Search Results (1,725)

Background: Vitamin D deficiency is highly prevalent in older adults and has been increasingly recognised as a potential contributor to cognitive decline, depressive symptomatology, and functional impairment. However, the clinical significance of specific 25-hydroxyvitamin D thresholds in relation to this multidomain geriatric phenotype remains incompletely characterised. Methods: We conducted a cross-sectional study of 1438 consecutive patients aged 65 years or older admitted for comprehensive geriatric assessment at a tertiary centre in Cluj-Napoca, Romania, between January 2023 and November 2025. Serum 25-hydroxyvitamin D [25(OH)D] was categorised as deficient (<20 ng/mL), insufficient (20–30 ng/mL), or sufficient (≥30 ng/mL). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE), depressive symptoms using the Geriatric Depression Scale (GDS-30 and GDS-SF), and functional status using Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL). Multivariable linear regression analyses were adjusted for age, body mass index, serum albumin, and estimated glomerular filtration rate (eGFR). Results: Suboptimal vitamin D status was highly prevalent in this geriatric cohort, with 43.3% of participants meeting criteria for frank deficiency (<20 ng/mL). Lower 25(OH)D concentrations were significantly associated with worse cognitive performance, greater depressive symptom burden, and higher functional dependency. Serum 25(OH)D correlated positively with MoCA and MMSE scores and inversely with ADL, IADL, and GDS scores. In adjusted models, vitamin D remained independently associated with MoCA, IADL, and GDS. Stratified analyses suggested that the main clinical deterioration occurred below 20 ng/mL, while the 20–30 ng/mL range behaved as an intermediate phenotype closer to sufficiency than to frank deficiency. Conclusions: In this large cohort of hospitalised older adults, serum 25(OH)D deficiency below 20 ng/mL was independently associated with poorer cognition, more depressive symptoms, and greater functional impairment. These findings support routine vitamin D assessment in geriatric practice and suggest that the <20 ng/mL threshold identifies a clinically relevant high-risk phenotype. Full article

Background: Selective estrogen receptor modulators (SERMs) are widely used for postmenopausal osteoporosis, yet whether treatment response attenuates with aging in routine practice remains unclear. We examined age- and site-specific responses to SERM therapy. Methods: We retrospectively analyzed postmenopausal women with primary osteoporosis treated with a SERM for 1 year (2017–2021). Participants were stratified by age (50–64, 65–74, and ≥75 years). We evaluated changes in bone mineral density (BMD) at the lumbar spine (L2–4) and femoral neck and changes in urinary NTX and serum BAP. Multivariable linear regression modeled BMD change ratios (1-year/baseline) adjusting for baseline site-specific BMD, estimated glomerular filtration rate (eGFR), and active vitamin D co-therapy (none, alfacalcidol, or eldecalcitol). The primary endpoint was the 1-year change in lumbar spine BMD; secondary endpoints included femoral neck BMD and bone turnover markers. Results: Lumbar spine BMD increased significantly across all age groups, whereas femoral neck BMD increased significantly only in women aged 50–64 years. However, BMD change ratios did not differ among age groups at either site. In adjusted models, age was not independently associated with BMD change at the lumbar spine or femoral neck. Lower baseline BMD predicted larger relative gains at both sites, and eldecalcitol co-therapy was independently associated with femoral neck BMD response. Conclusions: In real-world practice, BMD changes observed during SERM treatment were site-specific rather than clearly age-dependent. Lumbar spine BMD improved across age groups, whereas femoral neck changes were smaller and less consistent. Full article

