Search Results (241)

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

Background: Osteogenesis imperfecta (OI) is a rare genetic connective tissue disorder characterized by bone fragility, most often caused by pathogenic variants in type I collagen genes. In this context, we aimed to describe the clinical and epidemiological characteristics of patients with OI who were hospitalized for coronavirus disease (COVID)-19 in Brazil between 2020 and 2024. Methods: We conducted a retrospective descriptive analysis using data from the Brazilian Unified Health System (SUS, which stands for the Portuguese Sistema Único de Saúde) through the Open-Data-SUS platform. Patients with a confirmed diagnosis of OI and hospitalization due to COVID-19 were included. Descriptive statistical analysis was performed to evaluate demographic, clinical, and outcome-related variables. We included all hospitalized COVID-19 cases with a confirmed diagnosis of OI between 2020 and 2024. Results: Thirteen hospitalized patients with OI and COVID-19 were identified. Most were adults (9; 69.2%), male (7; 53.8%), self-identified as White (9; 69.2%), and all were residents of urban areas (13; 100.0%). The most frequent symptoms were fever (10; 76.9%), cough (9; 69.2%), oxygen desaturation (9; 69.2%), dyspnea (8; 61.5%), and respiratory distress (7; 53.8%). Two patients had heart disease, one had chronic lung disease, and one was obese. As for vaccination status, five patients (38.5%) had been vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Four patients (30.8%) required admission to an intensive care unit (ICU), and six (46.2%) required noninvasive ventilatory support. Among those admitted to the ICU, only two required invasive mechanical ventilation. The clinical outcome was death in two cases (15.4%). Both patients were male, White, and had not been vaccinated against SARS-CoV-2. One was 47 years old, was not admitted to the ICU, but required noninvasive ventilation. Despite the underlying condition most patients had favorable outcomes, consistent with an international report. Conclusions: This is the first report to describe the clinical and epidemiological profile of patients with OI hospitalized for COVID-19 in Brazil, providing initial insights into how a rare bone disorder intersects with an acute respiratory infection. The generally favorable outcomes observed—despite the underlying skeletal fragility—suggest that individuals with OI are not necessarily at disproportionate risk of severe COVID-19, particularly when appropriately monitored. The occurrence of deaths only among unvaccinated patients underscores the critical role of SARS-CoV-2 vaccination in this population. Although pharmacological treatment data were unavailable, the potential protective effects of bisphosphonates and vitamin D merit further exploration. These findings support the need for early preventive strategies, systematic vaccination efforts, and dedicated clinical protocols for rare disease populations during infectious disease outbreaks. Full article

Vitamin D is essential for calcium homeostasis, bone mineralization, immunity, and disease prevention. In a field study with Holstein-Friesian dairy cows, the impact of prepartum vitamin D₃ treatment on early postpartum placental gene expression, focusing on calcium metabolism, feto-placental growth, and immune response, had been investigated. Eight multiparous cows were treated with 10 mL vitamin D₃ (1 million IU cholecalciferol/mL) intramuscularly on day 273 of pregnancy, while eight others remained untreated and served as controls. Placental tissues were collected post-calving, and gene expression was analyzed using quantitative real-time PCR. Among 23 genes, 5 showed significant downregulation in the treated group: CaBP-9k (reduced by 88.1% from 32.80 ± 91.50 to 3.90 ± 8.54), ESR1 (reduced by 95.7% from 7.89 ± 17.87 to 0.34 ± 0.34), LHR (reduced by 96.5% from 3.75 ± 5.45 to 0.13 ± 0.17), NOD1 (reduced by 94.1% from 4.21 ± 7.00 to 0.25 ± 0.30), and TLR1 (reduced by 99.7% from 24.80 ± 61.45 to 0.07 ± 0.08). These results suggest that vitamin D₃ supplementation affects key pathways related to calcium transport, reproductive function, and immune response in the bovine placenta. These molecular changes may help to explain improved calcium homeostasis and reduced postpartum complications, offering insights into how targeted nutritional interventions can enhance reproductive efficiency in high-producing dairy cows. 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

