Search Results (1,433)

Vitamin K is a fat-soluble vitamin essential for the activation of vitamin K-dependent proteins involved in coagulation and other physiological processes. Neonates are particularly vulnerable to vitamin K deficiency due to limited placental transfer, low hepatic stores, immature liver function, and insufficient dietary intake, especially in exclusively breastfed infants. This review summarizes the biochemistry and pharmacokinetics of vitamin K, focusing on their role in the pathogenesis of late vitamin K deficiency bleeding (VKDB), including intracranial hemorrhage in early infancy. The limitations of conventional coagulation tests are discussed, highlighting the importance of functional biomarkers such as PIVKA-II (Proteins Induced by Vitamin K Absence or Antagonist-II) for the early detection of subclinical deficiency. Despite effective prophylaxis at birth, late VKDB cases still occur, likely due to declining vitamin K levels over time and nutritional factors. These findings underscore the need for prolonged vitamin K supplementation following adequate prophylaxis at birth, particularly to protect high-risk newborns from late VKDB. Strategies may include vitamin K-containing multivitamin supplementation in preterm infants, as well as daily oral vitamin K supplementation (150 µg/day) in exclusively breastfed infants, in order to ensure adequate vitamin K status during early infancy. Full article

Background: Lower limb arterial calcification (LLAC) is a robust imaging biomarker of peripheral artery disease (PAD) severity. Vitamin K antagonists are presumed to accelerate cardiovascular calcification. Direct oral anticoagulants (DOACs) may influence vascular calcification differently, but lower limb data are limited. Methods: We performed a single-center retrospective cross-sectional study comparing LLAC on clinically acquired non-contrast CT between DOAC users and controls without anticoagulation. Patients were propensity score-matched 1:1 (48 DOAC vs. 48 control; n = 96) using baseline clinical covariates. Associations between LLAC scores and perioperative or cardiovascular events were assessed. Segment-specific LLAC was quantified on non-contrast CT and normalized for arterial segment length. A prespecified exposure–duration sensitivity analysis compared the outcomes in patients with ≥5 years of continuous DOAC therapy (n = 22) versus matched controls. Results: In the matched cohort, total LLAC scores did not differ significantly between DOAC and control groups (infrarenal aorta: median 7596.0 vs. 8637.0 (p = 0.487), iliac segment: median 5689.5 vs. 5193.5 (p = 0.602). However, in patients with ≥5 years of DOAC use, LLAC scores were significantly lower in proximal segments: infrarenal aorta median 5593.5 vs. 11,185.0 (p = 0.001997) and iliac arteries 5624.5 vs. 11,501.0 (p = 0.001867)). Higher LLAC was associated with major adverse cardiovascular events (such as myocardial infarction, stroke, or significant bleeding) in controls (p = 0.0023) but not in DOAC-treated patients. Conclusions: In this propensity-matched, cross-sectional CT study, long-term DOAC exposure was associated with lower proximal LLAC scores in a small duration-defined subgroup, while the primary matched analysis showed no overall difference in total LLAC scores. Because baseline (pre-DOAC) imaging was unavailable and residual confounding/survivor bias is possible, these findings should be considered hypothesis-generating and require prospective validation. The cohort reflected a mixed lower-extremity vascular population rather than exclusively classic chronic atherosclerotic PAD, which may limit biological interpretation and generalizability. Full article

