Search Results (51,399)

Background/Objectives: ATPase family AAA domain-containing protein 2 (ATAD2) is an oncogenic chromatin regulator that amplifies E2F/MYC transcriptional programs, yet direct modulators remain scarce. Arecoline (ARE), the primary alkaloid of the areca nut, is a known carcinogen but paradoxically exhibits context-dependent anti-proliferative activities. In this study, we resolve this paradox by defining ARE’s anti-cancer mechanism. Methods: Breast cancer cell proliferation and colony formation assays were performed to evaluate the anti-proliferative effects of ARE. Cell-cycle distribution was analyzed to determine phase-specific effects. Transcriptomic profiling was conducted to identify affected gene networks. An unbiased Cellular Thermal Shift Assay–Mass Spectrometry (CETSA-MS) screening was used to identify direct protein targets, followed by CETSA–Western blotting for validation. Finally, in silico structure-based design was applied to generate novel derivatives with improved predicted properties. Results: ARE suppressed breast cancer cell proliferation and colony formation by inducing G1/S phase arrest. Transcriptomic analysis revealed that this phenotype was driven by profound suppression of the E2F/Cell Cycle gene network. CETSA-MS identified ATAD2 through multi-omics convergence, as the 67 direct targets were collectively most significantly enriched in the E2F pathway. CETSA–Western blotting confirmed that ARE binds and thermally stabilizes ATAD2. Mechanistically, ARE engagement of ATAD2 led to downregulation of key downstream proteins, including MYC and Cyclin D1, directly linking target modulation to G1/S arrest. Structure-based design further yielded novel derivatives with predicted enhanced ATAD2 binding and substantially reduced toxicity. Conclusions: Together, these findings uncover ATAD2 as a druggable target of ARE, establish proof-of-concept for repurposing this scaffold, and provide a rational framework for developing safer ATAD2-targeted therapies. Full article

Background: The infraclavicular brachial plexus block is a widely used regional anesthesia technique for surgery of the distal upper limb. Although generally considered safe—particularly with ultrasound guidance—a range of vascular, neurological, respiratory, and anesthetic-related complications continues to be reported. Understanding how anatomic factors can influence the occurrence of these events is essential for improving procedural safety. Objective: This narrative review aims to correlate clinically reported complications of the infraclavicular block with underlying anatomical mechanisms that may predispose to their development. Methods: A narrative review of the literature was conducted using PubMed, Scopus and Web of Science to identify clinical studies, observational series, and case reports published between 1995 and 2025 that documented complications associated with infraclavicular brachial plexus block in adults. Publications were selected based on relevance to vascular, neurological, respiratory, infectious, and local anesthetic systemic complications. Findings were synthesized descriptively, with emphasis on anatomical-clinical correlations rather than quantitative meta-analysis. Results: Reported complications include vascular puncture and hematoma formation, transient or persistent neurological deficits, Horner’s syndrome, hemidiaphragmatic paralysis, pneumothorax, local anesthetic systemic toxicity, and infectious complications. The incidence of these events varies widely across studies, reflecting differences in block technique, use of ultrasound guidance, injected anesthetic volume, and operator experience. Anatomical factors—such as the close relationship of the cords of the brachial plexus to the axillary vessels and the continuity of fascial planes—provide plausible explanations for these variations. Conclusions: Most complications of the infraclavicular block can be understood and anticipated through careful consideration of regional anatomy. Integrating anatomical knowledge with ultrasound guidance and optimized injection strategies may substantially reduce the risk of adverse events. This review highlights key anatomical mechanisms underlying reported complications and outlines practical implications for clinical practice. Full article

Primary hepatocyte cultures serve as an ex vivo model of liver physiology. This study aims to employ poly(vinyl alcohol) (PVA) nanofiber membranes (NMs) to establish a three-dimensional (3D) culture system that supports the long-term functionality of primary hepatocytes. Primary hepatocytes were monocultured on a PVA NM or indirectly cocultured with NIH3T3 fibroblasts on a distinct polycaprolactone (PCL) NM layer. Monocultured and cocultured hepatocytes maintained prolonged survival without supplemental growth factors. Cocultured hepatocytes formed larger aggregates composed of cell clusters attached to untreated nanofibers than monocultured cells. However, most primary hepatocytes cultured on NaOH-treated PVA NM and Arg–Gly–Asp (RGD) peptide-blended PVA (RGD-PVA) NM, under monoculture and coculture conditions, formed non-aggregated cells in a single-cell layer. In a bioinert assay, unstimulated dendritic cells were activated on untreated but not NaOH-treated PVA NM. CYP3A4 activity was higher in cocultured cells on RGD-PVA NM with fibroblasts than in monocultured cells on PVA and RGD-PVA NM. Functional hepatocyte cultures were successfully maintained in a 3D single-cell layer on RGD-PVA NM, along with fibroblasts in a layer-by-layer coculture, for a prolonged period. The prolonged culture of hepatocytes in a 3D single-cell layer may facilitate further drug discovery, toxicity studies, and translational liver research. Full article