Weaning is challenging for dairy calves, frequently resulting in digestive issues. This highlights the importance of implementing appropriate nutritional strategies to enhance gut health and support optimal growth. Postbiotics is a promising alternative to traditional probiotics, conferring health benefits without the risks associated with live bacteria. This study aimed to investigate the effect of dietary supplementation with a postbiotic from dead-cell Limosilactobacillus ingluviei C37 (postbiotic LIC37) on blood biochemical parameters and jejunal epithelium transcriptomic profiles in calves. Fourteen Holstein bull calves were randomly allocated into two groups (n = 7). The control group (CON) received a basic diet, while the postbiotic group (DCLI) was supplemented with 1 g/d of postbiotic LIC37 for 90 days. Blood samples were collected on days 76, 83, and 90, respectively. The jejunal epithelial tissue was obtained from four randomly selected calves per group at day 90 for transcriptome analysis. The results showed that postbiotic LIC37 supplementation reduced globulin, total protein, neutrophil (Neu) levels, and neutrophil-to-lymphocyte ratio (NLR) levels in the DCLI group (p < 0.05). Transcriptomic analysis identified 76 differentially expressed genes (DEGs), with significant upregulation of genes involved in fatty acid metabolism (FABP1), intestinal barrier function (B4GALNT2), and detoxification (GSTA1), alongside downregulation of immune response regulation (FCRLA, FCRL4). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses highlighted enrichment in pathways related to glutathione metabolism, drug metabolism, and vitamin digestion, indicating that postbiotic supplementation improved detoxification, oxidative stress defense, and nutrient absorption in calves. This study provides novel insights into the molecular mechanisms underlying the benefits of postbiotic LIC37 and supports its potential as a sustainable alternative to probiotics in calf nutrition. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease marked by impaired barrier function and immune dysregulation. This study explores transcriptomic differences between lesional (IL) and perilesional (PL) skin in patients with AD, focusing on barrier-related and vitamin D-associated pathways. RNA sequencing was performed on matched IL and PL biopsies from 21 adults with moderate-to-severe AD. Differential gene expression, pathway enrichment, and correlation analysis with clinical variables were assessed. A total of 8817 genes were differentially expressed in IL versus PL skin (padj < 0.05). Among genes with the highest level of dysregulation, strong upregulation was observed for inflammatory mediators (IL-19, IL-8, CXCL6), and epidermal remodeling and barrier-disrupting genes (MMP1, GJB2). The vitamin D pathway genes CYP27B1 and CYP24A1 were also significantly upregulated. In contrast, key barrier-related genes such as FLG2 and CGNL1 were markedly downregulated. While some patterns in gene expression showed subgroup-specific trends, no independent clinical predictors emerged in multivariate models. Reactome pathway analysis revealed the enrichment of pathways involved in keratinization, cornified envelope formation, IL-4/IL-13 signaling, chemokine activity, and antimicrobial responses, highlighting coordinated structural and immunologic dysregulation in lesional skin. Lesional skin in AD displays a distinct transcriptomic profile marked by barrier impairment, heightened inflammatory signaling, and activation of vitamin D-related pathways. These findings provide the first RNA-seq-based comparison of IL and adjacent PL skin in AD. We identify subclinical activation in PL skin and vitamin D pathway upregulation with disrupted gene coordination in lesions. These findings enhance our understanding of the molecular mechanisms underlying inflammation in AD. 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

Background/Objectives: Cervical cancer is a leading cancer-related cause of death among women, with recurrence being a serious clinical issue. Recent evidence demonstrates that long non-coding RNAs (lncRNAs) affect cancer recurrence. This research investigates vitamin D’s regulatory actions in the recurrence of cervical cancer, centering on the involvement of lncRNA. Clinical data on 738 patients shows that greater serum vitamin D levels are linked to reduced recurrence rates and enhanced disease-free survival (DFS). Methods: A transcriptomic analysis of CaSki cervical cancer cells using data from the GEO dataset GSE267715 identified that vitamin D controls genes that prevent cervical cancer recurrence. Machine learning predictors CatBoost, LightGBM, Extra Trees, and Logistic Regression and feature selection methods such as ANOVA F-test, mutual information, Chi-squared test, and Recursive Feature Elimination (RFE) are used to identify predictors of recurrence, evaluating model performance using accuracy, precision, recall, ROC AUC, confusion matrices, and ROC curves. Result: CatBoost performs the best overall, producing an accuracy of 95.27%. CatBoost provided an ROC AUC of 0.9930, a precision of 0.9296, and a recall of 0.9706, and this implies a significant trade-off between the ability to detect metastatic cases correctly. Conclusions: These data identify the therapeutic potential of vitamin D as a regulatory compound and lncRNA as a potential therapeutic target in the recurrence of cervical cancer. 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

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

Activated immune cells are highly susceptible to human immunodeficiency virus (HIV) infection. Vitamin D (VitD) induces antimicrobial responses and reduces cellular activation. We investigated VitD effects on HIV-1 replication, glucose uptake, and gene regulation using computational and in vitro approaches. CD4⁺ T cells from healthy male donors were treated with VitD and infected with HIV-1. After 72 h, p24 protein was measured to assess viral replication. VitD effects on anti- and pro-HIV genes were analyzed by a Boolean network model based on curated databases and the literature. CCR5 and CXCR4 coreceptor expression, AKT phosphorylation, and glucose uptake were evaluated by flow cytometry, and expression of some model-identified genes was quantified by qPCR. VitD reduced p24 by 53.2% (p = 0.0078). Boolean network modeling predicted that VitD upregulates antiviral, migration, and cell-differentiation related genes, while downregulating genes related to cellular activation, proliferation, glucose metabolism, and HIV replication, notably AKT1, CCNT1, SLC2A1, HIF1A, and PFKL. In vitro, VitD reduced AKT phosphorylation by 26.6% (p = 0.0156), transcription of CCNT1 by 22.7% (p = 0.0391), and glucose uptake by 22.8% (p = 0.0039) without affecting classic antiviral genes or coreceptor expression. These findings suggest an anti-HIV effect of VitD, mediated through AKT and glucose metabolism downmodulation, both involved in cell activation and HIV-1 replication. Full article

