Few studies have examined the secular trends of total calcium and vitamin D intake and their circulating levels together among adults in the United States (US). Understanding the trends of these nutrients may be useful for refining existing nutrition policy and guidelines.

The aim of this study was to report trends in total calcium and vitamin D intake and their circulating levels in the US population aged 18 years or older in 2007-2018.

This cross-sectional study identified adults aged 18 years or older in the US National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. Calcium and vitamin D intake including their supplements were the average of two 24-h recalls. Serum calcium and serum 25-hydroxyvitamin D [25(OH)D] were measured using established methods. Weighted regression was used to test trends in calcium and vitamin D intake, and serum total calcium and 25(OH)D levels.

This research included 16,751 participants, including 9,046 males and 7,705 females. Serum total calcium significantly decreased with survey years from 2007 to 2018 (9.42 to 9.31 mg/dL) (P trend <0.001). Calcium intake declined from 2009 to 2018 (1,070 to 1,010 mg/day; P trend <0.001). In contrast, vitamin D intake and serum 25(OH)D increased with survey years (5.8 to 11.0 mcg/day and 65.6 to 68.5 nmol/L, respectively; all P trend <0.001). The trends in calcium intake vs. serum total calcium (P trend interaction =0.267), and vitamin D intake vs. serum 25(OH)D with survey years were comparable (P trend interaction =0.190). Inadequate vitamin D intake decreased with survey years (86.0 to 80.2%; P trend = 0.002). Moderate vitamin D deficiency (22.3 to 21.5%; P trend = 0.043), but not severe vitamin D deficiency (3.3 to 2.9%; P trend = 0.119), also declined with calendar years.

From 2007 to 2018, US adults showed a decrease in serum total calcium, and an increase in serum 25(OH)D levels. Both trends were partly due to declined calcium and increased vitamin D intake.

COVID-19 manifestations range from asymptomatic to severe, and are influenced by host genetic factors. This study examined the association between vitamin D receptor (VDR) polymorphisms (TaqI and FokI) and transmembrane serine protease 2 (TMPRSS2) gene polymorphisms (rs12329760) and COVID-19 severity.

242 COVID-19 patients underwent genotyping using PCR-RFLP. Statistical analysis were conducted using SPSS v.21 and SHesis software, and validated by Sanger sequencing. The association of the VDR TaqI, FokI, and TMPRSS2 rs12329760 polymorphisms with COVID-19 severity was investigated. Computational analysis of TMPRSS2 was used to determine the pathogenicity and structural effects of these SNPs. For VDR TaqI, the 'TC' genotype showed higher prevalence in severe cases (50.5%) compared to mild cases (41.4%); however, no statistically significant association was observed [OR: 1.545 (0.893-2.675), p > 0.05]. Similar patterns were noted for the 'CC' genotype and 'C' allele, without statistical significance. For VDR FokI, the 'Ff' genotype showed higher prevalence in severe cases (25.8%) compared to mild cases (20.0%) [OR: 0.766 (0.199-2.951), p = 0.69], with no significant association. In haplotype analysis, elevated frequencies of 'Tf' and 'ft' haplotypes were observed in severe cases, but without statistical significance. For TMPRSS2 rs12329760, the 'CT' genotype showed a marginally higher prevalence in severe cases (50.5%) than in mild cases (49.7%) [OR: 0.805 (0.276-2.345), p > 0.05], without significant association. Computational analysis indicated that the variant does not demonstrate pathogenic effects but may influence protein stability.

This study revealed no statistically significant association between VDR (TaqI and FokI) and TMPRSS2 (rs12329760) polymorphisms and COVID-19 severity. Large-scale investigations and functional analysis are required to delineate the impact of these genetic variations on COVID-19 susceptibility and severity.

Vitamin D₃ has emerged as a potential therapeutic agent for alleviating tic symptoms in children with chronic tic disorders (CTDs). This study aims to evaluate the comparative efficacy of high-dose and low-dose vitamin D₃ supplementation on tic severity and serum 25-hydroxyvitamin D 25(OH)D levels in children with CTDs.

A randomized controlled trial was conducted with 83 children aged 4 to 15 years diagnosed with CTDs. Participants were randomly assigned to receive either high-dose vitamin D₃ (5,000 IU/day) or low-dose vitamin D₃ (1,000 IU/day) for three months. The primary outcome was tic severity, assessed using the Yale Global Tic Severity Scale (YGTSS), while secondary outcomes included changes in serum 25(OH)D and calcium levels. Tic severity and biochemical markers were measured at baseline and after the intervention to assess the effects of vitamin D₃ supplementation.

Both the high-dose and low-dose groups showed significant improvements in tic severity and increases in serum 25(OH)D levels (𝑝 < 0.05). The high-dose group exhibited a significantly greater reduction in tic severity and a more substantial increase in serum 25(OH)D levels compared to the low-dose group (𝑝 < 0.05). No significant differences were observed in serum calcium levels between the group (𝑝 > 0.05). Furthermore, multivariate linear regression analysis revealed a significant negative association between increases in serum 25(OH)D levels and reductions in tic severity (𝑡 = -2.816, 𝑝 < 0.05).

High-dose vitamin D₃ supplementation is more effective than low-dose supplementation in reducing tic severity and increasing serum 25(OH)D levels in children with CTDs. These findings suggest that high-dose vitamin D₃ may serve as a valuable adjunctive therapy for managing CTDs.

Influenza A is a respiratory virus that causes high infection rates and mortality worldwide, particularly affecting high-risk groups such as children, older adults, and individuals with chronic conditions. This retrospective study was conducted at a single tertiary hospital in Korea to analyze the epidemiological characteristics of influenza A infections from 2007 to 2024, focusing on age, sex, and seasonal variations. Using multiplex real-time PCR data from 23,284 individuals, we found that the overall positivity rate for influenza A was 5.6%, with seasonal fluctuations showing the highest rate in winter (14.0%) and the lowest in summer (0.5%). Age-based analysis revealed significantly higher positivity rates in older adults (7.9%) and adults (7.6%) than in children (5.0%) and infants (3.1%). No significant differences were observed in positivity rates between sexes (male: 5.43%, female: 5.76%, p = 0.428). These findings provide essential insights into the regional and seasonal patterns of influenza A, emphasizing the importance of targeted vaccination strategies, adaptive public health interventions, and continuous surveillance for effective prevention and outbreak control management.

Aging interventions have progressed in recent years due to the growing curiosity about how lifestyle impacts longevity. This study assessed the effects of SRW Laboratories' Cel System nutraceutical range on epigenetic methylation patterns, inflammation, physical performance, body composition, and epigenetic biomarkers of aging. A 1-year study was conducted with 51 individuals, collecting data at baseline, 3 months, 6 months, and 12 months. Participants were encouraged to walk 10 minutes and practice 5 minutes of mindfulness daily. Significant improvements in muscle strength, body function, and body composition metrics were observed. Epigenetic clock analysis showed a decrease in biological age with significant reductions in stem cell division rates. Immune cell subset analysis indicated significant changes, with increases in eosinophils and CD8T cells and decreases in B memory, CD4T memory, and T-regulatory cells. Predicted epigenetic biomarker proxies (EBPs) showed significant changes in retinol/TTHY, a regulator of cell growth, proliferation, and differentiation, and deoxycholic acid glucuronide levels, a metabolite of deoxycholic acid generated in the liver. Gene ontology analysis revealed significant CpG methylation changes in genes involved in critical biological processes related to aging, such as oxidative stress-induced premature senescence, pyrimidine deoxyribonucleotide metabolic process, TRAIL binding, hyaluronan biosynthetic process, neurotransmitter loading into synaptic vesicles, pore complex assembly, collagen biosynthetic process, protein phosphatase 2A binding activity, and activation of transcription factor binding. Our findings suggest that the Cel System supplement range may effectively reduce biological age and improve health metrics, warranting further investigation into its mechanistic pathways and long-term efficacy.

