Search Results (222)

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

Vitamin D deficiency is widespread. It increases the risk of several diseases. Therefore, researchers have long studied the factors that influence vitamin D levels in the body. These include its metabolism, catabolism, transport and binding of vitamin D to the receptor VDR. Currently, an increasing number of studies are focusing on genetic factors. Variations in vitamin D levels, including vitamin D deficiency, are under substantial genetic control. There is a reciprocity between the vitamin D system and epigenetic mechanisms. Vitamin D metabolism, on the one hand, is regulated by epigenetic mechanisms and, on the other hand, is involved in regulating epigenetic events. To appraise recent advances in nutrigenomics with its application in public health, several databases, including PubMed, Scopus and Web of Science, were investigated in detail. Nutri-epigenetics deals with the interplay between dietary components and the possible resulting changes in the epigenome. There is, therefore, great potential for the development of nutri-epigenetics. The purpose of the narrative review is to highlight the genetic aspects of vitamin D, its receptor VDR and vitamin D-related gene polymorphisms with a particular focus on vitamin D gene regulation. Particular attention is paid to the vitamin D response index. Full article

Background/Objectives: Endplate lesions of the lumbar spine are often asymptomatic and frequently observed incidentally by radiological assessment. Variants in the vitamin D receptor gene (VDR) and an increase in some biochemical markers related to the osteo-cartilaginous metabolism were found in patients with endplate lesions. The aim of this study was to identify biochemical and genetic markers putatively associated with the presence of endplate lesions of the lumbar spine. Methods: Quantification of circulating bone remodeling proteins was obtained from 10 patients with endplate lesions and compared with age- and sex-matched controls. Whole exome sequencing (WES) was performed on patient genomic DNA using the Novaseq 6000 platform (Illumina, San Diego, CA, USA), obtaining a median read depth of 117×–200×, with ≥98% of regions covering at least 20×. The sequencing product was aligned to the reference genome (GRCh38.p13-hg38) and analyzed with Geneyx software. Results: We observed modifications in the levels of circulating proteins involved in bone remodeling and angiogenesis. We identified variants of interest in aggrecan (ACAN), bone morphogenetic protein 4 (BMP4), cytochrome P450 family 3 subfamily A member 4 (CYP3A4), GLI family zinc finger 2 (GLI2), heparan sulfate proteoglycan 2 (HSPG2), and mesoderm posterior bHLH transcription factor 2 (MESP2). VDR polymorphism (rs2228570) was present in nine patients, with the homozygotic ones having more severe endplate lesions and higher levels of the analyzed circulating markers in comparison with heterozygotic patients. Conclusions: These data represent interesting evidence of genetic variants, particularly in VDR, and altered levels of circulating markers of bone remodeling associated with endplate lesions, which should be confirmed in a larger population. The hypothesis suggested by our results is that the endplate lesions could be the consequence of an altered ossification mechanism at the vertebral level. 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

Vitamin D, a hormone synthesized in the skin through ultraviolet B radiation (UVB), plays a crucial role not only in calcium and phosphate homeostasis but also in regulating skin homeostasis and modulating immune responses. In keratinocytes, vitamin D is converted to its active form, 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D), which interacts with the vitamin D receptor (VDR) to regulate gene expression involved in proliferation, differentiation, and antimicrobial defense. Dysregulation of this pathway has been implicated in inflammatory skin diseases such as psoriasis, atopic dermatitis, acne vulgaris, and hidradenitis suppurativa. These conditions are associated with altered epidermal differentiation, immune imbalance, and microbial interactions, where vitamin D plays a modulatory role by suppressing proinflammatory cytokines, enhancing antimicrobial peptide synthesis, and restoring skin barrier integrity. Topical vitamin D analogues have shown therapeutic benefits in psoriasis, while emerging evidence supports the adjunctive role of vitamin D supplementation in acne, hidradenitis suppurativa, and atopic dermatitis. Despite promising associations between low serum vitamin D levels and disease severity, a causal relationship remains uncertain. This review integrates molecular mechanisms with clinical findings, emphasizing the role of vitamin D in cutaneous physiology and pathology, and highlights the need for further research into targeted supplementation strategies in dermatological disorders. Full article