Background/Objectives: Obesity in young adults is a major public health concern and a key contributor to cardiometabolic risk. Vitamin K2 (VK2) has been proposed as a potential adjuvant therapy; however, evidence from randomized controlled trials remains limited. This study evaluated the effect of VK2 supplementation on cardiometabolic risk factors in young adults with overweight or obesity. Methods: In this 12-week randomized, double-blind, placebo-controlled trial (NCT05995522), men and women aged 18–35 years with overweight or obesity (BMI 25–40 kg/m²) were assigned to receive VK2 (menaquinone-4, 100 µg/day) or placebo. Both groups received standardized nutritional counseling. Body composition, blood pressure, glucose homeostasis, lipid profile, and vitamin K-dependent proteins were assessed at baseline and post-intervention. Between-group differences were analyzed using ANCOVA adjusted for baseline values. Results: Forty-six participants completed the study (placebo n = 24; VK2 n = 22). VK2 supplementation significantly reduced total cholesterol (−10.64 mg/dL, p = 0.038) and LDL cholesterol (−6.12 mg/dL, p = 0.005) compared with placebo. A reduction in systolic blood pressure showed a trend toward significance (−5.56 mm Hg, p = 0.067). No significant effects were observed on body composition, glucose metabolism, or vitamin K-dependent proteins. Conclusions: VK2 supplementation resulted in improvements in total and LDL cholesterol levels, with no significant changes in vitamin K-dependent proteins, and may represent a safe and potentially beneficial adjunct to nutritional strategies aimed at early cardiometabolic risk modulation. Full article

Gla-rich protein (GRP), also known as UCMA, is a vitamin K-dependent protein that has emerged as an important regulator of pathological calcification and inflammation. Vascular calcification is a major complication of chronic kidney disease and cardiovascular disorders and is now recognized as an active and tightly regulated process rather than a passive accumulation of minerals. Increasing evidence indicates that GRP plays a protective role in mineral homeostasis through its strong calcium-binding capacity and its dependence on vitamin K-mediated gamma carboxylation. This work represents a comprehensive narrative review aimed at summarizing and critically discussing the current scientific knowledge on GRP. Available experimental and clinical data are analyzed with respect to gene expression, molecular regulation, vitamin K dependency, and underlying mechanisms of action. Particular emphasis is placed on the dual function of GRP in inhibiting ectopic calcification and modulating inflammatory responses. The evidence linking altered GRP levels or changes in its carboxylation status with chronic kidney disease, vascular calcification, calcific aortic valve disease, osteoarthritis, and tumor-associated microcalcifications is systematically examined. Current findings collectively support the concept that GRP is a multifunctional protein operating at the interface of mineral metabolism, inflammation, and tissue remodeling. Despite promising experimental data, important knowledge gaps remain, including the absence of standardized assays capable of distinguishing different GRP forms and the lack of longitudinal clinical studies evaluating its predictive value. This manuscript highlights the potential of GRP as a biomarker of disturbed mineral homeostasis and cardiovascular risk, while emphasizing the need for further research to clarify its precise biological functions and clinical relevance. Full article

Background/Objectives: Vascular calcification and arterial stiffness are common in chronic kidney disease (CKD). Gla-rich protein (GRP) is a vitamin K-dependent protein implicated in mineral biology, but clinical evidence across CKD stages is limited. We evaluated associations of serum GRP with vascular calcification (VC) burden and arterial stiffness across CKD stages, including hemodialysis, compared with controls. Methods: In this prospective observational study, 185 adults were enrolled: controls (n = 61), individuals with CKD stage IIIb–IV (n = 61), and individuals with CKD stage V on hemodialysis (HD) (n = 63). Abdominal aortic calcification was assessed by the Kauppila score, and arterial stiffness was assessed by oscillometric pulse wave velocity (PWV). Serum GRP, FGF-23, and β-Klotho (KLb) were measured by ELISA. Non-parametric group comparisons and Bonferroni-corrected Spearman correlations were used. Results: GRP differed across groups (p < 0.001), showing a non-linear pattern with the lowest values in CKD IIIb–IV. PWV and Kauppila score increased across CKD stages (both p < 0.001). After Bonferroni correction, GRP correlated with KLb (ρ = 0.720) and FGF-23 (ρ = 0.625), but not with PWV or Kauppila score. In multivariable analyses, GRP showed a statistically significant but modest association with PWV and Kauppila score. Conclusions: In this CKD spectrum cohort, serum GRP was associated with CKD-MBD biochemical markers (KLb and FGF-23) much more strongly than with vascular phenotypes; its associations with vascular calcification burden and arterial stiffness were modest in multivariable modelling, supporting GRP as a marker of the CKD-MBD biochemical profile rather than a strong surrogate of vascular phenotype. Full article

