Search Results (233)

Background: Although total 25-hydroxyvitamin D (25(OH)D) measurements may not accurately reflect functional vitamin D status, vitamin D deficiency is common in hepatocellular carcinoma (HCC). The contribution of altered vitamin D-binding protein (VDBP) and albumin to impaired bioavailability is poorly characterized in liver cancer. Methods: We measured total, free, and bioavailable 25(OH)D, VDBP, and albumin in 46 HCC patients and 87 healthy controls during winter and summer. Correlations with Child–Pugh score, Barcelona Clinic Liver Cancer (BCLC) stage, and disease aetiology were evaluated. Results: HCC patients exhibited significantly lower VDBP (177.3 ± 237.0 vs. 239.9 ± 141.9 mg/L, p < 0.001) and albumin (35.9 ± 5.4 vs. 48.0 ± 3.9 g/L, p < 0.001) compared to winter controls. Total 25(OH)D was lower in HCC (39.3 ± 22.1 nmol/L) versus summer controls (75.0 ± 22.8 nmol/L, p < 0.001) but comparable to winter controls (p = 0.061). HCC patients lacked seasonal variation in vitamin D fractions, unlike the controls. VDBP negatively correlated with free (ρ = −0.606, p < 0.001) and bioavailable 25(OH)D (ρ = −0.541, p < 0.001). Child–Pugh score correlated positively with BCLC stage (ρ = 0.378, p = 0.012) and inversely with albumin (ρ = −0.565, p < 0.001). Conclusions: Free and bioavailable vitamin D are profoundly compromised in HCC, reflecting impaired hepatic synthetic function and systemic inflammation. These fractions may serve as novel metabolic biomarkers superior to total 25(OH)D for assessing vitamin D deficiency and guiding individualized supplementation strategies in patients with liver cancer. Full article

Vitamin D deficiency is associated with the risk of atopic diseases and respiratory infections. The activated vitamin D receptor (VDR) forms a dimer with the retinoid X receptor alpha (RXRA) and binds to VDR/RXRA composite elements (CEs) in enhancers of target genes. However, VDR/RXRA CEs are identified in only 11.5% of cases in ChIP-Seq peaks. Our hypothesis was that VDR could form a VDR-Partner complex with transcription factor for which CEs have not yet been identified. We utilized Web-MCOT to search for novel VDR/Partner CEs in regulatory DNA. The potential formation of the VDR-Partner protein complex was assessed using the AlphaFold machine learning model. Through real-time RT-PCR, we measured the expression of immune system genes in a culture of U937 macrophage-like cells incubated with the active metabolite of vitamin D, calcitriol. We have predicted novel VDR/NR2C2 and VDR/PPARG CEs in the regulatory regions of immune system genes. We found potential synergism of VDR/NR2C2 and VDR/RXRA CEs in relation to the IRF5 gene, as well as potential synergism of VDR/PPARG and VDR/RXRA CEs for MAPK13. Predicting new regulatory relationships through the identification of new potential VDR/Partner CEs may provide insight into the deep mechanisms of vitamin D involvement in the pathogenesis of atopic dermatitis, bronchial asthma, allergic rhinitis, and pulmonary infections. Full article

