Search Results (816)

Introduction: Dry Eye Syndrome (DES) is a multifactorial disorder of the ocular surface, characterized by complex interactions between environmental factors, immune dysregulation, and potential genetic predispositions. Vitamin D deficiency, known for its immunomodulatory properties, has increasingly been implicated in the pathogenesis of DES; however, the underlying mechanisms remain insufficiently elucidated. Of particular interest is the vitamin D receptor (VDR) gene, whose polymorphisms may influence the bioavailability and biological activity of vitamin D. Objective: The aim of this study was to investigate the association between serum 25-hydroxyvitamin D [25(OH)D₃] levels and selected polymorphisms in the VDR gene (Taq, Fok, Apa, and Bsm) in patients with DES and to analyze their potential clinical and genetic interactions. Methods: This prospective observational study included 60 patients with a confirmed diagnosis of DES. Serum 25(OH)D₃ levels were measured, and genotyping of four VDR single-nucleotide polymorphisms (SNPs) was performed using PCR followed by restriction fragment length polymorphism analysis. Genotype distributions were assessed in relation to vitamin D status using appropriate statistical tests and Hardy–Weinberg equilibrium analysis. Results: Over 85% of patients exhibited insufficient or deficient vitamin D levels. Among the analyzed SNPs, only the ApaI polymorphism (rs7975232) showed a statistically significant association with vitamin D status (p = 0.0384), with the homozygous AA genotype being more prevalent among patients with hypovitaminosis. The remaining polymorphisms (TaqI, FokI, BsmI) did not reach statistical significance; however, potential trends were observed that may warrant further investigation in larger cohorts. Conclusion: The findings suggest a potential role for VDR gene variability in the regulation of systemic vitamin D levels in patients with DES. Identification of specific genotypes may contribute to the development of personalized diagnostic and therapeutic strategies, particularly for patients with treatment-resistant forms of the disease. These results support the integration of genetic biomarkers and nutritional parameters into modern ophthalmologic practice. Full article

Cardiovascular diseases (CVDs) cover various pathologies including heart failure (HF). Furthermore, vitamin D is involved in the regulation of the cardiovascular system. This study aimed to assess the association between the vitamin D receptor (VDR) genotypes and the occurrence of cardiovascular disorders in the Algerian population. VDR gene polymorphisms were identified using the PCR-RFLP method. Moreover, plasma concentrations of 25-hydroxyvitamin-D were assessed by a chemiluminescent immunoassay method and plasma NT-proBNP levels were determined in vitro by immunoenzymatic analysis. Interestingly, our results indicate that the genotypic frequencies of ApaI polymorphism of the VDR gene were significantly higher in CVD patients compared to the control group. Moreover, higher numbers of AA genotypes and A alleles were found in the CVD group. Our data indicate that the group of CVD patients with HF compared to those without HF showed the same genotype and allele distribution. Furthermore, low vitamin D rates and high N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels according to the VDR rs7975232 genotype were noted in CVD patients compared to healthy controls. Our results indicate that ApaI polymorphism of the VDR gene and lower vitamin D level may be associated with increased cardiovascular risk. These findings indicate that the ApaI AA genotype could be considered as a new HF risk marker in the Algerian population. Full article