Background: Adipose tissue is increasingly recognized as a highly dynamic endocrine and immunometabolic organ with marked functional heterogeneity. It serves as a reservoir for the active form of vitamin D₃, 1α,25-dihydroxyvitamin D₃ or calcitriol (1α,25-D₃), since it expresses enzymes responsible for its activation and inactivation and contains the vitamin D receptor (VDR). Through both classical and non-classical mechanisms, calcitriol modulates adipocyte proliferation and differentiation, protein expression and energy metabolism. This review aims to explore the signal transduction mechanisms of calcitriol in adipocytes, detailing the classical pathways mediated by the nuclear VDR (VDRn), as well as non-classical pathways involving membrane-associated VDR (VDRm), microRNAs, AMP-activated protein kinase (AMPK), and sirtuin 1 (SIRT1). Methods: A literature search was conducted using PubMed, ScienceDirect, and MDPI-indexed journals, prioritizing studies published within the last 10 years to ensure the inclusion of up-to-date evidence. Results: This review summarizes current knowledge on both classical and non-classical signaling pathways that are activated by calcitriol and highlights key molecular targets with potential relevance for drug development and therapeutic intervention. Through VDRn, calcitriol regulates the expression of proteins involved in inflammation and energy metabolism. Additionally, it modulates cellular processes such as energy production and secretion via the AMPK/SIRT1 axis and microRNA-mediated pathways, contributing to mitochondrial function and metabolic homeostasis. Conclusions: Calcitriol plays a central role in adipocyte biology by integrating multiple signaling pathways that regulate metabolic and inflammatory responses. These mechanisms highlight its potential as a therapeutic target and biomarker in metabolic diseases. Moreover, microRNAs emerge as critical posttranscriptional regulators in these processes, reinforcing their relevance as both biomarkers and targets for future interventions. Full article

Age-related decline in immune system function is characterized by reduced numbers of naïve lymphocytes, the accumulation of senescent cells, impaired function of all immune cell types, and chronic low-grade inflammation (inflammaging). These alterations contribute to increased susceptibility to infections and malignancies, as well as to autoimmunity and other age-associated diseases. This article reviews current evidence on lifestyle interventions that may mitigate immune aging. Lifestyle-related strategies, including regular physical activity, nutritional interventions (e.g., different diets, caloric restriction, and other fasting-related approaches), stress reduction, and vaccination, are discussed as key modulators of immune function and systemic inflammation. Notably, vitamin D supplementation has been shown to reduce the incidence of autoimmune diseases by 22%. In comparison, caloric restriction has led to a decrease in CRP and TNF-α by 40% and 50%, respectively. Emerging complementary approaches, such as mind–body practices and controlled cold exposure, show promise, though current evidence remains limited and inconsistent. Therefore, integrated lifestyle strategies may slow aging-related immune decline and support healthy aging. However, longitudinal trials are required to define the optimal intervention parameters, population-specific thresholds, and the long-term durability of immune rejuvenation. Full article

Background/Objectives: Minipuberty represents the second phase of physiological activation of the reproductive axis and may play a role in postnatal genital development. Its course has been shown to be affected by untreated or inadequately treated maternal hypothyroidism. The aim of the present study was to investigate minipuberty in the sons of women with euthyroid autoimmune thyroiditis during pregnancy. Methods: This prospective matched cohort study included three groups of apparently healthy infant boys. Two groups comprised the male offspring of levothyroxine-naive, euthyroid women with autoimmune thyroiditis: one group was unsupplemented, and the other received vitamin D and selenium supplementation. The control group consisted of boys born to healthy women. Salivary concentrations of testosterone, androstenedione, DHEA-S, estradiol, and progesterone, along with urinary FSH and LH levels, were assessed longitudinally over the first 12 months of life. These hormonal measurements were evaluated in relation to genital development, including testicular volume and penile length, which were recorded at each study visit. Results: Compared with the offspring of healthy mothers, sons of women with autoimmune thyroiditis who did not receive supplementation exhibited lower concentrations of LH and testosterone, without a distinct peak, while the duration of hormone detectability did not differ between the groups. These hormonal alterations were accompanied by reduced penile length, with no differences observed in testicular volume. This group also exhibited lower DHEA-S concentrations, whereas levels of other hormones were comparable. In contrast, in the group receiving vitamin D and selenium supplementation, the dynamics of hormonal changes and genital organ growth did not differ from those observed in the control group. LH concentrations were inversely correlated with thyroid peroxidase antibody titers, which were lower in the supplemented group. Conclusions: The findings indicate an altered course of minipuberty in the sons of women with euthyroid autoimmune thyroiditis during pregnancy and suggest a potential benefit of exogenous vitamin D and selenium supplementation in this population. Full article