Background/Objectives: Orthodontic tooth movement is a biological process involving coordinated bone resorption and formation in response to mechanical stimulation. The aim of this study was to evaluate the temporal changes in C-terminal telopeptide of type I collagen (CTX), procollagen type I N-terminal propeptide (PINP), and vitamin D-binding protein (VDBP) levels in gingival crevicular fluid (GCF) and saliva during fixed orthodontic treatment, as well as to assess the relationships among these biomarkers. Methods: The study included a total of 27 systemically and periodontally healthy individuals comprising 14 males and 13 females. Clinical periodontal parameters were assessed at three time points: before treatment (T0), at 24–48 h (T1), and on day 40 (T2). GCF and saliva samples were collected at the same time points. Levels of CTX, PINP and VDBP in GCF and saliva were quantified using enzyme-linked immunosorbent assay. The data were analyzed using both parametric and non-parametric statistical tests. Temporal changes across the three time points were evaluated using mixed-effects models, differences between GCF and saliva biomarker levels were assessed using paired tests, and correlations were examined using Spearman correlation analysis. Results: GCF and salivary CTX levels demonstrated a significant increase from T0 to T1, while PINP levels exhibited a substantial rise from T1 to T2 (p < 0.001). Levels of VDBP in both GCF and saliva did not demonstrate significant temporal changes (p > 0.05). Higher VDBP levels in both fluids were found to be negatively associated with increases in CTX and positively associated with increases in PINP (p < 0.05). Furthermore, salivary CTX and VDBP levels exhibited a consistent increase compared to those measured in GCF at all time points (p < 0.05). Conclusions: Fixed orthodontic forces elicit sequential resorptive and formative responses in both GCF and saliva. The potential of VDBP to function as a local modulator is indicated, with the capacity to influence the balance between osteoclastic and osteoblastic activity. The evaluation of these biomarkers in non-invasive biological samples may offer a valuable approach for monitoring bone metabolism throughout orthodontic treatment. Full article

The ATP-binding cassette (ABC) transporter family is one of the oldest conserved protein families and is widely present in animal and plant cells. However, few studies have investigated the role of ABC in the forest musk deer (FMD; Moschus berezovskii). In this study, we employed bioinformatics methods to identify and analyze the ABC transporter genes in M. berezovskii to elucidate the potential function of ABC genes in musk secretion. A total of 51 members of the MbABC gene family were identified. The analysis encompassed various aspects including physical and chemical properties, phylogenetic tree, structure prediction, conserved motifs, gene structures, chromosome localization, collinearity analysis, and KEGG and GO enrichment. Collinearity analysis revealed that the ABC transporter gene family is conserved in FMD, Cervidae, and five Bovinae species. MbABCB6, MbABCD4, MbABCF3, and MbABCG5 are key genes in protein–protein interaction networks, which are primarily involved in the transport of vitamins, lipids, and proteins. Tissue expression analysis showed that MbABCs were expressed at different stages. The RT-qPCR analysis revealed that 12 MbABC genes were up-regulated in musk gland cells during the non-secretion phase and stimulation phase, particularly MbABCC4d and MbABCC3. This study provides comprehensive information on the ABC gene family in FMD which can be further used for their functional validation. Full article

Background/Objectives: Acute kidney injury (AKI) is a frequent and serious complication following left ventricular assist device (LVAD) implantation. This study aimed to predict AKI within 90 days post-LVAD by evaluating urinary levels of vitamin D binding protein (VDBP) and kidney injury molecule-1 (KIM-1). Methods: We prospectively enrolled 29 advanced heart failure patients undergoing LVAD implantation and categorized them into four groups based on pre-LVAD kidney function and hemodynamic stability. Early-morning urine samples were collected 24 h before and 1 week after surgery. Urinary VDBP and KIM-1 levels, normalized to creatinine, were measured. Results: Thirteen patients developed AKI postoperatively. Both biomarkers were significantly elevated in patients with pre-existing kidney dysfunction and hemodynamic instability, as well as in those who developed AKI. Pre-LVAD VDBP and KIM-1 levels were associated with a nearly two-fold increased AKI risk. After adjusting for kidney function and hemodynamic status, this risk rose to 776% for KIM-1 and 674% for VDBP. Conclusions: Urinary VDBP and KIM-1 are promising non-invasive biomarkers for predicting AKI in LVAD patients. The predictive performance can be greatly improved after combining with pre-LVAD kidney function and hemodynamic stability. Early measurement may help identify high-risk individuals and guide perioperative management. Full article

