Search Results (5,201)

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by a block of differentiation and uncontrolled expansion of myeloid progenitor cells. Standard treatment includes intensive induction chemotherapy, typically with cytarabine and anthracycline, followed by consolidation chemotherapy or allogeneic hematopoietic stem cell transplantation. However, these approaches are often associated with relapse and treatment-related toxicity. Accumulating evidence highlights a critical role for epigenetic dysregulation in driving disease initiation, progression, and therapeutic resistance. In this review, we examine an integrated framework of epigenetic regulation in AML, encompassing DNA methylation, histone post-translational modifications, chromatin remodeling, and RNA-mediated epigenetics. We discuss how alterations in key epigenetic regulators, such as DNMT3A, TET2, IDH1/2, EZH2, and histone-modifying enzymes, reshape the transcriptional and epigenetic landscape of leukemic cells. Particular emphasis is placed on epigenetically defined AML subtypes, including NPM1-mutated, DNMT3A-mutated, and KMT2A-rearranged AML, which illustrate distinct mechanisms of transcriptional and epigenetic dysregulation and confer unique therapeutic vulnerabilities. We further summarize current and emerging therapeutic strategies, ranging from conventional chemotherapy to molecularly targeted agents, epigenetic drugs, and immunotherapeutic approaches. Despite these advances, durable responses remain limited, highlighting the need to better understand epigenetic mechanisms to overcome resistance and improve patient outcomes. Full article

Oral squamous cell carcinoma (OSCC) remains a major global health burden with limited improvement in survival rates. While traditional risk factors such as tobacco and alcohol are well established, increasing evidence highlights the role of the oral microbiome in carcinogenesis. Among microbial species, Candida albicans (C. albicans) has emerged as a potential contributor to tumor-promoting processes. Clinical studies consistently report increased fungal colonization in oral potentially malignant disorders and OSCC, with associations to disease severity and recurrence. Mechanistically, C. albicans contributes to carcinogenesis through acetaldehyde production, chronic inflammation, oxidative stress, epithelial signaling modulation, and extracellular vesicle (EV)-mediated communication. These pathways promote tumor microenvironment remodeling and epithelial transformation. However, conflicting evidence exists regarding causality, suggesting that fungal colonization may also result from tumor-associated ecological changes. From a translational perspective, C. albicans and EV-associated signatures may represent promising biomarkers and therapeutic targets, although further validation is required. This review highlights the emerging role of fungal–host interactions in OSCC and underscores their potential in microbiome-informed precision oncology. Full article

The cell secretome includes extracellular vesicles (EVs), nanoscale lipid bilayer-enclosed particles that carry diverse bioactive cargos, including proteins, lipids, and nucleic acids. As key mediators of paracrine signaling, EVs reflect the molecular and functional characteristics of their parent cells and play critical roles in regulating tissue homeostasis and regeneration. Growing evidence supports their therapeutic potential across a wide range of diseases. However, the clinical translation of EV-based therapies remains limited by challenges related to yield, purity, targeting specificity, and functional consistency. Recent advances in biomimetic culture systems—particularly three-dimensional (3D) platforms that recapitulate features of the native extracellular matrix microenvironment—have demonstrated a strong influence on cell phenotype, secretory activity, and EV composition. This review highlights how biochemical and mechanical cues within 3D culture systems regulate EV biogenesis, cargo loading, and functional outcomes and discusses their implications for improving the scalability, efficacy, and clinical translation of EV-based therapeutics. Full article

The genus Epimedium L. comprises a group of perennial herbs widely distributed across East Asia, with five representative species that include Epimedium grandiflorum C. Morren, Epimedium brevicornu Maxim., Epimedium sagittatum (Sieb. et Zucc.) Maxim., Epimedium koreanum Nakai. and Epimedium pubescens Maxim. For centuries, these species have been used in traditional Chinese medicine for their aphrodisiac, anti-osteoporotic and estrogen-like properties in the treatment of erectile dysfunction, osteoporosis, rheumatoid arthritis and menopausal symptoms. The aim of this review is to present an extensive and updated synthesis of the phytochemistry, biological activities and therapeutic properties of these five species by examining the relationship between the phytochemical composition and their pharmacological properties. Phytochemical analyses indicate that Epimedium spp. are defined by their significant content of prenylated flavonol glycosides, including icariin, icaritin, icariside, baohuoside and epimedin A-C. Recent studies have confirmed that these compounds are responsible for the genus’ therapeutic potential. They possess a variety of effects, ranging from aphrodisiac and antioxidant properties to anti-inflammatory and immunomodulatory activities, as well as neuroprotective, cardioprotective and anticancer benefits. Although preclinical findings are increasingly compelling, robust clinical evidence is still lacking for all five species. Taken together, the data summarized here position Epimedium spp. as a valuable source of bioactive prenylated flavonoids, while underscoring that standardized methodologies and rigorous clinical trials are essential to translate this potential into validated therapeutic applications. Full article