Vitamin D is a fat-soluble secosteroid essential for skeletal development and calcium homeostasis, but it also exerts pleiotropic effects on numerous biological processes via its active metabolites. Vitamin D metabolites act as steroid hormones that regulate cell-cycle progression, proliferation, differentiation, apoptosis, immune responses, and multiple intracellular signaling pathways. Moreover, they modulate the expression of genes involved in carcinogenesis. As circulating vitamin D levels are influenced by diet, fortified foods, and supplementation, they represent a potentially modifiable factor. Whether vitamin D status affects cancer risk or disease progression in carriers of pathogenic BRCA1 variants remains unclear and continues to be actively investigated. Clarifying this relationship could have significant clinical implications for risk stratification and prevention in this high-risk population. This narrative review summarizes current evidence from epidemiological, clinical, and molecular studies examining the role of vitamin D in BRCA1 pathogenic variant carriers. It also highlights key limitations in the existing literature and identifies critical directions for future research, emphasizing the need for well-designed prospective studies in representative cohorts. Full article

Background: Nutritional biomarkers are linked to body composition changes, but limited evidence has studied how nutritional biomarkers relate to low muscle mass, excess adiposity, and both coexisting conditions across different physical activity levels. This study aims to investigate associations between low muscle mass, obesity, and low muscle mass with obesity and nutritional biomarkers across physical activity levels among U.S. adults across physical activity levels. Methods: This cross-sectional study analyzed data from adults aged 20–59 years from the 2015–2018 cycles of the National Health and Nutrition Examination Survey (NHANES) 2015–2018. Low muscle mass was defined by low appendicular lean mass relative to body weight (LALM/W). Obesity was classified using body mass index (BMI¹), waist circumference (WC²), and body fat percentage (FM%³), and low muscle mass with obesity was defined using three coexisting phenotypes (LALM/W-O1, LALM/W-O2, LALM/W-O3). Nutritional biomarkers included serum albumin, vitamin D, triglyceride, cholesterol, LDL cholesterol, iron, insulin resistance (HOMA IR), and high-sensitivity C-reactive protein (hs-CRP). Physical activity was categorized as inactive, insufficiently active, or sufficiently active based on MET minutes per week. Multivariable regression models accounted for the complex survey design and relevant covariates. Results: After adjustment, LALM/W was significantly associated with low serum albumin, low vitamin D, high triglyceride, high HOMA-IR, and high CRP. Obesity was significantly associated with low serum albumin, low vitamin D, high triglyceride, high LDL cholesterol, high HOMA-IR, and high CRP. LALM/W-O in all phenotypes were significantly associated with low serum albumin, low vitamin D, high triglyceride, high LDL cholesterol, high HOMA-IR, and high CRP. LALM/W-O phenotypes demonstrated the strongest associations, particularly with high HOMA-IR and hs-CRP. Although the associations varied by physical activity level, sufficiently active group was associated with lower odds of adverse nutritional biomarkers compared with insufficient activity. Conclusions: Nutritional biomarkers are associated with LALM/W and obesity. Sufficient physical activity was associated with fewer adverse outcomes. This suggests that adequate physical activity may be associated with better nutritional status and body composition. Full article

Background: Micronutrient deficiencies and physical inactivity can adversely affect child growth and development. This study assessed the effects of school-based physical activity and multi-micronutrient supplementation on micronutrient status among schoolchildren in Kilombero district, Tanzania. Methods: In a cluster-randomized trial, children aged 6–12 years were allocated to physical activity, multi-micronutrient supplementation, combined physical activity plus supplementation, or placebo control. Anthropometric and biochemical assessments were conducted at baseline, 14 months, and 26 months. Dried blood spot samples were available for 923 children at baseline. Complete-case analyses used biomarker-specific subsamples with valid baseline and 26-month measurements. Results: The primary complete-case sample included 243 children with valid paired measurements for zinc and serum transferrin receptor; vitamin D analyses were restricted to 52 children because of missing or invalid samples. At baseline, iron and vitamin D deficiencies were common, affecting 42.8% and 39.9% of children, respectively, while zinc deficiency affected 11.9%. At 26 months, allocation to the physical activity intervention was associated with lower odds of zinc deficiency, both when delivered alone (OR = 0.16) and when combined with supplementation (OR = 0.57). Supplementation alone was not significantly associated with reduced zinc deficiency. Iron status did not differ between intervention groups. Vitamin D findings should be interpreted with caution because analyses were based on a very small biomarker-specific subsample. Conclusions: School-based physical activity, alone or combined with multi-micronutrient supplementation, was associated with lower odds of zinc deficiency among Tanzanian schoolchildren. Supplementation alone showed no clear benefit for zinc or iron status. Vitamin D findings remain inconclusive because of substantial biomarker-specific missingness. Future trials should strengthen adherence monitoring, biomarker follow-up, and repeated assessment of dietary and contextual factors. Full article