Zinc oxide nanoparticles (ZnO-NPs) have gained increasing attention across food, biomedical, environmental, and many industrial fields due to their antimicrobial properties, chemical stability, and favorable physicochemical characteristics. In parallel, enzyme immobilization on nanostructured supports has emerged as an effective strategy to enhance enzyme stability, reusability, and functional performance in biosensing and biocatalytic systems. This mini-review summarizes recent advances in the synthesis of ZnO-NPs, with emphasis on green and biogenic approaches, and examines their integration with enzymes to form ZnO-enzyme hybrid systems. Key enzyme classes, immobilization strategies, and representative applications in food quality monitoring, biosensing, and food-processing-related biocatalysis are discussed. The novelty of this article is its comprehensive and application-oriented perspective. Unlike previous reviews that primarily addressed either ZnO nanoparticle synthesis or generic enzyme immobilization, this manuscript critically integrates strategies across the full value chain, from material preparation to functional application. In addition, the review critically evaluates toxicity, migration, safety, and regulatory considerations associated with ZnO-NPs, highlighting existing knowledge gaps and the need for standardized assessment frameworks. Despite promising proof-of-concept studies, challenges related to nanoparticle reproducibility, enzyme leaching, and long-term safety remain, underscoring the need for integrated and application-oriented research to enable safe and effective implementation of ZnO-enzyme hybrid technologies in many different sectors. Full article

Micro- and nanoplastics (MNPs) are increasingly contaminating atmospheric particulates, yet their influence on PM_2.5 chemistry and toxicity remains poorly understood. This study investigates how secondary MNPs derived from common products (water bottles, coffee cups, and food plates) alter the properties of PM_2.5. We evaluated PM_2.5 leaching characteristics, oxidative potential, inflammatory activity, and bacterial-based cytological and metabolomic responses after 24 h of exposure to three MNP doses. MNPs markedly altered PM_2.5 chromophoric composition, with bottle-derived (PET) MNPs inducing the strongest increases in aromaticity, humification, and slope factor, followed by coffee cups (PLA/paper) and food plates (PP). These leaching shifts aligned with polymer-specific redox behaviors: bottle-derived MNPs enhanced antioxidant enrichment at high PM_2.5, whereas cup-derived MNPs produced the most pronounced protein-denaturation-based inflammatory activity. Escherichia coli assays showed non-linear growth responses, elevated reactive oxygen species, altered carbohydrate secretion, and membrane and protein perturbations that paralleled PM_2.5 chemical reactivity. FTIR metabolomic fingerprints revealed dose- and polymer-dependent disruptions in polysaccharide, lipid, and protein domains. Overall, the results demonstrate a mechanistic cascade in which MNP exposure reshapes PM_2.5 chemistry, amplifies oxidative and inflammatory potential, and culminates in measurable cytological and metabolic stress, with polymer identity (PET > PLA/paper > PP) as the dominant driver. Full article

