Search Results (10,034)

Green nanotechnology is now well established, showcasing how natural precursors can replace hazardous synthesis routes. This review analyzes the diverse biotechnological applications of biogenic nanomaterials. In the biomedical field, they have demonstrated significant efficacy as antimicrobial agents, targeted drug delivery vehicles, wound healers, and theragnostic platforms. They also enhance food packaging security, optimize nano-fertilizers, and control insect pests. Additionally, their unique surface properties and catalytic activity make them key candidates for pollutant remediation and advanced chemical sensors. Ultimately, while green nanoparticles offer clear advantages over traditional chemical methods, key bottlenecks, like batch-to-batch reproducibility, industrial scalability, and long-term ecotoxicological and multigenerational impacts, still need to be addressed. Full article

Metallic and organometallic nanoparticles exhibit intriguing size- and morphology-dependent magnetic properties that differ markedly from their bulk counterparts. Here, we report a detailed synthesis and characterization of iron (Fe), copper (Cu), nickel (Ni), and cobalt (Co) nanostructures dispersed in carbon matrices derived from phthalocyanine (Pc), tetrakis(4-carboxyphenyl)porphyrin (TCPP), and tetraphenylporphyrin (TPP), with the detailed quantitative analysis focused primarily on iron phthalocyanine (FePc), iron tetrakis(4-carboxyphenyl)porphyrin (FeTCPP), and iron tetraphenylporphyrin (FeTPP). Using powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), scanning transmission electron microscopy (STEM), energy-dispersive X-ray spectroscopy (EDS), and magnetometry, we systematically investigate how precursor composition, annealing conditions, and nanostructure formation impact the resulting magnetic behaviors. We introduce a validation-aware image-analysis workflow for morphological, local periodic-contrast, and two-dimensional connectivity descriptors while distinguishing these image-derived quantities from direct measurements of bulk crystallinity, porosity, and three-dimensional connectivity. Hysteresis measurements at low temperatures reveal that iron-based compounds, particularly iron phthalocyanine (FePc) and iron tetrakis(4-carboxyphenyl)porphyrin (FeTCPP), exhibit notable saturation-like magnetization and stronger coercivity, respectively, whereas other precursors (e.g., Cu tetraphenylporphyrin, CuTPP) show weaker magnetic responses. These contrasting behaviors underscore the importance of understanding how candidate phase composition (e.g., metallic Fe, graphite-like carbon, or iron-carbide-related contributions), local morphology, and carbon structure correlate with magnetic characteristics. Microscopy and EDS support Fe-rich regions dispersed within carbonaceous matrices, and a representative Fe/O/C STEM–EDS field provides local evidence for a core–shell-like morphology without establishing a uniform shell thickness, composition, or local core phase across the full population. Our findings highlight the feasibility of tuning carbon–metal nanocomposites through controlled synthesis and post-annealing, thereby motivating future application-specific evaluations in areas such as magnetic hyperthermia, drug delivery, sensing, and electromagnetic materials. The image-analysis workflow also offers a reproducible framework for future studies seeking to relate nanoparticle morphology and magnetic properties to controlled processing. Full article

Background: The current study uses a computational technique to investigate synthesized thiazine compounds that exhibit potential interactions with the GABA_A receptor. A series of novel thiazine derivatives was synthesized via the cyclization reaction of chalcone with thiourea. Methods: For the synthesized compounds, spectroscopic characterization, namely FT-IR, ¹H NMR, ¹³C NMR, and mass spectrometry, was carried out. In addition, the AutoDock Vina 4.2 software was applied to carry out an in silico docking study. Results: The synthesized compounds C3 and C6 exhibited comparable predicted docking scores (−9.0 and −9.1 kcal/mol, respectively), with favorable predicted interactions at the GABAA receptor binding site. Furthermore, in silico ADMET analysis provided insights into the drug-likeness and pharmacokinetic profiles of the synthesized compounds; however, potential safety liabilities, including Ames positivity, hERG II liability, and hepatotoxicity, were predicted for some derivatives. Conclusions: It was determined that the synthesized compounds’ various physiologically significant and physiologically relevant parameters fell within the range of Lipinski’s rule of five. The synthesized compounds (C1–C10) were tested for anxiolytic activity by the elevated plus maze test, and compound C6 was found to be the most potent. Additionally, the in vitro GABA-AT enzyme activity assay showed that compound C6 had the highest inhibitory potential, with an IC50 of 13.29 ± 1.622 µM. Full article

