with critical illness published from January 2021 to August 2023. Personal files, reference lists of included studies, and previous reviews were also screened. Twelve studies reported on vitamin C, four studies on vitamin D, three studies on thiamin, two studies on multivitamins, and one study on cobalamin. The therapeutic effects of vitamin C appear mixed, although vitamin C monotherapy appears more promising than vitamin C combination therapy. Intramuscular administration of vitamin D appeared to lower mortality, mechanical ventilation duration, and intensive care unit stay, whereas enteral administration showed limited clinical benefits. Intravenous thiamin was not associated with improved outcomes in patients with septic shock or hypophosphatemia. Preliminary evidence suggests reduced vasopressor dose with cobalamin. Decreased disease severity and hospital stay in patients with COVID-19 with vitamins A-E requires further investigation, whereas providing solely B-group vitamins did not demonstrate therapeutic effects. It is currently premature to endorse the provision of high-dose micronutrients in critical illness to improve clinical outcomes. This review may help to inform the design of future trials that will help better elucidate the optimal dosage and form of micronutrients, methods of administration, and subgroups of patients with critical illness who may most benefit.

The vitamin D receptor (VDR) is an important candidate gene in musculoskeletal phenotypes. Polymorphisms in the VDR have been previously associated with several pathologies and muscular strength in athletes and elderly people; however, the literature reported contradictory results. The object of this research was to verify the association between the most studied VDR variants (rs2228570, rs7975232, and rs1544410) and the increase in muscle mass in elite young soccer players. A sample of 55 soccer players (15-18 years old) from a professional team were selected for this study. DNA was extracted by the salting-out method, and polymorphisms were genotyped by PCR-RFLP, followed by 2% agarose gel electrophoresis. To test the effect of the three SNPs (single nucleotide polymorphisms), a logistic regression analysis was applied. The body composition determination was carried out through the skinfold thickness method, and the muscular area of the arm and lower limb were calculated using the Frisancho formula. All three polymorphisms met the Hardy-Weinberg equilibrium (p > 0.05) and their frequencies fell within the worldwide variability. A significant correlation between rs1544410 and the increase in calf muscle mass was observed. Individuals carrying the A allele showed higher calf muscular mass than those carrying the G allele (p = 0.034). Moreover, a haplotype analysis applied to the two SNPs in linkage disequilibrium (rs7975232 and rs1544410) showed that the AG haplotype appeared negatively correlated to the calf muscle area. In conclusion, we confirm an association between VDR polymorphisms and muscular mass that could encourage the genetic screening of the VDR gene to identify a potential risk of injury and for individual nutritional interventions.

Vitamin D is an essential molecule for cellular homeostasis, playing a critical role in cell fate decisions including cell proliferation, differentiation, and viability. Accumulating evidence has revealed that expression of the vitamin D-metabolizing enzyme CYP24A1 is dysregulated in different types of human malignancy. CYP24A1 has been shown to be involved in the oncogenic property of a variety of carcinoma cells. However, the pathological relevance of CYP24A1 expression level in human oral malignancy remains to be clarified. In the present study, suppression of CYP24A1 expression in oral squamous cell carcinoma (OSCC) cells increased cell proliferation, invasive activity, colony formation efficacy, and tumor growth in vivo. In addition, knockout of CYP24A1 expression inhibited cell death induced by two different types of anticancer drugs, i.e., fluorouracil and cisplatin. Gene clustering by RNA-sequence analysis revealed that several signaling molecules associated with MYC are involved in CYP24A1-mediated oncogenic behaviors. Furthermore, decreased expression level of CYP24A1 was observed in 124/204 cases (61%) of OSCC and was shown to be associated with short relapse-free and overall survival periods. The results showed that a low expression level of CYP24A1 promotes the oncogenic activity of OSCC and is significantly associated with poor prognosis in patients with this malignancy.

Diarrhea is a leading cause of death in young children worldwide. Vitamin D deficiency impairs the body's ability to clear pathogens, reduces tight junction protein expression in intestinal epithelial cells, and enhances Th1-mediated intestinal inflammation. This study aimed to investigate the effects of serum vitamin D levels on acute invasive enteritis in children.

