Search Results (1,521)

The widespread production and poor management of plastic waste have led to the pervasive presence of microplastics (MPs) in environmental and biological systems. Among various polymers, polyethylene (PE) is the most widely produced plastic globally, primarily due to its use in single-use packaging. Its persistence in ecosystems and resistance to degradation processes result in the continuous formation of PE-derived MPs. These particles have been detected in human biological matrices, including blood, lungs, placenta, and even the brain, raising increasing concerns about their bioavailability and potential health effects. Once internalized, PE MPs can interact with cellular membranes, induce oxidative stress, inflammation, and apoptosis, and interfere with epigenetic regulatory pathways. In vitro studies on epithelial, immune, and neuronal cells reveal concentration-dependent cytotoxicity, mitochondrial dysfunction, membrane disruption, and activation of pro-inflammatory cytokines. Moreover, recent findings suggest that PE MPs can induce epithelial-to-mesenchymal transition (EMT), senescence, and epigenetic dysregulation, including altered expression of miRNAs and DNA methyltransferases. These cellular changes highlight the potential role of MPs in disease development, especially in cardiovascular, metabolic, and possibly cancer-related conditions. Despite growing evidence, no standardized method currently exists for quantifying MPs in human samples, complicating comparisons across studies. Further, MPs can carry harmful additives and environmental contaminants such as bisphenols, phthalates, dioxins, and heavy metals, which enhance their toxicity. Global estimates indicate that humans ingest and inhale tens of thousands of MPs particles each year, yet long-term human research remains limited. Given these findings, it is crucial to expand research on PE MP toxicodynamics and to establish regulatory policies to reduce their release. Promoting alternative biodegradable materials and improved waste management practices will be vital in decreasing human exposure to MPs and minimizing potential health risks. Full article

Extracellular matrix (ECM) bioscaffolds have demonstrated therapeutic potential across a variety of clinical and preclinical applications for tissue repair and regeneration. In parallel, these scaffolds and their components have shown the capacity to modulate the immune response. Unlike synthetic implants, which are often associated with chronic inflammation or fibrotic encapsulation, ECM bioscaffolds interact dynamically with host cells, promoting constructive tissue remodeling. This effect is largely attributed to the preservation of structural and biochemical cues—such as degradation products and matrix-bound nanovesicles (MBV). These cues influence immune cell behavior and support the transition from inflammation to resolution and functional tissue regeneration. However, the immunomodulatory properties of ECM bioscaffolds are dependent on the source tissue and, critically, on the methods used for decellularization. Inadequate removal of cellular components or the presence of residual chemicals can shift the host response towards a pro-inflammatory, non-constructive phenotype, ultimately compromising therapeutic outcomes. This review synthesizes current basic concepts on the innate immune response to ECM bioscaffolds, with particular attention to the inflammatory, proliferative, and remodeling phases following implantation. We explore how specific ECM features shape these responses and distinguish between pro-remodeling and pro-inflammatory outcomes. Additionally, we examine the impact of manufacturing practices and quality control on the preservation of ECM bioactivity. These insights challenge the conventional classification of ECM bioscaffolds as medical devices and support their recognition as biologically active materials with distinct immunoregulatory potential. A deeper understanding of these properties is critical for optimizing clinical applications and guiding the development of updated regulatory frameworks in regenerative medicine. Full article