Vitamin D is an open-cyclic steroidal trace organic compound that plays a crucial role in human metabolism and nutritional health. In recent years, Mendelian randomization (MR) has emerged as a widely adopted method for analyzing causal relationships, particularly in studying the association between Vitamin D and related diseases. However, no bibliometric analyses have been conducted to explore the research hotspots and trends regarding Vitamin D status in MR studies. This study utilized the Web of Science Core Collection as a source database and retrieved articles on Vitamin D status in MR published from 2014 to 2024. Bibliometric and visualization analyses utilized VOSviewer, Microsoft Excel 2021, and Scimago Graphica. An in-depth analysis of country or region, authors, journals, keywords, and references were performed to provide insights into the content related to the field. A total of 186 documents authored by 1122 contributors across 30 countries were identified. China and the University of Bristol had the highest publication counts, with 94 and 19 articles, respectively. The nutrients published the largest number of articles, and J Brent Richards was the largest contributors. The most frequently used keywords included "Mendelian randomization," "Vitamin D," "25-hydroxyVitamin D," "obesity," and "Type 2 Diabetes." The current research focuses on using MR methods to explore the associations between Vitamin D status and metabolic, cardiovascular, immune skin, psychiatric and neurological diseases. The related research in this field will continue to increase in the next few years, which is a promising research prospect in this field. This study systematically reviews the literature from the past decade, revealing research hotspots and trends in the field of Vitamin D status within MR studies. This information will provide a strong reference for readers and researchers.

Even though in mid-2023 the World Health Organization declared the end of the public health emergency of international concern status for COVID-19, many areas of uncertainty about SARS-CoV-2 infection pathophysiology remain. Although in the last 4 years pharmaceutical industries widely invested in the development of effective antiviral treatments and vaccines, large disparities in their availability worldwide still exist, thus fostering the investigation of nutritional supplements as adjuvant therapeutic approaches for disease management, especially in resource-limited settings. During the COVID-19 pandemic, vitamin D has been widely used as an over-the-counter solution to improve disease evolution, thanks to its known immunomodulatory and anti-inflammatory actions. Ecological and observational studies support a relationship between hypovitaminosis D and COVID-19 negative outcomes and, according to this evidence, several research groups investigated the role of vitamin D supplementation in protecting from SARS-CoV-2 infection and/or improving disease evolution. This narrative review is intended to offer insights into the existing data on vitamin D's biological effects in respiratory infections, especially in COVID-19. Furthermore, it will also offer a brief overview of the complex interplay between vitamin D and vaccine-elicited immune response, with special attention to anti-COVID-19 vaccines.

Vitamin D receptor (VDR) gene polymorphisms have been implicated in polycystic ovary syndrome (PCOS). Despite VDR gene polymorphisms importance and their risk for PCOS, they have not been extensively studied. The main objective was to evaluate the associations between VDR gene polymorphisms and risk for PCOS.

The current systematic review and meta-analysis examined VDR gene polymorphisms with PCOS in case-control and cohort studies. Relevant keywords were used to search Scopus, Web of Science, PubMed, MEDLINE, ScienceDirect, and Google Scholar for peer-reviewed publications until July 1, 2024. Selected papers were assessed for risk bias and quality using the Modified Newcastle-Ottawa scale. A meta-analysis was conducted using a random-effect model. The association between VDR gene polymorphism(s) and PCOS in women was reported as odds ratios (ORs) with 95 % confidence intervals (CIs).

Twenty eligible studies, including 5618 subjects, were included in systematic review and meta-analysis. This study revealed a significant association between ApaI (rs7975232; OR = 1.18, 95 % CI = 1.06-1.30, p < 0.01), BsmI (rs1544410; OR = 1.22, 95 % CI = 1.08-1.37, p < 0.01), Cdx2 (rs11568820; OR = 1.15, 95 % CI = 0.97-1.38, p < 0.01), and TaqI (rs731236; OR = 1.25, 95 % CI = 1.13-1.39, p < 0.01). However, there was no significant association in the FokI (rs22228570; OR = 1.01, 95 % CI = 0.91-1.112, p = 0.12) polymorphism with PCOS risk.

The present systematic review and meta-analysis shows that women with ApaI, BsmI, Cdx2, and TaqI VDR gene polymorphisms may have a higher risk of PCOS. This study was registered on the Prospective International Registry of Systematic Reviews (PROSPERO) with registration number CRD42024564851.

Mucormycosis is a severe, opportunistic infection caused by Mucorales, a taxonomical group of thermotolerant fungi primarily affecting the immunocompromised. Intra-abdominal involvement in mucormycosis is a rare entity, particularly in immunocompetent individuals. We present a fatal case of gallbladder and renal mucormycosis in an immunocompetent female, leading to septic shock and death. The diagnosis was confirmed via histopathology following cholecystectomy for suspected gangrenous cholecystitis and open right nephrectomy due to kidney infarction. Quantitative polymerase chain reaction of the tissue identified the presence of Apophysomyces ossiformis. The clinical picture was confounded by ongoing sepsis due to a Klebsiella pneumoniae-infected retroperitoneal hematoma, non-specific imaging findings, and the absence of traditional risk factors for mucormycosis, leading to a delayed diagnosis. Despite surgical debridement, initiation of liposomal amphotericin B with posaconazole, and aggressive treatment in the intensive care unit, the patient succumbed to complications of mucormycosis. Despite adequate antibiotic coverage, this case underscores the importance of considering Mucorales infection in otherwise immunocompetent patients with a deteriorating clinical condition. Early diagnosis and appropriate intervention are essential in enhancing mucormycosis survivability, though mortality rates remain high in severe cases.

The COVID-19 pandemic has drawn significant attention to factors affecting disease severity, especially in older adults. This study explores the relationship between Klotho, an anti-aging protein, and COVID-19 severity. Conducted at Tehran's Firouzgar Hospital, this case-control study involved 279 participants, assessing serum levels of Klotho, inflammatory markers (C-reactive protein (CRP), Interleukin 6 (IL-6)), and Vitamin D. The findings indicate significantly lower Klotho levels in COVID-19 patients, especially those in the ICU, which correlate with elevated inflammatory markers and reduced Vitamin D levels. This inverse relationship between Klotho levels and disease severity underscores the protein's potential modulatory role in the inflammatory response to COVID-19. The study not only highlights the importance of Klotho as a biomarker for aging and disease severity but also suggests its potential therapeutic value in managing COVID-19, offering a novel perspective on targeting aging-related pathways to mitigate the impact of the disease. These insights open new avenues for research and intervention strategies to leverage anti-aging mechanisms to combat COVID-19 and potentially other age-related diseases.

Besides its classical skeletal function, vitamin D plays a critical role in both skeletal muscle and the immune system. Interleukin-15 (IL-15), which is highly expressed, and secreted complexed with its receptor, IL-15Rα, by skeletal muscle, stimulates the development of immune cells and affects myogenesis and muscle mass. However, little is known about possible regulators of this myokine. To test whether vitamin D could be a regulator of muscle IL-15 and IL-15Rα expression, C2C12 myotubes were treated with vitamin D3 metabolites and analysis were performed in gastrocnemius muscles of rats treated with a single intraperitoneal dose of 1,25(OH)2D3. The role of VDR was investigated by siRNA technique in C2C12 myotubes and in gastrocnemius muscles of vitamin D receptor knockout (Vdr-KO) mice. Treatment of C2C12 myotubes with 1,25(OH)2D3 or 25(OH)D3 increased Il-15 gene expression in a dose-dependent manner and 1,25(OH)2D3 also moderately increased the relative Il-15 protein amount. Rats treated with a single dose of 1,25(OH)2D3 demonstrated a higher mRNA abundance of muscle Il-15 than controls. The 1,25(OH)2D3 effect on Il-15 was considerably weaker in C2C12 myotubes treated with Vdr-specific siRNA. Vdr-KO mice showed significantly lower muscle Il-15 mRNA than WT mice. Il-15Ra mRNA and Il-15/Il-15Rα protein abundance were unaffected by 1,25(OH)2D3-treatment or VDR functionality, and Cyp27b1 activity is not required for 25(OH)D3-mediated Il-15 gene expression. The results provide evidence for a regulatory role of hydroxyvitamin D3 metabolites on the Il-15 synthesis in skeletal muscle cells, which is largely mediated by the VDR.