Vitamin D deficiency is highly prevalent in Pakistan, but there is limited data on its genetic aspects. This case–control pilot study aimed to determine the association of rs782153744, rs200183599, rs118204011, and rs28934604 with vitamin D deficiency along rs7041 which has been studied in our population. The DNA of a total of 600 subjects (300 cases and 300 controls) was extracted and genotyped by tetra ARMS PCR, followed by Sanger DNA sequencing of exon 4 of the CYP2R1 and CYP27B1 genes and exon 8 of the GC gene. SNP Stat was employed to analyze the data, while logistic regression was used to calculate the p-values and odds ratios (ORs). The R package version R studio (2025.05.1) Build 513 was used to statistically analyze rs782153744. In silico modeling of wild and mutant CYP2R1 and GC proteins was performed in Swiss-Model, Swiss-Dock, Discovery Studio, and PyMol using 3c6g and IJ78 as templates to perform binding pocket analysis of vitamin D3. The rs782153744 showed a protective association in the additive (OR: 0.15, 95% CI: 0.08–0.27, p-value < 0.001), recessive (OR: 0.19, 95% CI: 0.10–0.33, p-value < 0.001), and dominant (OR: 0.19, CI = 0.10–0.33, p-value < 0.001) models, while GC rs7041 (T > A, T > G) displayed a p-value < 0.0001 across all genetic models. Sanger sequencing yielded insignificant results, and the SNPs rs200183599, rs118204011, and rs28934604 had no significant association with vitamin D deficiency. The molecular pocket analysis of wild and mutant CYP2R1 proteins carrying rs782153744 polymorphisms revealed no changes. GC proteins carrying the rs7041 polymorphism revealed a shift in their 3D and 2D configuration, as well as a change in the amino acid residue of the binding pocket of VD3. The risk-associated rs7041 and protective rs782153744 variants back genetic screening for vitamin D deficiency risk stratification, allowing targeted supplementation in predisposed subjects and assisting in formulating a genotype-specific therapeutic approach. Full article

Multiple sclerosis (MS) is a chronic autoimmune neurodegenerative disorder characterized by progressive demyelination and axonal degeneration within the central nervous system, driven by complex genomic and epigenomic dysregulation. Its pathogenesis involves aberrant DNA methylation patterns at CpG islands of numbers of genes like OLIG1 and OLIG2 disrupting protein expression at myelin with compromised oligodendrocyte differentiation. Furthermore, histone modifications, particularly H3K4me3 and H3K27ac, alter the promoter regions of genes responsible for myelination, affecting myelin synthesis. MS exhibits chromosomal instability and copy number variations in immune-regulatory gene loci, contributing to the elevated expression of genes for pro-inflammatory cytokines (TNF-α, IL-6) and reductions in anti-inflammatory molecules (IL-10, TGF-β1). Vitamin D deficiency correlates with compromised immune regulation through hypermethylation and reduced chromatin accessibility of vitamin D receptor (VDR) dysfunction and is reported to be associated with dopaminergic neuronal loss. Vitamin D supplementation demonstrates therapeutic potential through binding with VDR, which facilitates nuclear translocation and subsequent transcriptional activation of target genes via vitamin D response elements (VDREs), resulting in suppression of NF-κB signalling, enhancement of regulatory T-cell (T_reg) responses due to upregulation of specific genes like FOXP3, downregulation of pro-inflammatory pathways, and potential restoration of the chromatin accessibility of oligodendrocyte-specific gene promoters, which normalizes oligodendrocyte activity. Identification of differentially methylated regions (DMRs) and differentially expressed genes (DEGs) that are in proximity to VDR-mediated gene regulation supports vitamin D supplementation as a promising, economically viable, and sustainable therapeutic strategy for MS. This systematic review integrates clinical evidence and eventual bioinformatical meta-analyses that reference transcriptome and methylome profiling and identify prospective molecular targets that represent potential genetic and epigenetic biomarkers for personalized therapeutic intervention. Full article