Background and Objectives: Endometrial adenocarcinoma is among the most prevalent malignancies of the female reproductive system, and therapeutic options remain limited, particularly in advanced stages. In recent years, natural agents, especially flavonoids, have gained considerable interest for their capacity to enhance the effectiveness of chemotherapeutic drugs and modulate tumor-related molecular mechanisms. Hesperidin, a citrus-derived flavonoid, is recognized for its antioxidant and anti-inflammatory effects, while Gemcitabine, a nucleoside analog, is widely used in cancer treatment. Investigating their combined effects on endometrial carcinoma cells could yield novel insights into multimodal therapeutic development. This current study aimed to assess the impact of Hesperidin (Hes) and Gemcitabine (Gem) on ISHIKAWA cells, a human endometrial adenocarcinoma model, with particular attention to pathways associated with hypoxia, angiogenesis, apoptosis, and oxidative stress. Materials and Methods: ISHIKAWA cells were treated with varying concentrations of Hes (50–200 µM) and Gem (10–50 nM), either individually or together, for 24 and 48 h. Cell viability was determined using the MTT assay, while apoptosis was measured by Caspase-3/7 activity and NucBlue nuclear staining. Intracellular reactive oxygen species (ROS) generation was quantified via DCFH-DA fluorescence. Expression levels of HIF-1α, VEGF, Bax, Bcl-2, and Caspase-3 were examined by RT-qPCR. Synergistic interactions were analyzed with the Chou–Talalay combination index. Biological enrichment was further explored using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results: Both Hes and Gem significantly decreased ISHIKAWA cell viability in a concentration- and time-dependent manner (p < 0.001). The combined treatment induced stronger apoptotic effects, as reflected by increased Caspase-3/7 activity and nuclear morphological changes. RT-qPCR demonstrated upregulation of Bax and Caspase-3, together with downregulation of Bcl-2, HIF-1α, and VEGF. While Hes reduced intracellular ROS, Gem elevated it; their combination produced a balanced oxidative response. All dose combinations displayed strong synergism (CI < 1). GO and KEGG enrichment confirmed the involvement of apoptosis-, angiogenesis-, and hypoxia-related pathways. Conclusions: Co-treatment with Hes and Gem exhibits synergistic anticancer activity in endometrial cancer cells by promoting apoptosis, suppressing angiogenesis- and hypoxia-related gene expression, and modulating oxidative stress. This combined therapeutic approach highlights its potential as a promising adjuvant option, warranting further evaluation in in vivo and translational studies. Full article

Keratinocytes are the primary cells of the epidermis layer in our skin. They play a crucial role in maintaining skin health, responding to injuries, and counteracting disease progression. Understanding their behaviour is essential for advancing wound healing therapies, improving outcomes in regenerative medicine, and developing numerical models that accurately mimic skin deformation. To create physically representative models, it is essential to evaluate the nuanced ways in which keratinocytes deform, interact, and respond to mechanical and biochemical signals. This has prompted researchers to investigate various computational methods that capture these dynamics effectively. This review summarises the main mathematical and biomechanical modelling techniques (with particular focus on the literature published since 2010). It includes reaction–diffusion frameworks, finite element analysis, viscoelastic models, stochastic simulations, and agent-based approaches. We also highlight how machine learning is being integrated to accelerate model calibration, improve image-based analyses, and enhance predictive simulations. While these models have significantly improved our understanding of keratinocyte function, many approaches rely on idealised assumptions. These may be two-dimensional unicellular analysis, simplistic material properties, or uncoupled analyses between mechanical and biochemical factors. We discuss the need for multiscale, integrative modelling frameworks that bridge these computational and experimental approaches. A more holistic representation of keratinocyte behaviour could enhance the development of personalised therapies, improve disease modelling, and refine bioengineered skin substitutes for clinical applications. Full article

Immune cells play a pivotal role in orchestrating tissue repair, executing functions such as debris clearance, extracellular matrix remodeling, and modulation of cytokine secretion profiles. However, when their activity is dysregulated or inadequately directed, these same processes can give rise to chronic inflammation and foreign body reactions (FBR), ultimately leading to fibrosis and compromised biomaterial performance. The immunological landscape following injury or biomaterial implantation is profoundly influenced by the physicochemical properties of material surfaces. By strategically tailoring these surface characteristics, it becomes possible to modulate immune cell responses—governing their adhesion, recruitment, proliferation, polarization, and cytokine expression patterns. This review elucidates the multifaceted roles of immune cells in tissue repair and their dynamic interactions with implanted biomaterials. It then explores how specific surface attributes—such as topography, chemistry, stiffness, and wettability—influence immune behavior. Particular emphasis is placed on recent advances in surface modification techniques aimed at engineering next-generation biomaterials that mitigate adverse immune responses while actively promoting regenerative healing. The review concludes by offering critical insights into the future of immunomodulatory biomaterial design, highlighting both emerging opportunities and persisting challenges in the field. Full article