Nonlamellar liquid crystalline nanodispersions produced from single monoacylglycerols or from their combinations with fatty acids or other amphiphiles have attracted interest owing to their structural versatility and tunability. In this study, we investigated the effect of dilinolein (DLO) incorporation on the structural features of Pluronic F127-stabilized monolinolein (MLO) nanodispersions using small-angle X-ray scattering (SAXS), cryogenic transmission electron microscopy (cryo-TEM), and dynamic light scattering (DLS). We report a lipid composition-dependent direct colloidal transformation from hexosomes, defined as nanoparticles with an ordered internal inverse hexagonal (H₂) phase, toward nanoparticles with highly disordered internal nanostructures upon the partial replacement of MLO by DLO. Small-angle X-ray scattering (SAXS) measurements showed that, at relatively low DLO content, the MLO-rich MLO:DLO 90:10 (w/w) nanodispersion retained an ordered internal H₂ phase, with three well-defined characteristic Bragg peaks, whereas the SAXS patterns recorded for nanodispersions containing ≥20 wt% DLO displayed loss of the characteristic H₂ Bragg reflections and broad correlation maxima, indicating loss of long-range internal periodicity and the emergence of highly disordered internal nanostructures. Similarly, the control nanodispersion prepared from DLO alone displayed a broad, low-intensity correlation maximum rather than distinct Bragg peaks, consistent with a highly disordered internal nanostructure. For the nanodispersions displaying broad SAXS correlation maxima, the SAXS-derived characteristic distance decreased monotonically from 4.53 to 2.87 nm as the DLO fraction increased. Additional cryo-TEM observations of two nanodispersions containing relatively high DLO contents revealed predominantly spherical nanoparticles characterized by an intense lipid core and discernible internal nanoscale features. However, these internal features were not sufficiently resolved to allow full characterization and unambiguous assignment of the internal phase, consistent with a highly disordered inverse nanostructure that may include an L₂-like inverse-micellar organization alongside other possible arrangements such as nanoemulsion droplets. Taken together, the SAXS and cryo-TEM observations indicate a composition-driven colloidal transformation from hexosomes with a well-defined internal H₂ phase toward nanoparticles with a highly disordered internal phase as the DLO content increases. The experimental findings suggest that DLO modifies lipid packing at the MLO–water interface and promotes more negative spontaneous curvature, favoring the observed structural transformation. The ability to tune the internal nanostructure by lipid composition while maintaining nanoscale particle size and low dispersity makes these nanodispersions attractive platforms for drug nanocarrier development. Full article

Developing effective oral formulations for poorly soluble anticancer drugs remains a major pharmaceutical challenge due to the combined limitations of solubility, permeability, and efflux transporter activity. In this work, we investigated the influence of the nonionic surfactants Cremophor EL, Pluronic P-85, and Pluronic F-68 on the solubility and intestinal permeability of the anticancer drug etoposide. All surfactants significantly increased etoposide aqueous solubility. While in vitro permeability across an artificial membrane demonstrated the expected solubility-permeability tradeoff, in vivo SPIP studies in rats revealed a distinctive solubility-permeability interplay for Cremophor EL and Pluronic P-85, which simultaneously enhanced solubility and permeability, likely through P-gp inhibition. In contrast, Pluronic F-68 exhibited the classical solubility-permeability tradeoff, consistent with its reported negligible P-gp inhibitory activity. Mechanistic analysis indicated that surfactant hydrophobicity and molecular weight critically influence P-gp inhibition via ATPase modulation. Surfactants with higher hydrophobicity and moderate molecular weight can integrate into the phospholipid bilayer, enabling direct interaction with P-gp and disruption of its ATPase function. These findings provide strategic insights for the rational design of oral formulations capable of overcoming the solubility-permeability tradeoff, improving the bioavailability of challenging anticancer drugs, and may facilitate the transition from intravenous to oral chemotherapy. Full article

