BACKGROUND: Despite secondary prevention with aspirin, patients with stable cardiovascular disease (CVD) remain at elevated long-term risk of major adverse cardiovascular events. The Cardiovascular Outcomes in People Using Anticoagulant Strategies (COMPASS) double-blind, randomized clinical trial demonstrated that aspirin plus low-dose rivaroxaban (COMPASS regime) significantly decreased the incidence of major adverse cardiovascular events by 24% compared with aspirin alone. However, the mechanisms underlying these potential synergistic/nonantithrombotic effects remain elusive. Extracellular vesicles (EVs) are crucial messengers regulating a myriad of biological/pathological processes and are highly implicated in CVD. OBJECTIVES: We hypothesized that circulating EV profiles reflect the cardioprotective properties of the COMPASS regime. METHODS: A cohort of stable CVD patients (N = 40) who participated in the COMPASS trial and were previously randomized to receive aspirin were prospectively recruited and assigned a revised regimen of open-label aspirin plus rivaroxaban. Blood samples were obtained at baseline (aspirin only) and 6-month follow-up. Plasma EV concentration, size, and origin were analyzed by nanoparticle tracking analysis and flow cytometry. EVs were enriched by ultracentrifugation for proteomic analysis. RESULTS: The COMPASS regime fundamentally altered small (<200 nm) and large (200-1000 nm) EV concentration and size compared with aspirin alone. Crucially, levels of platelet-derived and myeloperoxidase-positive EVs became significantly decreased at follow-up. Comparative proteomic characterization further revealed a significant decrease in highly proinflammatory protein expression at follow-up. CONCLUSION: The observed changes in EV subpopulations, together with the differential protein expression profiles, suggest amelioration of an underlying proinflammatory and prothrombotic state upon dual therapy, which may be of clinical relevance toward understanding the fundamental mechanism underlying the reported superior cardiovascular outcomes associated with this antithrombotic regimen.
- MeSH
- Aspirin * administration & dosage therapeutic use adverse effects MeSH
- Double-Blind Method MeSH
- Extracellular Vesicles * metabolism drug effects MeSH
- Platelet Aggregation Inhibitors * administration & dosage adverse effects therapeutic use MeSH
- Factor Xa Inhibitors * administration & dosage adverse effects therapeutic use MeSH
- Cardiovascular Diseases * blood prevention & control drug therapy MeSH
- Drug Therapy, Combination * MeSH
- Middle Aged MeSH
- Humans MeSH
- Inflammation Mediators blood MeSH
- Prospective Studies MeSH
- Proteomics methods MeSH
- Rivaroxaban * administration & dosage MeSH
- Aged MeSH
- Thrombosis blood prevention & control drug therapy MeSH
- Treatment Outcome MeSH
- Inflammation blood MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Randomized Controlled Trial MeSH
There is growing interest in the role of extracellular vesicles (EVs) in neonatal pathology. This study aimed to characterise circulating EVs following preterm birth. This single-centre prospective observational study included cord and postnatal plasma from preterm (n = 101) and full-term infants (n = 66). EVs were analysed using nanoparticle tracking analysis, flow cytometry, proteomics and procoagulant activity assay. We found changes in the concentration, size, cellular origin and proteomic content of circulating EVs in preterm infants during perinatal adaptation. To understand if these changes were related to prematurity or normal adaptation to extrauterine life, they were also investigated in term infants. There was a dramatic increase in the concentration of small and large EVs on Day 3 in the preterm group; specific subsets of platelet (CD42b+ and CD62P+), endothelial (VEGFR2) and tissue factor EVs were elevated. Differentially expressed proteins relating to haemostasis, pulmonary physiology and immunity were identified between Day 1 and 3 in preterm infants. These changes have never previously been described in a large cohort of preterm infants and differ from healthy term infants. These findings have major implications for future neonatal EV studies, particularly the timing of sample collection. Further work is required to understand the clinical implications of this unique EV profile following preterm birth.