Background and Objectives: Vitamin D supplementation is effective for allergic rhinitis; however, its usefulness is unclear. We conducted a systematic review and meta-analysis to examine the conditions in which vitamin D supplementation was effective in allergic rhinitis management. Materials and Methods: Randomized controlled trials of vitamin D supplementation used for patients with allergic rhinitis were searched for across different databases. We extracted scores on patients' symptoms and the medication types used as the baseline treatments and performed a meta-analysis to evaluate the effect of vitamin D supplementation on allergic rhinitis symptoms. Meta-regression and subgroup analyses were performed for the average age, proportion of female participants, concomitant medications, vitamin D administration durations, and baseline serum 25-hydroxyvitamin D levels. Results: In total, 2389 articles were screened, and 5 randomized controlled trials (RCTs) were included in the meta-analysis. Compared with placebos, vitamin D supplementation alleviated allergic rhinitis symptoms, although the difference was not significant; there was significant heterogeneity among studies (standardized mean difference [SMD] = -2.69, 95% confidence interval [CI]: -6.20 to 0.82, I2 = 98%, p < 0.01). The proportion of female participants in the RCTs (slope: 0.21, p = 0.026) and concomitant corticosteroid use (slope: -9.16, p = 0.005) influenced the vitamin D response. Compared with the placebos, vitamin D supplementation without corticosteroids alleviated the allergic rhinitis symptoms (SMD = -0.56, 95% CI: -0.90 to -0.23). Combination treatment with corticosteroids also non-significantly alleviated symptoms. Additionally, the heterogeneity between studies was significant (SMD = -5.97, 95% CI: -13.55 to 1.16, I2 = 99%, p < 0.01). Conclusions: The study results suggest that vitamin D supplementation alleviates allergic rhinitis symptoms, although the effects differ according to the patient's sex and concomitant medications.

The importance of vitamin D for a well-functioning immune system is becoming increasingly evident. Nevertheless, the other fat-soluble vitamins A, E and K also seem to play a central role regarding the adequate function of immune cells and to counteract excessive immune reactions and inflammatory processes. However, recognizing hidden hunger, particularly micronutrient deficiencies in vulnerable groups like the elderly, is crucial because older adults often lack sufficient micronutrients for various reasons. This review summarizes the latest findings on the immune modulating functions of fat-soluble vitamins in a physiological and pathophysiological context, provides a graphical comparison of the Recommended Daily Allowances between Deutschland, Austria, Confoederatio Helvetica (D-A-CH; eng. GSA, Germany, Switzerland, Austria), Deutsche Gesellschaft für Ernährung (DGE; eng. German Nutrition Society) and National Institutes of Health (NIH) across all age groups and, in particular, addresses the question regarding the benefits of supplementation of the respective micronutrients for the aging population of industrialized nations to strengthen the immune system. The following review highlights the importance of fat-soluble vitamins A, D, E and K which play critical roles in maintaining immune system function and, in some cases, in preventing excessive immune activation. Therefore, a better understanding of the relevance of adequate blood levels and consequently potential supplementation strategies may contribute to the prevention and management of infectious diseases as well as better overall health of the elderly.

Recurrent implantation failure (RIF) is a significant obstacle in assisted reproductive technology, affecting approximately 10 % of couples undergoing in vitro fertilization (IVF). Emerging evidence suggests that vaginal probiotics and vitamin D supplementation may improve reproductive outcomes. This randomized clinical trial evaluated the effects of these interventions on fertility in women with RIF and thin endometrium (<6 mm). A total of 112 women with a history of RIF were randomized into four groups: vaginal probiotics, vitamin D supplementation, a combination of both, or standard IVF treatment (control). The primary outcome was the pregnancy rate, confirmed by β-hCG testing and ultrasound. Secondary outcomes included changes in Th1/Th2 ratio, natural killer (NK) cell activity, and cytokine profiles. The combination group demonstrated the highest pregnancy rate (46.4 %), which was significantly higher compared with the probiotics ((14.2 %), p = 0.008), vitamin D ((17.8 %), p = 0.002), and control groups ((10.7 %), p = 0.003). Only the combination therapy significantly reduced the Th1/Th2 ratio (p < 0.001) and NK cell activity (p < 0.001), while significantly increasing IL-4 and TGF-β and decreasing IFN-γ levels (all p < 0.001). These findings suggest that combined vaginal probiotics and vitamin D supplementation may improve pregnancy outcomes by modulating the immune responses in women with RIF. This dual intervention may represent a promising strategy for enhancing fertility in this population of RIF patients.

Aging is a complex and heterogeneous biological process characterized by telomere attrition, genomic instability, mitochondrial dysfunction, and disruption in nutrient sensing. Besides contributing to the progression of cancer, metabolic disorders, and neurodegenerative diseases, these manifestations of aging also adversely affect organ function. It is crucial to understand these mechanisms and identify interventions to modulate them to promote healthy aging and prevent age-related diseases. Vitamins have emerged as potential modulators of aging beyond their traditional roles in health maintenance. There is an increasing body of evidence that hormetic effects of vitamins are responsible for activating cellular stress responses, repair mechanisms, and homeostatic processes when mild stress is induced by certain vitamins. It is evident from this dual role that vitamins play a significant role in preventing frailty, promoting resilience, and mitigating age-related cellular damage. Moreover, addressing vitamin deficiencies in the elderly could have a significant impact on slowing aging and extending life expectancy. A review of recent advances in the role of vitamins in delaying aging processes and promoting multiorgan health is presented in this article. The purpose of this paper is to provide a comprehensive framework for using vitamins as strategic tools for fostering longevity and vitality. It offers a fresh perspective on vitamins' role in aging research by bridging biological mechanisms and clinical opportunities.

Keloid disease, a fibroproliferative skin disorder, is characterised by scar tissue growth that extends beyond the original wound boundaries. Despite advancements, current treatments, particularly surgical excision, often result in high recurrence rates, ranging from 45% to 100%. Recent investigations into the role of vitamin D (vit D) in keloids present a promising avenue for novel therapeutic strategies. Studies have highlighted the multifaceted involvement of vit D, including its immunomodulatory effects and influence on key processes such as fibroblast activity, collagen production and extracellular matrix dynamics. Additionally, emerging research has explored the potential impact of vit D on epithelial-to-mesenchymal transition and endothelial dysfunction, both of which are implicated in keloid formation and progression. This review consolidates the current evidence linking vitamin D deficiency to keloid pathogenesis, shedding light on potential mechanisms and therapeutic targets. By elucidating the intricate interplay between vit D signalling and keloid development, this study paves the way for innovative treatment approaches that may enhance patient outcomes and mitigate the burden of this challenging dermatological condition.

Immune function is affected by vitamin D status, but the optimal serum 25-hydroxy vitamin D [25(OH)D] concentration for immune function is not known.

We hypothesized that 25(OH)D would be associated with markers of inflammation and immune activation.

We identified associations between 25(OH)D and immune markers from 361 healthy adults using polynomial regression. Linear regression was used to define the slope (β) of significant linear associations, and piecewise regression identified inflection points (IPs) for curvilinear associations with P < 0.05. IPs with a slope difference (SD) P < 0.05 before and after were significant.

25(OH)D had linear, negative associations with interleukin (IL)-6 (β: -0.126; P = 0.009) and macrophage-derived chemokine (MDC) (β: -0.108; P = 0.04) and a linear, positive association with matrix metalloproteinase (MMP)-1 (β: 0.108; P = 0.04). Among the significant curvilinear associations, 2 showed negative associations below but positive associations above an IP with nearly significant SD P values, including percentage of effector-memory CD8 T cells (IP: 56.2 nmol/L; SD P = 0.067) and platelet concentration (IP: 38.9 nmol/L; SD P = 0.058). The opposite associations, positive below and negative above an IP, were seen for eotaxin (IP: 49.5 nmol/L; SD P = 0.049); interferon (IFN)-γ-induced protein-10 (IP-10) (IP: 71.8 nmol/L; SD P = 0.02); percentage of CD4 T cells expressing programmed cell death protein (PD)-1 (IP: 71.2 nmol/L; SD P = 0.01); percentage of Tregs expressing human leukocyte antigen, DR isotype (HLA-DR) (IP: 67.5 nmol/L; SD P < 0.0001); percentage of memory Tregs (IP: 68.8 nmol/L; SD P = 0.002); and percentage of memory Tregs expressing HLA-DR (IP: 68.8 nmol/L; SD P = 0.0008).