The current experiment aimed to investigate the effects of sodium butyrate (SB) and vitamin D3 (VD3) supplementation on the growth performance, immune status, antioxidant capacity, and gut health of young broilers under cold stress. A total of 144 1-day-old Arbor Acres chicks were randomly allotted to three treatments with 6 replicates of 8 birds: (1) basal diet; (2) basal diet + cold stress; and (3) basal diet with 1 g/kg SB and 2000 IU/kg VD3 + cold stress. Birds were exposed to cold stress at 16 ± 1 °C for 72 h (d 18–21) and 26 ± 1 °C for the control. The results indicated that the SB/VD3 diet could alleviate the reduction in average daily gain (ADG) caused by cold stress (p < 0.05). The SB/VD3 diet decreased the serum endotoxin level and ileal interleukin-1β gene expression and upregulated interleukin-10 and nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression compared with cold-stressed birds (p < 0.05). Furthermore, cold stress altered the composition of gut microbiota, including a decrease in Clostridium_sensu_stricto_1, whereas the SB/VD3 diet prevented the reduction. In conclusion, the SB/VD3 diet mitigated the negative effects of cold stress on growth performance and the intestines by strengthening intestinal barrier function and stabilizing gut microbiota balance in broiler chicks, and these results can help to manage cold stress. Full article

Background/Objectives: The relationship between diet, micronutrient supplementation, and metabolic regulation emphasizes the potential of nutritional strategies to address obesity and related disorders. Certain vitamins have the potential to enhance thermogenesis and metabolic health. However, the impact of multivitamin supplementation on white adipose tissue (WAT) browning, the gut microbiome (GM), and metabolic function is not well understood. This study investigated the effects of multivitamin supplementation on obesity-related metabolic dysfunction in mice fed a high-fat diet (HFD) or a low-fat diet (LFD). Methods: Male C57BL/6J mice were assigned to group 1: control chow diet (CHD); 2: control HFD; 3: multivitamin-supplemented HFD (Mv-HFD); 4: control LFD; or 5: multivitamin-supplemented LFD (Mv-LFD). Diets, either supplemented with multivitamins A, D, B₁, B₅, and C or non-supplemented, were administered for 12 weeks. Metabolic parameters, adipose tissue browning, and the GM composition were analyzed. Results: The Mv-HFD significantly reduced weight gain, adipose tissue mass, blood glucose levels, and insulin resistance induced by an HFD. Additionally, it increased energy expenditure and thermogenic gene expression in WAT. Both the Mv-HFD and Mv-LFD improved the GM composition by increasing beneficial bacteria. Conclusions: Multivitamin supplementation improved metabolic health by potentially promoting WAT browning, enhancing energy expenditure, and modulating the GM composition. These findings suggest that multivitamins could offer a promising strategy for combating obesity and associated metabolic dysfunction. Full article

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. Full article

Background/Objectives: Prostate cancer (PC) is the most common non-cutaneous cancer in men globally, and one which displays significant racial disparities. Men of African descent (AF) are more likely to develop PC and face higher mortality compared to men of European descent (EU). The biological mechanisms underlying these differences remain unclear. Long non-coding RNAs (lncRNAs), recognized as key regulators of gene expression and immune processes, have emerged as potential contributors to these disparities. This study aimed to investigate the regulatory role of lncRNAs in localized PC in AF men relative to those of EU and assess their involvement in immune response and inflammation. Methods: A systems biology approach was employed to analyze differentially expressed (DE) lncRNAs and their roles in prostate cancer (PC). Immune-related pathways were investigated through over-representation analysis of lncRNA–mRNA networks. The study also examined the effects of vitamin D supplementation on lncRNA expression in African descent (AF) PC patients, highlighting their potential regulatory roles in immune response and inflammation. Results: Key lncRNAs specific to AF men were identified, with several being implicated for immune response and inflammatory processes. Notably, 10 out of the top 11 ranked lncRNAs demonstrated strong interactions with immune-related genes. Pathway analysis revealed their regulatory influence on antigen processing and presentation, chemokine signaling, and ribosome pathways, suggesting their critical roles in immune regulation. Conclusions: These findings highlight the pivotal role of lncRNAs in PC racial disparities, particularly through immune modulation. The identified lncRNAs may serve as potential biomarkers or therapeutic targets to address racial disparities in PC outcomes. Full article