Search Results (1,535)

Background: Vitamin B12 deficiency, hyperhomocysteinemia, and diabetes are emerging determinants of cardiovascular risk, particularly among women. Early detection and treatment represent an important public health opportunity to reduce the burden of disease and promote health equity. Objective: We aimed to quantify the prevalence of vitamin B12 deficiency, hyperhomocysteinemia, and diabetes, and to evaluate the potential impact of detecting and addressing these conditions on reducing CVD risk in adult Mexican women. Methods: We analyzed data from 1197 women aged 20–49 years from Mexico’s 2022–2023 National Health and Nutrition Survey (ENSANUT). Serum vitamin B12, folate, and homocysteine were quantified, and 10-year CVD risk was estimated using Framingham and Globorisk models. Population-attributable fractions and cost–benefit analyses were used to assess preventable CVD cases and the economic feasibility of nationwide vitamin B12 supplementation. Results: Nationwide, 37.2% of women have vitamin B12 deficiency, and 30.6% have borderline levels. In Southern Mexico, the prevalence of vitamin B12 deficiency is higher, reaching 52.4%. Elevated homocysteine levels were detected in 12.3% of women. The predicted number of preventable CVD cases ranged from 10,000 to 14,000, and the benefit–cost ratio exceeded 1, supporting economic feasibility. Conclusions: Vitamin B12 deficiency and hyperhomocysteinemia are very common among Mexican women and are associated with an increased cardiovascular risk, especially in those aged 40 to 49. The analysis showed that implementing a national vitamin B12 supplementation strategy could be a cost-effective preventive measure, with a benefit–cost ratio ranging from 1.93 in the base case to 2.98 when broader societal savings are taken into account. These findings highlight the potential of targeted nutritional interventions to reduce the burden of cardiovascular disease in women. Full article

Vitamin homeostasis plays a critical role in inflammatory bowel disease management, yet the protective mechanisms and clinical utility of specific vitamins remain incompletely characterized. Within this context, a two-sample Mendelian randomization analysis leveraging genetic instruments for measuring circulating vitamin levels identified folate as a protective factor against ulcerative colitis (UC). To validate these findings, a DSS-induced colitis model was established with serial serum folate measurements. Therapeutic folate supplements were subsequently administered, followed by a comprehensive evaluation of epithelial barrier modulation through in vivo and recombinant TNF-α/IFN-γ-induced in vitro models. This included assessment of junctional proteins, ultrastructural analysis by transmission electron microscopy, and functional quantification of barrier integrity using transepithelial electrical resistance with paracellular permeability assays in epithelial monolayers. Molecular mechanisms were investigated through RNA sequencing complemented by immunoblot validation of key pathway components. The results demonstrated decreased serum folate levels in DSS-induced colitis mice, whereas folate supplementation ameliorated disease severity and attenuated intestinal inflammation and histopathological damage. Crucially, folate restored epithelial barrier structural integrity and function both in vivo and in vitro. Mechanistically, folate mediated barrier restoration through suppression of the PI3K/AKT/NF-κB/MLCK/MLC2 signaling axis. Collectively, the results of this study provide mechanistic insights that support the use of folate as an active therapeutic molecule in patients with UC. Full article

