Search Results (59)

Gynecological malignancies (ovarian, endometrial, and cervical cancers), including disseminated intravascular coagulation (DIC), often provoke systemic coagulopathy. In recent years, tumor-derived, tissue factor–positive microparticles (TF⁺ MPs) have emerged as potent drivers of cancer-associated thrombosis and possibly DIC. These small (0.1–1 µm) membrane vesicles bud from cancer cell surfaces and carry procoagulant factors (phosphatidylserine and TF) on their surface. We review how TF⁺ MPs are generated by tumor cells and amplify the extrinsic coagulation cascade, potentially triggering DIC in patients with advanced gynecologic cancers. Clinical studies have linked el evated TF⁺ MP levels and activity to venous thromboembolism (VTE) in cancer, and small case series suggest dramatically high MP–TF activity in cancer-related DIC. We summarize evidence that TF⁺ MPs from ovarian tumors carry exceptionally high TF procoagulant activity (median ~80 pg/mL), and nearly all patients with cancer-associated VTE or DIC have MP–TF levels above normal. This review discusses diagnostic implications (e.g., measuring MP–TF activity as a biomarker) and treatment strategies (through the reduction in tumors, anticoagulation, and experimental TF inhibitors) in this setting. We also identify gaps in knowledge (standardized MP assays, prospective studies) and propose future directions (targeting MP formation or TF signaling). Two summary tables highlight recent studies of TF⁺ MPs in gynecologic cancer and their clinical outcomes. Illustrative figures depict the TF⁺ MP-triggered coagulation cascade and a conceptual framework for clinical management. Understanding TF⁺ MPs in gynecological cancer could improve the prediction and management of DIC and related thromboses. Full article

Quercetin (Que) is widely recognized for its antioxidant and neuroprotective properties; however, its clinical potential remains limited due to poor solubility and low oral bioavailability. Nasal powders have emerged as a promising strategy to overcome these limitations, taking advantage of nose-to-brain delivery, offering a direct, non-invasive route to the central nervous system while bypassing first-pass metabolism. This study aims to extend previous work by systematically investigating the impact of different preparation methods (spray drying vs. lyophilization) and the incorporation of hydroxypropyl methylcellulose (HPMC) and mannitol/lecithin microparticles (MLMPs) on the physicochemical characteristics, structural properties, and in vitro diffusion behavior of HPβCD-based nasal powder formulations of Que. Thermal behavior and stability were analyzed using TGA, while morphology and particle distribution were assessed via Scanning Electron Microscopy. In vitro diffusion studies using Franz cells and regenerated cellulose membranes were conducted under simulated nasal conditions. Among all tested formulations, the spray-dried HPβCD/Que powder (F4) showed the highest permeation (0.11 ± 0.01 mg/cm² at 120 min). The inclusion of HPMC improved thermal stability but reduced Que diffusion, likely due to increased viscosity and matrix formation. Blending with MLMPs enhanced powder flow and dose placement, although it modestly reduced diffusion efficiency. Overall, this study highlights the potential of HPβCD-based spray-dried powders for nasal Que delivery and demonstrates how HPMC and MLMPs can be strategically employed to tailor performance characteristics. Full article

In this work, the toxicity level of nano- and microparticles obtained by underwater welding was assessed. The toxicity of nano- and microparticles obtained by underwater welding was evaluated on three types of marine microalgae: Heterosigma akashiwo (Ochrophyta), Porphyridium purpureum (Rhodophyta), and Attheya ussuriensis (Bacillariophyta). The aim was to study the environmental risks associated with the ingress of micro- and nanoparticles of metal oxides into the marine environment. Water samples containing suspensions from wet welding and cutting processes were analyzed by inductively coupled plasma mass spectrometry (ICP-MS) to determine heavy metal concentrations. Biotesting included evaluation of growth inhibition, cell size change, and membrane potential of microalgae using flow cytometry. The results showed that samples APL-1 and APL-2 (flux-cored wire) were the most toxic, causing concentration-dependent growth inhibition of H. akashiwo and A. ussuriensis (p < 0.0001) as well as membrane depolarization. For P. purpureum, ELc and ELw (coated electrodes) samples stimulated growth, indicating species-specific responses. The stability of the nanoparticles and their bioavailability were found to play a key role in the mechanisms of toxicity. The study highlights the need to control the composition of materials for underwater welding and to develop environmentally friendly technologies. The data obtained are important for predicting the long-term effects of pollution of marine ecosystems by substances formed during underwater welding. Full article