These findings are consistent with low vitamin D status allowing and higher vitamin D status dampening inflammation and immune activation. IP analysis identified possible thresholds for vitamin D effects on immune function. Two of 3 IPs at ∼50 nmol/L show higher inflammation below this concentration, suggesting 50 nmol/L as a minimum target for dampening inflammation. IPs at ∼70 nmol/L identify a threshold for CD4 T-cell activity, including Treg activation and IFN-γ-driven production of the T-cell chemokine IP-10, suggesting an optimal concentration for regulating adaptive immunity. This study was registered at clinicaltrials.gov as NCT02367287.

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide. They occur in the urinary system when a microorganism, commonly present on the perineal skin or rectum, reaches the bladder through the urethra, and adheres to the luminal surface of uroepithelial cells, forming biofilms. The treatment of UTIs includes antibiotics, but their indiscriminate use has favored the development of multidrug-resistant bacteria strains, which represent a serious challenge to today's microbiology. The pathogenesis of the infection and antibiotic resistance synergistically contribute to hindering the eradication of the disease while favoring the establishment of persistent infections. The repeated requirement for antibiotic treatment and the limited therapeutic options have further contributed to the increase in antibiotic resistance and the occurrence of potential relapses by therapeutic failure. To limit antimicrobial resistance and broaden the choice of non-antibiotic preventive approaches, this review reports studies focused on the bacteriostatic/bactericidal activity, inhibition of bacterial adhesion and quorum sensing, restoration of uroepithelial integrity and immune response of molecules, vitamins, and compounds obtained from plants. To date, different supplementations are recommended by the European Association of Urology for the management of UTIs as an alternative approach to antibiotic treatment, while a variety of bioactive compounds are under investigation, mostly at the level of in vitro and preclinical studies. Although the evidence is promising, they are far from being included in the clinical practice of UTIs.

This study aims to investigate the association between vitamin D levels and the risk of severe acute exacerbations of chronic obstructive pulmonary disease (AECOPD).

We conducted a prospective observational study with 636 COPD patients admitted for exacerbations between January 2021 and December 2022. Patients were categorized based on serum 25-hydroxyvitamin D levels: severe deficiency (<10 ng/mL), deficiency (10-20 ng/mL), insufficiency (20-30 ng/mL), or sufficiency (>30 ng/mL). Severe exacerbation was defined when the patient visits an emergency room or is hospitalized due to COPD exacerbation. Multivariate Cox regression was used to evaluate the risk associated with vitamin D deficiency.

Over an 18-month follow-up, 178 (28.0%) patients experienced at least one severe exacerbation. The severe deficiency group had the highest exacerbation rate (40.6%), followed by deficiency (27.8%), insufficiency (22.5%), and sufficiency (18.1%) groups (P<0.01). Multivariate Cox regression analysis showed that severe vitamin D deficiency was significantly associated with an increased risk of severe exacerbations (HR=2.74, 95% CI: 1.55-4.84; P<0.01) compared to vitamin D sufficiency.

Severe vitamin D deficiency is a significant predictor of severe COPD exacerbations, highlighting the importance of routine vitamin D assessment and supplementation in COPD management.

Long COVID (LC) is characterized by persistent symptoms at least 3 months after a SARS-COV-2 infection. LC has been associated with fungal translocation, gut dysfunction, and enhanced systemic inflammation. Currently, there is no approved treatment for this condition. The anti-inflammatory effect of vitamins K2 and D3 was shown to help attenuate the course of acute COVID-19 infection.

This trial aims to investigate the effects of vitamins K2/D3 on LC symptoms, as well as gut and inflammatory markers, in people with established long COVID. Our hypothesis is that by attenuating systemic inflammation, vitamins K2/D3 will improve long COVID symptoms.

This single-site randomized controlled study enrolled adults experiencing ≥2 moderate LC symptoms at least 3 months after a COVID-19 infection. The RECOVER Long COVID Research Index and number and type of LC symptoms were considered. Participants were randomized 2:1 to daily 240 µg K2 (pure MK-7 form) and 2000 UI vitamin D3 or standard of care (SOC) for 24 weeks. The endpoints were changes in symptomatology and in select inflammatory, metabolic, and gut biomarkers at 24 weeks.

We enrolled 151 participants (n = 98 received vit K2/D3 and 53 received SOC). The median age was 46 years; 71% were female and 29% were non-white. Baseline demographics were balanced between groups. At 24 weeks, the active treatment group only had a sharp increase in 25(OH) D, indicating good treatment adherence. In the vitamin K2/D3 arm, there was a 7.1% decrease in the proportion who had an LC Index ≥12 (vs. a 7.2% increase in the SOC group; p = 0.01). The average number of LC symptoms remained stable in the vitamin K2/D3 arm but increased in the SOC arm (p = 0.03). Additionally, reductions in oxidized LDL, inflammatory markers sTNF-RI and sCD163, and fungal translocation marker (1,3)-β-d-glucan were observed in the vitamin K2/D3 arm compared to the SOC arm (p < 0.01) over 24 weeks.

Vitamins K2/D3 improved the RECOVER Long COVID Index, the number of LC symptoms, and several gut and inflammatory markers. Vitamins K2/D3 provide a promising safe intervention for people suffering from long COVID.

During the COVID-19 pandemic, several observational studies proved a certain efficacy of nutraceuticals, herbal products, and other dietary supplements as adjuvant therapies used alongside antiviral drugs. Although their use has not been widespread in Italy, according to preliminary evidence, many supplements with demonstrated immunomodulatory effects, such as vitamins C and D, herbal medicines and essential oils, might relieve the respiratory symptoms of COVID-19, since SARS-CoV-2 can activate inflammasome-mediated inflammatory signaling pathways. Other observational studies have shown that herbal treatments, such as Echinacea purpurea and ginseng, help alleviate respiratory symptoms and reduce serum levels of inflammatory cytokines, which are typically overexpressed in both adult and pediatric SARS-CoV-2 patients. Further, vitamins C and D can attenuate the immune response thanks to their cytokine suppression ability and to their known antimicrobial activity and potential to modulate T helper cell response. The strong immune response triggered by SARS-CoV-2 infection is responsible for the severity of the disease. Preliminary data have also shown that L-arginine, an endothelial-derived relaxing factor, is able to modulate endothelial damage, which appears to be one of the main targets of this systemic disease. Finally, some essential oils and their isolated compounds, such as eucalyptol, may be helpful in reducing many of the respiratory symptoms of COVID-19, although others, such as menthol, are not recommended, since it can lead to an undervaluation of the clinical status of a patient. In this narrative review, despite the lack of strong evidence in this field, we aimed to give an overview of the current available literature (mainly observational and cross-sectional studies) regarding herbal products and dietary supplements and their use in the treatment of mild disease from SARS-CoV-2 infection. Obviously, dietary supplements and herbal products do not constitute a standardized treatment for COVID-19 disease, but they could represent an adjunctive and useful treatment when used together with antivirals.