Background/Objectives: Vitamin D, universally recognized for its role in calcium–phosphate homeostasis and skeletal health, has emerged as a key immuno-endocrine modulator. Its active metabolite interacts with the vitamin D receptor (VDR) across immune and endocrine cell populations, influencing gene transcription, cytokine balance, and immune tolerance. This narrative review synthesizes mechanistic, epidemiological, and clinical evidence on the role of vitamin D in immune modulation across autoimmune and infectious diseases. Methods: This narrative review incorporated a structured and comprehensive literature search across PubMed/MEDLINE, Scopus, Web of Science, Embase, and Google Scholar. Results: Vitamin D modulates both innate and adaptive immunity through antimicrobial peptide induction, macrophage and NK cell activation, and promotion of tolerogenic dendritic cells. Clinical and interventional trial outcomes remain heterogeneous and are influenced by baseline vitamin D status, dosing regimens, genetic variability, and disease context. Conclusions: Vitamin D functions in endocrine and immune regulation, contributing to host defense and immune tolerance. Current evidence supports that for autoimmune and infectious conditions, well-designed randomized trials are required to clarify effective dosing, identify responsive subpopulations, and elucidate genetic determinants of therapeutic benefit. Full article

Background/Objectives: Rheumatoid arthritis (RA) has been associated with accelerated atherosclerosis and cerebrovascular alterations. Our 2017 study compared 60 RA patients to healthy controls, assessing vascular, neurological, and cognitive parameters. The present study is a follow-up of these RA patients to evaluate disease progression and vascular changes over time, using their 2017 results as baseline. Methods: In 2023, we reassessed 43 of the original 60 RA patients using laboratory testing, carotid ultrasound, functional transcranial Doppler (TCD) and brain magnetic resonance imaging (MRI) examinations. Changes over time were analyzed within the same individuals. Results: Inflammatory markers and lipid profiles showed a trend toward improvement, though changes were not statistically significant, except for a significant increase in vitamin D (p < 0.001) and a decrease in Disease Activity Score in 28 Joints (DAS28) scores (p < 0.001). Carotid ultrasound revealed a significant increase in plaque burden (p = 0.022 on the right side and p = 0.008 on the left), while carotid intima media thickness (cIMT) showed a non-significant rise. TCD measurements indicated significantly increased pulsatility (p < 0.001 on the right, p = 0.001 on the left side) and resistance (p = 0.001 on the right, p = 0.012 on the left side) indices and reduced flow velocities (p < 0.001 on the right and p = 0.001 on the left side) in bilateral middle cerebral arteries (MCAs). The cerebrovascular reserve capacity was significantly lower on the right side overall (p = 0.013), with further decline noted in the methotrexate (MTX)-treated subgroup on the left side (p = 0.043). MRI findings showed non-significant numerical trends toward worsening lacunar small-vessel disease (p = 0.405) and cerebral atrophy (p = 0.063), with higher but stable lacunar infarction scores among MTX users (p = 0.023). Conclusions: Despite improved inflammatory control, RA patients demonstrated progressive vascular and hemodynamic alterations over time, while MRI changes should be interpreted as trends. These findings support multimodal vascular monitoring in RA. Full article