Introduction: Chronic spontaneous urticaria (CSU), vitiligo, and Hashimoto’s thyroiditis (HT) frequently co-occur in the same patients, suggesting a shared autoimmune pathogenesis. These conditions are increasingly recognized as components of polyautoimmunity, with overlapping clinical, immunological, and pathogenetic features. Among the proposed common mechanisms, vitamin D deficiency and oxidative stress (OS) have emerged as key contributors. We aimed to explore the shared immunopathogenic pathways linking these conditions, with a focus on the interplay between vitamin D status and redox imbalance. Methods: An extensive narrative review of the current literature regarding the associations among CSU, vitiligo, and HT, focusing on the role of vitamin D status, OS, and nitrosative stress, and shared immunological pathways was conducted. Discussion: Vitamin D deficiency was consistently observed across all three conditions and is associated with increased disease activity and poorer clinical outcomes. Several polymorphisms in the vitamin D receptor (VDR) and binding protein genes correlate with disease susceptibility. OS and nitrosative stress markers, such as malondialdehyde (MDA) and nitric oxide (NO) metabolites, are elevated in patients with CSU, vitiligo, and HT, and are linked to tissue-specific immune activation, apoptosis, and loss of self-tolerance. Evidence suggests that vitamin D and antioxidant supplementation may provide clinical benefit. In vitiligo, narrowband ultraviolet B (NB-UVB) phototherapy not only promotes repigmentation through melanocyte stimulation but also reduces ROS production and modulates local immune responses. Conclusions: The coexistence of CSU, vitiligo, and HT reflects a broader systemic autoimmune tendency, with vitamin D deficiency and redox imbalance serving as potential unifying mechanisms. Routine assessment of vitamin D levels and OS parameters may enhance diagnostic precision and inform therapeutic strategies. Antioxidant-based interventions represent promising avenues in the integrated management of autoimmune skin and endocrine disorders. Full article

Osteoarthritis is a prevalent and disabling condition in companion dogs, yet existing treatments are primarily symptomatic and limited by safety concerns. EF-M2, a defined derivative of vitamin D-binding protein, selectively biases macrophages toward an anti-inflammatory phenotype in vitro. We conducted a randomised, double-blind, placebo-controlled trial (IMPAWS-OA-1) in 60 client-owned dogs with naturally occurring hip or elbow osteoarthritis. Animals were allocated to subcutaneous EF-M2 (0.1 µg/kg) given thrice weekly or twice weekly, or to saline placebo for four weeks, followed by four weeks off-drug. The primary endpoint was change in Canine Brief Pain Inventory–Pain Severity Score (CBPI-PSS) at Day 28. EF-M2 produced dose–frequency-dependent benefits: LS-mean ΔPSS was −2.11 for thrice weekly, −1.42 for twice weekly, and −0.54 for placebo (arm effect p < 0.001). Objective measures showed parallel improvements in peak vertical force and accelerometery. Serum biomarkers confirmed macrophage repolarisation (ARG1/iNOS ratio, IL-10 increase, TNF-α decrease), correlating with clinical response. Adverse events were infrequent and mild, with no excess over placebo. In conclusion, EF-M2 achieved clinically meaningful pain relief, functional gains, and biomarker shifts without safety signals, establishing first-in-species proof that targeted macrophage modulation may be a viable disease-modifying approach for canine osteoarthritis. Full article

Vitamin D is converted to a steroid hormone by 25-hydroxylation in the liver and then by 1-hydroxylation in the kidney to produce the circulating hormone 1,25-dihydroxy vitamin D [1,25(OH₂D]. This hormone then functions in cells of the intestinal mucosa and in bone to maintain whole-body calcium homeostasis. Classical vitamin D deficiency thus results in defective calcium homeostasis. Yet vitamin D deficiency is often reported in people with various diseases not associated with whole-body calcium homeostasis. Because of these associations with vitamin D deficiency, clinical trials have been undertaken to determine whether raising vitamin D status could be an effective treatment for such diseases. However, the results of such clinical trials have largely been inconclusive. The steroidal autocrine or paracrine role of locally produced 1,25(OH)₂D in many nonrenal cells throughout the body is protective against a range of pathological changes. In vitamin D deficiency such protection becomes defective. A disease process may thus be initiated, and then progress, while vitamin D status is inadequate, as in the months of winter in temperate regions of the world. The subsequent correction of vitamin D deficiency may no longer be able to protect patients when the disease process has already become established. To maintain the many protective roles of vitamin D against disease, it is important that public health strategies aim to maintain adequate vitamin D status throughout the year. Full article