This prospective cohort study included 82 children aged 1-3 years with clinically diagnosed acute invasive enteritis at Sichuan Maternal and Child Health Hospital from February 2021 to February 2022, alongside a control group of 80 healthy children. Fecal specimens were collected for routine tests and occult blood analysis, while blood samples were taken for routine tests, C-reactive protein, and 25-OHD levels. Comparative analyses were performed between groups, and multifactorial logistic regression was used to identify factors influencing invasive enteritis.

The study group showed significantly lower serum 25-OHD levels (27.95 ± 9.91 ng/mL) compared to controls (32.76 ± 10.23 ng/mL, p < .01). Among the study group, 19.5% (16/82) had levels <20 ng/mL, versus 12.5% (10/80) in controls. Regular vitamin D supplementation was lower in the study group (58.5% vs. 77.5%, p < .05). Outdoor activity duration was also reduced (2.57 ± 0.98 h vs. 3.04 ± 0.88 h, p < .01). Multivariate analysis identified that exclusive breastfeeding, greater outdoor activity time and regular vitamin D supplementation were all associated with reduced risk of invasive enteritis (p < .05).

The findings indicate an association between low serum 25-OHD levels and acute invasive enteritis in children aged 1-3 years, suggesting that consistent vitamin D supplementation and sufficient outdoor activity may protect against this condition.

Vitamin D's role extends beyond classical calcium and phosphate homeostasis to encompass a pivotal influence on immune modulation and metabolic health. The mechanisms by which vitamin D exerts these effects involve its conversion to hormonally active calcitriol, which binds intracellular vitamin D receptors, initiating various downstream cascades. In this review, we tease out the evidence showing the relationship between vitamin D deficiency and prediabetes within the context of subclinical inflammation, with a special focus on the novel monocyte-to-HDL ratio (MHR), a novel inflammatory marker reflecting subclinical inflammation. This was based on a thorough literature review using reputable databases covering the period from 1980 to 2024. In light of this, we discuss calcitriol's anti-inflammatory effects and consequently link vitamin D deficiency to both overt and subclinical inflammation. Additionally, the utility of several biomarkers, notably MHR, in investigating this association is also discussed. We further reviewed the role of vitamin D deficiency in precipitating prediabetes and type 2 diabetes mellitus (T2DM) via insulin resistance, decreased insulin synthesis and secretion, and subclinical inflammation. Taken together, this mini review highlights that vitamin D deficiency is significantly associated with subclinical inflammation, playing a critical role in the development of prediabetes and the progression to T2DM. Addressing vitamin D deficiency through appropriate interventions may serve as a preventative measure against the development of prediabetes and T2DM.

Vitamin D supplementation may prevent acute respiratory infections (ARIs). This study aimed to identify the optimal methods of vitamin D supplementation.

PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov registry were searched from database inception through July 13, 2023. Randomized-controlled trials (RCTs) were included. Data were pooled using random-effects model. The primary outcome was the proportion of participants with one or more ARIs.

The analysis included 43 RCTs with 49320 participants. Forty RCTs were considered to be at low risk for bias. The main pairwise meta-analysis indicated there were no significant preventive effects of vitamin D supplementation against ARIs (risk ratio [RR]: 0.99, 95% confidence interval [CI]: 0.97 to 1.01, I2 = 49.6%). The subgroup dose-response meta-analysis indicated that the optimal vitamin D supplementation doses ranged between 400-1200 IU/day for both summer-sparing and winter-dominant subgroups. The subgroup pairwise meta-analysis also revealed significant preventive effects of vitamin D supplementation in subgroups of daily dosing (RR: 0.92, 95% CI: 0.85 to 0.99, I2 = 55.7%, number needed to treat [NNT]: 36), trials duration < 4 months (RR: 0.81, 95% CI: 0.67 to 0.97, I2 = 48.8%, NNT: 16), summer-sparing seasons (RR: 0.85, 95% CI: 0.74 to 0.98, I2 = 55.8%, NNT: 26), and winter-dominant seasons (RR: 0.79, 95% CI: 0.71 to 0.89, I2 = 9.7%, NNT: 10).

Vitamin D supplementation may slightly prevent ARIs when taken daily at doses between 400 and 1200 IU/d during spring, autumn, or winter, which should be further examined in future clinical trials.