Background/Objectives: Atrial fibrillation (AF) is highly prevalent among older adults and is associated with increased thromboembolic risk. Although anticoagulant therapy (AC) is strongly recommended, its use in elderly and multimorbid patients remains suboptimal. This study aimed to describe long-term trends in AC prescribing patterns among hospitalized older patients with AF. Methods: We conducted a retrospective observational analysis using data from the Italian REPOSI registry, including patients aged ≥65 years hospitalized with AF between 2010 and 2023. AC at admission and discharge was analyzed, including vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs), and antiplatelet agents. Temporal trends, admission-to-discharge treatment changes, and patient characteristics associated with therapy modification were assessed descriptively. Results: The study included 2061 AF patients, characterized by multimorbidity and high thromboembolic risk. A marked shift from VKAs to DOACs was observed over time. However, a substantial proportion of cases remained without AC or received only antiplatelet therapy at both admission and discharge, with untreated individuals being generally older and more clinically complex. DOAC use increased steadily but showed a slight decline at discharge after 2020. Clinical variables available in the registry only partially explained AC changes during hospitalization. Conclusions: Despite increasing adoption of DOACs, AC underuse remains frequent among elderly hospitalized patients with AF. These real-world data highlight persistent challenges in AC management in complex older adults and underscore the need for more comprehensive clinical information and data-driven tools to support individualized therapeutic decision-making. Full article

Second-generation anticoagulant rodenticides (SGARs) were developed to overcome warfarin resistance in rodent populations; however, their prolonged hepatic retention has raised concerns regarding secondary poisoning of non-target wildlife. All major SGARs exist as cis–trans isomeric pairs, and differences in biological half-life between isomers have been reported, yet the molecular basis for such isomer-dependent pharmacokinetic behavior remains poorly understood. In this study, we conducted an integrated evaluation of cis and trans isomers of SGARs using in vivo, in vitro, and in silico approaches, with vitamin K epoxide reductase (VKOR) serving as the molecular target. The individual compounds exhibited distinct isomer-dependent profiles in hepatic retention, inhibitory potency (IC₅₀), and VKOR interaction-related properties. Molecular dynamics simulations further revealed isomer-dependent differences in torsional flexibility around specific rotatable bonds and in ligand–VKOR interaction fractions. For flocoumafen and bromadiolone, the presence of an ether oxygen was associated with increased torsional and orientational flexibility and enhanced hydrogen-bonding potential, which may facilitate metabolic processing and contribute to the relatively faster elimination of cis isomers. Collectively, these results suggest that isomer-specific VKOR interaction patterns may contribute, in a compound-dependent manner, to isomer-dependent pharmacokinetic behavior, offering structural perspectives for the design of rodenticides with reduced ecological risk. Full article

Protease-activated receptor-1 (PAR-1) is a key regulator of mesenchymal stem cell (MSC) migration and tissue integration. Dabigatran, a direct thrombin inhibitor widely used as a non-vitamin K oral anticoagulant (NOAC), may affect PAR-1-mediated signaling pathways. This study investigated the effects of dabigatran on cell viability, apoptosis, and PAR-1 activity in adipose-derived MSCs (ADMSCs) in vitro. ADMSCs were exposed to five concentrations of dabigatran etexilate with thrombin activation. Cell viability was assessed using the MTT assay, apoptosis and morphological changes were evaluated via acridine orange/propidium iodide staining, and PAR-1 expression was analyzed by immunofluorescence. Results showed that high dabigatran concentration significantly reduced cell viability and induced apoptotic morphological changes. In contrast, lower, non-cytotoxic concentrations preserved normal fibroblastic morphology and maintained cell viability while reducing PAR-1 surface expression compared with thrombin-activated controls. These findings indicate that dabigatran at non-cytotoxic doses can modulate PAR-1 activity without compromising ADMSC survival. In conclusion, dabigatran influences MSC-related cellular functions beyond its anticoagulant properties. Full article