Background/Objectives: Nutrition during the reproductive years shapes women’s immediate health, fertility, pregnancy outcomes, and long-term offspring well-being. This position paper narratively synthesizes and critically appraises evidence on how dietary patterns, macro-/micronutrients, and supplementation influence women’s health, female fertility, and reproductive outcomes, to inform practical recommendations. Methods: We narratively reviewed recent reviews, cohort studies, clinical trials, and public-health guidance on macronutrients, key micronutrients, dietary patterns (with emphasis on the Mediterranean diet), ultra-processed food (UPF) intake, and targeted supplementation relevant to menstrual, metabolic, cardiovascular, skeletal, and reproductive outcomes. Results: Balanced, diverse diets rich in whole and minimally processed foods support hormonal regulation, ovulatory function, healthy gestation, and chronic-disease risk reduction. Priority nutrients include iron, folate, calcium, vitamin D, zinc, vitamin B12, and long-chain omega-3s (DHA), with supplementation considered when dietary intake or bioavailability is inadequate. Evidence consistently links Mediterranean-style eating to improved metabolic health, insulin sensitivity, IVF success, lower gestational diabetes risk, and favorable neonatal outcomes. High UPF consumption is associated with poorer diet quality, inflammation, adverse pregnancy outcomes, and potential reproductive impairment, warranting a reduction in favor of nutrient-dense foods. Diet also influences cardiovascular and bone health through effects on lipids, glycemia, blood pressure, and mineral/vitamin status, with fiber-rich carbohydrates, unsaturated fats (notably olive oil), and adequate calcium–vitamin D emerging as central levers. Conclusions: For women of childbearing age, a Mediterranean-aligned, minimally processed dietary pattern—tailored to individual needs and complemented by prudent use of folate, iron, vitamin D, calcium, B12, and DHA when indicated—offers robust benefits across reproductive, metabolic, cardiovascular, and skeletal domains. Public-health actions should improve access to healthy foods, curb UPF marketing, and embed personalized nutrition counseling in routine care; further longitudinal research from preconception through postpartum is needed. Full article

Objectives: To investigate the clinical value of cerebrospinal fluid (CSF) testing for biogenic amine, pterins, amino acids, and folates in paediatric onset epilepsies. Methods: Retrospective clinical and biochemical phenotyping of patients with epilepsy who underwent diagnostic CSF measurement of monoamine neurotransmitters, pterins, folates, and amino acids between 2009 and 2022. Results: The studied cohort included 123 patients with epilepsy (mean age at the procedure: 4.54 ± 3.65 years). The diagnostic yield for primary neurotransmitter disorders was 1.68% and zero for inherited amino acid and folate metabolism disorders. Patients with higher seizure frequency showed higher levels of CSF homovanillic acid (HVA) and HVA/5-hydroxyindolacetic acid (5HIAA) ratio. Lower levels of 3-O-methyldopa (3-OMD) were found in patients with co-occurring neurodevelopmental disorders, and lower levels of biopterin, 3-methoxy-4-hydroxyphenylglycol (3-MHPG) and 5-methyltetrahydrofolate (5-MTHF) in those with movement disorders. Significantly lower CSF glutamine levels were found in patients receiving antiseizure medications as polytherapy. Patients with a history of status epilepticus had significantly lower levels of CSF aspartic acid, glycine, leucine, ornithine, and valine, and higher levels of CSF serine. Conclusions: CSF analysis disclosed differences in the concentrations of various metabolites that might be related to the severity of the epilepsy, the presence of comorbid conditions, and medications. Full article

Sour soup, a traditional fermented specialty from Northeast China, is renowned for its distinctive aroma and various health benefits. Here, we report the probiotic properties of Lactiplantibacillus plantarum Z45—a strain isolated from sour soup broth—along with its fermentative potential in sour soup production. This strain is suitable for food fermentation due to its absence of biogenic amine production and non-hemolytic activity. It exhibited strong tolerance to simulated gastrointestinal conditions and demonstrated high adherence capability to Caco-2 cells. Additionally, the strain displayed antioxidant and antimicrobial activities. Whole-genome sequencing revealed that Z45 carries no virulence or antibiotic resistance genes. It also harbors multiple carbohydrate-active enzymes and a complete folate biosynthesis pathway, alongside genes associated with stress response, antioxidant activity, and adhesion. Subsequently, Z45 was employed as a starter culture for sour soup fermentation, and its effects on the physicochemical and sensory properties of the product were evaluated. The results indicated that fermentation with Z45 did not alter the physicochemical properties of sour soup but significantly enhanced its sensory attributes. Compared to spontaneous fermentation, Z45-fermented sour soup showed reduced levels of harmful biogenic amines, improved flavor and overall sensory quality, notable enrichment of Lactobacillus and Oscillospirales in the microbial community, and upregulation of beneficial metabolites such as flavonoids and glycerophosphocholine. In summary, Lactiplantibacillus plantarum Z45 is safe, demonstrates probiotic potential, and holds promise for improving the quality and functional properties of fermented foods. Full article