Background/Objectives: Pomegranate (Punica granatum) peel, often discarded as waste, contains abundant bioactive compounds such as polyphenols, vitamins, flavonoids, tannins, anthocyanins, and many more. This contributes to remarkable bioactivities, including anticancer, anti-inflammatory, antioxidant, antibacterial, and antifungal properties. Pancreatic cancer is a deadly cancer with a 9% survival rate. Its aggressiveness, invasiveness, quick metastasis, and poor prognosis significantly decrease the survival rate. Thus, we aim to explore pomegranate peel as a possible alternative medication for treating pancreatic cancer through virtual methods. Methods: Firstly, bioactive compounds were collected from multiple databases and screened for oral bioavailability (OB) ≥ 0.3 and drug likeness (DL) ≥ 0.18 scores. Simultaneously, network pharmacology was employed to extract the most probable targets for pancreatic cancer. Further computational analyses were performed, including molecular docking, molecular dynamics simulation, and in silico pharmacokinetics evaluation. Results: Consequently, the top 10 key targets from network analysis were AKT1, IL6, TNF, SRC, STAT3, EGFR, BCL2, HSP90AA1, HIF1A, and PTGS2. However, only AKT1, EGFR, BCL2, HSP90AA1, and PTGS2 exhibited strong binding affinities with pomegranate compounds, which are significantly declared in affected cells to enhance cancer progression. Outcomes from molecular dynamics simulations, particularly RMSD, RMSF, hydrogen bonding, and radius of gyration (Rg), confirmed stable interactions between 1-O-Galloyl-beta-D-glucose, epicatechin, phloridzin, and epicatechin gallate with respective target proteins. Conclusions: This suggests that pomegranate peels hold anticancer bioactive compounds for treating pancreatic cancer. Surprisingly, most compounds adhere to Lipinski’s and Pfizer’s rules and display no toxicity. However, as this study relies entirely on computational methods, experimental validation is necessary to confirm these findings and assess real-world efficacy and potential side effects. Full article

Vitamin D is a key micronutrient in the function of the skeletomuscular system. Athletes are at increased risk of developing vitamin D deficiency during the execution of very demanding disciplines such as CrossFit^®. Single-nucleotide polymorphisms (SNPs) may influence circulating 25-hydroxy-vitamin D (25(OH)D) levels. An observational, longitudinal pilot study was conducted with 50 trained males according to specific inclusion criteria. Blood samples were obtained to determine 25(OH)D, vitamin D-binding protein (VDBP), vitamin D-receptor (VDR)circulating levels, and the presence of SNPs after DNA isolation and genotyping: rs10741657 to CYP2R1, rs2282679 to GC and rs2228570 to VDR genes. Significant differences (p < 0.05) in 25(OH)D concentration were determined between the biallelic combinations of rs228679 (GC) and rs228570 (VDR). The VDBP and VDR proteins did not show different levels in the case of the rs10741657 (CYP2R1) alleles. Statistically significant weak positive correlations (p < 0.05) were observed between 25(OH)D and AA-alleles of the CYP2R1 and VDR genes, and TT-alleles of the GC gene. Additionally, AA (rs10741657 and rs2228570) and TT (rs2282679) have a probability between 2 and 4 of having major effects on the concentration of 25(OH)D. Conversely, GG alleles present a probability of suboptimal values of 25(OH)D of 69%, 34%, and 24% for VDR, GC, and CYP2R1, respectively, showing a strong moderate positive correlation (r = 0.41) between the degrees of sports performance and 25(OH)D plasma levels. CYP2R1 (rs10741657), GC (rs2282679), and VDR (rs2228570) affect the concentration of serum 25(OH)D, as an indicator of vitamin D status and play a critical role in the sports performance of CrossFit^® practitioners. Full article