Chronic low-grade inflammation is a common feature of obesity and plays a crucial role in the progression of its complications. Vitamin D (VitD) plays an important role in modulating the immune response and regulating inflammation. Thus, this systematic review and meta-analysis aimed to evaluate the effects of isolated VitD supplementation on main inflammatory markers in overweight and obese individuals with no comorbidities and with VitD deficiency. We hypothesized that the increase in serum VitD concentrations after supplementation would significantly reduce the concentrations of inflammatory markers. The search was conducted in Medline/PubMed, SCOPUS, EMBASE, and Web of Science. Eleven randomized placebo-controlled studies were included in the final analysis, with a total of 504 participants and daily (1000-7000 international units) or bolus (100,000-200,000 international units) doses of VitD lasting from 2 to 26 weeks. The VitD supplementation did not influence C-reactive protein (mean difference [MD]: 0.01; 95% confidence interval [CI] -0.37, 0.39; P = .97), interleukin-6 (MD: -0.34; 95% CI -1.09, 0.42; P = .38), and tumor necrosis factor concentrations (MD: -0.02; 95% CI -0.23, 0.19; P = .85). In the analysis considering the studies with a significant increase in serum VitD concentrations, VitD supplementation also did not influence C-reactive protein (MD: -0.17; 95% CI -0.88, 0.54; P = .64), interleukin-6 (MD: -0.47; 95% CI -1.31, 0.37; P = .27), and tumor necrosis factor concentrations (MD: 0.01; 95% CI -1.34, 1.37; P = .98). This meta-analysis suggests that VitD supplementation does not significantly alter inflammatory markers in overweight and obese individuals.

Growth Hormone Deficiency (GHD) is a rare disease marked by a complete or partial reduction in the production of growth hormone. Vitamin D deficiency is frequent and may be associated with several pathologies. However, the association between GHD and vitamin D deficiency has not been extensively studied. This study aimed to analyse VDR gene polymorphisms related to vitamin D status to ensure better care for patients with GHD.

A case-control study was conducted at the Children's Hospital of Tunis in collaboration with the Farhat Hached's Hospital of Sousse, including patients with GHD and healthy subjects. Genetic analysis of the VDR gene polymorphisms was performed using PCR-RFLP technique. Haplotypes were examined with Haploview software, while statistical analyses were carried out using SPSS and R programming language.

Our study revealed significant differences in vitamin D (p = 0, 049) and calcium concentrations between patients and healthy subjects, which were lower in the GHD group (p = 0,018). A comparison of allelic and genotypic frequencies of the five polymorphisms indicated an association between the FokI polymorphism and GHD. Furthermore, significant difference was observed between the ApaI genotypes and PTH (p = 0,019) and ALP (p = 0,035). FokI genotypes were associated with phosphorus (p = 0,021). Additionally, One haplotype, CTAGT, exhibited a significant difference between the patients and healthy subjects (p = 0,002).

Our study findings indicate that hypovitaminosis D is common among patients with GHD, even when undergoing treatment with rhGH. This underscores the critical importance of vitamin D supplementation during treatment.

Breast cancer (BC) is a heterogeneous disease, with the ductal subtype exhibiting significant cellular diversity that influences prognosis and response to treatment. Single-cell RNA sequencing data from the GEO database were utilized in this study to investigate the underlying mechanisms of cellular heterogeneity and to identify potential prognostic markers and therapeutic targets.

Bioinformatics analysis was conducted using R packages to analyze the single-cell sequencing data. The presence of highly variable genes and differences in malignant potency within the same BC samples were examined. Differential gene expression and biological function between Type 1 and Type 2 ductal epithelial cells were identified. Lasso regression and Cox proportional hazards regression analyses were employed to identify genes associated with patient prognosis. Experimental validation was performed in vitro and in vivo to confirm the functional relevance of the identified genes.

The analysis revealed notable heterogeneity among BC cells, with the presence of highly variable genes and differences in malignant behavior within the same samples. Significant disparities in gene expression and biological function were identified between Type 1 and Type 2 ductal epithelial cells. Through regression analyses, CYP24A1 and TFPI2 were identified as pivotal genes associated with patient prognosis. Kaplan-Meier curves demonstrated their prognostic significance, and experimental validation confirmed their inhibitory effects on malignant behaviors of ductal BC cells.