Background: Methotrexate (MTX) is a well-established therapeutic agent for psoriasis owing to its anti-inflammatory and immunomodulatory effects. However, its clinical use is limited by insufficient local accumulation in skin lesions and the potential risk of systemic exposure. Dunaliella salina-derived exosome (DsEXO) has favorable biocompatibility, low immunogenicity and potential skin delivery capacity, making it a promising natural nanocarrier for topical MTX delivery. This study aimed to construct Dunaliella salina-derived exosome loaded with methotrexate (DsEXO@MTX) and evaluate its therapeutic efficacy and potential mechanisms in psoriasis-like skin inflammation. Methods: DsEXO@MTX was prepared and characterized in terms of morphology, particle size, surface charge and drug-loading capacity. Cellular uptake, skin retention and tissue distribution were evaluated using fluorescence imaging and skin section analysis. Therapeutic efficacy was evaluated in an imiquimod-induced psoriasis-like mouse model by clinical scoring, histopathological examination, spleen index measurement and Ki-67 immunofluorescence staining. STAT3 phosphorylation and Th17/Treg differentiation were further examined to explore the potential immunomodulatory mechanism. Results: DsEXO@MTX exhibited a relatively uniform particle size distribution and drug-loading capacity. In vivo fluorescence imaging and skin section analysis showed that DsEXO@MTX enhanced local skin retention and promoted fluorescence distribution in epidermal and dermal regions. It significantly alleviated IMQ-induced erythema, scaling, epidermal thickening, inflammatory infiltration, splenomegaly and abnormal keratinocyte proliferation in psoriasis-like mice. Mechanistically, DsEXO@MTX reduced STAT3 phosphorylation and modulated Th17/Treg differentiation, suggesting restoration of immune balance in psoriatic inflammation. Conclusions: DsEXO@MTX represents a natural exosome-like nanovesicle-mediated topical MTX delivery system that improves local drug delivery and enhances therapeutic efficacy in IMQ-induced psoriasis-like skin inflammation, particularly when administered topically. These findings provide a potential strategy for safer and more efficient local treatment of psoriasis. Full article

Background: Pathological angiogenesis and stromal fibrosis after ocular chemical injury are primary drivers of corneal opacification and permanent vision loss. Topical administration of anti-VEGFA antibody is hampered by rapid tear clearance and poor penetration across the corneal epithelial barrier, resulting in insufficient intraocular drug accumulation and suboptimal therapeutic efficacy. Although intraocular injection elevates local drug concentration, this invasive procedure carries risks of complications and is not suitable for long-term repeated treatment. This study constructed red cabbage-derived exosome-like nanovesicles (Rabexo) to load an anti-VEGFA antibody, formulated into PVA/HA hydrogel, aiming to develop a topical sustained-release ocular delivery system for alleviating corneal angiogenic and fibrotic lesions. Methods: Rabexo was isolated and physicochemically characterized. Anti-VEGFA antibody was encapsulated into Rabexo via electroporation to prepare aV-Rabexo, which was further incorporated into commercial PVA/HA hydrogel. Cellular uptake, anti-angiogenic functions were verified in vitro, and therapeutic efficacy was evaluated in a mouse corneal alkali burn model via ophthalmic topical administration. Results: The prepared Rabexo showed uniform size and favorable colloidal stability with 40.3% antibody encapsulation efficiency. aV-Rabexo exhibited stronger in vitro anti-migration, anti-proliferation and anti-tube formation effects than free antibody. In vivo, aV-Rabexo-Gel substantially suppressed corneal neovascular area and length, restored stromal collagen arrangement, and downregulated CD31, VEGFA and α-SMA expression at day 14 post-injury, with statistically significant differences compared with the free antibody gel. Conclusions: This plant-derived nanocarrier hydrogel system realizes synergistic therapeutic effects via nanocarrier delivery, antibody neutralization and prolonged ocular retention. With advantages of easy production and low immunogenicity, it provides a promising non-surgical strategy for treating ocular surface pathological angiogenesis and fibrosis. Full article