Vitamin D plays a crucial role in the regulation of the immune system, with immunomodulatory effects that are key in the prevention of colorectal cancer (CRC). Over the past decades, research has shown that this steroid hormone impacts much more than bone health, significantly influencing immune responses. Vitamin D enhances immune organ functions such as the spleen and lymph nodes, and boosts T-cell activity, which is essential in defending the body against tumors. Additionally, vitamin D mitigates inflammatory responses closely linked to cancer development, reducing the inflammation that contributes to CRC. It acts via vitamin D receptors (VDRs) expressed on immune cells, modulating immune responses. Adequate vitamin D levels influence gene expression related to inflammation and cell proliferation, inhibiting tumor development. Vitamin D also activates mechanisms that suppress cancer cell survival, proliferation, migration, and metastasis. Low levels of vitamin D have been associated with an increased risk of CRC, with deficiency correlating with higher disease incidence. Lifestyle factors, such as a diet high in red meat and calories but low in fiber, fruits, and vegetables, as well as physical inactivity, contribute significantly to CRC risk. Insufficient calcium and vitamin D intake are also linked to disease occurrence and poorer clinical outcomes. Maintaining optimal vitamin D levels and adequate dietary intake is crucial in preventing CRC and improving patient prognosis. This review explores the role of vitamin D in immune regulation and summarizes findings from randomized clinical trials assessing the effects of vitamin D supplementation on CRC outcomes. Full article

Lumbar disc degeneration (LDD) is a common musculoskeletal disorder that leads to chronic pain and functional impairment. Recent studies have suggested that the vitamin D receptor (VDR) plays a key part in regulating matrix metabolism, inflammation, and apoptosis in intervertebral discs (IVDs). The objective of this study was to examine cytokine expression and DNA methylation status of the VDR gene in blood leukocytes and lumbar disc tissues from patients with varying degrees of LDD severity. We aimed to explore correlations between VDR expression, methylation status, and clinical parameters such as pain intensity and functional disability. We conducted a prospective case-control study including 50 participants 35 LDD patients and 15 lumbar disc herniation (LDH) controls. Blood and lumbar disc tissue samples were collected for RNA and DNA extraction, followed by quantitative real-time PCR for gene expression and methylation-specific polymerase chain reaction for VDR promoter methylation analysis. Serum and nucleus pulposus (NP) VDR protein levels were measured using enzyme-linked immunosorbent assay. Clinical parameters, including pain intensity (NRS) and functional disability (ODI), were assessed. LDD patients exhibited significantly lower VDR mRNA expression in both blood leukocytes and NP tissue compared to controls (p < 0.05). LDD patients had significantly greater serum TNF-α levels than controls (p < 0.001); however, serum IL-1β levels were not different between two groups. Serum VDR protein levels were elevated in LDD patients (p = 0.016), whereas NP VDR protein was significantly reduced in the LDD group (p = 0.013). VDR promoter methylation was significantly higher in both the blood and NP tissue of LDD patients compared to controls (p < 0.001). Additionally, higher VDR promoter methylation in blood was correlated with advanced disc degeneration (p < 0.05), while NP methylation was associated with all grades of degeneration (p < 0.001). Serum VDR protein levels were inversely correlated with pain intensity (r = −0.39, p = 0.02), while NP VDR levels positively correlated with NRS scores (r = 0.43, p = 0.01). Aberrant VDR expression and increased promoter methylation are associated with LDD severity. Dysregulated VDR signaling, potentially mediated by DNA methylation, may play a critical role in the pathophysiology of LDD. These findings suggest that VDR could be a novel biomarker reflecting disease severity and a potential therapeutic target for managing LDD. Full article