Hydrodynamic cavitation (HC) is an emerging non-thermal technology that is capable of improving the quality and shelf life of fruit juices while retaining heat-sensitive bioactive compounds. This study optimized a mixed-fruit juice (MFJ) blend—60% mandarin, 25% pineapple, and 15% watermelon using a D-optimal mixture design. The MFJ was subjected to HC at varying pressures (4–6 bar) and times (40–60 min) and compared to thermal treatment (90 °C for 30 s). The optimized predicted HC treatment (5 bar/52 min) effectively maintained pH, titratable acidity, and TSS. Notably, HC at 6 bar for 60 min reduced the sedimentation index by 2% and lowered viscosity to 3.56 cP. Compared to thermal processing, the optimized HC-treated sample demonstrated superior nutrient retention, preserving 82.29% of vitamin C, 93.50% of total phenolics, 87.43% of flavonoids, and 61.67% of antioxidant activity. Microbial safety was also improved, achieving a 1.35 log CFU/mL reduction in total plate count and 47.96% peroxidase inactivation. While sensory evaluation showed slightly lower acceptability for HC-treated juice (6.36) versus the control (7.14), it significantly outperformed thermal treatment (3.83). Furthermore, the cavitated sample demonstrated superior bioactive retention after 14 days of storage at 4 °C, with total phenolic content retained at 31.55 ± 0.9 mg GAE/100 mL. The findings suggest that hydrodynamic cavitation can be considered a promising non-thermal processing technology for improving physicochemical stability, preserving bioactive compounds, and extending the shelf life of functional fruit beverages. This underscores HC’s potential as a viable, high-quality alternative to traditional pasteurization in the beverage industry. Full article

Background/Objectives: Leukocyte telomere length (TL) is a marker of biological aging associated with cardiovascular disease, chronic kidney disease, and malignancy in the general population. Its long-term prognostic significance in systemic lupus erythematosus (SLE) remains unclear. We aimed to evaluate the association between baseline TL and long-term clinical outcomes in patients with SLE. Methods: Prospective cohort study including 97 Caucasian women with SLE. Relative TL was measured in whole blood using quantitative polymerase chain reaction (qPCR) at baseline. A control group of 50 healthy Caucasian women from the same geographical region was included for comparison. Patients were followed for a mean of 9.7 ± 2.8 years. Outcomes included thrombotic cardiovascular events, damage accrual, incident malignancy, and chronic kidney disease. Associations were assessed using multivariable regression models adjusted for potential confounders. Results: Mean age was 51.6 ± 13.8 years and mean relative TL was 4.3 ± 1.0. Relative TL was inversely associated with age (β = −0.20, p = 0.048) and was shorter in patients with hematological manifestations (p = 0.038). No differences in relative TL were observed between SLE patients and controls. Relative TL was not associated with disease activity, cumulative damage, cardiovascular risk factors, vitamin D levels, or subclinical atherosclerosis. During follow-up, 13.4% of patients experienced cardiovascular events, 10.3% developed malignancy, and 11.3% developed chronic kidney disease. Relative TL was initially associated with long-term damage accrual, glomerular filtration rate and cardiovascular events; however, after adjustment for age, only the association with glomerular filtration rate remained at the limit of statistical significance (p = 0.05). Conclusions: In this prospective cohort, relative TL was primarily associated with aging, hematological manifestations, and glomerular filtration rate, but not with disease activity or most long-term clinical outcomes. These findings suggest that TL reflects biological aging rather than disease-specific processes and has limited utility as a prognostic biomarker in SLE. Full article

This study evaluated the association between vitamin D3 levels, transplanted kidney function, and body composition in 315 stable renal transplant recipients (median 7.7 years post-transplant). The biochemical profile included eGFR, PTH, calcium, phosphorus, and 25(OH)D₃ levels. Vitamin D status was defined as deficiency (<20 ng/mL), insufficiency (20–30 ng/mL), or optimal (>30 ng/mL). Body composition was assessed via bioelectrical impedance analysis, capturing parameters such as BMI, visceral fat area, and phase angle. Multivariable quantile regression models were used to assess the associations between clinical/metabolic parameters and graft function. Vitamin D3 supplementation was prescribed in 61.5% of patients, with 49.7% receiving active analogues and 50.3% cholecalciferol. Results showed that 25(OH)D₃ levels did not correlate with graft function in the total population, and no significant differences in eGFR were observed regarding vitamin D status. In multivariable models, 25(OH)D₃ levels correlated significantly only with calcium levels. No significant correlations were observed between vitamin D and transplant vintage, age, eGFR, or any anthropometric and body composition parameters. Full article