This study focuses on the isolation, characterization, and evaluation of cytotoxicity of triterpenes extracted from argan pulp. The unsaponifiable lipids extracted from argan pulp are separated into five fractions, two of which are triterpene fractions F2 (composed of α-amyrin, β-amyrin, lupeol, ψ-taraxasterol, taraxasterol) and F4 (erythrodiol). The extraction process utilized solvent-based methods followed by purification through column chromatography. Structural elucidation was carried out using GC-MS and NMR techniques. The cytotoxic activity of the fractions was evaluated against HepG2, MCF-7, and HeLa cell lines. Fraction F4 exhibited IC₅₀ values of 45.58, 71.24, and 98.80 µg/mL, respectively, while fraction F2 showed IC₅₀ values of 122.6, 167.8, and 212.7 µg/mL. Annexin V–FITC/PI flow-cytometry analysis was performed on HepG2 cancer cells and THLE-2 non-tumor cells treated with F4. The results showed a concentration-dependent increase in apoptosis in HepG2 cells, with minimal necrosis. To complement the experimental results, computational analyses were performed to evaluate the pharmacokinetic properties. The triterpenes showed favorable drug-like characteristics and low predicted toxicity. Molecular docking revealed strong interactions with key cancer-related targets, including BCL-2, estrogen receptor α, and HPV16 E6. Full article

Consensus molecular subtype 4 (CMS4) colorectal cancer (CRC) is associated with an aggressive clinical course and poor survival, yet the biological basis of heterogeneity within this subtype remains incompletely understood. DNA methylation is an epigenetic mechanism involved in transcriptional regulation, cellular differentiation, and colorectal tumorigenesis. Here, we integrated single-cell RNA sequencing (scRNA-seq), bulk data, and promoter DNA methylation data to characterize CMS4-associated cancer cell states and methylation-related features. Using the scAB algorithm, we integrated scRNA-seq with bulk CMS4 data and identified CMS4-related cells distributed across multiple patients. Single-cell analyses of cell–cell communication and transcriptional regulation revealed a CMS4-related cancer cell population characterized by macrophage migration inhibitory factor (MIF)-centered intercellular communication, enhanced caudal type homeobox 1 (CDX1) and Kruppel-like factor 5 (KLF5) regulon activity, and gene modules enriched in differentiation-related pathways. CytoTRACE analysis further stratified CMS4 cancer cells into poorly and well-differentiated states, yielding 802 differentially expressed genes (DEGs). Linking these differentiation-associated DEGs with bulk expression and promoter methylation data identified 218 methylation-associated DEGs showing significant inverse methylation expression correlations, suggesting a link between differentiation-related heterogeneity and promoter methylation. Univariable Cox regression followed by LASSO regression further prioritized eight genes for construction of the methylation and differentiation-related prognostic model (MeDiff-PM). MeDiff-PM consistently stratified overall survival in the TCGA CMS4 cohort and two independent validation cohorts, with cutoff-independent continuous Cox analyses further supporting its prognostic association across cohorts. And MeDiff-PM remained prognostically significant after adjustment for available clinical variables. High MeDiff-PM risk scores were associated with activation of P53, WNT, and ubiquitin-mediated proteolysis pathways and with consistent predicted drug response differences for compounds across three CMS4 cohorts. While individual in silico knockout analysis suggested links between MeDiff-PM genes and metallothionein-related and immune-associated transcriptional responses. Collectively, these findings indicate that methylation-associated differentiation features represent a molecular dimension of intra-CMS4 heterogeneity and provide a biologically informed framework for prognostic stratification within CMS4 CRC. Full article