Background: Depression is a significant complication of the peripartum period that can result in profound long-term detrimental implications for the affected woman, her child, and her family. It is possible that micronutrient imbalances could contribute to the development of perinatal depression through their roles in neurotransmitter synthesis and neuroendocrine and neuroimmune pathways. Micronutrient imbalances are more likely during the perinatal period due to the additional physiological demands on the body during this time. The objective of this systematic review was to review and summarise the existing evidence regarding the association between micronutrient levels and perinatal depression. Methods: MEDLINE, EMBASE, PsycINFO, CINAHL, Scopus, and Web of Science were searched for studies examining blood levels of micronutrients and assessment of depression within the peripartum period using validated rating tools. Results: A total of 58 studies met the eligibility criteria and were included in this review. Of these, 31 studies reported a significant inverse association between perinatal depression and at least one of the following: vitamin D, iron status, vitamin B12, folate, or zinc. Vitamin D was the most frequently investigated nutrient, examined in 28 of the 58 articles. The remaining 27 did not demonstrate a significant association. Conclusion: This review found that vitamin D deficiency has the greatest evidence of an association with perinatal depression. The evidence for other micronutrients is mixed, inconclusive, or limited. Further research is required to determine the significance of these micronutrients in the development of perinatal depression. Full article

Immune checkpoint inhibitors (ICIs) targeting PD-L1 and CD47 are clinically limited by severe off-target toxicities. To address this issue, immunotherapeutic prodrug strategies have been developed, aimed at preventing antibodies from binding to targets in healthy tissues and thereby reducing systemic toxicity. Existing strategies include prodrug technologies that mask the active sites of antibodies via peptide or polyethylene glycol (PEG) modification—yet these approaches also cause antibodies to lose their targeting ability. Herein, we propose an antibody prodrug strategy (termed FA-PEG-S-Ab) with active targeting capability. By modifying antibodies with folate-PEG-disulfide and PEG-disulfide linkages, we developed two novel prodrugs: FA-PEG-S-Atz (PD-L1-blocking prodrug) and FA-PEG-S-Hu5 (CD47-blocking prodrug). This strategy functions through two key steps: first, folate binding to folate receptor α (FRα)-mediated tumor-specific targeting enables the prodrugs to accumulate specifically in tumor tissues; subsequently, the high concentration of glutathione (GSH) in the tumor microenvironment (TME) specifically cleaves the disulfide bonds, removing the PEG shield, releasing the antibody, and restoring the antibody’s antigen-binding activity. In vitro experiments confirmed that the modified antibody prodrug FA-PEG-S-Hu5 exhibits high affinity for FRα (K_D = 4.02 × 10⁻⁹ M) and effectively masks the antibody’s binding activity (K_D from 1.05 × 10⁻¹¹ M to 2.10 × 10⁻⁸ M). Following activation by GSH in the TME, this masking effect is reversed, and the antibody regains its binding affinity (K_D = 2.14 × 10⁻¹⁰ M). Crucially, FA-PEG-S-Hu5 completely eliminates hemolytic toxicity. This “folate targeting delivery + TME activation” prodrug strategy is expected to provide a new solution for addressing the off-target toxicities of conventional ICIs. Full article

Wool traits such as fiber diameter, fiber length, and greasy fleece yield are economically significant characteristics in sheep breeding programs. Traditional genome-wide association studies (GWAS) have identified relevant genomic regions but often fail to capture the non-linear and polygenic architecture underlying these traits. In this study, we implemented a two-stage machine learning (ML)-based GWAS framework to dissect the genetic basis of wool traits in Central Anatolian Merino sheep. Phenotypic records were collected from 228 animals, genotyped with the Illumina OvineSNP50 BeadChip. In the first stage, feature selection was conducted using LASSO, Ridge Regression, and Elastic Net, generating a consensus SNP panel per trait. In the second stage, association modeling with Random Forest and Support Vector Regression (SVR) identified the most predictive models (R² up to 0.86). Candidate gene annotation highlighted biologically relevant loci: MTHFD2L and EPGN (folate metabolism and keratinocyte proliferation) for fiber diameter; COL5A2, COL3A1, ITFG1, and ELMO1 (extracellular matrix integrity and actin remodeling) for staple length; and FAP, DPP4, PLCH1, and NPTX1 (extracellular matrix remodeling, proteolysis, and sebaceous gland function) for greasy fleece yield. These findings demonstrate the utility of ML-enhanced GWAS pipelines in identifying biologically meaningful markers and propose novel targets for genomic selection strategies to improve wool quality and yield in indigenous sheep populations. Full article