Background: Sea buckthorn (Hippophae rhamnoides L.), the superfood of the present era, is widely recognized for its high content of nutrients and bioactive compounds. However, dietary products and by-products derived from different parts of the fruit differ markedly in their biochemical composition, which may influence their nutritional and biological effects. Drosophila melanogaster represents a well-established in vivo model for studying the impact of dietary components on nutritional status, development, and viability under defined nutritional conditions. Methods: Four sea buckthorn-derived matrices—seed flour, seed oil, pulp, and fruit pomace powder—were analyzed for fatty acid, amino acid, polyphenol, and antioxidant contents. Their effects were evaluated in D. melanogaster under zero-nutrient, normal-nutrient, and high-sugar diets, assessing viability and developmental dynamics across various product types and concentrations. Results: Substantial compositional differences were observed between the samples. Seed flour and fruit pomace powder were rich in proteins, essential amino acids, polyphenols, flavonoids, and condensed tannins, whereas seed oil predominantly contained fatty acids with limited antioxidant capacity. Consistent with these compositional profiles, diet- and product-specific biological effects were observed. Under zero-nutrient conditions, high concentrations of fruit pomace powder (100 g/L) supported larval and adult viability and resulted in developmental patterns comparable to those observed under a normal-nutrient diet. Under normal-nutrient and high-sugar diets, the matrices modulated development and viability without apparent toxicity, with fruit pomace powder consistently showing the most favorable effects. Conclusions: The biological responses of D. melanogaster are closely linked to the biochemical composition of the matrices and the dietary context. Fruit pomace powder emerged as the most effective product, highlighting its potential as a functional dietary ingredient and a valuable source of nutrients and bioactive compounds. Full article

Background: Following the earthquakes that occurred in Turkey in 2023, the resulting demolition dust (DD) negatively impacted air quality and led to an increase in respiratory diseases. Although the harmful effects of crystalline and amorphous silica are known, the effects of hydrated cement dust (HCD), autoclaved aerated concrete dust (AACD), and DD on the lungs have not been sufficiently investigated. This rat study presents the first experimental data on the toxicity of these dusts. Methods: In the study, the structural properties of dust particles smaller than 5 µm were characterized using XRD analysis. Subsequently, 48 female rats were divided into four groups: HCD, AACD, DD, and control. The relevant dust suspensions were administered to the experimental groups, and physiological saline was administered to the control group intranasally a total of five times over a 15-day period, once every 3 days. Subsequently, bronchoalveolar lavage fluid, blood, and lung tissues were analyzed. Results: An increase in emphysema was observed in all exposure groups, and this increase was significant in the AAC and HC groups. Inflammation and alveolar wall thickness increased in the HC and DD groups. Goblet cell hyperplasia was detected only in the HC group; increases in CD68⁺ macrophages and TGF-β, as well as elevated hydroxyproline, were detected only in the DD group and supported the fibrotic response (p < 0.05). Neutrophil increase was specific to the AAC group. In all exposure groups, Akt/NF-κB pathway proteins, caspase-9, and MPO levels increased, while Bcl-xl levels decreased (p < 0.05). The findings indicate that the examined dusts trigger inflammation and apoptosis. Conclusion: Exposure to HCD, AACD, and DD causes lung damage by modulating the Akt/NF-κB signaling cascade; it enhances the apoptotic process through Bcl-xl suppression and caspase-9 increase. DD also induces a marked fibrotic response. Full article

Recently, complementary and alternative medicine (CAM) has been actively employed for patients experiencing symptoms unresponsive to Western medical treatments like drug therapy. The natural compounds carotenoids and astaxanthin (AST) have demonstrated various beneficial biological actions for human health in several studies. Given their broad pharmacological activities and reduced toxicity, ASTs possess significant potential as resources for the development of natural analgesic drugs. Given recent studies showing that AST can modulate neuronal excitability, including nociceptive sensory transmission through voltage-gated Ca²⁺ channels and the n-methyl-D-aspartate (NMDA) glutamate receptor, and inhibit the cyclooxygenase-2 cascade, AST holds promise as a CAM, particularly as a therapeutic agent for nociceptive and pathological pain. Based on the in vivo research findings from our laboratory presented in this review, we have confirmed that carotenoid ASTs possess: (i) an intravenous anesthetic effect on both nociceptive and inflammatory pain comparable to existing analgesics such as ketamine; and (ii) an anti-inflammatory effect on chronic pain with an efficacy almost equivalent to that of the commonly used non-steroidal anti-inflammatory drug (NSAID) celecoxib. Therefore, these findings suggest that, as natural compounds, ASTs contribute to the relief of nociceptive and inflammatory pain, implying their potential for clinical application. Full article