- MeSH
- Extracellular Vesicles * metabolism MeSH
- Adaptation, Physiological * MeSH
- Humans MeSH
- Infant, Premature * blood MeSH
- Infant, Newborn MeSH
- Prospective Studies MeSH
- Proteomics methods MeSH
- Pregnancy MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Infant, Newborn MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH
Breast milk is crucial for infant health, offering essential nutrients and immune protection. However, despite increasing exposure risks from nanoparticles (NPs), their potential infiltration into human breast milk remains poorly understood. This study provides a comprehensive chemical profile of NPs in human breast milk, analyzing their elemental composition, surface charge, hydrodynamic size, and crystallinity. NPs were detected in 42 out of 53 milk samples, with concentrations reaching up to 1.12 × 1011 particles/mL. These particles comprised nine elements, with O, Si, Fe, Cu, and Al being the most frequently detected across all samples. We establish a mechanistic axis for NP infiltration, involving penetration of the intestine/air-blood barriers, circulation in blood vessels, crossing the blood-milk barrier via transcytosis or immune cell-mediated transfer, and eventual accumulation in milk. Structure-activity relationship analysis reveals that smaller, neutral-charged NPs exhibit stronger infiltration capacity, offering potential for regulating NP behavior at biological barriers through engineering design. This study provides the chemical profiles of NPs in human breast milk and uncovers their infiltration pathways.
- MeSH
- Humans MeSH
- Milk, Human * chemistry metabolism MeSH
- Nanoparticles * chemistry analysis MeSH
- Particle Size MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Many photosensitive substances suitable for photodynamic therapy (PDT) have limited applications due to their insufficient solubility in polar solvents. Our research overcomes this challenge by means of nanotechnology in order to transform hydrophobic compounds into stable aqueous solutions, enabling them to use their full potential and unique properties in cancer therapy. In this study, the novel nano-composite cGQDs-PEG-curcumin was developed to overcome the insolubility of curcumin in water and its extraordinary efficacy in PDT was evaluated. Complex characterization was performed using high-resolution transmission electron microscopy (HR-TEM), FTIR, and UV-Vis spectroscopy. Further analysis involved fluorescence lifetime imaging (FLIM), and its cellular localization was mapped with confocal microscopy. In order to evaluate PDT effectiveness, cells treated with cGQDs-PEG-curcumin were irradiated with 5 J/cm2 of 414 nm light. After irradiation, cell viability assay, scanning electron microscopy (SEM), reactive oxygen species (ROS) detection, comet assay, and γH2AX-based DNA double-strand breaks (DSBs) detection were assessed and revealed a remarkable ability of the nano-composite to induce DNA damage after irradiation without ROS production. Our findings highlight the potential of cGQDs-PEG-curcumin as a cutting-edge PDT agent, capable of disrupting cell membrane and nucleolar integrity and impairing ribosomal synthesis, which is crucial for proliferating tumour cells.
- MeSH
- Cell Nucleolus * drug effects metabolism MeSH
- DNA Breaks, Double-Stranded drug effects MeSH
- Photochemotherapy * methods MeSH
- Photosensitizing Agents * pharmacology MeSH
- Graphite * chemistry pharmacology MeSH
- Curcumin * pharmacology chemistry MeSH
- Quantum Dots * chemistry MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Neoplasms * drug therapy MeSH
- Polyethylene Glycols * chemistry pharmacology MeSH
- DNA Damage * drug effects MeSH
- Reactive Oxygen Species metabolism MeSH
- Cell Survival drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Cholinesterases, specifically acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), play critical roles in neurotransmission and are key targets for inhibitors with therapeutic and toxicological significance. This review focuses on the development and application of fluorometric and colorimetric biosensors for the detection of cholinesterase inhibitors. These biosensors take advantage of the unique properties of AChE and BChE to provide sensitive and selective detection methods essential for environmental monitoring, food safety, and clinical diagnostics. Recent advances in assay techniques, including the use of gold nanoparticles, pseudoperoxidase nanomaterials, and innovative enzyme-substrate interactions, are highlighted. This review also discusses challenges and future directions for optimizing these biosensors for practical applications, emphasizing their potential to enhance public health and safety.