Understanding the molecular structure and water transport behavior in anion-exchange membranes (AEMs) is essential for advancing efficient and cost-effective alkaline fuel cells. In this study, large-scale all-atom molecular dynamics simulations of QPAF-4, a promising AEM material, were performed at multiple water uptakes (λ = 2, 3, 6, and 13). The simulated systems comprised approximately 1.4 to 2.1 million atoms and spanned approximately 26 nm, thus enabling direct comparison with both wide-angle X-ray scattering (WAXS) and small-angle X-ray scattering (SAXS) experiments. The simulations successfully reproduced experimentally observed structure factors, accurately capturing microphase-separated morphologies at the mesoscale ($~$8 nm). Decomposition of the SAXS profile into atom pairs suggests that increasing water uptake may facilitate the aggregation of fluorinated alkyl chains. Furthermore, the calculated pair distribution functions showed excellent agreement with WAXS data, suggesting that the atomistic details were accurately reproduced. The water dynamics exhibited strong dependence on hydration level: At low water uptake, mean squared displacement showed persistent subdiffusive behavior even at long timescales ($~$200 ns), whereas almost normal diffusion was observed when water uptake was high. These results suggest that water mobility may be significantly influenced by nanoconfinement and strong interactions exerted by polymer chains and counterions under dry conditions. These findings provide a basis for the rational design and optimization of high-performance membrane materials. Full article

Understanding and accurately modelling mass transport phenomena in anode-supported solid oxide fuel cells (SOFCs) is essential for improving efficiency and mitigating performance losses due to concentration polarization. This study presents a one-dimensional, isothermal, multi-component diffusion framework based on the Stefan–Maxwell (SM) formulation to evaluate hydrogen, water vapour, and nitrogen transport in two different porous ceramic support materials: calcia-stabilized zirconia (CSZ) and magnesia magnesium aluminate (MMA). Both SM binary and SM ternary models are implemented to capture species interactions under varying hydrogen concentrations and operating temperatures. The SM formulation enables direct calculation of concentration polarization as well as the spatial distribution of gas species across the anode support’s thickness. Simulations are conducted for two representative fuel mixtures—20% H₂ (steam-rich, depleted fuel) and 50% H₂ (steam-lean)—across a temperature range of 500–1000 °C and varying electrode thicknesses. They are validated against experimental data from the literature, and the influence of electrode thickness and fuel composition on polarization losses is systematically assessed. The results show that the ternary SM model provides superior accuracy in predicting overpotentials, especially under low-hydrogen conditions where multi-component interactions dominate. MMA consistently exhibits lower polarization losses than CSZ due to enhanced gas diffusivity. This work offers a validated, computationally efficient framework for evaluating mass transport limitations in porous anode supports and offers insights for optimizing electrode design and operational strategies, bridging the gap between simplified analytical models and full-scale multiphysics simulations. Full article

Arthroscopic Superior Capsular Reconstruction has emerged as a promising surgical intervention for irreparable massive rotator cuff tears, aiming to restore glenohumeral joint stability and improve patient outcomes. A critical determinant of ASCR success is the selection of an appropriate graft material. This review explores the spectrum of grafts utilized in ASCR, including autografts, allografts, xenografts, and synthetic materials. The primary focus is on how the inherent biological properties of these grafts—such as cellularity, vascularity, immunogenicity, and extracellular matrix composition—profoundly influence the processes of graft healing, integration into host tissues, and ultimately, the rates of re-tearing. Autografts, particularly fascia lata, often demonstrate superior biological incorporation due to their viable cells and non-immunogenic nature, leading to high healing rates. Allografts, while offering advantages like reduced donor site morbidity, present biological challenges related to decellularization processes and slower remodeling, resulting in more variable healing outcomes. Xenografts face significant immunological hurdles, often leading to rejection and poor integration. Synthetic grafts provide an off-the-shelf option but interact with host tissue primarily as a scaffold, without true biological integration. Understanding the nuanced biological characteristics of each graft type is paramount for surgeons aiming to optimize healing environments and minimize re-tear rates, thereby enhancing the long-term efficacy of ASCR. Full article