Individual variations in the active form of vitamin D (Vit.D) arise from a combination of dietary intake, sun exposure, and genetic factors, making it complex and challenging to maintain optimal levels. Among Vit.D-related genes, variations in CYP2R1 and CYP27B1 influence Vit.D synthesis, CYP24A1 regulates its inactivation, and the Vit.D receptor (VDR) mediates Vit.D signaling. These genetic variations contribute to substantial differences in Vit.D concentrations and associated clinical effects. However, there has been a lack of comprehensive, simultaneous exploration of these key genes and their clinical implications. This review provides a systematic analysis of genetic variants in Vit.D-related P450 genes identified in human clinical studies, along with in silico predictions of their functional consequences. Since multiple genes seem to influence the body’s response to Vit.D, studying just one genetic variant may not fully explain Vit.D deficiency. A comprehensive evaluation of all Vit.D-related genes could offer valuable insights for advancing personalized medicine in Vit.D management. This study provides a foundation for developing a more personalized approach to Vit.D supplementation and regulation, guided by genetic information. Full article

Acute kidney injury (AKI) is a common critical clinical disease with high morbidity and mortality rates. Ischemia-reperfusion (IR) is the main cause of AKI, and there is no effective treatment or prevention. Therefore, it is critical to screen for effective therapeutic agents and to find therapeutic targets. DKS26 is a derivative of oleanolic acid (OA) optimized for bioavailability while retaining the anti-inflammatory, antioxidant, and anti-apoptotic properties of OA. This study aimed to investigate the therapeutic effects of DKS26 on AKI and its underlying molecular mechanisms. We established an AKI model in vivo and in vitro and observed that DKS26 had an ameliorative effect on IR or H/R-induced renal tubular epithelial cell injury and reduced oxidative stress, inflammation, and apoptosis. Meanwhile, Swiss TargetPrediction and AutoDock Vina analysis revealed that DKS26 may interact with vitamin D receptors (VDR) through hydrogen bonding, suggesting that DKS26 may exert effects through VDR. In this study, we found that DKS26 treatment enhanced the stability of the VDR protein, promoted the binding of VDR to p-NF-κB P65^Ser311, reduced the entry of p-NF-κB P65^Ser311 into the nucleus, and inhibited the transcription of downstream inflammatory genes as well as their own expression, thus exerting its protective effect. In summary, these findings suggest that DKS26 may be a promising preventive strategy and provide a theoretical and experimental basis for AKI treatment. Full article

Objectives: The BsmI polymorphism of the VDR gene (vitamin D receptor) is one of the important genetic variants influencing the development of osteoporosis. Measurement and evaluation of the 25-hydroxyvitamin D (25(OH)D) concentration in individuals with reduced bone mineral density are essential because deficiency of this hormone causes impaired bone mineralization, leads to low BMD (bone mineral density), and influences fracture formation. The aim of the study was to investigate the relationship between the VDR gene BsmI polymorphism and 25(OH)D levels in Slovak postmenopausal women. Materials and Methods: The study population consisted of 287 untreated postmenopausal women, who were divided into three groups based on T-scores: normal (CG = 65), osteopenia (OPE = 126), and osteoporosis (OPO = 96). DNA isolation was performed using a standard protocol. Genetic analyses of the BsmI (rs1544410) polymorphism of the VDR gene were performed using the TaqMan SNP genotyping assays. Biochemical analysis of total 25(OH)D was performed in blood serum using the electrochemiluminescence method. Results: The chi-square test confirmed that the mutant T allele was not associated with the development of osteoporosis (p = 0.419). Through Kruskal–Wallis analysis, we found significant differences (p < 0.05, p < 0.01) in total 25(OH)D concentrations in individual genotypes of the BsmI variant of the VDR gene between the groups of women studied. Conclusions: It can be concluded that the VDR gene and its variant BsmI as well as 25(OH)D total may be relevant markers in the etiology of the search for individuals at risk of osteoporosis. Full article