- MeSH
- Acetylcholinesterase chemistry metabolism MeSH
- Biosensing Techniques * methods MeSH
- Butyrylcholinesterase chemistry metabolism MeSH
- Cholinesterase Inhibitors * analysis MeSH
- Fluorometry * methods MeSH
- Colorimetry * methods MeSH
- Metal Nanoparticles chemistry MeSH
- Humans MeSH
- Gold chemistry MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Imbalanced redox homeostasis, involving either oxidative stress or reductive stress, can profoundly impact cellular functions, contributing to various diseases. While the implications of oxidative stress in the adverse effects of nanoparticles have been extensively studied, our comprehension of reductive stress within the context of nano-redox system interactions remains limited. Here we illuminate a domino effect initiated by the dehydrogenase-like activity of transition metal borides. Specifically, seven transition metal borides were identified to emulate the enzymatic activity of natural dehydrogenases, resulting in heightened levels of reductive constituents within critical biological redox pairs in cells. Mass cytometry analysis provides compelling evidence that reductive stress initiates an immunosuppressive environment within lung tissues, promoting the metastasis of breast cancer cells to the lungs. In summary, our study unveils the chemical basis of nano-induced reductive stress and establishes a mechanistic axis that interlinks dehydrogenase-like activity, reductive stress, immunosuppression and tumour metastasis.
- MeSH
- Catalysis MeSH
- Humans MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Lung Neoplasms secondary immunology MeSH
- Breast Neoplasms pathology immunology MeSH
- Oxidation-Reduction MeSH
- Oxidative Stress * drug effects MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
A substantial threat to worldwide health, the proliferation of antibiotic-resistant bacteria compels researchers to seek innovative antibacterial substances. This systematic review assesses the role of nanoparticles, particularly Calcium oxide and Silicon oxide nanoparticles, in infection control. The article examines the mechanisms by which these nanoparticles act against various bacteria and evaluates their potential as novel agents in infection control strategies. A systematic literature search from 2015 to 2024 encompassing Web of Science, PubMed, Wiley, Science Direct, and Google Scholar, yielded 70 publications meeting the review criteria. This comprehensive methodology provides a thorough understanding of the capabilities and limitations of Calcium oxide and Silicon oxide nanoparticles as antibacterial agents. The review aims to build a solid foundation for the utilization of nanoparticles in addressing the obstacles presented by antibiotic resistance by combining data from various investigations. Additionally, it aims to explore the safety and environmental implications associated with their use in clinical and environmental settings, providing a comprehensive analysis that may contribute to future studies and real-world applications in the field of antimicrobial technology.
- MeSH
- Anti-Bacterial Agents * pharmacology MeSH
- Infection Control methods MeSH
- Humans MeSH
- Nanoparticles * therapeutic use MeSH
- Silicon Dioxide chemistry MeSH
- Oxides * pharmacology MeSH
- Calcium Compounds * pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Systematic Review MeSH
TiO2 nanoparticles (NPs) are extensively used in various applications, highlighting the importance of ongoing research into their effects. This work belongs among rare whole-body inhalation studies investigating the effects of TiO2 NPs on mice. Unlike previous studies, the concentration of TiO2 NPs in the inhalation chamber (130.8 μg/m3) was significantly lower. This 11-week study on mice confirmed in vivo the presence of TiO2 NPs in lung macrophages and type II pneumocytes including their intracellular localization by using the electron microscopy and the state-of-the-art methods detecting NPs' chemical identity/crystal structure, such as the energy-dispersed X-ray spectroscopy (EDX), cathodoluminescence (CL), and detailed diffraction pattern analysis using powder nanobeam diffraction (PNBD). For the first time in inhalation study in vivo, the alterations in erythrocyte morphology with evidence of echinocytes and stomatocytes, accompanied by iron accumulation in spleen, liver, and kidney, are reported following NP's exposure. Together with the histopathological evidence of hyperaemia in the spleen and kidney, and haemosiderin presence in the spleen, the finding of NPs containing iron might suggest the increased decomposition of damaged erythrocytes. The detection of TiO2 NPs on erythrocytes through CL analysis confirmed their potential systemic availability. On the contrary, TiO2 NPs were not confirmed in other organs (spleen, liver, and kidney); Ti was detected only in the kidney near the detection limit.