Type 1 diabetes mellitus (T1DM) is characterized by autoimmune β-cell destruction and absolute insulin deficiency. While insulin remains the cornerstone of treatment, the adjunctive use of oral hypoglycemic agents (OHAs) has been explored, though clinical evidence in T1DM remains sparse. Mitochondrial dysfunction is increasingly recognized in the pathogenesis and complications of T1DM, and some OHAs are known to modulate mitochondrial pathways, primarily studied in type 2 diabetes mellitus. This review aimed to synthesize existing evidence regarding the roles of OHAs in T1DM, with a specific focus on their potential impact on mitochondrial function. Following PRISMA guidelines, eligible studies investigating mitochondrial dysfunction in T1DM or the effects of OHAs on mitochondrial function in T1DM were included. Of 997 articles screened, 24 studies met inclusion criteria. Twenty studies described the mechanisms of mitochondrial dysfunction in T1DM, highlighting oxidative stress, impaired ATP production, disrupted proteostasis, apoptosis, and altered mitochondrial dynamics. Four preclinical studies suggested that metformin and empagliflozin may improve mitochondrial quality control in an adenosine monophosphate-activated protein kinase (AMPK)-dependent manner by enhancing biogenesis and preventing mitochondrial fission in T1DM. Certain OHAs may modulate mitochondrial dysfunction in T1DM, but clinical translation remains speculative and requires further investigation regarding their potential as adjunctive therapy. Full article

Against the background of cultural consumption and the digital communication of cultural heritage, this study examines how regional cultural resources can be translated into recognizable, understandable, and shareable visual expressions in traditional food packaging. Using Huizhou architectural cultural genes and Huangshan sesame cake packaging as the research context, AI-assisted design was employed to generate packaging stimuli. A semiotics-based structural model was then developed to explore how visual symbol perception influences purchase and dissemination intentions through cultural cognition and cultural identity. Based on 287 valid responses and PLS-SEM analysis, the results show that perceptions of architectural form, color, and AI-assisted design significantly enhanced cultural cognition; graphic symbol perception showed only a weak or marginal effect, whereas structure and style perception did not show a significant effect. Cultural cognition strengthened cultural identity, which further promoted purchase and dissemination intentions. The findings provide consumer-level evidence that AI-assisted visual translation of regional architectural heritage in traditional food packaging may support potential cultural communication at the levels of consumer perception and behavioral intention by enhancing cultural cognition and cultural identity. Full article

The skin is the largest organ of the human body and acts as a major protective barrier against external agents. However, the highly organized stratum corneum limits the effective delivery of many therapeutic compounds, especially hydrophilic and high-molecular-weight drugs. Conventional topical formulations often exhibit poor permeability, low bioavailability, and limited targeting efficiency. This review discusses recent advances in nanotechnology-based drug delivery systems, including bio-based, biodegradable, and biocompatible polymeric nanocarriers for dermal and transdermal applications, with particular emphasis on vesicular, polymeric, and hybrid nanosystems. Nanocarriers such as liposomes, ethosomes, transfersomes, polymeric nanoparticles, micelles, nanogels, and lipid–polymer hybrid systems have demonstrated improved drug solubility, stability, controlled release, and skin permeation for localized (dermal) delivery compared with conventional formulations. In addition, biodegradable polymeric materials enhance dermal deposition and prolong drug retention, leading to improved therapeutic efficacy. These nanosystems can facilitate enhanced transdermal drug transport under optimized conditions; however, the extent of systemic delivery varies widely depending on drug physicochemical properties, formulation characteristics, and application conditions. Drug transport may occur through intercellular, transcellular, and follicular pathways, resulting in enhanced bioavailability and site-specific delivery. Claims regarding transdermal (systemic) absorption are restricted to cases supported by in vivo or clinical evidence. Furthermore, combining nanocarriers with microneedles and stimuli-responsive platforms has expanded the potential for controlled and on-demand transdermal delivery. Recent preclinical and clinical studies have reported that nanocarrier-based methotrexate gels reduced PASI-like scores by over 70% in psoriatic models, while oleic acid vesicle formulations achieved more than 95% cure rates in rodent models of tinea corporis. Despite these advances, challenges related to large-scale production, stability, regulatory approval, and clinical translation remain significant. Future developments integrating smart nanocarriers, bio-based polymeric biomaterials, wearable technologies, and AI-assisted design may improve personalized dermatological therapies. These innovations in nanocarrier drug delivery are accelerating the translation of advanced therapies to the clinic, promising safer, more effective and personalized dermatological treatments. Full article