Alkaloids have garnered significant interest as potential anticancer agents. Vitamin D receptor (VDR) plays a role in preventing the progression of colorectal cancer (CRC) and may be a crucial mediator of the anticancer effects produced by certain alkaloids. The search for novel anticancer drugs that induce VDR expression and act through the VDR could improve the clinical outcomes of CRC patients. The anticancer and pro-apoptotic effects of coclaurine and reticuline were investigated using CRISPR/Cas9-edited VDR/knockout (KO) and wild-type (WT) CRC HCT116 cell lines. Western blotting, RT-qPCR, confocal microscopy, cell viability, scratch assays, and flow cytometry were employed to assess VDR expression and cellular localization, cell growth, wound-healing, cytotoxicity, apoptotic status, cell cycle progression, and VDR-mediated gene expression. Coclaurine and reticuline dose-dependently inhibited HCT116-WT cell viability, decreased wound-healing, and increased VDR nuclear localization and gene expression while downregulating the oncogenic genes SNAIL1 and SNAIL2. Both alkaloids induced late apoptosis in HCT116-WT cells, increased the cleavage of PARP and caspase-3, and upregulated Bax and TP53 while decreasing BCL-2. Both alkaloids caused HCT116-WT cell growth arrest in the S-phase, which is associated with cyclin A1 overexpression. Coclaurine and reticuline lost their anticancer effects in HCT116-VDR/KO cells. Docking studies revealed that both alkaloids occupied the VDR’s active site. These findings demonstrate that coclaurine and reticuline exert anti-CRC and pro-apoptotic activities via the VDR, suggesting them as natural therapeutic candidates. The use of in vivo CRC models is needed to validate the anticancer activities of coclaurine and reticuline. 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

Vitamin D, long recognized for its essential role in calcium–phosphate balance and bone health, has increasingly been identified as a pleiotropic regulator of metabolic, cardiovascular, and renal function. Deficiency of vitamin D is widespread worldwide and has been linked to a higher risk of insulin resistance, type 2 diabetes, atherosclerosis, hypertension, and chronic kidney disease. Meta-analyses suggest that each 10 nmol/L (≈4 ng/mL) increase in serum 25-hydroxyvitamin D [25(OH)D] is associated with about a 4% lower risk of type 2 diabetes, whereas other analyses indicate an approximately 10% reduction in cardiovascular event risk per 10 ng/mL (≈25 nmol/L) increment in circulating 25(OH)D concentration. Clinical and epidemiological studies suggest that optimal 25(OH)D concentrations may protect against cardiometabolic and renal complications, though supplementation trials show heterogeneous outcomes depending on baseline vitamin D status, genetic background, and dosage. By synthesizing current knowledge, this work highlights vitamin D status as a potentially modifiable determinant of global disease burden and a target for preventive and therapeutic strategies. Full article

Vitamin D plays a key role in pregnancy beyond calcium–phosphate regulation, modulating immune responses and glucose metabolism via the vitamin D receptor (VDR). Placental expression may be altered in gestational diabetes mellitus (GDM). This study aimed to assess placental VDR expression in GDM and evaluate its association with maternal vitamin D levels and clinical parameters. VDR expression in the placental tissue of 53 women with GDM and 26 healthy controls was assessed semi-quantitatively by immunohistochemistry. Maternal serum 25-hydroxyvitamin D (25(OH)D) levels, body mass index, weight gain, neonatal outcomes, and other variables were evaluated. Univariate and multivariate linear regression analyses were performed. VDR expression was significantly higher in the GDM group compared to controls (p = 0.0297 for mean, p = 0.0378 for median). No significant differences were observed in serum 25(OH)D concentrations between groups. Stepwise regression revealed that diabetes was the only independent predictor of VDR expression. Within the GDM subgroup, VDR expression was not associated with any clinical parameters, including maternal vitamin D status. Upregulated placental VDR in GDM may represent an adaptive response to metabolic stress. These findings suggest complex regulation of vitamin D signalling in diabetic pregnancies, warranting further investigation. Full article

Background: Vitamin D receptor (VDR) polymorphisms may influence immune regulation and musculoskeletal health, but their perioperative role is not well understood. This study investigated the rs2228570 (FokI) variant in relation to inflammatory, hematologic, and patient-reported outcomes in orthopedic patients. Methods: We genotyped 300 orthopedic patients and 200 healthy controls using real-time PCR. Regression models in patients adjusted for age and body mass index (BMI) examined associations between rs2228570 genotypes and laboratory as well as clinical outcomes. Results: The CC genotype (homozygous cytosine) was associated with higher white blood cell count (β = 0.52, p = 0.0435), higher lymphocyte count (β = 0.26, p = 0.00025), higher hemoglobin (β = 0.57, p = 0.00197), and higher hematocrit (β = 1.42, p = 0.01102). The TT genotype (homozygous thymine) was associated with higher C-reactive protein (β = 10.90, p = 0.00329), lower mean corpuscular volume (β = −1.63, p = 0.04909), and higher health-related quality of life assessed by the 36-Item Short-Form Health Survey (SF-36) (β = 6.31, p = 0.00009). Conclusions: The rs2228570 polymorphism in the VDR gene is associated with distinct perioperative inflammatory, hematologic, and patient-reported profiles. These findings support the potential clinical utility of VDR genotyping, in combination with routine laboratory tests, to refine perioperative risk stratification and guide personalized rehabilitation in orthopedic patients. Full article