Currently, the main method for producing the vitamin C precursor 2-keto-l-gulonic acid (2-KLG) is a two-step fermentation process, in which secondary sterilization and fermentation processes result in higher costs and energy consumption. Consequently, the development of a one-step fermentation process is seen as a more desirable approach for 2-KLG production. In this study, we used Gluconobacter oxydans WTF0512 and Ketogulonicigenium vulgare WTF0114 as co-cultured strains for the production of 2-KLG from d-sorbitol via one-step fermentation. The fermentation behaviors of G. oxydans WTF0512 and K. vulgare WTF0114 were initially investigated. Subsequently, the fermentation process and medium were optimized, and the titer of 2-KLG reached 132.99 ± 0.52 g/L, with a molar conversion rate of 92.42%, which, to the best of our knowledge, is the highest production via one-step fermentation reported to date. These findings will provide a basis for developing a more economical large-scale one-step fermentation process for the production of 2-KLG. Full article

This study focuses on the production and characterization of polyvinyl alcohol (PVA)-chitosan (CS)-based nanoparticles loaded with vitamin E (VitE) and ephedrine (Ep) via electrospraying for intranasal drug delivery in narcolepsy treatment. The nanoparticles were successfully synthesized using optimized parameters (15.5 kV voltage, 0.3 mL/h flow rate, 25 G needle size, and 14 cm distance). Scanning electron microscopy (SEM) analysis confirmed the formation of spherical particles with an average size of 350–500 nm, while energy-dispersive X-ray spectroscopy (EDS) mapping revealed a homogeneous elemental distribution with oxygen (51.74%), silicon (24.48%), carbon (6.47%), zinc (6.08%), and aluminum (3.82%). Fourier-transform infrared (FTIR) spectra demonstrated the successful encapsulation of VitE and Ep through characteristic peaks at 3285 cm⁻¹ (OH stretching), 1731 cm⁻¹ (C=O stretching), and 1086 cm⁻¹ (C-O-C stretching). In vitro drug release analysis indicated a controlled and sustained release profile, with cumulative VitE and Ep release reaching 78.6% and 84.3%, respectively, over 48 h in phosphate-buffered saline (PBS, pH 7.4). Antioxidant activity assessment using the DPPH assay confirmed an R² value of 18.84 µg/mL, demonstrating significant free radical scavenging potential. The antibacterial activity, tested via the disk diffusion method, exhibited inhibition zones of 18.31 ± 5.8 mm (E. coli) and 21.51 ± 1.57 mm (S. aureus), confirming strong antimicrobial properties. These findings suggest that the developed electrosprayed PVA/CS nanoparticles loaded with VitE and Ep offer a promising intranasal delivery system with enhanced bioavailability, controlled release, antioxidant capacity, and antibacterial properties, making them a viable candidate for narcolepsy treatment. Full article

Background: The clinical outcomes of patients with intracranial haemorrhage (ICH) whilst using direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) are uncertain. This study aimed to assess outcomes and management in patients receiving DOACs compared with those receiving VKAs. Methods: In this retrospective study, patients hospitalised during the period from 1 January 2017 to 31 December 2023 for traumatic and non-traumatic ICH and using oral anticoagulants (OACs) were included. The primary outcomes were mortality and functional outcomes, as measured by the modified Rankin Scale (mRS) during admission and 90-day follow-up. ICH management and complications were studied and compared between the two OAC groups. Results: A total of 171 eligible patients were included, comprising 24 patients on DOACs and 147 patients on VKAs. Patients receiving DOACs were older (79.1 vs. 66.8, p < 0.001) and had a higher proportion of traumatic ICH (75.0% vs. 46.3%, p = 0.009) than those receiving VKAs. In-hospital and 90-day outcomes were not statistically different between the two groups, with an adjusted odds ratio (aOR) of 1.30 (0.39–4.36) for in-hospital mortality, p = 0.67, and an aOR of 0.89 (0.33–2.41) for mRS 0–2 at 90 days, p = 0.83. In total, 81.3% of patients received at least one reversal agent; fresh frozen plasma was commonly used in the VKA group (78.9% vs. 33.3%, p < 0.001), whereas prothrombin complex concentrate was significantly prescribed in patients with DOAC-associated ICH (29.2% vs. 3.4%, p < 0.001). Conclusions: Patients with DOAC-associated ICH had comparable in-hospital and long-term clinical outcomes to those with VKA use. Full article