Background/Objectives: Platelet-dependent thrombotic risk increases with age. Little is known, however, about the potential effect of vitamins on platelet reactivity in older subjects. Methods: Therefore, in the present study we examined the dependencies of whole blood platelet aggregability (in response to arachidonic acid (AA), collagen (COL) or adenosinediphosphate (ADP), using impedance aggregometry) in older men and women (60–65 yr, n = 246) on the intakes of vitamins (vitamins A, E, C, B₆, B₁₂ and D, niacin, thiamine, riboflavin, retinol, β-carotene and folates) with a typical daily diet (vitamin contents estimated using Dieta 5.0 software). Results: Overall, significant negative bootstrap-boosted partial correlation coefficients, adjusted for selected cardiovascular risk factors, were revealed for AA and β-carotene, and ADP and β-carotene, riboflavin, vitamin B₆ and niacin. These findings were further validated by the outcomes of the bootstrap-boosted canonical analysis, confirming the relationships revealed for ADP, and to a lesser extent for AA. COL-dependent platelet aggregation appeared to not be associated with the amount of vitamins in the subjects’ daily diet. Conclusions: Hence, we conclude that the intake of vitamins in the daily diet of older subjects is negatively associated with platelet aggregability in an agonist- and vitamin-specific manner. Full article

Background: Albania is undergoing rapid nutrition transition, yet cardiometabolic (CM) risk in young adults is poorly characterized. We report baseline, cross-sectional findings from a WHO-aligned sentinel study examining diet, physical activity and early CM phenotypes, with fat quality examined as a modifiable exposure. Methods: Young adults recruited on campus (n = 262; median age, 21 years; 172 women, 90 men) underwent standardized anthropometry, seated blood pressure (BP) and fasting glucose (FG). Diet was assessed by two interviewer-administered 24 h recalls and activity outlined by the IPAQ-short form. We derived potential renal acid load (PRAL) and a MASLD-oriented nutrient score, computed a composite CM risk score (cCMRS: sex-standardized mean of WHtR, mean arterial pressure, FG) and fitted prespecified energy-partition models for isocaloric +5% of energy substitutions (SFA → PUFA; SFA → MUFA) with Benjamini–Hochberg false discovery rate (FDR) control. Results: Despite normal average BMI (23.4), risk clustering was common: elevated BP in 63% of men and 30% of women, impaired FG (100–125 mg/dL) in almost one third and central adiposity (WHtR ≥ 0.5) in 51% of men and 24% of women. Diets were SFA-rich (~17–19%E), sodium-dense and low in fiber and several micronutrients (e.g., vitamin D, folate, potassium). In isocaloric models, SFA → PUFA was associated with more favorable nutrient signatures: MASLD-oriented score −28% (p < 0.001; FDR-significant) and PRAL −33% (p = 0.007; FDR-borderline/suggestive). Conclusions: A waist-centric CM subphenotype—central adiposity co-occurring with upward BP shifts and intermittent dysglycemia—was detectable in young adults despite normal average BMI, against a background of poor diet quality and low activity. These baseline surveillance signals are not causal effects. Integration into routine with WHO-aligned NCD surveillance is feasible. Prospective follow-up (biomarker calibration, device-based activity, repeated waves) will refine inferences and inform scalable proactive prevention. Full article