The nasal mucosa, being accessible and highly vascularized, opens up new opportunities for the systemic administration of drugs. However, there are several protective functions like the mucociliary clearance, a physiological barrier which represents is a difficult obstacle for drug candidates to overcome. For this reason, effective testing procedures are required in the preclinical phase of pharmaceutical development. Based on a recently reported immortalized porcine nasal epithelial cell line, we developed a test platform based on a tissue-compatible microfluidic chip. In this study, a biomimetic glass chip, which was equipped with a controlled bidirectional airflow to induce a physiologically relevant wall shear stress on the epithelial cell layer, was microfabricated. By developing a membrane transfer technique, the epithelial cell layer could be pre-cultivated in a static holder prior to cultivation in a microfluidic environment. The dynamic cultivation within the chip showed a homogenous distribution of the mucus film on top of the cell layer and a significant increase in cilia formation compared to the static cultivation condition. In addition, the recording of the ciliary transport mechanism by microparticle image velocimetry was successful. Using FITC-dextran 4000 as an example, it was shown that this nasal mucosa on a chip is suitable for permeation studies. The obtained permeation coefficient was in the range of values determined by means of other established in vitro and in vivo models. This novel nasal mucosa on chip could, in future, be automated and used as a substitute for animal testing. Full article

Endotoxins or lipopolysaccharides (LPS), found in the outer membrane of Gram-negative bacterial cell walls, can stimulate the human innate immune system, leading to life-threatening symptoms. Therefore, regulatory limits for endotoxin content apply to injectable pharmaceuticals, and excess LPS must be removed before commercialization. The majority of available endotoxin removal systems are based on the non-specific adsorption of LPS to charged and/or hydrophobic surfaces. Albeit effective to remove endotoxins, the lack of specificity can result in the unwanted loss of essential proteins from the pharmaceutical formulation. In this work, we developed microparticles conjugated to anti-Lipid A antibodies for selective endotoxin removal. Anti-Lipid A particles were characterized using flow cytometry and microscopy techniques. These particles exhibited a depletion capacity > 6 ×10³ endotoxin units/mg particles from water, as determined with two independent methods (Limulus Amebocyte Lysate test and nanoparticle tracking analysis). Additionally, we compared these particles with a non-specific endotoxin removal system in a series of formulations of increasing complexity: bovine serum albumin in water < insulin in buffer < birch pollen extracts. We demonstrated that the specific anti-Lipid A particles show a higher protein recovery without compromising their endotoxin removal capacity. Consequently, we believe that the specificity layer integrated by the anti-Lipid A antibody could be advantageous to enhance product yield. Full article

Membranous CD14 is crucial in the phagocytic activity of neutrophils. However, the role of CD14(+) microparticles (MPs) derived from apoptotic neutrophils (apo-MP) during the phagocytic process is not clear. All trans-retinoic acid (ATRA) induces acute promyelocytic leukemic NB4 cells along granulocytic differentiation. In this study, we investigated the role of CD14(+)apo-MP in the cell–cell interaction during the phagocytic process of apoptotic cells by viable ATRA-NB4 cells. We firstly demonstrate that CD14 expression and phagocytic activity of NB4 cells were upregulated simultaneously after ATRA treatment in a time-dependent manner, and both were significantly enhanced via concurrent lipopolysaccharide treatment. The phagocytic activity of ATRA-NB4 cells and lipopolysaccharide-treated ATRA-NB4 cells were both significantly attenuated by pre-treating cells with an antibody specific to either CD14 or TLR4. Further flow cytometric analysis demonstrates that apoptotic ATRA-NB4 cells release CD14(+)apo-MP in an idarubicin dosage-dependent manner. Both CD14 expression and the phagocytic activity of viable ATRA-NB4 cells were significantly enhanced after incubation with apo-MP harvested from apoptotic ATRA-NB4 cells, and the apo-MP-enhanced phagocytic activity was significantly attenuated by pre-treating apo-MP with an anti-CD14 antibody before incubation with viable cells. We conclude that CD14(+)apo-MP derived from apoptotic ATRA-NB4 cells promotes the phagocytic activity of viable ATRA-NB4 cells in engulfing apoptotic cells. Full article