The use of different marine resources, including various colouring agents, is rooted in human history. They have been used as nutrients and medicaments and in luxury products. Readily available marine biological pigments (MBPs) are considered inexpensive materials, since they can be used as colourants. MBPs form part of the ‘’blue technology’’ approach for industrial colouring applications, including staining, textile dyeing, and uses to give fashionable colours to luxury products. They serve as nutrient additives, cosmetic ingredients, and as parts of beauty products. Today, they still are broadly used in the context of diverse new applications. MBPs can be concentrated differently on the bodies of marine creatures, providing each pigment its unique colour and properties. MBPs like carotenoids can complement important cell activities, like photosynthesis. They can function independently or support other micro- and macromolecules. MBPs are essential for their host’s survival. Outside their primary hosts (in the context of uses on and in consumers’ corpora), they either stay unmodified or can be changed by association with specific micro- and macromolecules. A few types of MBPs have been extracted, purified, identified, and formulated as drugs or pure chemicals. MBPs share common properties, such as functioning as antioxidants, can protect against sunlight and UV waves, and can improve vision. They take part in health protection and disease treatment, including anticancer, anti-inflammatory, anti-neurodegeneration, anti-ageing, and anti-wrinkle functions, and can function as an antimicrobial. With many undiscovered properties, MBPs represent a source for de novo applications with innumerable chances that might offer mastery of the fields of colour-based applications. This review summaries the importance of MBPs and addresses important applicable properties that make them attractive for nutraceutical, medicinal, pharmaceutical, and cosmeceutical uses, in addition to various industrial applications, and discusses historical and contemporary facts that have attracted human attention, both in the past and today, along with setting out expectations for the future of MBPs. Full article

Antiretroviral therapy (ART) is essential for controlling human immunodeficiency virus (HIV) infection, requiring strict daily adherence for lifelong viral suppression. However, this continuous oral dosing results in persistent exposure of the gastrointestinal tract (GIT), raising the need to investigate the effects of TC-ART (Tri-combination Abacavir, Dolutegravir, Lamivudine–ART) on epithelial integrity, barrier recovery mechanisms, and surface barrier architecture. TC-ART exposure (125 µM to 4000 µM) showed marked alterations in transepithelial resistance, permeability, and wound-healing abilities even at sub-cytotoxic doses. The dose exposure range at the mid-dose level showed the highest transcriptional activity, characterized by a downregulation of junctional genes [claudins (CLDNs), desmoglein’s (DSGs), and junctional plakoglobin (JUP)] and signaling mediators [the signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase 1 and 3 (MAPK1/3), and catenin beta 1 (CTNNB1)], along with reduced IL-9 expression that is linked to mucin loss. These transcriptional changes were consistent with structural findings, including partial transepithelial electrical resistance (TEER) recovery followed by a decline, delayed wound closure, and waning of the apical mucin layer in a dose-dependent manner. However, several cytokines, like IL-2 and IL-6, showed increased secretion despite lower transcriptional levels, suggesting alternative regulatory control during early stress responses. Together, these results support that TC-ART exposure alters epithelial responses in a way that may transition from early adaptation to signs of impaired recovery, leading to a gradual decline in mucosal barrier function. Such concentration- and time-dependent epithelial stress may contribute to gastrointestinal disturbances observed in treated HIV populations, emphasizing the need for incorporating intestinal epithelial health endpoints in drug safety evaluations. Full article

Background: The leading cause of cancer-related deaths globally is lung cancer, and the P2X7 receptor (P2X7R) is a promising therapeutic target due to its role in the disease progression. Methods: A deep learning-based molecular generation framework that integrates a fragment-based drug method with Relational Graph Convolutional Networks (RGCNs) and a Wasserstein Generative Adversarial Network (WGAN) was employed. Known P2X7R targeting drugs were fragmented to construct a fragment library, which was used to generate new candidate molecules. The generated molecules from the model were evaluated for chemical validity, novelty, Lipinski’s Rule of Five compliance, quantitative estimate of drug-likeness (QED), lipophilicity (LogP), similarity using the Tanimoto coefficient, and binding affinity through molecular docking. Results: The model generated 4498 chemically valid molecules, including 968 unique and 384 novel molecules. Approximately 97% satisfied standard drug-likeness criteria, with QED values predominantly above 0.6 and LogP values within acceptable pharmacokinetic ranges. The novel molecules demonstrated an improved docking score against P2X7R compared to the seed molecules. Conclusions: Despite training on 5000 SMILES due to limited computational resources, the model achieved high validity, strong molecular diversity, and drug-like physicochemical properties, demonstrating the feasibility of a scalable, target-specific AI pipeline for lung cancer drug discovery using fragment-based molecular generation, RGCN and WGAN. Nevertheless, the biological activity of the generated molecules remains experimentally unvalidated, and the findings are based solely on computational analyses. Full article