Background and Objectives: Venous thromboembolic disease (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a major cause of morbidity and mortality worldwide and imposes a substantial financial burden on health systems due to both the direct and indirect costs of acute management and long-term complications. This systematic review aimed to assess patient satisfaction with anticoagulation therapy for VTE and to highlight potential differences according to the type of anticoagulant. The review focused on factors influencing the patient experience, such as perceived efficacy, ease of use, adverse effects, and health-related quality of life. Materials and Methods: A systematic review, without quantitative meta-analysis, was conducted in accordance with PRISMA 2020 guidelines. Articles were identified through searches in major databases (PubMed, Scopus, Cochrane Library and others) using keywords including “patient satisfaction”, “anticoagulation”, “venous thromboembolic disease”, and “quality of life”. In total, 21 studies published between 2009 and 2025 met the inclusion criteria. The studies assessed patient satisfaction with different types of anticoagulation, including vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs), and low-molecular-weight heparin (LMWH) injections. Results: Across the included studies, patients generally reported higher levels of treatment satisfaction with DOACs compared with VKAs, mainly due to the absence of routine laboratory monitoring and fewer dietary restrictions. However, satisfaction varied according to age, sex, and clinical status. In specific patient populations, such as those with cancer-associated thrombosis, factors including fewer drug–drug interactions and perceptions of safety with LMWH appeared to influence treatment choice and satisfaction. Adverse effects, particularly bleeding, were identified as major drivers of dissatisfaction. Several studies suggested that higher treatment satisfaction was associated with better adherence, while quality of life appeared to improve in patients treated with DOACs in comparison with VKAs. Conclusions: Patient satisfaction is a critical component of successful VTE management. Overall, DOACs appear to be associated with higher treatment satisfaction than traditional therapies such as VKAs, although further high-quality research is needed to individualise anticoagulation strategies. Systematic incorporation of patient-reported satisfaction into clinical decision-making and into international guidelines may improve adherence, enhance quality of life, and ultimately increase the effectiveness of anticoagulation therapy. Full article

Background/Objectives: Mild cognitive impairment (MCI), the prodromal stage of Alzheimer’s disease, may be influenced by nutritional status and genetic susceptibility. This systematic review synthesised evidence on how nutritional biomarkers interact with genetic variants, particularly APOE ε4, to influence cognitive outcomes in individuals with MCI. Methods: Following PRISMA 2020 guidelines, seven studies were included (three longitudinal, two randomised controlled trials, and two cross-sectional) involving adults aged ≥55 years with MCI. Nutritional exposures comprised plasma or serum concentrations of vitamins A, D, E, the vitamin B group, lipids, selenium, and ketogenic medium-chain triglycerides. Genetic risk was assessed primarily through APOE ε4 status. Risk of bias was assessed using RoB 2 and ROBINS-I, and certainty of evidence using GRADE. Due to heterogeneity in biomarkers, cognitive tools, and study designs, findings were synthesised narratively. Results: Across nutrient categories, higher concentrations of vitamin D, selenium, and antioxidants were associated with better cognitive outcomes. kMCT supplementation improved episodic memory and brain energy metabolism. Evidence for nutrient–gene interactions was mixed: APOE ε4 modified responses to vitamin B group and selenium but showed limited influence on vitamin D, lipids, or kMCT effects. Heterogeneity in biomarker assays, cognitive tools, and genetic stratification limited comparability across studies. Conclusions: Nutritional biomarkers appear to influence cognitive trajectories in MCI, and some associations may differ by APOE ε4 status. However, small samples and limited genetic stratification constrain interpretation. Future research should prioritise standardised biomarker measurement, genetically stratified cohorts, and individual participant data meta-analyses to clarify nutrient–gene interactions in MCI. Full article