- MeSH
- Administration, Inhalation MeSH
- Erythrocytes * drug effects pathology MeSH
- Inhalation Exposure * adverse effects MeSH
- Metal Nanoparticles * toxicity MeSH
- Mice MeSH
- Nanoparticles * toxicity MeSH
- Lung * drug effects metabolism pathology MeSH
- Toxicity Tests, Subchronic MeSH
- Titanium * toxicity pharmacokinetics administration & dosage MeSH
- Tissue Distribution MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: The advancement of nanotechnology underscores the imperative need for establishing in silico predictive models to assess safety, particularly in the context of chronic respiratory afflictions such as lung fibrosis, a pathogenic transformation that is irreversible. While the compilation of predictive descriptors is pivotal for in silico model development, key features specifically tailored for predicting lung fibrosis remain elusive. This study aimed to uncover the essential predictive descriptors governing nanoparticle-induced pulmonary fibrosis. METHODS: We conducted a comprehensive analysis of the trajectory of metal oxide nanoparticles (MeONPs) within pulmonary systems. Two biological media (simulated lung fluid and phagolysosomal simulated fluid) and two cell lines (macrophages and epithelial cells) were meticulously chosen to scrutinize MeONP behaviors. Their interactions with MeONPs, also referred to as nano-bio interactions, can lead to alterations in the properties of the MeONPs as well as specific cellular responses. Physicochemical properties of MeONPs were assessed in biological media. The impact of MeONPs on cell membranes, lysosomes, mitochondria, and cytoplasmic components was evaluated using fluorescent probes, colorimetric enzyme substrates, and ELISA. The fibrogenic potential of MeONPs in mouse lungs was assessed by examining collagen deposition and growth factor release. Random forest classification was employed for analyzing in chemico, in vitro and in vivo data to identify predictive descriptors. RESULTS: The nano-bio interactions induced diverse changes in the 4 characteristics of MeONPs and had variable effects on the 14 cellular functions, which were quantitatively evaluated in chemico and in vitro. Among these 18 quantitative features, seven features were found to play key roles in predicting the pro-fibrogenic potential of MeONPs. Notably, IL-1β was identified as the most important feature, contributing 27.8% to the model's prediction. Mitochondrial activity (specifically NADH levels) in macrophages followed closely with a contribution of 17.6%. The remaining five key features include TGF-β1 release and NADH levels in epithelial cells, dissolution in lysosomal simulated fluids, zeta potential, and the hydrodynamic size of MeONPs. CONCLUSIONS: The pro-fibrogenic potential of MeONPs can be predicted by combination of key features at nano-bio interfaces, simulating their behavior and interactions within the lung environment. Among the 18 quantitative features, a combination of seven in chemico and in vitro descriptors could be leveraged to predict lung fibrosis in animals. Our findings offer crucial insights for developing in silico predictive models for nano-induced pulmonary fibrosis.
- MeSH
- A549 Cells MeSH
- Metal Nanoparticles * toxicity chemistry MeSH
- Humans MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Lung drug effects pathology metabolism MeSH
- Pulmonary Fibrosis * chemically induced metabolism pathology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
MicroRNAs (miRNAs) are small non-coding RNAs (18-22 nucleotides) that regulate gene expression and are associated with various diseases, including Laryngeal Cancer (LCa), which has a high mortality rate due to late diagnosis. Traditional methods for miRNA detection present several drawbacks (time-consuming steps, high cost and high false positive rate). Early-stage diagnosis and selective detection of miRNAs remain challenging. This study proposes a 3D flexible biosensor that combines nanofibers (NFs), gold nanoparticles (AuNPs), and an inverse molecular sentinel (iMS) for enzyme-free, SERS-based detection of miRNA-223-3p, evaluated as a potential LCa biomarker. The electrospun flexible nanofibers decorated with AuNPs enhance Raman signal. Selective detection of miRNA-223-3p is achieved by immobilizing an iMS-DNA probe labeled with a Raman reporter (Cyanine 3) on the AuNPs. The iMS distinctive stem-and-loop structure undergoes a conformational change upon interaction with the miRNA-223-3p, producing an "on to off" SERS signal. The proposed sensor demonstrated a linear detection range from 10 to 250 fM, with a limit of detection (LOD) of 19.50 ± 0.05 fM. The sensor selectivity was confirmed by analyzing the SERS signal behaviour in the presence of both Non-complementary miRNA and miRNA with three mismatched base pairs. This easily fabricable sensor requires no amplification and offers key advantages, including sensitivity, flexibility, and cost-effectiveness.
- MeSH
- Biosensing Techniques * methods MeSH
- Early Detection of Cancer methods MeSH
- Metal Nanoparticles * chemistry MeSH
- Humans MeSH
- Limit of Detection MeSH
- MicroRNAs * analysis genetics MeSH
- Laryngeal Neoplasms * diagnosis genetics MeSH
- Nanofibers * chemistry MeSH
- Spectrum Analysis, Raman * methods MeSH
- Gold * chemistry MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