Multiple Sclerosis (MS) is a chronic disease with autoimmune and neurodegenerative features that affect the nervous system. Genetic predisposition and environmental factors, such as vitamin D deficiency and dysbiosis activating a pro-inflammatory response, have a role in the etiology of the disease. In this context, the interactions of vitamin D with the gut microbiota and immune system have attracted attention in recent years. Vitamin D (1,25-dihydroxycholecalciferol) modulates the immune response by binding to the Vitamin D receptor (VDR). This pathway supports the functions of regulatory T cells by suppressing the activity of T helper cells 1 and 17 (Th1 and Th17). In MS patients, dysbiosis is characterized by a decrease in microbial diversity, and an increase in pro-inflammatory species is observed when compared to healthy individuals. Vitamin D has protective effects on eubiosis via VDR in intestinal epithelial cells, also reducing intestinal permeability by regulating tight junction proteins. In this way, vitamin D may contribute to the prevention of systemic inflammation. Although the relationship between vitamin D and the immune system is well documented, studies that address the triad of vitamin D level, gut microbiota, and immune response in MS are still limited. Full article

Background/Objectives: Anemia, particularly iron-deficiency anemia (IDA), and stunting remain notable early childhood public health challenges in Indonesia; however, studies are still scarce. This study aimed to determine the co-occurrence of anemia and stunting (CAS), their prevalence, and the associated factors, as well as to describe the erythrocyte parameters. Methods: Approximately 2200 children aged 6–24 months were identified by midwives to have problematic nutritional status at Bandung Regency, West Java, Indonesia. These children were included in the population frame for a cohort study of vitamin D deficiency, vitamin D binding protein, and its impact on neurodevelopmental functions. A cross-sectional study was nested in the cohort study. The subjects were selected by stratified random sampling of 270 villages to meet the required number of samples. Medical doctors reassessed the anthropometric measurements and performed guided interviews to collect associated factors for IDA and CAS. Erythrocyte profiles of the children were examined from venous blood. Results: One hundred and ninety-four subjects were included in the analysis, among which 54.1% were stunted. Anemia was present in 40.7% of the subjects, largely due to IDA (87.3%). A wasting child and the factor of low paternal education (up to elementary school) were associated with IDA (aOR of 7.12 and aOR of 3.32, p < 0.05, respectively). Co-occurrence of anemia and stunting was found in 41/194 (21.1%) subjects, but it did not show significant association. Conclusions: Anemia and stunting were prevalent among children aged 6–24 months, but no associations were found between anemia and stunting in this study. Iron deficiency was the main cause of anemia, and it was associated with wasting and low paternal education. Full article

Preterm birth (PTB; <37 weeks’ gestation) is a persistent problem in the United States that affects non-Hispanic Black women at much higher rates than White women. Several biomarkers have been associated with PTB, including vitamin D deficiency (VDD) and low levels of vitamin D-binding protein (VDBP). However, no biomarker has been found to predict PTB. To identify a predictive biomarker of PTB, gene expression differences were determined in Black women with PTB and full-term births and between women with high and low levels of plasma vitamin D and high and low VDBP levels. In this pilot study of 19 pregnant women from the Biosocial Impact on Black Births (BIBB) study, we found that 47 genes were upregulated and 16 genes were downregulated in women with PTB as compared with women who had a full-term birth, 361 genes were downregulated and 61 genes were upregulated in women with VDD as compared with those that had vitamin D sufficiency, and 44 genes were upregulated and 295 were downregulated in women with low VDBP. Several genes expressed by neutrophils were downregulated in the PTB, VDD, and low VDBP groups. These findings support the idea that vitamin D and VDBP status may be important clinical markers influencing the gene expression of genes associated with PTB. Full article