This study highlights the cellular heterogeneity in ductal subtype breast cancer and delineates the differential gene expressions and biological functions between Type 1 and Type 2 ductal epithelial cells. The genes CYP24A1 and TFPI2 emerged as promising prognostic markers and therapeutic targets, exhibiting inhibitory effects on BC cell malignancy in vitro and in vivo. These findings offer the potential for improved BC management and the development of targeted treatment strategies.

Low serum vitamin D levels have been associated with a variety of health conditions which has led the medical community but also the general population to evaluate vitamin D status quite liberally. Nevertheless, there remain questions about the efficacy and cost-effectiveness of such a broad and untargeted approach. This review therefore aims to summarize the current evidence and recommendations on when and how to evaluate vitamin D status in human health and disease. For the general population, most guidelines do not recommend universal screening but suggest a targeted approach in populations at risk. Also, some guidelines do not even recommend evaluating vitamin D status when vitamin D substitution is indicated anyway, such as in children or patients receiving anti-osteoporosis drugs. In those guidelines that recommend the screening of vitamin D status, serum 25(OH)D levels are universally proposed as the preferred screening tool. However, little attention is given to analytical considerations and almost no guidelines discuss the timing and frequency of screening. Finally, there is the known variability in diagnostic thresholds for defining vitamin D insufficiency and deficiency. Overall, the existing guidelines on the evaluation of vitamin D status differ broadly in screening strategy and screening implementation, and none of these guidelines discusses alternative screening modes, for instance, the vitamin metabolic ratio. Efforts to harmonize these different guidelines are needed to enhance their efficacy and cost-effectiveness.

Several single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) have been observed in association with susceptibility to various pathologies, including autism, major depression, age-related changes in cognitive functioning, and Parkinson's and Alzheimer's diseases. This study aimed to establish the association between Fok1/Apa1 polymorphic variants and anxious/depressive symptoms in nonclinical adolescents from central Italy, with the goal of identifying the risk of developing both symptoms. We found no significant difference in genotype distribution or dominant/recessive models of Fok1/Apa1 VDR polymorphic variants between subjects with anxious/depressive symptoms and controls. HN9.10e cell lines carrying the AA genotype for Fok1 and the CC genotype for Apa1 responded better to treatment with vitamin D3 than cell lines carrying the AG genotype for Fok1 and CA genotype for Apa1. Cell lines carrying the GG genotype for Fok1 and the AA genotype for Apa1 did not respond at all, suggesting avenues for future studies in both the general population and individuals with mental and/or neuropsychiatric disorders. These studies suggest that the level of response to vitamin D3 administered to prevent and/or treat mental or neurological disorders could depend on the polymorphic variants of the vitamin D receptor.

Our study aims to examine the independent and combined associations of serum 25-hydroxyvitamin D [25(OH)D] concentrations and physical activity (PA) status with phenotypic age (PhenoAge).

The analysis included 18,738 participants from the NHANES 2007-2010 & 2015-2018. Phenotypic Age Acceleration (PhenoAgeAccel) was calculated as the residuals from regressing PhenoAge on chronological age. Weighted multivariable logistic regression models were used to analysis the relationship between 25(OH)D and PA with PhenoAgeAccel. Population attributable fraction (PAF) was used to estimate the proportion of PhenoAgeAccel which could be avoided if exposure were eliminated.

The multivariate-adjusted OR (95%CI) for PhenoAgeAccel with high 25(OH)D and adequate PA were 0.657 (0.549,0.787) (p < 0.001) for all, 0.663 (0.538,0.818) (p < 0.001) for participants whose age ≤65years old. Furthermore, there was multiplicative interaction between 25(OH)D and PA in age ≤65 years old group (0.729 (0.542,0.979), p = 0.036). High 25(OH)D level and adequate PA reduced the risk of PhenoAgeAccel by 14.3 % and 14.2 %, respectively. Notably, 30.7 % decrease was attributable to both high 25(OH)D level and engaging in adequate PA concurrently. Combining 25(OH)D above 80.4 nmol/l with PA decreased PhenoAge by 1.291 years (p < 0.001).