SARS-CoV-2, the causative virus of COVID-19, increases the risk of pregnancy complications including hypertensive disorders and placental inflammation. The spike glycoprotein mediates viral cell entry by interacting with the angiotensin-converting enzyme (ACE)2 in conjunction with the transmembrane serine protease 2 (TMPRSS2). ACE1, ACE2 and renin are components of the renin-angiotensin system (RAS), which regulates blood pressure. As the placenta expresses all these proteins, it is a target for SARS-CoV-2 and a source of blood pressure modulators. Noteworthy, an ACE1/ACE2 ratio imbalance can lead to RAS dysregulation and a bad prognosis in COVID-19 patients. Calcitriol, the most active vitamin D metabolite, negatively regulates RAS, reduces inflammation, and enhances antiviral immunity, thereby protecting against COVID-19 severity. However, contrasting information exists on the regulatory role of calcitriol upon RAS components and SARS-CoV-2 receptors; while the impact of calcitriol on spike-induced inflammation in placental cells has not been explored. Thus, we studied the effects of calcitriol on these parameters using the trophoblast cell line HTR-8/SVneo and primary syncytiotrophoblasts. By RT-qPCR, ELISA, and immunocytochemistry, we found that the spike enhanced proinflammatory cytokines expression and secretion, while calcitriol significantly downregulated this effect. Calcitriol also diminished ACE1, ACE2, TMPRSS2, and renin gene expression, as well as ACE1/ACE2 mRNA ratio. CONCLUSIONS: In the human placenta, calcitriol reduced the gene expression of main RAS components and TMPRSS2, resulting in the inhibition of spike-induced inflammation. This outcome suggest that vitamin D participates in restricting SARS-CoV-2 placental infection by rendering trophoblasts less permissive to infection while helping to regulate maternal blood pressure and decreasing inflammation.

The coronavirus disease 2019 (COVID-19) is spreading continuously worldwide. Maintenance hemodialysis (MHD) patients are a particular group at higher risk of contracting COVID-19. The aim of the present study was to investigate the various risk factors that contribute to the occurrence of co-infection with COVID-19 among patients with MHD. A retrospective analysis was conducted on 171 patients with MHD. The characteristics and outcomes were examined among patients with MHD who were infected with COVID-19 and those who were not. Moreover, risk factors associated with survival or mortality among the COVID-19-infected patients with MHD were analyzed. The results of the present study revealed that the mean level of 25-hydroxyvitamin D [25(OH)D] in patients with MHD was 22.3±11.28 ng/ml. However, there was no significant difference in the levels of 25(OH)D between patients with MHD with and without COVID-19. Logistic regression analysis revealed that decreased levels of intact parathyroid hormone (iPTH) and increased levels of serum ferritin were associated with an increased risk of COVID-19 in these patients. Additionally, the levels of 25(OH)D and albumin were decreased in the deceased patients. Similarly, logistic regression analysis was performed to identify risk factors for mortality in patients with MHD with COVID-19, which revealed that decreased levels of 25(OH)D were associated with an increased risk of mortality in these patients. The results of the present study indicated that iPTH and serum ferritin levels could potentially increase the risk of COVID-19 among patients with MHD. Additionally, 25(OH)D levels may influence the mortality rate among patients with MHD who have been infected with COVID-19.

Several nutrients are crucial in enhancing the immune system and preserving the structural integrity of bodily tissue barriers. Vitamin D (VD) and zinc (Zn) have received considerable interest due to their immunomodulatory properties and ability to enhance the body's immune defenses. Due to their antiviral, anti-inflammatory, antioxidative, and immunomodulatory properties, the two nutritional powerhouses VD and Zn are crucial for innate and adaptive immunity. As observed with COVID-19, deficiencies in these micronutrients impair immune responses, increasing susceptibility to viral infections and severe disease. Ensuring an adequate intake of VD and Zn emerges as a promising strategy for fortifying the immune system. Ongoing clinical trials are actively investigating their potential therapeutic advantages. Beyond the immediate context of the pandemic, these micronutrients offer valuable tools for enhancing immunity and overall well-being, especially in the face of future viral threats. This analysis emphasizes the enduring significance of VD and Zn as both treatment and preventive measures against potential viral challenges beyond the current health crisis. The overview delves into the immunomodulatory potential of VD and Zn in combating viral infections, with particular attention to their effects on animals. It provides a comprehensive summary of current research findings regarding their individual and synergistic impacts on immune function, underlining their potential in treating and preventing viral infections. Overall, this overview underscores the need for further research to understand how VD and Zn can modulate the immune response in combatting viral diseases in animals.

Vitamin D deficiency is prevalent among patients undergoing hemodialysis. This study aimed to investigate the associations between vitamin D levels and clinical parameters with the risk of COVID-19 infection, severity, and mortality in hemodialysis patients with end-stage kidney disease (ESKD).

This retrospective cohort study included 198 hemodialysis patients from a single center. Vitamin D deficiency was defined by the last measurement of 25-hydroxycholecalciferol less than 20 ng/mL. Vitamin D deficiency and vitamin D supplements were combined to categorize patients into three groups: deficiency, uncertain deficiency, and likely sufficient. COVID-19 infection status, severity, and outcomes were recorded. Statistical analyses were performed to assess the associations between vitamin D levels and COVID-19 severity and mortality.

Among the 198 patients, 73 patients (37%) were in the deficiency group, 29 patients (15%) had uncertain deficiency, and 96 patients (48%) were likely sufficient. The overall COVID-19 infection rate was 59%. The deficiency group had a similar infection rate (60.3%) compared to those with likely sufficient levels (54.2%). However, the severity and mortality rates of vitamin D deficiency group had a significantly higher rate than those with likely sufficient levels. Multivariate logistic regression analysis showed that vitamin D deficiency and uncertain deficiency group were significantly associated with an increased risk of COVID-19 severity (OR = 22.57, p = 0.01 and OR = 15.8, p = 0.03, respectively). Uncertain deficiency group was significantly associated with an increased risk of COVID-19 mortality (OR = 12.93, p = 0.04), while the deficiency group should similarly trend but did not reach statistical significance.

Vitamin D deficiency is associated with an increased risk of COVID-19 severity in hemodialysis patients with ESKD. These findings suggest that monitoring and managing vitamin D levels may be important in reducing the risk of COVID-19 severity in this vulnerable population.

Immunosenescence, the age-related decline in immune function, is a complex biological process with profound implications for health and longevity. This phenomenon, characterized by alterations in both innate and adaptive immunity, increases susceptibility to infections, reduces vaccine efficacy, and contributes to the development of age-related diseases. At the cellular level, immunosenescence manifests as decreased production of naive T and B cells, accumulation of memory and senescent cells, thymic involution, and dysregulated cytokine production. Recent advances in molecular biology have shed light on the underlying mechanisms of immunosenescence, including telomere attrition, epigenetic alterations, mitochondrial dysfunction, and changes in key signaling pathways such as NF-κB and mTOR. These molecular changes lead to functional impairments in various immune cell types, altering their proliferative capacity, differentiation, and effector functions. Emerging research suggests that lifestyle factors may modulate the rate and extent of immunosenescence at both cellular and molecular levels. Physical activity, nutrition, stress management, and sleep patterns have been shown to influence immune cell function, inflammatory markers, and oxidative stress in older adults. This review provides a comprehensive analysis of the molecular and cellular mechanisms underlying immunosenescence and explores how lifestyle interventions may impact these processes. We will examine the current understanding of immunosenescence at the genomic, epigenomic, and proteomic levels, and discuss how various lifestyle factors can potentially mitigate or partially reverse aspects of immune aging. By integrating recent findings from immunology, gerontology, and molecular biology, we aim to elucidate the intricate interplay between lifestyle and immune aging at the molecular level, potentially informing future strategies for maintaining immune competence in aging populations.

As identified in 1936 by Hans Selye, stress is shaping diseases through the induction of inflammation. But inflammation display some yin yang properties. On one hand inflammation is merging with the innate immune response aimed to fight infectious or sterile insults, on the other hand inflammation favors chronic physical or psychological disorders. Nature has equipped the cells, the organs, and the individuals with mediators and mechanisms that allow them to deal with stress, and even a good stress (eustress) has been associated with homeostasis. Likewise, societies and the planet are exposed to stressful settings, but wars and global warming suggest that the regulatory mechanisms are poorly efficient. In this review we list some inducers of the physiological stress, psychologic stress, societal stress, and planetary stress, and mention some of the great number of parameters which affect and modulate the response to stress and render it different from an individual to another, from the cellular level to the societal one. The cell, the organ, the individual, the society, and the planet share many stressors of which the consequences are extremely interconnected ending in the domino effect and the butterfly effect.