The aim of this study was to evaluate the haemostatic potential and biocompatibility of a newly developed composite material for its use in blood-contacting applications. Based on promising reports on polylactide (PLA), sodium alginate (ALG), and bioactive additives such as hardystonite (HT) and zinc sulphide (ZnS), a melt-blown PLA nonwoven was modified via dip-coating using an ALG solution as a matrix for incorporating HT and ZnS particles, resulting in the PLA-ALG-ZnS-HT composite. The material was characterised in terms of surface morphology, specific surface area, pore volume, average pore size, and zeta potential (pH~7.4). Haemostatic activity was assessed by measuring blood coagulation parameters, while biocompatibility was evaluated through the viability of human peripheral blood mononuclear (PBM) cells and human foreskin fibroblasts (Hs68). Genotoxicity was analysed using the comet assay and plasmid relaxation test. Results confirmed a uniform alginate coating with dispersed HT and ZnS particles on PLA fibres. The modification increased the surface area and pore volume and caused a shift toward less negative zeta potential. Haemostatic testing showed prolonged activated partial thromboplastin time (aPTT), likely due to Zn²⁺ interactions with clotting factors. Biocompatibility tests showed high cell viability and no genotoxic effects. Our findings suggest that the PLA-ALG-ZnS-HT composite is safe for blood and skin cells and may serve as an anticoagulant material. Full article

The use of nanoparticles has revolutionized drug delivery by enabling targeted and controlled therapeutic release. However, their interactions with intracellular organelles, particularly lysosomes, are not yet fully understood. This study delineates the differential effects of two widely used nanocarriers—mesoporous silica (MSNs) and albumin (ANPs) nanoparticles—on lysosomal biology, with a focus on the expression and activity of cathepsins (CtsB and CtsD), which are key proteases involved in protein degradation and maintaining cellular balance. These two types of nanoparticles, differing in their material and degradability, exhibit distinct behaviors inside the cell. We demonstrate that inorganic MSNs cause significant changes in lysosomal function by altering lysosomal content and cathepsin levels, without triggering lysosomal membrane permeabilization—a typical response to organic particle stress. In contrast, ANPs—which are susceptible to lysosomal cathepsin degradation—induce milder changes in cathepsin expression and maintain lysosomal integrity. Our results highlight that the composition of nanocarriers plays a pivotal role in modulating lysosomal protease activity and maintaining overall cellular homeostasis, highlighting the importance of these parameters in the rational design of drug delivery platforms. Full article

Polymers and polymer composites offer versatile possibilities for engineering the physico-chemical properties of materials on micro- and macroscopic scales. This review provides an overview of polymeric and polymer-decorated particles that can serve as drug-delivery vectors: linear polymers, star polymers, diblock-copolymer micelles, polymer-grafted nanoparticles, polymersomes, stealth liposomes, microgels, and biomolecular condensates. The physico-chemical interactions between the delivery vectors and biological cells range from chemical interactions on the molecular scale to deformation energies on the particle scale. The focus of this review is on the structure and elastic properties of these particles, as well as their circulation in blood and cellular uptake. Furthermore, the effects of polymer decoration in vivo (e.g., of glycosylated plasma membranes, cortical cytoskeletal networks, and naturally occurring condensates) on drug delivery are discussed. Full article

Proximity biotinylation, which utilizes various biotin ligating enzymes (BioID, TurboID, etc.), is widely used as a powerful tool for identifying novel protein–protein interactions. However, this method has a significant limitation: the use of streptavidin on beads for enriching biotinylated proteins often results in a high background of peptides from streptavidin itself, which interferes with identification by peptide mass fingerprinting. This limitation makes it practically impossible to study samples containing a small amount of material, such as individual insect tissues. In this study, we compared different precipitation and elution conditions for the purification of biotinylated proteins from protein extracts of Drosophila melanogaster S2 cells. We found that biotinylated proteins can be purified using anti-biotin antibodies, although with lower efficiency than streptavidin-based resin. We also demonstrated that protease-resistant streptavidin (prS), previously tested in mammalian cells, can be used effectively to purify biotinylated proteins from tissues of D. melanogaster. In our experiments, prS showed precipitation efficiency comparable to regular streptavidin but generated a lower background in peptide fingerprinting. To further demonstrate the applicability of prS for studying protein–protein interactions in D. melanogaster tissues, we carried out experiments to identify interaction partners of the ecdysone receptor (EcR) in D. melanogaster ovarian tissue using TurboID-based proximity biotinylation. As a result, EcR was found to interact with both previously described and novel protein partners in Drosophila ovaries. Full article