Higher 25(OH)D level was associated with lower risk of biological ageing. Combining 25(OH)D and PA demonstrated enhanced protective effects, especially in middle or young adults. These findings underscore the importance of outdoor PA in slowing down the aging process.

To evaluate the impact of cholecalciferol (D₃) supplementation using clinical and paraclinical variables in patients with RA and vitamin D insufficiency and deficiency.

A randomized, double-blind, placebo-controlled study included patients from 5 to 40 years with a diagnosis of RA and vitamin D insufficiency and deficiency. They were supplemented for 8 weeks with 4000 or 5000 IU, depending on age. Total nasal symptoms score (TNSS) was measured monthly and 25(OH)D₃ levels at baseline and at the end of the study.

A total of 31 patients were included, with a mean age of 18.19 years. In the active group, there was a significant improvement in symptomatology with respect to the TNSS score and an increase in serum vitamin D levels (p < 0.01). There were no adverse reactions with cholecalciferol or placebo.

Supplementing patients with vitamin D₃, at the evaluated dose, together with conventional treatent for allergic rhinitis results in symptoms and quality of life improvement in patients with this disease.

Colorectal cancer (CRC) is one of the most common cancers diagnosed in the world. Although environmental and genetic factors play a major role in the pathogenesis of CRC, extensive research has suggested that vitamin D may play a pivotal role in the development of CRC. Vitamin D, primarily obtained through sunlight exposure, dietary sources, and supplements, has long been recognized for its essential functions in maintaining health, including immune regulation. This article delves into the intricate relationship between vitamin D, the immune system, gut flora, and the prevention of CRC. It presents a synthesis of epidemiological data, experimental studies, and clinical trials, highlighting the mechanisms by which vitamin D influences immune cell function, cytokine production, and inflammation. By enhancing the immune system's surveillance and anti-tumor activity, vitamin D may offer a promising avenue for CRC prevention. Furthermore, this comprehensive review delves into the prospective clinical applications of vitamin D supplementation and delineates the forthcoming avenues of research in this dynamic domain. Additionally, the paper tentatively outlines a spectrum of prophylactic impacts of vitamin D on CRC, emphasizing its significant potential in reducing CRC risk through shedding light on its mechanisms, encompassing antineoplastic mechanisms, influences on the immune system, and modulation of the gut microbiome.

The growing interest in vitamin D deficiency as a potential contributor to coronary artery disease (CAD) has prompted increased scrutiny. Nevertheless, its status as a confirmed risk factor remains unestablished. This study seeks to explore the connection between serum vitamin D levels and CAD.

Employing a cross-sectional approach, 205 patients eligible for coronary computed tomography angiography (CCTA) were chosen. Serum vitamin D levels were assessed and juxtaposed with the outcomes of CCTA, which encompassed the coronary artery calcium score (CACS), as well as the presence and severity of coronary artery involvement attributed to atherosclerotic plaques.

The average age of the participants was 61.4 ±10.8 years, and the mean serum vitamin D level was 19.6 ±10.3 ng/dl (ranging from 4.7 to 39.7 ng/dl). In total, 52.1% of the participants (n = 107) exhibited vitamin D deficiency, while 47.9% (n = 98) had no deficient levels of vitamin D. The mean serum vitamin D level was notably lower in patients with severe coronary artery disease (CAD) (p < 0.0001). According to the Spearman test, a significant negative correlation (-0.48) was identified between the serum vitamin D level and CACS (p < 0.0001). Conversely, the mean CACS in the vitamin D deficient group was significantly higher than in the insufficient and non-insufficient vitamin D groups (p < 0.0001 for both comparisons).

There was a correlation between vitamin D deficiency and both CACS and the severity of coronary artery stenosis.

Vitamin D plays a major role in the musculoskeletal and immune system. Understanding the comprehensive mechanism of vitamin D receptors and the enzyme of vitamin D induction (CYP2R1) and inhibition (CYP24A1) in its metabolism is interesting. This study aims to understand vitamin D metabolism in Indonesian pediatrics, specifically in Jakarta, which has abundant sun exposure.