ICU-acquired weakness (ICUAW) is a clinical condition characterized by muscle weakness in critically ill patients that is not directly attributable to the underlying illness. It affects approximately 40% of intensive care unit patients, primarily impairing the limbs and respiratory muscles, and can compromise motor and respiratory function even after recovery from acute illness. ICUAW exhibits heterogeneous phenotypes. In addition, diverse risk factors influence its occurrence. Although this condition is recognized, the underlying mechanisms contributing to critical illness-associated muscle dysfunction remain poorly understood and are likely interrelated. This review summarizes the current experimental evidence from translational studies involving diverse muscle biopsies under various conditions, providing insights into normal skeletal muscle physiology and its alterations in critical illness-associated muscle dysfunction. Here, we focus on muscle ultrastructure, mitochondrial function, atrophy, protein breakdown, inflammation, and key molecular pathways, with consideration of the proposed role of NLRP3 inflammasome signalling, for which direct experimental evidence in human skeletal muscle during critical illness remains limited and constitutes a priority area for future mechanistic research. Full article

Background: Heritable thoracic aortic disease (HTAD) encompass a heterogeneous spectrum of conditions characterized by increased susceptibility to developing thoracic aortic aneurysm and life-threatening complications, including aortic dissection and rupture. Despite distinct underlying mechanisms involving extracellular matrix integrity, vascular smooth muscle cell function, and dysregulation of signaling pathways, these disorders converge on a shared vulnerability of the aortic wall. Although acute events typically occur in adulthood, the disease process often begins early in life, making HTAD highly relevant in pediatric practice, where early recognition and longitudinal management are essential. Aims: This narrative review provides a biology- and genetics-oriented, translational complement to current consensus recommendations, framing pediatric HTAD as a developmentally shaped disorder of the aortic wall in which genotype increasingly informs diagnosis, surveillance, and treatment. Methods: Relevant studies were identified through a comprehensive PubMed search, with particular focus on pathogenic mechanisms, current clinical guidelines, follow-up strategies and emerging genetic perspectives. Results: Genetic testing is emerging as a key tool for the management of HTAD, although its clinical utility remains limited by provisional genotype–phenotype correlations and inconclusive results. Current risk stratification is still mainly based on aortic diameter surveillance, while pharmacological strategies are predominantly extrapolated from Marfan syndrome trials, highlighting important gaps in evidence. Conclusions: Genetic advances are expanding management opportunities in HTAD, but their clinical translation remains challenging. Disease-specific risk models integrating genetic and clinical data may improve individualized risk stratification, treatment strategies and clinical outcomes. Full article

Neuroinflammation plays an essential role in the pathogenesis of several associated brain diseases, including neurodegenerative disorders (Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS)), and traumatic brain injury (TBI). In these diseases, persistent microglial and astrocyte aggregates, elevated proinflammatory cytokines, and oxidative stress drive neuronal injury and cognitive disability. Rho GTPases, in particular the Rho family members Ras homolog family member A (RhoA), Ras-related C3 botulinum toxin substrate 1 (Rac1), and cell division control protein 42 homolog (CDC42), regulate neuroinflammation, cytoskeletal dynamics, immune responses, and the maintenance of BBB integrity. These proteins are involved in many neuropathological diseases due to dysregulation, making them interesting therapeutic targets. Bioactives used in herbal care have attracted interest for their ability to influence neuroinflammation and even their anti-neurodegenerative activity. Studies show that flavonoids, alkaloids, polyphenols, and other botanical compounds alter Rho GTPase activity, which, in turn, leads to decreased inflammation. This review critically summarizes current evidence regarding phytochemical regulation of Rho GTPase signaling in neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), with particular emphasis on the underlying molecular mechanisms, context-dependent signaling responses, and current translational challenges. Furthermore, existing knowledge gaps and future research priorities are discussed to facilitate the development of mechanism-based therapeutic strategies targeting Rho GTPases. Full article