The detection of aliphatic and aromatic biogenic amines (BAs) is important in food spoilage, environmental monitoring, and disease diagnosis and treatment. Existing fluorescent probes predominantly detect aliphatic BAs with single signal variation and low sensitivity, impairing the adaptability of discriminative sensing platforms. Herein, we present a visual chemosensor (galactose-functionalized pyrrolopyrrole aza-BODIPY, PPAB-Gal) that simultaneously detects eight aliphatic and aromatic BAs in a real-time and intuitive way based on their unique electronic and structural features. Our findings reveal that the dual colorimetric and ratiometric emission changes are rapidly produced in presence of eight BAs through a noncovalent interaction (π–π stacking and hydrogen bond)-assisted chromophore reaction. Specifically, other lone-pair electrons containing compounds, such as secondary amines, tertiary amines, NH₃, and thiol, fail to exhibit these changes. As a result, superior sensing performances with distinctly dual signals (Δλ_ab = 130 nm, Δλ_em = 150 nm), a low LOD (~25 nM), and fast response time (<2 min) were obtained. Based on these advantages, a qualitative and smartphone-assisted sensing platform with a PPAB-Gal-loaded TLC plate is developed for visual detection of putrescine and cadaverine vapor. More importantly, we construct a connection between a standard quantitative index for the TVBN value and fluorescence signals to quantitatively determine the freshness of tuna and shrimp, and the method is facile and convenient for real-time and on-site detection in practical application. Furthermore, since the overexpressed spermine is an important biomarker of cancer diagnosis and treatment, PPAB-Gal NPs can be used to ratiometrically image spermine in living cells. This work provides a promising sensing method for BAs with a novel fluorescent material in food safety fields and biomedical assays. Full article

The increasing demand for smart bone substitutes has boosted the implementation of biomaterials possibly endowed with both pro-osteogenic and pro-angiogenic capabilities, among which bioactive glasses hold great potential. Hence, two Poly(ε-caprolactone) (PCL)-based composites were loaded at 10 wt.%, with either pristine (SBA3) or copper-doped (SBA3_Cu) silica-based bioactive glasses, through a solvent casting method with chloroform. Neat PCL was used as a control. Samples produced by 3D printing underwent SEM and EDX analyses, and the following were measured: tensile strength and hardness, surface roughness, ion release through ICP-OES, surface free energy, and optical contact angle. Adipose-derived mesenchymal stem cells (ASCs) and human microvascular endothelial cells (HMEC-1) were used to test the biocompatibility of the materials through cell adhesion, spreading, and viability assays. A significant improvement in tensile strength and hardness was observed especially with Cu-doped composites. Both SBA3 and SBA3_Cu added to the PCL favored the early adhesion and the proliferation of HMEC-1 after 3 and 7 days, while ASCs proliferated significantly the most on the SBA-containing composite, at all the time points. Cellular morphology analysis highlighted interesting adaptation patterns to the samples. Further biological characterizations are needed to understand thoroughly how specific bioactive glasses may interact with different cellular types. Full article

Periodontal disease in dogs leads to progressive bone loss and adversely impacts overall health. However, cost-effective regenerative strategies are still limited in veterinary practice. This study aimed to develop and evaluate a novel tannic acid (TA)–gelatin-based hydrogel (Gel), incorporating graphene oxide (GO) and hydroxyapatite nanoparticles (HA), as a potential barrier material for guided tissue regeneration (GTR) applications. The hydrogels—Gel, Gel-GO, Gel-HA, and Gel-GO-HA—were characterized for chemical structure, molecular interactions, surface morphology, nanoparticle dispersion, and tensile strength. Cytotoxicity was assessed using L929 fibroblasts (ISO 10993-5), while cell viability/proliferation, morphology, and alkaline phosphatase (ALP) production were evaluated using canine periodontal ligament-derived cells. Results show that crosslinking with tannic acid enhanced the incorporation of graphene oxide and hydroxyapatite nanoparticles via hydrogen bonding into TA–gelatin-based hydrogels. This combination increased surface roughness, reduced degradation rate, and enabled shape memory behavior, critical for guided tissue regeneration (GTR) membranes. The extracts from Gel-HA-GO showed that cytotoxicity was both time- and concentration-dependent in L929 fibroblasts, whereas enhanced cell proliferation and increased ALP production were observed in cultures derived from canine periodontal ligament cells. These findings suggest that TA–gelatin-based hydrogels incorporating GO and HA demonstrated favorable mechanical and physicochemical properties, biocompatibility, and osteogenic potential. These attributes suggest their viability as a promising composite for the development of innovative GTR strategies to address periodontal tissue loss in veterinary medicine. Full article