Plant foods have been the cornerstone of human diets since ancient times, fueling civilization and shaping cultures. Plants became central to sustainable food systems, offering diverse and nutritious options for the future. Sea buckthorn (Hippophae rhamnoides L.) has attracted growing scientific interest due to the presence of bioactive compounds, polyphenols, fatty acids, phytosterols, carotenoids, vitamins, and minerals in its fruit, seeds, and leaves. Moreover, sea buckthorn exhibit antioxidant, anti-inflammatory, antimicrobial, antidiabetic, antihyperlipidemic, anticancer, hepatoprotective, neuroprotective, and metabolic regulatory properties supported by in vitro and in vivo models. The biological activity of these phytochemical compounds plays a crucial role in regulating the AMP-activated protein kinase (AMPK) and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathways, as well as pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), cell proliferation, and apoptosis. Furthermore, its potential against microbial growth, including S. aureus, S. epidermidis, S. intermedius, and S. pyogenes, among others, not only expands its applications in the pharmaceutical industry but also attracts researchers to incorporate it into food products. This could lead to the discovery of plant-based therapeutic products without significant adverse effects. However, further exploration of each component’s potential side effects is necessary to support the commercialization of formulated products in either the pharmaceutical or food industries, ensuring the highest safety standards for consumers. Including studies on bioavailability and pharmacodynamics could further strengthen the scientific evidence supporting the specific phytochemicals in sea buckthorn and their mechanistic interactions. Full article

Background: In Spain, the number of patients anticoagulated with vitamin K antagonists (VKAs) is high. Among them, poor adherence is common, which may be justified by a low level of knowledge, and could affect their quality of life. We analyzed treatment adherence, health-related quality of life, and knowledge level about treatment, and evaluated the possible influence of these factors on patients’ time in the therapeutic range while also studying potential differences between patients under routine monitoring or self-monitoring. Methodology: A cross-sectional descriptive study was conducted using three validated and cross-culturally adapted questionnaires to study therapeutic adherence, health-related quality of life, and knowledge level about VKA treatment in a sample of anticoagulated patients. Additionally, it was assessed whether they were self-monitoring or not; the Rosendaal Time in Therapeutic Range (TTRr) was also administered for each patient at the time of recruitment. Descriptive analysis of all variables was performed, and a logistic regression model was constructed to evaluate the possible interaction of variables. Results: Ninety-eight patients participated and were selected sequentially from those attending the oral anticoagulation clinic at Hospital Universitario Virgen de la Victoria in Malaga. Of these, 39 were men and 59 were women. The mean age of these participants was 60.62 years (SD 11.67). Sixty-six were under conventional monitoring and thirty-two followed the self-monitoring program. The DecaMIRT had a mean score of 39.22 (SD 8.57), the SF-12 mean score was 31.73 (SD 6.21), and the knowledge questionnaire’s was 14.2 (SD 2.6). The mean TTRr value was 63.88 (SD 22.99). Self-monitored patients showed better results in DECAMirt and knowledge. Discussion: Overall, patients included in the sample presented satisfactory values in these three questionnaires, which seems to indicate that this was a treatment-compliant group with a correct quality of life, and adequately informed about their treatment. Conclusions: The work of nurses responsible for these aspects appears crucial in achieving these results. We aim to extend this study by focusing on groups with poorer results to design specific activities that allow for improvement in care and, as much as possible, homogenize outcomes. For this purpose, we intend to use all available tools, including those derived from the use of health-oriented artificial intelligence. Full article