Background: Autism spectrum disorder (ASD) is associated with immune dysregulation in a subset of individuals, though findings remain heterogeneous and poorly defined, particularly regarding immune subtypes and metabolic context. Methods: We analyzed whole-blood microarray data from GSE18123 (GPL570: ASD n = 46, controls n = 19; GPL6244: ASD n = 68, controls n = 21) using an integrated immunometabolic framework. CD4⁺ T-cell transcriptional programs were used to assign dominant immune phenotypes (TH1, TH2, TH17, Tfh, FOXP3⁺ Treg, Tr1-like). Metabolic demand was quantified via the τ-axis; execution capacity was assessed using cytosolic and mitochondrial energy compensation ratios (CECR, MECR). Induction–execution mismatch was captured by three Gap metrics (Cytosolic, Warburg, Global). Functional validation correlated these metrics with transcriptional signatures of folate transport, one-carbon metabolism, receptor-mediated micronutrient uptake (LRP2–CUBN–AMN), cobalamin processing, and vitamin D activation across both platforms. Results: Six immunometabolic CD4⁺ subtypes were identified within ASD. τ-axis discrimination was strongest for Tr1-like (AUC = 0.811) and Tfh (AUC = 0.825) states, while TH17 profiles were indistinguishable from controls. Despite variation in metabolic demand, CECR and MECR remained relatively preserved, indicating decoupling between induction and execution capacity. Global Gap values were most negative in Tfh and TH1 states and positive in TH17 and controls. Negative Gap states showed coordinated suppression of ATP-intensive micronutrient acquisition pathways, including folate transport (FOLR1/2, SLC19A1), megalin–cubilin-mediated uptake (r ≈ 0.77–0.79), and vitamin D activation (CYP27B1). Intracellular cobalamin processing was upregulated in proportion to metabolic demand (r > 0.9). Findings were directionally replicated across both datasets. Conclusions: These data demonstrate that ASD exhibits structured immunometabolic heterogeneity characterized by subtype-specific demand–capacity imbalance. The Global Gap framework provides transcriptomic evidence of energetic deficit in Tfh- and Tr1-like-dominant states. Future clinical studies should incorporate subtype-stratified assessment of micronutrient status and metabolic execution capacity. Full article

The vitamin D receptor (VDR) plays a pivotal role in maintaining epidermal barrier homeostasis and regulating cutaneous inflammatory responses. However, the cosmetic application of vitamin D and its active metabolites is limited by photoinstability, formulation challenges, and regulatory considerations. In this study, we evaluated a synthetic VDR-activating peptide (VDR-Pep) as a potential functional cosmetic ingredient capable of modulating VDR-associated signaling pathways in human keratinocytes. In situ proximity ligation assays (PLAs) demonstrated that VDR-Pep enhanced the heterodimerization of VDR and retinoid X receptor (RXR), indicating activation of canonical VDR signaling. Treatment with VDR-Pep significantly increased the expression of S100A3 and key terminal differentiation markers, including filaggrin, involucrin, and loricrin, in a dose-dependent manner. In addition, VDR-Pep stimulated intracellular calcium mobilization at levels comparable to or exceeding those induced by 1,25-dihydroxyvitamin D₃. Under UVB-induced stress conditions, the peptide attenuated the expression of the pro-inflammatory cytokine interleukin-6 (IL-6) and enhanced NRF2-associated transcriptional engagement, as evidenced by increased interaction between NRF2 and RNA polymerase II. Collectively, these findings suggest that VDR-Pep supports epidermal homeostasis through coordinated modulation of VDR/RXR signaling, calcium-mediated differentiation, barrier-related protein expression, inflammatory responses, and antioxidant-associated pathways. The results indicate that VDR-targeting peptides may represent a promising non-hormonal strategy for cosmetic formulations aimed at reinforcing skin barrier function and improving resilience to environmental stress. Future studies should focus on validating these effects in in vivo human skin models, assessing long-term safety and efficacy, and optimizing formulation stability for practical cosmetic applications. Full article