Many health benefits are associated with Vitamin D (VitD), although deficiency is associated with poor health outcomes and the increased risk of cancer development. For example, many tissue-specific enzymes are involved in VitD metabolism, and mutations or deletions within Vitamin D receptor (VDR) genes are known to increase the cancer risk by altering their functions or bioavailability, although less is known about these phenomena in oral cancers. Using well-characterized, commercially available oral cell lines (OKF4, HGF-1, SCC4, SCC9, SCC15, SCC25, and CAL27), the mRNA expression of P450 cytochrome VitD metabolic enzymes and receptor genes by qPCR revealed differential results. One oral cancer line (SCC15) did not express either the Vitamin D receptor (VDR) or FOK1 polymorphism and was also least affected by VitD3 administration in growth assays. In contrast, most oral cancers were missing one or more hydrolase (CYP2R1 and CYP24A1) or hydrolate (CYP27A1 and CYP27B1) enzymes. SCC25 was missing both the hydrolate enzymes and was the most inhibited in the VitD3 growth assays, while SCC4 was missing both the hydroxylase enzymes and was the least inhibited by VitD2. These associations between mRNA expression (or lack thereof) and VitD3 and VitD2 responsiveness can be used to identify molecular targets, which may lead to effective screening tools for VitD-related, complementary and alternative therapies. Full article

Background: Vitamin D insufficiency/deficiency is a highly prevalent condition worldwide. At the same time, chronic inflammation is a versatile pathophysiological feature and a common correlate of various disorders, including vitamin D deficiency. Methods: We investigated the possible association of inflammation with 25-hydroxyvitamin D3 (25OHD3) levels and its down-stream pathway by exploring vitamin D-binding protein (DBP) and vitamin D receptor (VDR) genes for single-nucleotide polymorphisms (SNPs), in healthy non-elderly Bahraini adults. Plasma levels of 25OHD3 were measured by chemiluminescence, and six SNPs, four in the GC gene (rs2282679AC, rs4588CA, rs7041GT, and rs2298849TC) and two in the VDR gene (rs731236TC and rs12721377AG) were genotyped by real-time PCR. The concentrations of five inflammatory biomarkers, IL6, IL8, procalcitonin (PCT), TREM1, and uPAR, were measured by ELISA. Results: The results showed no association between the 25OHD3 level and any of the inflammatory markers’ levels. However, three tested SNPs were significantly associated with the concentrations of tested biomarkers except for IL6. The TT mutant genotype of rs2298849TC was associated with lower levels of IL8 and higher levels of PCT and TREM1, the AA mutant genotype of rs2282679AC was associated with decreased levels of IL8 (p ≤ 0.001) and increased levels of TREM1 (p = 0.005), and the GG wild genotype of rs12721377AG was associated with increased levels of 25OHD3 (p = 0.026). Conclusions: Although chronic inflammation is not associated with the vitamin D system in the blood, it is downstream, as revealed by DBP and VDR genotyping. Alternatively, DBP and VDR pursue other functions beyond the vitamin D pathway. Full article