A cross-sectional study with comparative, correlative, and multivariate analysis on vitamin D, vitamin D receptor, CYP2R1, and CYP24A1 levels was conducted on 46 children with no known morbidity.

Subjects were mostly male (52.2%), age group of 2-6 years (34.8%), and had sufficient vitamin D status (43.5%, median 27.55 ng/mL). Age was found to have a negative correlation with vitamin D levels (p < 0.001; r = -0.625) and CYP2R1 (p = 0.035; r = -0.311). Significant positive associations were found between CYP24A1 and CYP2R1 (p = 0.046; r = 0.296). Participants aged 0-2 are more likely to have a higher level of vitamin D status compared to those aged >2 years (OR 42.092, 95% CI [4.532-390.914], p = 0.001). VDR levels were significantly lower in insufficient vitamin D levels than in the sufficient group (p = 0.018). VDR and vitamin D status had a positive relation (OR 7.023, 95% CI [1.864-26.453], p = 0.004).

Vitamin D levels decrease with the increase in age. Vitamin D receptor level has an inline-level progression with vitamin D level. CYP2R1 and CYP24A1 suggest a directly proportional relationship. Vitamin D screening and supplementation in children older than 2 years old are suggested.

Autoimmune thyroid diseases (AITD) are among the most frequent autoimmune disorders, with a multifactorial etiology in which both genetic and environmental determinants are probably involved. Celiac disease (CeD) also represents a public concern, given its increasing prevalence due to the recent improvement of screening programs, leading to the detection of silent subtypes. The two conditions may be closely associated due to common risk factors, including genetic setting, changes in the composition and diversity of the gut microbiota, and deficiency of nutrients like vitamin D. This comprehensive review discussed the current evidence on the pivotal role of vitamin D in modulating both gut microbiota dysbiosis and immune system dysfunction, shedding light on the possible relevance of an adequate intake of this nutrient in the primary prevention of AITD and CeD. While future technology-based strategies for proper vitamin D supplementation could be attractive in the context of personalized medicine, several issues remain to be defined, including standardized assays for vitamin D determination, timely recommendations on vitamin D intake for immune system functioning, and longitudinal studies and randomized controlled trials to definitely establish a causal relationship between serum vitamin D levels and the onset of AITD and CeD.

Clinical and preclinical studies have provided conflicting data on the postulated beneficial effects of vitamin D in patients with prostate cancer. In this opinion piece, we discuss reasons for discrepancies between preclinical and clinical vitamin D studies. Different criteria have been used as evidence for the key roles of vitamin D. Clinical studies report integrative cancer outcome criteria such as incidence and mortality in relation to vitamin D status over time. In contrast, preclinical vitamin D studies report molecular and cellular changes resulting from treatment with the biologically active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (calcitriol) in tissues. However, these reported changes in preclinical in vitro studies are often the result of treatment with biologically irrelevant high calcitriol concentrations. In typical experiments, the used calcitriol concentrations exceed the calcitriol concentrations in normal and malignant prostate tissue by 100 to 1000 times. This raises reasonable concerns regarding the postulated biological effects and mechanisms of these preclinical vitamin D approaches in relation to clinical relevance. This is not restricted to prostate cancer, as detailed data regarding the tissue-specific concentrations of vitamin D metabolites are currently lacking. The application of unnaturally high concentrations of calcitriol in preclinical studies appears to be a major reason why the results of preclinical in vitro studies hardly match up with outcomes of vitamin D-related clinical studies. Regarding future studies addressing these concerns, we suggest establishing reference ranges of tissue-specific vitamin D metabolites within various cancer entities, carrying out model studies on human cancer cells and patient-derived organoids with biologically relevant calcitriol concentrations, and lastly improving the design of vitamin D clinical trials where results from preclinical studies guide the protocols and endpoints within these trials.