Purpose: To assess the association between hair loss in females and various biomarkers including hemoglobin, iron, ferritin, zinc, selenium, calcium, vitamin D, vitamin B12, folic acid, and thyroid hormones. Patients and methods: This study enrolled 100 women presenting with hair loss and 100 age-matched healthy controls. Venous blood samples were collected for analysis of hematological, hormonal and biochemical parameters. Results: The mean age of participants was comparable between groups (43.06 ± 10.76 vs. 41.39 ± 7.94 years; p = 0.88). Hair loss in females had significantly lower mean levels of Hb (11.45 ± 0.39 vs. 13.09 ± 0.46 g/dL; p < 0.001), iron (70.14 ± 7.85 vs. 94.42 ± 5.61 µg/dL; p < 0.001) and ferritin (39.34 ± 3.71 vs. 48.09 ± 5.31 ng/mL), all with p < 0.001. Serum levels of selenium (67.11 ± 5.53 vs. 71.45 ± 4.05 µg/L), zinc (86.07 ± 3.98 vs. 88.87 ± 2.03 µg/L), copper (90.71 ± 3.48 vs. 104.84 ± 5.38 µg/L), and calcium (8.61 ± 0.28 vs. 9.11 ± 0.27 mg/dL) were significantly reduced in women with hair loss (p < 0.001). Thyroid hormones were also significantly lower in the hair loss group, including TSH (1.74 ± 0.25 vs. 2.35 ± 0.39 µIU/mL) and FREE T4 (1.11 ± 0.11 vs. 1.32 ± 0.12 ng/dL), despite remaining within the normal reference ranges. Patients also showed lower serum folate (6.17 ± 0.63 vs. 6.96 ± 0.41 ng/mL), vitamin B12 (185.52 ± 35.27 vs. 258.30 ± 52.84 pg/mL), and vitamin D (26.32 ± 2.98 vs. 32.20 ± 3.76 ng/dL) levels (p < 0.001). Conclusions: Hair loss in females is significantly associated with reduced levels of circulating hemoglobin, iron, copper, selenium, vitamin D, vitamin B12, folate, thyroid-stimulating hormone and FREE T4 hormone. Full article

Quantum dots (QDs) have emerged as promising nanomaterials in cancer therapeutics owing to their tunable optical properties, versatile surface functionalization, and potential for simultaneous imaging and drug delivery. This review focuses on targeted quantum dots (TQDs), highlighting their role in overcoming the limitations of passive drug delivery strategies, such as poor specificity, high systemic toxicity, and limited therapeutic efficacy. We begin by outlining the fundamentals of QDs, including their types, heterostructures, and biomedical formulations. Recent advances in tailoring QD physicochemical properties to the cancer microenvironment are discussed, with emphasis on routes of administration and targeting strategies. The review critically examines different molecular targeting approaches—such as folate receptors, transferrin receptors, aptamers, antibodies, peptides, and hyaluronic acid—used to enhance therapeutic precision. Furthermore, we summarize progress in TQD-based combination therapies, including chemotherapy–photodynamic therapy, photothermal therapy, radiotherapy, and multimodal platforms that integrate therapy with imaging. Special attention is given to the role of QDs in theranostic, hydrogels, nanocomposites, and hybrid systems that enable controlled drug release and real-time monitoring. Despite significant advancements, challenges remain regarding biocompatibility, safety, and regulatory approval. Overall, this review provides an integrative perspective on the design, functionalization, and biomedical applications of TQDs, underscoring their potential to improve cancer treatment outcomes through enhanced specificity, reduced side effects, and multifunctional theranostic capabilities. Highlight of novelty: This review uniquely emphasizes the latest advances in targeted quantum dots (TQDs), particularly in surface functionalization, hybrid nanostructures, biodistribution, and multimodal theranostic applications, providing an updated perspective that extends beyond conventional QD-based cancer therapies. Full article