Designing consumer products with lower environmental impact and acceptable cost requires designers to interpret life-cycle evidence across competing alternatives. This study compares two contrasting weighting approaches for multi-criteria decision-making in sustainability-focused consumer product design: the stakeholder-preference-driven Analytic Hierarchy Process (AHP) and the data-driven Criteria Importance Through Intercriteria Correlation–Technique for Order of Preference by Similarity to Ideal Solution (CRITIC–TOPSIS) method. An electric-bike case study was constructed from 24 feasible configurations defined by frame material, battery type, tire material, and coating method. Environmental performance was quantified using Life Cycle Assessment (LCA) with ReCiPe midpoint indicators, and economic performance was represented using a component-level life-cycle cost proxy. The methods identified broadly similar high- and low-performing regions of the design space, but they differed in the ranking of specific alternatives. Statistical comparison showed strong agreement among the ranking methods, although differences remained in the exact ordering of some alternatives. These findings show that weighting methods do not determine product sustainability on their own; rather, they shape how environmental and economic evidence is translated into design decisions. For consumer product development, AHP is useful when stakeholder priorities must be made explicit, whereas CRITIC–TOPSIS is advantageous when repeatable data-driven screening is needed. Full article

Edible coatings are widely studied as food-compatible formulations for reducing moisture loss, oxidation, microbial spoilage, oil uptake, and quality deterioration. Their translation from laboratory formulation to industrial use, however, depends not only on film-forming composition but also on controlled deposition, retained dose, surface coverage, drying history, defect formation, hygienic operation, and reproducible performance on heterogeneous food surfaces. An OpenAlex-supported evidence-map audit (2014–2026) was used to separate direct food-coating validation from adjacent engineering models. This review reframes edible coatings as engineered deposited interfaces and proposes a claim-controlled, evidence-tiered framework linking food-grade biopolymer fluids, processability, atomization, droplet impact, wet-film evolution, dry-film structure, image-based metrology, multiphase modeling, and food-performance endpoints. This review outlines the prerequisites for future digital-twin-ready edible coating workflows by linking functional biopolymer fluids, deposition technologies, droplet physics, intelligent image metrology, Computational Fluid Dynamics (CFD), Volume of Fluid (VOF), uncertainty reporting, food-performance endpoints, safety, Life-Cycle Assessment (LCA), Techno-Economic Analysis (TEA) and patent-aware innovation. Digital twins are treated as a future integration target that depends on validated inputs, standardized reporting, deposition metrology and food-specific model validation. The central argument is that progress in edible coatings requires fewer isolated formulation claims and stronger validated links between deposited-interface properties and food-relevant function. A minimum reporting checklist is proposed to support reproducible comparison of deposition routes, coating structures, and translation potential. Full article