(1) Background: In recent years, there has been a growing interest in understanding the innate immunity of the mouth, particularly the mechanisms through which vitamin D influences oral health. Researchers have increasingly focused on the association between vitamin D and the antimicrobial peptide LL-37 since the CAMP gene, responsible for encoding the LL-37 peptide, is a direct target of both vitamin D and its receptor (vitamin D receptor, VDR). This study aimed to explore the correlation between the 25-hydroxyvitamin D (25(OH)D) levels and the concentration of the LL-37 peptide in both serum and saliva. The objective was to compare the serum concentrations of 25(OH)D and ll-37 with those in saliva and to access the correlations between the two compounds. (2) Methods: Serum and whole saliva samples were collected from 72 healthy adults (mean age 28.68 ± 8.35). The levels of 25(OH)D and LL-37 were assessed in both the saliva and serum samples using commercially available enzyme-linked immunosorbent assay (ELISA) kits. (3) Results: The 25(OH)D levels in the serum (median 5.92 ng/mL, min–max 2.7–10.4 ng/mL) correlated with the LL-37 serum levels (62 ng/mL, min–max 18–378 ng/mL; Pearson’s r 0.328, p = 0.005). Additionally, the 25(OH)D levels in saliva (median 1.16 ng/mL, min–max 0.54–2.12 ng/mL) strongly correlated with the LL-37 salivary levels (median 44 ng/mL, min–max 6.5–205 ng/mL; Pearson’s r 0.667, p < 0.001). The 25(OH)D salivary levels demonstrated a robust correlation with the LL-37 salivary levels. (4) Conclusions: This discovery emphasizes the complex interplay between vitamin D and LL-37 and lay the groundwork for the further exploration of vitamin D’s role in oral immune function. Full article

Background/Objectives: Low bone mineral density increases the risk of bone fractures, and this condition is especially common in postmenopausal women. Genetic factors significantly influence bone mineral density. This meta-analysis examined the relationship between vitamin D receptor (VDR) gene polymorphisms (BsmI, ApaI, and TaqI) and bone mineral density in postmenopausal women in the Middle East and North Africa (MENA) region. Methods: The PubMed, Embase, Scopus, and Web of Science databases were searched from inception to March 2024 for case–control studies on VDR BsmI, ApaI, and TaqI polymorphisms and their relationship with low bone density. Associations with low bone mineral density were tested with respect to different genetic models (dominant, recessive, allelic) using RevMan v5.3. Results: The meta-analysis included seven studies for BsmI, six for ApaI, and seven for TaqI, representing 704/689 cases/controls for BsmI, 914/711 for ApaI, and 974/895 for TaqI. No significant association was found between VDR polymorphisms and low bone mineral density in postmenopausal women, except in the dominant model (CC + CG vs. GG) for the BsmI variant (OR = 1.27, 95% CI: 1.01–1.59, p = 0.04). Conclusions: We found a modest association between the BsmI polymorphism and increased risk of low bone mineral density (BMD) in postmenopausal women from the MENA region, suggesting its potential as a biomarker. No associations were observed for ApaI or TaqI. These findings highlight the complex genetic–environmental interactions influencing BMD. Full article

Vitamin D receptor [VDR] expression promotes LL37 expression, possibly contributing to host defense. The hypothesis was that an increase in 25 hydroxyvitamin D [25vitD] could lead to enhanced VDR expression and increased LL-37 production, thereby contributing to improved prognosis in critically ill patients. Methods: A nonblinded, randomized controlled trial was conducted. A total of 207 patients admitted to ICU with severe SARS-CoV-2 pneumonia were included and received different doses of cholecalciferol (500 MU, 3 MU/day, no cholecalciferol) during their ICU and hospital stay. 25vitD levels as well as LL37 and monocytes’ VDR gene expression were evaluated on admission and after. Clinical evolution, ICU mortality, hospital mortality, and 60-day mortality were evaluated. Results: The median age was 57.7 years and the majority of patients were Caucasian [87.4%] and male [70.5%]. There was a significant difference in 25vitD levels between groups on the third [p = 0.002] and seventh [p < 0.001] days. Patients supplemented with 500 MU of cholecalciferol had a very significant increase in monocytes’ VDR gene expression and showed a better clinical evolution in the ICU, with a significant correlation to evolution factors. Higher LL37 on admission had a significant negative association with hospital and ICU mortality, lost after adjustment for comorbidities to a nearly significant association with ICU, hospital, and 60-day mortality. Conclusion: Supplementation with higher doses of cholecalciferol may contribute to a significant increase in 25vitD levels but not in LL37 levels. Higher LL37 levels on admission may be related to a decrease in ICU, hospital, and 60-day mortality. VDR gene expression in monocytes is much higher in patients supplemented with higher doses of cholecalciferol. Full article