Background/Objectives: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of motor function, which affects mobility and leads to secondary complications, including altered dietary intake due to dysphagia, fatigue, and hypermetabolism, particularly affecting vitamin consumption, which are essential micronutrients for neuromuscular performance. The specific relationship between vitamin intake and muscle activation is not well understood in patients with ALS; thus, it is relevant to identify blood biomarkers that reflect muscle status. Methods: A cross-sectional study was conducted with 61 patients with bulbar- or spinal-onset ALS. The dietary intake of B vitamins (B1, B2, B6, B12, folate, and niacin); vitamins C, A, D, and E; and the B6/protein ratio were assessed using a seven-day dietary record and a Food Frequency Questionnaire. Blood concentrations of butyrylcholinesterase (BuChE), albumin, haptoglobin, C-reactive protein (CRP), and paraoxonase 1 (PON1) were determined. Basal muscle activation was measured using surface electromyography of the biceps brachii, triceps brachii, rectus femoris, and tibialis anterior muscles. Two confirmatory predictive models were developed to evaluate the effects of muscle damage and vitamin intake on muscle strength. Results: Arm muscle activation was negatively predicted by the B6/protein ratio (β = −0.33). Leg activation was positively predicted by vitamin B9 (β = 0.39) and B6/protein (β = 0.17) and negatively predicted by vitamin A (β = −0.24). For biomarkers, albumin (β = 0.18) and PON1 (β = 0.28) positively predicted activation. For legs, albumin predicted activation (β = 0.31), whereas BuChE and haptoglobin predicted negative activation (β = −0.32 and β = −0.15, respectively). Conclusions: Weak associations were observed in patients with ALS: vitamin B9 intake showed a modest association with leg activation, the B6/protein ratio exhibited inconsistent associations across muscle groups, and vitamin A showed a negative association with leg activation. Albumin demonstrated the most consistent association as a potential biomarker of muscle function. These findings are exploratory and require validation in larger, longitudinal studies. Full article

Objectives: The aim of this study was to assess nutrient intake among individuals adhering to the Christian Orthodox Church (COC) fasting and to investigate potential differences in dietary intake according to Body Mass Index (BMI) classification. Methods: This cross-sectional study enrolled participants through announcements at public universities, churches, and monasteries, targeting both urban and religious adult populations. A total of 228 adults with a BMI exceeding 25 kg/m² were enrolled. Of these, 121 had followed COC fasting practices for at least 10 years or since childhood, while 107 non-fasters were age-matched. Exclusion criteria included age under 18 years, refusal to provide consent, absence from measurements, non-communicable diseases, food allergies, pregnancy, or lactation. Results: Overweight and obesity rates were similar in both groups. Furthermore, there were no statistically significant differences in body composition measurements [body fat %, fat mass (kg), fat free mass (kg), waist circumference]. Diastolic and systolic blood pressure was significantly higher in non-fasters. Non-fasters reported higher intake of sugar, dietary protein, fats (saturated and polyunsaturated), and cholesterol. Fasters consumed lower amounts of vitamin A, vitamins B (B2, B3, B6, B12, folate, pantothenic acid), iron, phosphorus, sodium, zinc, and calcium. Serum folic acid levels were higher, and fasting glucose and phosphorus levels were lower in fasters. Distinct dietary patterns were observed between groups, with fasters consuming more fish and traditional plant-based foods, while non-fasters consumed higher amounts of meat, dairy products, and alcohol. Conclusions: COC fasting is associated with favorable dietary and metabolic profiles, including improved glucose regulation. However, its impact on weight status appears limited. Full article

Background: Peripheral neuropathy (PN) represents a considerable and rapidly growing global health burden, with diabetic PN alone impacting nearly half of diabetic patients. Evidence from experimental studies highlighted that folate supplementation may protect nerve health by supporting myelin maintenance, minimizing oxidative stress, and enhancing neurotrophic factors. Nevertheless, its clinical efficacy and safety in managing PN have not yet been established. This study seeks to evaluate the role of folate in managing PN regarding the efficacy and safety endpoints. Methods: Up to July 2025, a comprehensive search of four electronic databases, encompassing PubMed, Scopus, Web of Science, and Cochrane Library, was executed, collecting studies evaluating the folate in managing PN. Outcomes included pain scores, symptom improvement endpoints, Neuropathy Total Symptom Score (NTSS) scores, epidermal nerve fiber density (ENFD), biomarkers, and side effects. Results: The narrative synthesis demonstrated consistent symptomatic benefits with pain reductions reaching 3 points, with symptom resolution rates of 87.5% and NTSS-6 score enhancements varying from 0.9 to 1.5 points. Notably, objective structural improvements in ENFD were observed, with increases reaching 97%. Furthermore, folate showed an excellent safety and tolerability profile with only one adverse event reported among 1367 individuals. Folate significantly decreased homocysteine and high-sensitivity C-reactive protein (hs-CRP) levels. Conclusions: Folate showed promising symptomatic benefits for peripheral neuropathy, with objective structural improvements (ENFD) and favourable biomarker changes (homocysteine, hs-CRP reduction), with an excellent safety profile. Full article