Vitamin D is increasingly recognized as a key regulator of epithelial barrier integrity and mucosal immune homeostasis, with implications extending far beyond skeletal health. Through the vitamin D receptor (VDR), vitamin D regulates epithelial cohesion, innate immune responses, and tight-junction gene expression. This review explores the multifactorial role of vitamin D in modulating inflammation and preserving tissue barriers, with particular emphasis on its effects on tight junction (TJ) regulation and disease states characterized by barrier dysfunction, namely atopic dermatitis, psoriasis, inflammatory bowel disease (IBD), and celiac disease. In these settings, vitamin D/VDR signaling exerts protective actions by enhancing barrier structure, suppressing Th1/Th17-driven inflammation, modulating the gut and skin microbiome, and promoting epithelial repair. Animal studies and clinical data suggest that vitamin D supplementation can restore TJ expression, reduce disease activity, and improve clinical outcomes in both intestinal and dermatologic diseases. In the cardiovascular system, the role of vitamin D remains complex. While vitamin D influences endothelial function, insulin sensitivity, and systemic inflammation, supplementation trials yield mixed results, indicating a need for individualized approaches. Overall, this review synthesizes mechanistic, translational, and clinical data supporting vitamin D as a crucial modulator of barrier integrity and inflammation. These findings highlight its therapeutic relevance in chronic diseases characterized by immune dysregulation and epithelial disruption. Full article

HER2-positive breast cancer is an aggressive subtype, often associated with shorter progression-free and overall survival. Estrogen receptor (ER) expression within this subtype leads to distinct growth patterns and treatment responses. Calcitriol, the active form of vitamin D, induces ERα expression in ER-negative breast cancer cells, thereby sensitizing them to the antiproliferative effects of antiestrogens. When combined with neratinib, calcitriol enhanced cell growth inhibition. Therefore, we investigated whether adding calcitriol to the combined treatment with antiestrogens and neratinib could further inhibit the proliferation of HER2-positive breast cancer cells, regardless of their ER status. The BT-474 (ER-positive/HER2-positive) and SK-BR-3 (ER-negative/HER2-positive) breast cancer cell lines were pretreated with calcitriol to modulate ER expression, followed by treatment with calcitriol in combination with neratinib, with or without antiestrogens. Proliferation assays, cell cycle analysis, and Western blotting were then performed to assess treatment effects. The results demonstrated that calcitriol and neratinib, per se, significantly inhibited cell proliferation in a concentration-dependent manner in the HER2-positive cell lines. Notably, calcitriol enhanced the antiproliferative response of combined neratinib and antiestrogen treatment. Calcitriol, alone or in combination, modulated vitamin D receptor and ERα expression, reduced AKT and ERK phosphorylation, and promoted G1 phase arrest. These findings support the potential of this combinatorial approach as a therapeutic strategy for HER2-positive breast cancer. Full article