The paper presents theoretical and experimental investigations of the behavior of an electrolyte solution with three types of ions near an ion-selective microparticle with electrokinetically and pressure-driven flow. A special experimental cell has been developed for the investigations. An anion-selective spherical particle composed of ion-exchange resin is fixed in the center of the cell. An enriched region with a high salt concentration appears at the anode side of the particle when an electric field is turned on, according to the nonequilibrium electrosmosis behavior. A similar region exists near a flat anion-selective membrane. However, the enriched region near the particle produces a concentration jet that spreads downstream akin to a wake behind an axisymmetrical body. The fluorescent cations of Rhodamine-6G dye are chosen as the third species in the experiments. The ions of Rhodamine-6G have a 10-fold lower diffusion coefficient than the ions of potassium while bearing the same valency. This paper shows that the concentration jet behavior is described accurately enough with the mathematical model of a far axisymmetric wake behind a body in a fluid flow. The third species also forms an enriched jet, but its distribution turns out to be more complex. The concentration of the third species increases in the jet with an increase in pressure gradient. The pressure-driven flow stabilizes the jet, yet electroconvection has been observed near the microparticle for sufficiently strong electric fields. The electrokinetic instability and the electroconvection partially destroy the concentration jet of salt and the third species. The conducted experiments show good qualitative agreement with the numerical simulations. The presented results could be used in future for implementing microdevices based on membrane technology for solving problems of detection and preconcentration, and thus simplifying chemical and medical analyses utilizing the superconcentration phenomenon. Such devices are called membrane sensors, and are actively being studied. Full article

Extracellular vesicles (EVs) are cell-derived membrane structures that are formed by budding from the plasma membrane or originate from the endosomal system. These microparticles (100 nm–100 µm) or nanoparticles (>100 nm) can transport complex cargos to other cells and, thus, provide communication and intercellular regulation. Various cells, such as hepatocytes, liver sinusoidal endothelial cells (LSECs) or hepatic stellate cells (HSCs), secrete and take up EVs in the healthy liver, and the amount, size and content of these vesicles are markedly altered under pathophysiological conditions. A comprehensive knowledge of the modified EV-related processes is very important, as they are of great value as biomarkers or therapeutic targets. In this review, we summarize the latest knowledge on hepatic EVs and the role they play in the homeostatic processes in the healthy liver. In addition, we discuss the characteristic changes of EVs and their potential exacerbating or ameliorating effects in certain liver diseases, such as non-alcoholic fatty liver disease (NAFLD), alcoholic fatty liver disease (AFLD), drug induced liver injury (DILI), autoimmune hepatitis (AIH), hepatocarcinoma (HCC) and viral hepatitis. Full article

Extracellular vesicles (EVs) are membrane-bound vesicles that can be released by all cell types. They may have different biogenesis, physical features, and cargo. EVs are important biomarkers for the diagnosis and prediction of many diseases due to their essential role in intercellular communication, their highly variable cargoes, and their accumulation in various body fluids. These natural particles have been investigated as potential therapeutic materials for many diseases. In our previous studies, the clinical usage of tumor-cell-derived microparticles (T-MPs) as a novel medication delivery system was examined. This review summarizes the clinical translation of EVs and related clinical trials, aiming to provide suggestions for safer and more effective oncology therapeutic systems, particularly in biotherapeutic and immunotherapeutic systems. Full article