Tolerogenic vaccines represent a therapeutic approach to induce antigen-specific immune tolerance to disease-relevant antigens. As general immunosuppression comes with significant side effects, including heightened risk of infections and reduced anti-tumor immunity, antigen-specific tolerance by vaccination would be game changing in the treatment of immunological conditions such as autoimmunity, anti-drug antibody responses, transplantation rejection, and hypersensitivity. Tolerogenic vaccines induce antigen-specific tolerance by promoting tolerogenic antigen presenting cells, regulatory T cells, and regulatory B cells, or by suppressing or depleting antigen-specific pathogenic T and B cells. The design of tolerogenic vaccines vary greatly, but they all deliver a disease-relevant antigen with or without a tolerogenic adjuvant. Tolerogenic adjuvants are molecules which mediate anti-inflammatory or immunoregulatory effects and enhance vaccine efficacy by modulating the immune environment to favor a tolerogenic immune response to the vaccine antigen. Tolerogenic adjuvants act through several mechanisms, including immunosuppression, modulation of cytokine signaling, vitamin signaling, and modulation of immunological synapse signaling. This review seeks to provide a comprehensive examination of tolerogenic adjuvants currently utilized in tolerogenic vaccines, describing their mechanism of action and examples of their use in human clinical trials and animal models of disease.

Background/Objectives: Vitamin D receptor (VDR) agonists are commonly used in clinical practice for their roles in calcium regulation and potential benefits in various diseases. However, their safety profiles, particularly for compounds available as food supplements, remain underexplored in real-world settings. This study aimed to analyze the safety profiles of VDR agonists using the EudraVigilance database, focusing on adverse drug reactions (ADRs) reported between 1 January 2004 and 23 June 2024. Methods: Data for ten VDR agonists were collected, de-duplicated, and analyzed to identify specific safety signals. Risk factors for specific ADRs were assessed using multiple logistic regression. Results: This study analyzed 5,369,581 reports in the EudraVigilance system, from which 17,947 reports (0.33%) involving 80,050 ADRs were linked to VDR agonists. The most-reported drugs were cholecalciferol (12,944 cases) and calcitriol (1355 cases). Serious ADRs were more prevalent with paricalcitol, alfacalcidol, and calcitriol than with cholecalciferol (p < 0.05). Hypercalcemia was a hallmark ADR for all VDR agonists, with the highest risk linked to dihydrotachysterol (ROR = 5668; 95%CI = 3332 to 9641; p < 0.0001), alfacalcidol (ROR = 965.7; 95%CI = 843.6 to 1106; p < 0.0001), and calcitriol (ROR = 726.0; 95%CI = 634.6 to 830.5; p < 0.0001). Logistic regression highlighted dehydration, overdose, and concomitant administration of calcium salts as major predictors of hypercalcemia. The co-administration of multiple VDR agonists was also found to increase hypercalcemia risk. However, the disproportionality analysis showed that only active VDR agonists (e.g., calcitriol, alfacalcidol) were associated with severe complications like renal and urinary disorders and cardiac issues due to hypercalcemia. Natural precursors (cholecalciferol, ergocalciferol) were more often linked to non-calcemic ADRs such as gastrointestinal symptoms, which were more prevalent in infants and children compared to adults. Conclusions: The safety profiles of VDR agonists differ significantly between compounds. Active derivatives require close monitoring for serious calcemia-related complications, whereas cholecalciferol is associated with less severe ADRs, primarily in at-risk populations. These findings highlight the need for targeted safety monitoring and further research into the real-world uses of VDR agonists.

Autism spectrum disorder (ASD) presents unique challenges related to feeding and nutritional management. Children with ASD often experience feeding difficulties, including food selectivity, refusal, and gastrointestinal issues. Various interventions have been explored to address these challenges, including dietary modifications, vitamin supplementation, feeding therapy, and behavioral interventions.

To provide a comprehensive overview of the current evidence on nutritional management in ASD. We examine the effectiveness of dietary interventions, vitamin supplements, feeding therapy, behavioral interventions, and mealtime practices in addressing the feeding challenges and nutritional needs of children with ASD.

We systematically searched relevant literature up to June 2024, using databases such as PubMed, PsycINFO, and Scopus. Studies were included if they investigated dietary interventions, nutritional supplements, or behavioral strategies to improve feeding behaviors in children with ASD. We assessed the quality of the studies and synthesized findings on the impact of various interventions on feeding difficulties and nutritional outcomes. Data extraction focused on intervention types, study designs, participant characteristics, outcomes measured, and intervention effectiveness.

The review identified 316 studies that met the inclusion criteria. The evidence indicates that while dietary interventions and nutritional supplements may offer benefits in managing specific symptoms or deficiencies, the effectiveness of these approaches varies. Feeding therapy and behavioral interventions, including gradual exposure and positive reinforcement, promise to improve food acceptance and mealtime behaviors. The findings also highlight the importance of creating supportive mealtime environments tailored to the sensory and behavioral needs of children with ASD.

Nutritional management for children with ASD requires a multifaceted approach that includes dietary modifications, supplementation, feeding therapy, and behavioral strategies. The review underscores the need for personalized interventions and further research to refine treatment protocols and improve outcomes. Collaborative efforts among healthcare providers, educators, and families are essential to optimize this population's nutritional health and feeding practices. Enhancing our understanding of intervention sustainability and long-term outcomes is essential for optimizing care and improving the quality of life for children with ASD and their families.

Observational studies have reported an association between Vitamin D deficiency and an increased risk of bronchiectasis. This study aims to investigate the causal relationship between Vitamin D levels and bronchiectasis using a 2-sample Mendelian randomization (MR) analysis. Data from 2 genome-wide association studies (GWAS) based on European ancestry were analyzed: serum vitamin D levels (sample size = 441,291 [UK Biobank]) and bronchiectasis (sample size = 187,830 [cases = 1107, controls = 186,723; FinnGen]). Inverse-variance weighted (IVW) analysis was primarily used to assess the causal effect of 25(OH)D levels on bronchiectasis, supplemented by Mendelian randomization Egger regression (MR-Egger), weighted median, simple mode, and weighted mode analyses. Additionally, MR-Egger intercept test and MR-Pleiotropy Residual Sum and Outlier methods were implemented to determine pleiotropy, and Cochran's Q test was conducted for heterogeneity testing. Leave-one-out analysis and Bayesian weighted Mendelian randomization was also used to assess the robustness of the results. The MR analysis suggested no significant causal effects of serum 25(OH)D levels on bronchiectasis using the IVW method (odds ratio = 1.550; 95% confidence interval [CI]: 0.908-2.315; P = .120). These results were consistent across MR-Egger regression, weighted median, simple mode, and weighted mode analyses. No significant heterogeneity, pleiotropy, or bias was detected in instrumental variables. Additionally, no evidence supported the causal effects of bronchiectasis on serum vitamin D levels (β = -0.002, 95% CI: -0.007 to 0.003; P = .463). Our study found no significant causal association between serum 25(OH)D levels and bronchiectasis, in either direction. A larger sample-sized randomized controlled trial (RCT) is needed to further investigate this potential causal relationship.

Periprosthetic joint infection (PJI) is a multifactorial disease, and the risk of contracting infection is determined by the complex interplays between environmental and host-related factors. While research has shown that certain individuals may have a genetic predisposition for PJI, the existing literature is scarce, and the heterogeneity in the assessed genes limits its clinical applicability. Our review on genetic susceptibility for PJI has the following two objectives: (1) Explore the potential risk of developing PJI based on specific genetic polymorphisms or allelic variations; and (2) Characterize the regulatory cascades involved in the risk of developing PJI. This review focused on clinical studies investigating the association between genetic mutations or variations with the development of PJI. The genes investigated in these studies included toll-like receptors and humoral pattern recognition molecules, cytokines, chemokines, mannose-binding lectin (MBL), bone metabolism molecules, and human leukocyte antigen. Among these genes, polymorphisms in IL-1, MBL, vitamin D receptors, HLA-C, and HLA-DQ might have a relevant impact on the development of PJI. The literature surrounding this topic is limited, but emerging transcriptomic and genome-wide association studies hold promise for identifying at-risk genes. This advancement could pave the way for incorporating genetic testing into preoperative risk stratification, enhancing personalized patient care.