Introduction: Work-related musculoskeletal disorders are common among nursing staff and may affect functionality, psychological well-being, and work performance. Brief, culturally adapted, and psychometrically sound instruments are needed to characterize musculoskeletal risk in occupational settings. This study aimed to translate, culturally adapt, and examine the structural validity and internal reliability of the abbreviated version of the Örebro Musculoskeletal Screening Questionnaire in Peruvian nurses with musculoskeletal symptoms. Methods: An instrumental, cross-sectional study was conducted with a sample of 170 Peruvian nurses. The Spanish-adapted version of the ÖMSQ-12S was administered. Descriptive statistics, corrected item-total correlations, confirmatory factor analysis using the robust maximum likelihood estimator, internal reliability through Cronbach’s alpha and composite reliability, convergent validity through average variance extracted, and discriminant validity using the Fornell–Larcker criterion were analyzed. Results: The original three-dimensional 12-item model showed inadequate fit: χ²(51) = 276.301, CFI = 0.713, TLI = 0.628, RMSEA = 0.161, and SRMR = 0.190. Due to low and divergent factor loadings, a refined 11-item, four-factor solution was evaluated: functionality/satisfaction, fear-avoidance, psychological aspects, and characteristics of the musculoskeletal problem. This model showed better fit: χ²(37) = 58.190, CFI = 0.971, TLI = 0.957, RMSEA = 0.058, and SRMR = 0.039. Reliability was adequate across all factors (α = 0.773–0.893; CR = 0.779–0.895). Convergent validity was acceptable in most dimensions, although discriminant validity was limited between psychological aspects and characteristics of the musculoskeletal problem. Conclusions: The ÖMSQ-11S showed preliminary evidence of structural validity and internal reliability in Peruvian nurses with musculoskeletal symptoms. However, its use as a predictive tool or universal occupational screening instrument requires further studies with longitudinal designs, more heterogeneous samples, and external clinical or occupational criteria. Full article

Rufinus’ Latin translation preserves Origen’s tenth homily on Leviticus as a sermon on the Day of Atonement fast and the goat sent into the wilderness. The homily begins from Leviticus 16, reads the two-goat rite through Christ’s passion, and brings Matthew 6 into the practice of Christian fasting before giving the command Ieiuna ab omni peccato, “Fast from every sin.” In the transmitted Latin order of Hom. Lev. 10.2, that command is plainly moral, but the clauses that follow give the moral exhortation an alimentary form: cibus malitiae, epulae voluptatis, vinum luxuriae, panes furtivos perversae doctrinae, and fallaces philosophiae cibos. The Christian is warned against what may be taken in, desired, or allowed to form judgment. Proverbs 4 and 9 provide a sapiential setting for this food-language, while the Rufinus-transmitted Commentary on the Song of Songs offers closer Origenian evidence for the association of food, wine, doctrine, knowledge, false knowledge, and destructive teaching. The homily then returns to bodily fasting: scheduled fasts, continentia ventris et gutturis, the cutting away of ciborum affluentia, and the fast undertaken to feed the poor. Christian fasting is presented as a discipline of reception, refusal, bodily restraint, and care for another person’s hunger. Full article

Background/Objectives: eccDNA is a promising cancer biomarker in liquid biopsy. However, the reliability and reproducibility of eccDNA studies rely on the standardization of pre-analytical handling and processing of eccDNA, as well as transparent methodological reporting. Although evidence-based guidelines for cell-free DNA handling provide clear recommendations for plasma/serum processing, the extent to which eccDNA studies report and adhere to these key procedures remains uncertain. Methods: We systematically reviewed 14 studies (2017–2025) assessing eccDNA in plasma or serum from cancer patients. Each study was evaluated against 22 checklist items summarized from the NCI Biospecimen Collection and Processing Guideline, categorized into biospecimen collection, blood processing, and eccDNA processing. Items were classified as “reported,” “not reported,” or “deviated from NCI guideline,” and missing/deviation rates were calculated. Results: Publication was largely post-guideline (13/14 after 2020). Reporting gaps were widespread. Items with 100% missing were venipuncture site (14/14), freeze–thaw cycles (14/14), and fitness for downstream analysis/pre-assay QC (14/14). Other frequently missing elements included blood volume (10/14; 71%), collection tube type (7/14; 50%), date/time from draw to processing (11/14; 79%), second centrifugation parameters (8/14; 57%), storage temperature before freezing (6/14; 43%), frozen storage duration (13/14; 93%), and post-thaw handling (13/14; 93%). By contrast, the extraction method was consistently reported (0% missing), and most reported quantification (21% missing). Deviations from the NCI guideline were uncommon when items were reported, such as a blood processing delay (2/14; 14%) and the use of circulating nucleic acid kits for eccDNA extraction (1/14; 7%). Conclusions: Inconsistent reporting of pre-analytical procedures limits the reproducibility, transparency, and clinical translation of eccDNA research. We propose a concise reporting checklist informed by the NCI guideline. By focusing on the most frequently underreported aspects of key pre-analytical eccDNA procedures, the checklist provides researchers with an efficient and succinct methodological reporting framework that will enhance transparency and promote standardization in future eccDNA studies. Full article