Background: Hypovitaminosis D has been associated with worse rheumatoid arthritis (RA) manifestations. Notably, different genetic studies have reported that approximately 65% of hypovitaminosis D can be partially explained using the presence of single-nucleotide variants (SNVs) in key genes involved in its metabolism. This study aimed to investigate the association and gene–gene interactions of four SNVs in vitamin D metabolism genes, rs10741657 (CYP2R1), rs10877012 (CYP27B1), rs4809959 (CYP24A1), and rs731236 TaqI (VDR), with hypovitaminosis D, RA, and its clinical disease activity in a Mexican mestizo population. Methods: This study was conducted among females: 204 RA patients and 204 control subjects (CS). Vitamin D serum levels (calcidiol) were analyzed using ELISA, SNVs through allelic discrimination with TaqMan^® probes, and were analyzed using a multifactor dimensionality reduction (MDR) method. Results: MDR analysis suggested that GG and TT genotypes of rs10877012 (CYP27B1) were linked to lower calcidiol levels, while the CT and CC genotypes of rs731236 TaqI (VDR) were associated with increased RA susceptibility and higher disease activity. Logistic regression confirmed that the GG genotype of rs10877012 (CYP27B1) was associated with hypovitaminosis D (OR = 1.8; CI: 1.1–3.0; p = 0.01), and the CT genotype of rs731236 TaqI (VDR) with RA (OR = 1.9; CI: 1.2–2.9; p < 0.01) and high DAS28-ESR (OR = 3.6; CI: 1.3–10.7; p < 0.01). Conclusions: The GG genotype of rs10877012 CYP27B1 was associated with susceptibility to hypovitaminosis D, whereas the CT genotype of rs731236 TaqI VDR confers susceptibility to RA and high clinical disease activity in the Mexican mestizo population. Full article

Paraoxonase 1 (PON1) is an antioxidant enzyme that plays physio-pathological roles. Prior in silico analysis revealed the presence of response elements of the nuclear receptor superfamily in the PON1 promoter, comparable to glucocorticoid receptors (GR), the vitamin D receptor (VDR), and the pregnenolone X receptor (PXR). The aim of this study was to evaluate the effects of 1α,25-dihydroxyvitamin D₃, a ligand specific to VDR, on the expression and activity of PON1 in hepatocarcinoma cells (HepG2 cells). PON1 activities (arylesterase/AREase and lactonase/LACase) were determined by spectrophotometry. Quantitative real-time PCR was used to evaluate the effect of VDR and PXR on the mRNA levels of PON1 and CYP3A4 genes. Molecular models and dynamics simulations were built using specialized software. Treatments with 1α,25-dyhydroxyvitamin D₃ (calcitriol), its active hormonal form, resulted in an induction of PON1 mRNA and AREase activity compared to control cultures. These results suggest that calcitriol plays a role in the regulation of PON1 transcription and provide evidence that this hormone increases PON1 levels in HepG2 cells. In addition, the molecular modeling suggests that calcitriol enhances PON1 activity and this increase could be caused by direct interaction on the PON1 protein. This study shows the effects of calcitriol on PON1 expression, proposing a new molecular mechanism for the transcriptional regulation of PON1 through a process linked to VDR activation and direct interaction of calcitriol on the PON1 protein. Full article

Atopic dermatitis (AD), a common chronic inflammatory disease in children and adults, is often studied to find the best way to prevent or reduce its severity. One of the substances tested so far is vitamin D. The main aim of this paper was to determine whether vitamin D truly brings benefits to people with AD or whether its action is too insignificant to have clinical significance. The review covered articles—observational studies, several animal studies and randomized controlled trials (RCTs)—available in the PubMed database and published after 2019. Full-text manuscripts in English were used. Observational studies presented both therapeutic effects of vitamin D and its lack of influence on AD. They also determined that vitamin D receptor (VDR) polymorphism may indeed affect the occurrence and severity of this disease. Similarly, the results of vitamin D’s effect on AD are inconclusive in RCTs. Meanwhile, animal studies showed only the attenuation of disease symptoms in mice. The still-growing number of studies on vitamin D and its association with AD, due to many internal and external distorting factors, has not been able to provide us with definitive results. It is necessary to conduct further appropriately designed large-scale studies, including long-term observation. Full article