Vitamin D3 (VD3) is a steroid hormone that plays pivotal roles in pathophysiology, and 1,25(OH)2D3 is the most active form of VD3. In the current study, the crucial role of VD3 in maintaining energy homeostasis under short-term fasting conditions was investigated. Our results confirmed that glucose-depriving pathways were inhibited while glucose-producing pathways were strengthened in zebrafish after fasting for 24 or 48 h. Moreover, VD3 anabolism in zebrafish was significantly suppressed in a time-dependent manner under short-fasting conditions. After fasting for 24 or 48 h, zebrafish fed with VD3 displayed a higher gluconeogenesis level and lower glycolysis level in the liver, and the serum glucose was maintained at higher levels, compared to those fed without VD3. Additionally, VD3 augmented the expression of fatty acids (FAs) transporter cd36 and lipogenesis in the liver, while enhancing lipolysis in the dorsal muscle. Similar results were obtained in cyp2r1-/- zebrafish, in which VD3 metabolism is obstructed. Importantly, it was observed that VD3 induced the production of gut GLP-1, which is considered to possess a potent gluconeogenic function in zebrafish. Meanwhile, the gene expression of proprotein convertase subtilisin/kexin type 1 (pcsk1), a GLP-1 processing enzyme, was also induced in the intestine of short-term fasted zebrafish. Notably, gut microbiota and its metabolite acetate were involved in VD3-regulated pcsk1 expression and GLP-1 production under short-term fasting conditions. In summary, our study demonstrated that VD3 regulated GLP-1 production in zebrafish by influencing gut microbiota and its metabolite, contributing to energy homeostasis and ameliorating hypoglycemia under short-term fasting conditions.

Eldecalcitol (ED-71), a novel active form of vitamin D, shows potential in treating osteoporosis. However, its underlying mechanisms of action remain to be determined. This study aimed to investigate the effect of ED-71 on bone regeneration and to illustrate its mode of action. The in-vitro model was developed using rat primary osteoblasts cultured under high-glucose conditions, and these cells were treated with ED-71. Additionally, an in vivo model of cranial bone defects was established in type 2 diabetic rats, and ED-71 was administered by gavage. The results demonstrated that ED-71 prevented osteoblast cell death, enhanced rat primary osteoblasts' osteogenic capacity, and attenuated the overexpression of hypoxia-inducible factor 1α (HIF1α) induced by high glucose levels. Furthermore, ED-71 increased glutathione peroxidase 4 (GPX4) levels and inhibited ferroptosis in response to hyperglycemic stimulation. Notably, interference with the HIF1α activator and ferroptosis activator Erastin significantly reduced the therapeutic effects of edetate osteolysis. These findings were further tested in vivo experiments. These results suggest that ED-71 activates the HIF1α pathway in vivo and in vitro, effectively relieving the ferroptosis induced by high glucose. Significantly, ED-71 may improve osteogenic disorders caused by diabetes.

Vitamin D is a promising anticancer agent for the prevention and treatment of several cancers, including melanoma. Low 25-hydroxyvitamin D levels, a routinely used marker for vitamin D, have been suggested as one of the factors in the development and progression of melanoma. The parent vitamin D needs activation by cytochrome P450 (CYP) enzymes to exert its actions via the vitamin D receptor (VDR). This review discusses the role of vitamin D in melanoma and how CYP-mediated metabolism can potentially affect the actions of vitamin D. Through interacting with the retinoid X receptor, VDR signaling leads to anti-inflammatory, antioxidative, and anticancer actions. Calcitriol, the dihydroxylated form of vitamin D3, is the most active and potent ligand of VDR. CYP27A1, CYP27B1, and CYP2R1 are involved in the activation of vitamin D, whereas CYP24A1 and CYP3A4 are responsible for the degradation of the active vitamin D. CYP24A1, the primary catabolic enzyme of calcitriol, is overexpressed in melanoma tissues and cells. Several drug classes and natural health products can modulate vitamin D-related CYP enzymes and eventually cause lower levels of vitamin D and its active metabolites in tissues. Although the role of vitamin D in the development of melanoma is yet to be fully elucidated, it has been proposed that melanoma prevention may be significantly aided by increased vitamin D signaling. Furthermore, selective targeting of the catabolic enzymes responsible for vitamin D degradation could be a plausible strategy in melanoma therapy. Vitamin D signaling can be improved by utilizing dietary supplements or by modulating CYP metabolism. A positive association exists between the intake of vitamin D supplements and improved prognosis for melanoma patients. Further investigation is required to determine the function of vitamin D supplementation and specific enzyme targeting in the prevention of melanoma.