With ongoing development in the process industries, the accumulation of industrial inorganic solid wastes (IISWs) has become increasingly significant. IISWs are characterized by large volume and toxicity and pose challenges in treatment and control. IISWs from chemical processes mainly include red mud (RM), zinc slag, lithium slag (LS), electrolytic manganese residue (EMR), phosphogypsum (PG), water treatment sludge (WTS), sewage sludge, blast furnace slag (BFS), steel slag (SS), coal fly ash (CFA), coal gasification slag (CGS), copper smelting slag (CSS), and lead smelting slag (LSS). Having been chemically processed, they exhibit complex compositions that pose challenges for further utilization. In this paper, we comprehensively review the preparation of adsorbents from IISWs as raw materials, the applications of IISW-derived adsorbents, and their adsorption mechanisms. The obtained adsorbents include modified IISWs, zeolites, porous ceramics, and composite and hybrid adsorbents. The adsorption mechanisms, such as van der Waals forces, electrostatic interactions, and π–π interactions, contribute to the rapid adsorption kinetics and high adsorption capacity observed in these adsorbents. Full article

Fluorescent dyes are commonly used as tracers in hydrological investigations to quantify transport pathways, residence times, mixing behavior, and connectivity in surface water, groundwater, and coastal systems. Despite their long history of application, the ecological implications of deliberate dye releases are not well understood. This review synthesizes current knowledge on the physico-chemical characteristics, environmental behavior, and ecotoxicological effects of major dye classes, with emphasis on rhodamines, fluorescein derivatives, and sulfonated xanthene dyes commonly used in water tracing studies. Toxicity data for algae, cyanobacteria, invertebrates, and fish show large inter-specific variability. Some dyes, particularly rhodamine B and eosin Y, show acute or sub-lethal effects at concentrations detected during poorly controlled applications. By contrast, dyes with high polarity and extensive sulfonation (e.g., rhodamine WT, sulforhodamine B, pyranine, and fluorescein) show consistently low toxicity and minimal bioaccumulation potential. Environmental fate processes, including photolysis, sorption, and transformation into potentially more reactive products, influence exposure dynamics, especially in clear, shallow, or slow-moving systems. This review also evaluates regulatory frameworks and operational guidance for safe use, identifies gaps in toxicological and fate data, and proposes recommendations for minimizing environmental impact through dye selection, mass optimization, injection design, and monitoring. The findings support the continued use of fluorescent dyes but highlight the need for more systematic assessment of transformation products, chronic and sub-lethal responses, and cumulative exposure in sensitive environments. Full article

Background: Erectile dysfunction is a common late effect of prostate radiotherapy. Hydrogel spacers aim to reduce radiation exposure to nearby structures by increasing the distance between the prostate and surrounding tissues, potentially preserving sexual function. Methods: In this retrospective cohort study of 117 prostate cancer patients who received hydrogel spacers, we compared pre- and post-insertion radiation dose and anatomical positioning of erectile structures using paired t-tests. Longitudinal sexual function, assessed via EPIC scores, was modeled using linear mixed-effects regression with natural splines (df = 3), incorporating random intercepts and slopes to account for within-subject variability. Results: Spacer insertion significantly reduced radiation dose to the left and right neurovascular bundles (mean reductions: 1.66 Gy, 95% CI: 1.32–2.00; and 1.64 Gy, 95% CI: 1.28–2.01, respectively; p < 0.01) and the right perineal artery (1.33 Gy, 95% CI: 0.57–2.09; p < 0.01). No significant dose changes were observed for the penile bulb or left perineal artery, nor in anatomical distances. However, spatial displacement was confirmed by significant overlap and integrated volume changes. Longitudinal modeling showed a significant decline in sexual function between 12 and ≥36 months post-treatment (Spline 2: β = –12.72, 95% CI: −18.52–−6.92 and Spline 3: β = –6.68, 95% CI: −10.96–−2.40; p < 0.01). Conclusions: Hydrogel spacer insertion was associated with significant reductions in radiation dose to erectile structures, most notably the neurovascular bundles and the right perineal artery. However, longitudinal analyses revealed no corresponding preservation of sexual function. These findings suggest that while hydrogel spacers effectively reduce radiation exposure to key anatomical structures, their clinical benefit for maintaining erectile function remains uncertain. Full article