The histopathology area is being redefined with the use of artificial intelligence (AI), providing robust tools to help bridge cellular morphology, functional assays, and multi-omics data in stem cell research. The ability of stem cells to undergo self-renewal and differentiation is key in regenerative medicine, but their research requires the careful characterization of morphological and molecular phenotypic traits. Traditional histopathology is invaluable, but its application can be limited by inter-observer variability and restricted scalability. These limitations are circumvented by AI-based techniques, such as machine learning and deep learning, which are capable of classifying cells, performing quantitative morphometry, and forecasting stem cell behavior. Adding AI to genomics, proteomics, and metabolomics will contribute to the further identification of biomarkers and pathways that regulate stem cell fate. This convergence provides new possibilities for precision medicine, personalized therapies, and translational uses like drug discovery and disease modeling. However, its potential has not yet been realized because of the existing difficulties in data quality, variability, regulatory control, and ethical issues, especially in terms of the transparency and justice of AI systems. Emphasized areas for the future include explainable AI, federated learning, and a multimodal framework that integrates imaging, sequencing, and clinical data. Interdisciplinary partnerships and adequate regulatory frameworks will help AI-enabled histopathology reshape stem cell studies and speed up the process of translating regenerative medicine into clinical applications. Full article

The use of animal models to study mental illnesses, such as depression, requires proper standardization and extensive expertise. Achieving good construct, face, and predictive validity in depression models is quite challenging. Currently, only a few environmental models, mostly based on chronic stress, and a limited number of genetic models fulfill these criteria. In the quest for new antidepressants, initial screening tests are employed as a preliminary step in research. While these tests do not always meet the requirements of a disease model, they are useful for the early identification of substances that may have antidepressant potential, paving the way for further studies based on established models. This approach to discovering antidepressants was originally designed for traditional medications, which typically act by modulating serotonergic, noradrenergic, and dopaminergic systems, and require multi-week administration to produce a therapeutic effect. In contrast, the new antidepressant ketamine offers rapid therapeutic effects following a single dose and exhibits distinctive behavioral outcomes in both screening tests and animal depression models. These effects have inspired a new model for the search for rapid-acting ketamine-like antidepressants. This review presents the behavioral effects of ketamine and discusses the methodologies used in the search for novel rapid-acting antidepressant drugs (RAADs). Full article

Background/Objectives: Glucagon-like peptide-1 (GLP-1) receptor agonists and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists are used long term for obesity and diabetes, but their oesophageal safety is uncertain: weight loss may reduce Barrett’s oesophagus and adenocarcinoma risk, whereas delayed gastric emptying may worsen reflux. We performed a genetic assessment of target-mediated oesophageal safety. Methods: Two-sample drug-target Mendelian randomisation used cis-expression quantitative trait loci for both receptors (31,684 participants). Outcomes were European genome-wide association studies of gastro-oesophageal reflux disease and the Barrett’s oesophagus/oesophageal adenocarcinoma axis, with a trans-ancestry squamous cell carcinoma comparator. A prespecified gated workflow required positive-control validation, and target specificity required genetic colocalisation (posterior probability of a shared causal variant ≥ 0.70). Candidate metabolic mediators were examined in two-step analyses, and findings were replicated in an independent Finnish population (FinnGen R12). Results: Genetically proxied GLP-1 receptor expression was not associated with reflux disease (odds ratio 0.97, 95% confidence interval 0.85–1.11), arguing against a substantial target-mediated reflux liability; the GIP receptor estimate was not estimable. For the Barrett’s oesophagus/adenocarcinoma endpoint, estimates were near the null for both receptors (GLP-1R 0.96, 0.47–1.96; GIPR 1.00, 0.42–2.37); colocalisation was uninformative because the outcome loci carried no detectable association signal, and wide intervals did not exclude moderate effects. The null reflux findings were reproduced in FinnGen. Adiposity showed the most consistent pathway association, whereas glycaemic traits did not, including when HbA1c was instrumented from a population-based genome-wide association study providing an order of magnitude more variants. Conclusions: GLP-1 receptor perturbation was not associated with reflux disease, providing cautious genetic reassurance. For the Barrett’s oesophagus/adenocarcinoma axis, no target-specific association was demonstrated, but colocalisation was uninformative because the outcome loci carried no detectable signal, and imprecision precludes firm safety conclusions; larger adenocarcinoma-specific studies are warranted. Full article