Many cellular functions are regulated by cell surface charges, such as intercellular signaling and metabolism. Noninvasive measurement of surface charge distribution of a single cell plays a vital role in understanding cellular functions via cell membranes. We report a method for cell surface charge mapping via photoelectric interactions. A cell is placed on an array of microelectrodes fabricated on a transparent ITO (indium tin oxide) surface. An incident light irradiates the ITO surface from the backside. Because of the influence of the cell surface charge (or zeta potential), the photocurrent and the absorption of the incident light are changed, inducing a magnitude change of the reflected light. Hence, the cell surface charge distribution can be quantified by analyzing the reflected light intensity. This method does not need physical or chemical modification of the cell surface. We validated this method using charged microparticles (MPs) and two types of cells, i.e., human dermal fibroblast cells (HDFs) and human mesenchymal stem cells (hMSC). The measured average zeta potentials were in good agreement with the standard electrophoresis light scattering method. Full article

Antihistamines such as levocetirizine dihydrochloride (LC) are commercially used in oral tablets and oral drops to reduce allergic symptoms. In this study, LC was nano-spray-dried using three mucoadhesive polymers and four cyclodextrin species to form composite powders for nasal administration. The product was composed of hydroxypropyl methylcellulose polymer, including LC as a zwitterion, after neutralization by NaOH, and XRD investigations verified its amorphous state. This and a sulfobutylated-beta-cyclodextrin sodium salt-containing sample showed crystal peaks due to NaCl content as products of the neutralization reaction in the solutions before drying. The average particle size of the spherical microparticles was between 2.42 and 3.44 µm, except for those containing a polyvinyl alcohol excipient, which were characterized by a medium diameter of 29.80 µm. The drug was completely and immediately liberated from all the samples at pH 5.6 and 32 °C; i.e., the carriers did not change the good dissolution behavior of LC. A permeability test was carried out by dipping the synthetic cellulose ester membrane in isopropyl myristate using modified horizontal diffusion cells. The spray-dried powder with β-cyclodextrin showed the highest permeability (188.37 µg/cm²/h), as this additive was the least hydrophilic. Products prepared with other cyclodextrins (randomly methylated-beta-cyclodextrin, sulfobutylated-beta-cyclodextrin sodium salt and (hydroxypropyl)-beta-cyclodextrin) showed similar or slightly higher penetration abilities than LC. Other polymer excipients resulted in lower penetration of the active agent than the pure LC. Full article

In biomedical diagnosis, the efficient separation and purification of specific targets from clinical samples is the desired first step. Herein, the concept of virtual filter membranes based on optically-induced dielectrophoresis (ODEP) manipulation in a microfluidic channel is proposed as a light screening membrane for the separation of polystyrene (PS) microparticles with three different diameters of 15.8, 10.8 and 5.8 µm. The ODEP manipulation velocity of three types of PS microparticles reacted with the color brightness setting was investigated to determine the light intensity to induce an ODEP force higher than the drag force of fluid speed. The color brightness of the light bar in three areas of the light screening membrane was selected as 60%, 70% and 100% to isolate PS microparticles with diameters of 15.8, 10.8 and 5.8 µm, respectively. With a double light bar and a flow rate of 3 µL/min, the recovery rate and isolation purity was improved by 95.1~100% and 94.4~98.6% from the mixture of three types of PS microparticles within 2 min, respectively. This proposed light screening membrane could be a candidate for the separation of small-volume and rare biomedical samples, including circulating tumor cells (CTCs) and bacteria in the blood. Full article

While there has been intensive research on the influence of microplastics (MPs) on aquatic organisms and humans, their effect on microorganisms is relatively little-known. The present study describes the response of the Trichoderma harzianum strain to low-density polyethylene (LDPE) microparticles. MPs, either separately or with metolachlor (MET), were added to the cultures. Initially, MP was not found to have a negative effect on fungal growth and MET degradation. After 72 h of cultivation, the content of fungal biomass in samples with MPs was almost three times higher than that in the cultures without MPs. Additionally, a 75% degradation of the initial MET was observed. However, due to the qualitative and quantitative changes in individual classes of phospholipids, cell membrane permeability was increased. Additionally, MPs induced the overproduction of reactive oxygen species. The activity of superoxide dismutase and catalase was also increased in response to MPs. Despite these defense mechanisms, there was enhanced lipid peroxidation in the cultures containing the LDPE microparticles. The results of the study may fill the knowledge gap on the influence of MPs on filamentous fungi. The findings will be helpful in future research on the biodegradation of contaminants coexisting with MPs in soil. Full article