Liposomes remain one of the most utilized drug delivery systems due to their numerous advantages. However, they face significant challenges primarily due to their low colloidal stability as well as their rapid clearance by the reticuloendothelial and mononuclear phagocyte systems. Surface modifications have been identified as a highly effective approach to address these challenges. Various molecules can be utilized as surface modifiers. However, polysaccharides are widely employed in this regard, due to their unique characteristics, such as biocompatibility, biodegradability, and non-toxicity, as well as their ability to interact with the liposomal surface through different mechanisms. The aim of the present review is to provide a thorough analysis of polysaccharide-modified liposomes, highlighting recent advancements in their design, synthesis, and therapeutic applications. The utilization of polysaccharides as surface modifiers has been demonstrated to have several notable effects on liposomes. These effects include the enhancement of liposome properties, the provision of “stealth” properties, and the augmentation of colloidal stability. This review provides a comprehensive, polysaccharide-oriented analysis of liposomal surface modification strategies, along with a novel focus on the correlation between polysaccharide structure, modification method, and the resulting physicochemical and biological performance of the designed hybrid liposomes across a wide range of applications. Full article

Cotton fabrics are widely used in textiles due to their comfort and breathability, but their high flammability (limiting oxygen index (LOI) ≤ 18%) poses serious safety risks. While conventional flame-retardant treatments often rely on synthetic chemicals or toxic additives, biobased alternatives remain underdeveloped. The flame resistance of cotton fabrics may be enhanced using multilayer biocoatings of chitosan and sodium alginate applied via layer-by-layer (LBL) assembly—a sustainable and scalable approach. Cotton samples were coated with chitosan and sodium alginate bilayers (1, 2, 5, and 10 layers) using the LBL method. Flame resistance was evaluated using vertical flame tests and limiting oxygen index (LOI) testing according to ASTM D2863-09. The sample coated with 10 bilayers significantly outperformed uncoated cotton and lower-layer samples. With a char length of 9.72 cm (68% reduction), no dripping was observed in the vertical flame tests, and the LOI value was 23.47% compared to uncoated cotton (LOI = 18.04%). These improvements were attributed to the formation of a cohesive and protective carbon layer, which is likely capable of inhibiting the formation of flammable gases. Biomaterial multilayer coatings made from biomaterials, such as chitosan and sodium alginate, represent a promising and environmentally friendly alternative to traditional methods in improving cotton’s flame resistance. The development of this technology points to potential applications in protective textiles and industrial safety clothing. Notably, chitosan and sodium alginate coatings are biocompatible. The term “biomaterials” refers to materials intended for interaction with biological systems, particularly for biomedical-related applications. The term “biobased materials” is used exclusively to describe materials derived from renewable biological sources. Full article

The undegradable characteristics of heavy metals on environmental quality have become a serious human health concern. A study was conducted in a potato field to investigate the impact of soil amended with animal manure or biochar on the transport of toxic heavy metals and nitrates to runoff and seepage water. The soil in 18 field plots was separated, and each of 3 plots was mixed with biochar, chicken manure, vermicompost, sewage sludge, or cow manure, with 3 plots used as the control. Following a natural rainfall event, the impact of soil treatments on the runoff and infiltration water volume was monitored. Runoff water from the soil amended with biochar exhibited 10.6 L plot⁻¹, whereas cow manure exhibited 4.1 L plot⁻¹, indicating about 61% reduction in runoff water volume. The vermicompost-amended soil increased the seepage water volume from 1.6 L plot⁻¹ in the control treatment to 4.4 L plot⁻¹, indicating a 175% increase in percolating water, a desirable attribute to direct rainfall water towards the plant roots. The concentrations of Pb, Cd, Ni, Mn, Cr, Mg, Cu, and K in infiltration water were greater in runoff sediments, highlighting the need for runoff sediment remediation technology. Full article

Climate change is increasing forest vulnerability, and extreme disturbances such as windstorms can cause major economic and social losses. Forest recovery after such events often relies on salvage logging and extensive planting of seedlings produced in nurseries to rapidly restore forest cover. While effective, these interventions, particularly when applied over large areas, may also produce environmental impacts that are largely absent under spontaneous regeneration. Following the Vaia windstorm in northern Italy in 2018, several reforestation interventions were implemented to restore forest cover. We focused on one intervention and conducted a life cycle assessment to quantify its environmental impacts, using the planting of 800 four-year-old Norway spruce (Picea abies (L.) H. Karst) seedlings as the functional unit, combined with chipping on the site of forest biomass residues. The largest contributions were to global warming potential (443.91 kg CO₂ eq), human toxicity (167.72 kg 1,4-DCB eq), and freshwater ecotoxicity (142.43 kg 1,4-DCB eq). Seedling production and field establishment dominated these impact categories. Among field operations, manufacturing and transporting plastic shelters for seedling protection accounted for the highest share of global warming potential. Full article