Vitamin D is a key molecule in calcium and phosphate homeostasis; however, increasing evidence has recently shown that it also plays a crucial role in the immune system, both innate and adaptive. A deregulation of vitamin D levels, due also to mutations and polymorphisms in the genes of the vitamin D pathway, determines severe alterations in the homeostasis of the organism, resulting in a higher risk of onset of some diseases, including osteoporosis. This review gives an overview of the influence of vitamin D levels on the pathogenesis of osteoporosis, between bone homeostasis and immune system.

In this cross-sectional study including patients with type 2 diabetes mellitus (T2DM) we aimed to explore the relationship between serum 25-hydroxy vitamin (25(OH)D) level and liver steatosis and fibrosis in the Chinese population.

Patients visiting 16 clinical centers with T2DM were recruited. Their liver steatosis and fibrosis status were then assessed using elastography. Factors associated with steatosis and fibrosis were explored using regression analysis. Correlations between serum 25(OH)D levels and other patient characteristics were analyzed using linear regression.

In total, 1,513 patients with T2DM were included in the study. The prevalence of steatosis and fibrosis was 69.7%, and 34.6%, separately. A lower level of 25(OH)D was detected in patients with liver steatosis compared to those without, although it was not an independent predictor of this condition. However, 25(OH)D level was independently associated with liver fibrosis even when adjusted for age, sex, body mass index, hemoglobin A1c, insulin, and homeostatic model assessment of insulin resistance (OR = 0.964 [0.935-0.993], P = 0.015). When patients were separated into subgroups by sex, a correlation between 25(OH)D and fibrosis was identified in the male group (OR = 0.969 [0.940-0.998], P = 0.038).

In conclusion, this multi-center, cross-sectional study in patients with T2DM showed that serum 25-hydroxy vitamin D level was strongly associated with liver fibrosis and this relationship was more pronounced in male patients.

https://clinicaltrials.gov/ct2/show/, identifier NCT05597709.

Objective: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is characterized by type 2 inflammation, and studies have shown that conventional therapy usually yields unsatisfactory results. While recent studies have indicated the potential effect of vitamin D on allergic and inflammatory diseases, including CRSwNP. Therefore, this study aimed to investigate the relationship between serum vitamin D levels and the severity of CRSwNP using endoscopic evaluations, imaging, patient-reported outcome measures, absolute eosinophilic count, and serum vitamin D levels and determine the prevalence of vitamin D deficiency in patients with CRSwNP. Methods: Serum vitamin D levels were measured in 104 patients with uncontrolled CRSwNP, who failed maximum medical management and were scheduled for functional endoscopic sinus surgery. Vitamin D levels were compared between patients using the Lund- Mackay (LM) score, Sinonasal Outcome Test-22 (SNOT-22), total nasal polyp scores, and absolute eosinophil counts. Results: The 104 included patients had an average age of 42.09 ± 13.3 years, and 63.5% of them were male. Mean value of vitamin D was 57.9 ± 31.2 nmol/L. The average SNOT-22 score was 65.49 ± 21.3. The mean LM score was 14.48 ± 6.64. The total nasal polyp score was 4.3 ± 2.08. Vitamin D levels were negatively correlated with LM score (r = -.210, P = .032) and polyp grade (r = -.264, P = .007), but did not correlate with other variables. Conclusions: Our study indicates that vitamin D deficiency or insufficiency is common in patients with CRSwNP. We found that low serum vitamin D levels were negatively correlated with the Lund-Mackay score and the total nasal polyp score, providing additional support for an association between low vitamin D levels and a greater severity of CRSwNP.

From the observation of a negative relationship between UV-B exposure and cancer rates, we hypothesized that vitamin D (VD) may play a protective role in oncogenesis. Moreover, repurposing a well-known and relatively safe drug for conditions with dismal prospects, such as pancreatic ductal adenocarcinoma (PDAC), is a tempting idea. Thus, we aimed to summarize the current knowledge regarding the role of VD in the prevention and treatment of PDAC.

We conducted a systematic review of VD and PDAC using Medline-indexed studies accessed through PubMed as the primary data source. This study aimed to identify articles focusing on the role of VD as a risk and prognostic factor for PDAC, mechanistic studies evaluating the effects of VD or vitamin D analogs (VDAs) in PDAC models, and clinical trials on VDAs in PDAC. After the screening, 97 studies were included in the final manuscript.

Even though the results from epidemiologic studies were contradictory, basic research has demonstrated that VD can act on PDAC cells either directly, inhibiting proliferation, apoptosis, EMT, migration, invasion, and stemness, or indirectly, through stromal remodeling. A better understanding of the consequences of VD-induced tumor-stroma cross-talk alterations is needed to determine whether VD/VDAs can be used to our own advantage in the treatment of PDAC.

Vitamin D has an immunomodulatory property influencing the activity of NKT cells. We aimed to study the impact of osteopontin (OPN), a key driver of fibrosis, on NKT cells' vitamin D receptor (VDR) and activity alterations.

Liver fibrosis was induced in BALB/C mice with carbon-tetrachloride (CCl4) for 8 weeks with either vitamin D [100 ng/kg] or InVivoMAb anti-mouse OPN [100 μg/kg] 2X/week started at week-4 of CCl4. The liver injury profile of serum ALT, AST, and inflammatory cytokines were evaluated. Histopathological findings were assessed via H&E staining and Sirius-Red staining. Fibrotic genes of αSMA, CREBP, and collagen III were assessed using RT-PCR. Fast blood sugar, insulin, liver cholesterol, and triglyceride were evaluated. Liver tissue-resident (tr)-NKT cells were obtained for VDR expressions, molecular pathways of p-STAT1 and P-STAT-5, and activation markers of CD107a and NKp46 using flow cytometry.

Following vitamin D treatment, H&E staining revealed reduced microvascular and macrovascular steatosis, while Sirius-Red staining showed less fibrosis accumulation in liver fibrosis mice than in untreated counterparts. Results were associated with a significant decrease in serum cytokines of IL-β/IL-6/IL-4/OPN/TNF-α and serum AST and ALT by 2-fold and 3-fold, respectively. Fibrotic markers showed an average 1.3-fold decrease in αSMA, CREB, and Col-III in liver fibrosis mice following vitamin D treatment. Quantitated liver cholesterol and triglycerides, serum insulin, and fasting blood sugar ameliorated their levels following vitamin D treatment in liver fibrosis mice. OPN-neutralizing antibody over-expressed VDR on trNKT cells and increased CD107a and NKp46 activities of 3.1 and 3.5 folds, respectively, associated with increasing in p-STAT1 and p-STAT5 phosphorylation. These results were accompanied with a decrease in hepatic-stellate-cell activation markers of αSMA, Col-III, and desmin.

VDR expressions affect trNKT cells activity and could modulate progressions of liver fibrosis. Using an OPN-neutralizing antibody exhibited an antifibrotic effect by alleviating the liver injury profile through NKT cells. It is also suggested as an immunomodulatory target of liver fibrosis.

The aim of our research was to evaluate and analyze serum 25(OH) vitamin D and parathyroid hormone (PTH) levels to investigate whether vitamin D deficiency serves as a risk factor for an increased incidence of acute respiratory infections (ARI) in children. Serum PTH levels were used as an indicator of vitamin D sufficiency, as normal PTH levels require an optimal concentration of 25(OH) vitamin D. The study included 129 children, divided into five subgroups: children with acute bronchopneumonia (n = 42), acute laryngotracheitis (n = 7), acute bronchiolitis (n = 32), acute bronchitis (n = 18), and a control group (n = 30). No statistically significant differences in 25(OH)D levels were observed between the overall population of children with ARI and the control group (p = 0.073). However, significant differences in 25(OH)D levels were identified between the control group and children with bronchopneumonia, acute bronchitis, and laryngotracheitis (p < 0.01, p < 0.05). Regarding PTH levels, statistical significance was found between the control group and the acute bronchiolitis group, due to the high percentage of children with hypervitaminosis in this subgroup. These results highlight the crucial role of vitamin D in the onset and progression of acute respiratory tract infections in children, emphasizing its impact on their overall respiratory health.