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the etiologic agent that causes the coronavirus disease (COVID-19) identified in Wuhan, in 2019. Men are more prone to developing severe manifestations than women, suggesting a possible crucial role of sex hormones. 17,β-Estradiol (E2) and 1,25 α dihydroxyvitamin D₃ (calcitriol) act upon gene pathways as immunomodulators in several infectious respiratory diseases. In this study, we aimed to evaluate the influence of E2 and calcitriol on the VSV-based pseudovirus SARS-CoV-2 and SARS-CoV-2 infection in vitro. We infected Vero E6 cells with the recombinant VSV-based pseudovirus SARS-CoV-2 and the SARS-CoV-2 viruses according to the pre-treatment and pre–post-treatment models. The Angiotensin-Converting Enzyme 2 (ACE2) and Vitamin D Receptor (VDR) gene expression did not change under different treatments. The VSV-based pseudovirus SARS-CoV-2 infection showed a significant decrease in the focus-forming unit count in the presence of E2 and calcitriol (either alone or in combination) in the pre-treatment model, while in the pre–post-treatment model, the infection was inhibited only in the presence of E2. Th SARS-CoV-2 infection highlighted a decrease in viral titres in the presence of E2 and calcitriol only in the pre–post-treatment model. 17,β-Estradiol and calcitriol can exert an inhibitory effect on SARS-CoV-2 infections, demonstrating their protective role against viral infections. Full article

Sarcopenia is a progressive age-related musculoskeletal disorder characterized by loss of muscle mass, strength, and physical performance, contributing to functional decline and increased risk of disability. Emerging evidence suggests that vitamin D (Vit D) plays a pivotal role in skeletal muscle physiology beyond its classical functions in bone metabolism. This review aims to critically analyze the relationship between serum Vit D levels and sarcopenia in older adults, focusing on pathophysiological mechanisms, diagnostic criteria, clinical evidence, and preventive strategies. An integrative narrative review of observational studies, randomized controlled trials, and meta-analyses published in the last decade was conducted. The analysis incorporated international diagnostic criteria for sarcopenia (EWGSOP2, AWGS, FNIH, IWGS), current guidelines for Vit D sufficiency, and molecular mechanisms related to Vit D receptor (VDR) signaling in muscle tissue. Low serum 25-hydroxyvitamin D levels are consistently associated with decreased muscle strength, reduced physical performance, and increased prevalence of sarcopenia. Although interventional trials using Vit D supplementation report variable results, benefits are more evident in individuals with baseline deficiency and when combined with protein intake and resistance training. Mechanistically, Vit D influences muscle health via genomic and non-genomic pathways, regulating calcium homeostasis, mitochondrial function, oxidative stress, and inflammatory signaling. Vit D deficiency represents a modifiable risk factor for sarcopenia and functional impairment in older adults. While current evidence supports its role in muscular health, future high-quality trials are needed to establish optimal serum thresholds and dosing strategies for prevention and treatment. An individualized, multimodal approach involving supplementation, exercise, and nutritional optimization appears most promising. Full article

Environmental exposure to per- and polyfluoroalkyl substances (PFASs) has been increasingly associated with skin disorders, including atopic dermatitis (AD); however, the underlying molecular mechanisms remain unclear. This study aimed to evaluate the effects of perfluorononanoic acid (PFNA) and perfluorooctanoic acid (PFOA)—two widely detected PFASs—on epidermal function and gene expression in Human Epithelial Keratinocyte, neonatal (HEKn). We assessed cell viability, morphology, and transcriptomic changes using in vitro assays and RNA-seq analysis from a neonatal cohort. PFASs induced dose-dependent cytotoxicity and downregulation of barrier-related genes. Ingenuity pathway analysis identified calcitriol as a suppressed upstream regulator. Functional validation revealed that calcitriol partially reversed the PFAS-induced suppression of antimicrobial peptide genes. These findings support the hypothesis that PFASs may contribute to AD-like skin pathology by impairing vitamin D receptor signaling and antimicrobial defense, and calcitriol demonstrates potential as a protective modulator. This study provides mechanistic insights into the impact of environmental toxicants on skin homeostasis and suggests a potential protective role for calcitriol in PFAS-induced skin barrier damage. Full article