Vitamin D is an essential nutrient for maintaining blood calcium and phosphorus levels and controlling bone density. Deficiency in it leads to rickets, osteomalacia, osteoporosis, and various other diseases. Recently, it has gained attention for reportedly reducing the risk of COVID-19 severity. However, there are no reports evaluating pregnant women in the Hokkaido region of Japan. This study aims to elucidate the current status of vitamin D levels in pregnant women in the Hokkaido region.

This study measured the serum concentrations of Vitamin D2 and D3 in 206 pregnant women participating in the Japan Environment and Children's Study-Hokkaido sub-cohort at the Hokkaido Regional Center. It analyzed the relationship between these concentrations and the months, seasons, and sunshine hours.

The mean maternal age was 31.7 ± 4.7 years, and the mean prepregnancy BMI was 21.0 ± 2.5 kg/m2. Only two women have given birth at least once. Regarding sunscreen use, 65 participants (31.6%) responded "often" or "sometimes." Five women used the supplement containing Vitamin D. The value of 25(OH)D2 was above 1 ng/ml in four of them. The average 25(OH)D3 level was 12.1 ng/ml, with a median of 11.0 ng/ml. Four participants (1.9%) had levels below 5 ng/ml. The highest median of 25(OH)D3 was in July, and the lowest was in April. The concentration of 25(OH)D3 was significantly higher in summer than in winter. A correlation was found between 25(OH)D3 and sunshine hours, with 25(OH)D3 concentrations gradually increasing as sunshine hours increase.

It was found that almost all pregnant women in Hokkaido were deficient in vitamin D. It is necessary to implement measures to enhance vitamin D levels in pregnant women to safeguard the health of women and fetuses in Hokkaido.

The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D), binds to the vitamin D receptor (VDR) with high affinity. The VDR then heterodimerizes with the retinoid X receptor (RXR) and associates with vitamin D response elements (VDREs) to regulate the transcription of target genes. Bexarotene (Bex) is an RXR ligand (rexinoid) developed to treat cutaneous T-cell lymphoma and is a putative therapeutic for other diseases. We postulate that VDR ligands (1,25D) and RXR ligands (Bex/analogs) can "synergize" to "super-activate" the VDR-RXR heterodimer. This "cross-talk" could allow disorders treated with high-dose Bex therapy (leading to significant adverse side effects) to instead be treated using both low-dose Bex and vitamin D. Thus, we designed experiments to examine the effect of both VDR and RXR ligands, alone and in combination, to activate VDR-RXR-mediated transcription. The goal was to determine if selected RXR-specific ligands can synergize with vitamin D to amplify RXR-VDR activity. The results demonstrate a synergistic effect with both Bex and 1,25D which could be further modulated by (1) the protein levels (or polymorphic version) of VDR present in the cell, (2) the concentration of the ligands, (3) the cellular "background" (e.g., brain cells versus kidney cells), (4) the nature of the VDRE platform, or (5) the type of rexinoid (Bex analogs). Our findings suggest that diseases that respond to treatment with either vitamin D, or with rexinoids, may be amenable to enhanced therapeutic potential by employing multi-ligand dosing via combinatorial therapy.

The interaction of the SARS-CoV-2 spike protein with membrane-bound angiotensin-converting enzyme-2 (ACE-2) receptors in epithelial cells facilitates viral entry into human cells. Despite this, ACE-2 exerts significant protective effects against coronaviruses by neutralizing viruses in circulation and mitigating inflammation. While SARS-CoV-2 reduces ACE-2 expression, vitamin D increases it, counteracting the virus's harmful effects. Vitamin D's beneficial actions are mediated through complex molecular mechanisms involving innate and adaptive immune systems. Meanwhile, vitamin D status [25(OH)D concentration] is inversely correlated with severity, complications, and mortality rates from COVID-19. This study explores mechanisms through which vitamin D inhibits SARS-CoV-2 replication, including the suppression of transcription enzymes, reduced inflammation and oxidative stress, and increased expression of neutralizing antibodies and antimicrobial peptides. Both hypovitaminosis D and SARS-CoV-2 elevate renin levels, the rate-limiting step in the renin-angiotensin-aldosterone system (RAS); it increases ACE-1 but reduces ACE-2 expression. This imbalance leads to elevated levels of the pro-inflammatory, pro-coagulatory, and vasoconstricting peptide angiotensin-II (Ang-II), leading to widespread inflammation. It also causes increased membrane permeability, allowing fluid and viruses to infiltrate soft tissues, lungs, and the vascular system. In contrast, sufficient vitamin D levels suppress renin expression, reducing RAS activity, lowering ACE-1, and increasing ACE-2 levels. ACE-2 cleaves Ang-II to generate Ang(1-7), a vasodilatory, anti-inflammatory, and anti-thrombotic peptide that mitigates oxidative stress and counteracts the harmful effects of SARS-CoV-2. Excess ACE-2 molecules spill into the bloodstream as soluble receptors, neutralizing and facilitating the destruction of the virus. These combined mechanisms reduce viral replication, load, and spread. Hence, vitamin D facilitates rapid recovery and minimizes transmission to others. Overall, vitamin D enhances the immune response and counteracts the pathological effects of SARS-CoV-2. Additionally, data suggests that widely used anti-hypertensive agents-angiotensin receptor blockers and ACE inhibitors-may lessen the adverse impacts of SARS-CoV-2, although they are less potent than vitamin D.

Frailty is a common geriatric syndrome associated with reduced reserves and increased vulnerability to stressors among older adults. Vitamin D deficiency has been implicated in frailty, as it is essential for maintaining musculoskeletal functions. The relationship between dynamic changes in vitamin D levels and frailty over time has not been extensively studied.

This study utilized data from the UK Biobank. Baseline and longitudinal changes in vitamin D levels were measured. Frailty status was assessed using both the frailty phenotype and frailty index approaches and classified as robust, pre-frail, or frail. Changes in frailty status were assessed by frailty phenotype at baseline (2006-2010) and the follow-up (2012-2013). Mixed effect model was performed to examine the association between vitamin D levels and frailty status. Using multistate transition models, we assessed the impact of increasing vitamin D levels on the probabilities of transitioning between robust, pre-frail, and frail states.

Based on the frailty phenotype, 287 926 individuals (64.8%) were identified as having various degrees of frailty (median age 58.00 [51.00, 64.00] years, 55.9% females). Using the frailty index approach, 250 566 individuals (56%) were found to have different levels of frailty (median age 59.00 [51.00, 64.00] years, 55.3% females). Baseline vitamin D levels were found to be significantly associated with frailty status (frailty phenotype: ORfrail 0.78, 95% CI [0.76, 0.79], P < 0.001; frailty index: ORfrail 0.80, 95% CI [0.78, 0.81], P < 0.001). Dynamic changes in vitamin D levels were also found to be associated with changes in frailty over time. Furthermore, increasing vitamin D levels were associated with a transition from frailty to a healthier status. A higher degree of vitamin D (estimated at 1 nmol/L) was associated with a lower risk of transitioning from robust to prefrail (HR 0.997, 95% CI [0.995, 0.999]) and from prefrail to frail (HR 0.992, 95% CI [0.988, 0.995]).

This study highlights the importance of vitamin D in the context of frailty. Low vitamin D levels are associated with increased frailty risk, while increasing vitamin D levels may contribute to improving frailty status. Recognizing the relationship between vitamin D levels and frailty can inform personalized management and early interventions for frail individuals. Further research is needed to explore the potential effects of vitamin D interventions on frailty and deepen our understanding of the biological connections between vitamin D and frailty.