Advancing our understanding of the mechanism of the interaction between inhaled pollutant microparticles and cell membrane components is useful to study the impact of fine particulate matter on human health. In this paper, we focus on the effect of cholesterol (Chol) molecules on the surface properties of a model membrane in the presence of silica microparticles (MPs). Mixed monolayers containing phospholipid-dipalmitoylphosphatidylcholine (DPPC), Chol and silica particle dispersions (MPs; 0.033% w/w, 0.33% w/w and 0.83% w/w) were formed and studied using the Langmuir monolayer technique complemented by Brewster Angle Microscopy (BAM) images. It was shown that Chol caused a condensation of the DPPC monolayer, which influenced the penetration of MPs and their interactions with the model membrane. The relaxation experiments of the lipid–MP monolayer proved that the presence of Chol molecules in the monolayer led to the formation of lipid and MP complexes. Strong interactions between Chol and MPs contributed to the formation of more stable monolayers. The presented results can be useful to better comprehend the interaction between particulate materials and the lipid components of biomembranes. Full article

Nano- and microparticles enter the body through the respiratory airways and the digestive system, or form as biominerals in the gall bladder, salivary glands, urinary bladder, kidney, or diabetic pancreas. Calcium, magnesium, and phosphate ions can precipitate from biological fluids in the presence of mucin as hybrid nanoparticles. Calcium carbonate nanocrystallites also trap mucin and are assembled into hybrid microparticles. Both mucin and calcium carbonate polymorphs (calcite, aragonite, and vaterite) are known to be components of such biominerals as gallstones which provoke inflammatory reactions. Our study was aimed at evaluation of neutrophil activation by hybrid vaterite–mucin microparticles (CCM). Vaterite microparticles (CC) and CCM were prepared under standard conditions. The diameter of CC and CCM was 3.3 ± 0.8 µm and 5.8 ± 0.7 µm, with ƺ-potentials of −1 ± 1 mV and −7 ± 1 mV, respectively. CC microparticles injured less than 2% of erythrocytes in 2 h at 1.5 mg mL⁻¹, and no hemolysis was detected with CCM; this let us exclude direct damage of cellular membranes by microparticles. Activation of neutrophils was analyzed by luminol- and lucigenin-dependent chemiluminescence (Lum-CL and Luc-CL), by cytokine gene expression (IL-6, IL-8, IL-10) and release (IL-1β, IL-6, IL-8, IL-10, TNF-α), and by light microscopy of stained smears. There was a 10-fold and higher increase in the amplitude of Lum-CL and Luc-CL after stimulation of neutrophils with CCM relative to CC. Adsorption of mucin onto prefabricated CC microparticles also contributed to activation of neutrophil CL, unlike mucin adsorption onto yeast cell walls (zymosan); adsorbed mucin partially suppressed zymosan-stimulated production of oxidants by neutrophils. Preliminary treatment of CCM with 0.1–10 mM NaOCl decreased subsequent activation of Lum-CL and Luc-CL of neutrophils depending on the used NaOCl concentration, presumably because of the surface mucin oxidation. Based on the results of ELISA, incubation of neutrophils with CCM downregulated IL-6 production but upregulated that of IL-8. IL-6 and IL-8 gene expression in neutrophils was not affected by CC or CCM according to RT²-PCR data, which means that post-translational regulation was involved. Light microscopy revealed adhesion of CC and CCM microparticles onto the neutrophils; CCM increased neutrophil aggregation with a tendency to form neutrophil extracellular traps (NETs). We came to the conclusion that the main features of neutrophil reaction to mucin–vaterite hybrid microparticles are increased oxidant production, cell aggregation, and NET-like structure formation, but without significant cytokine release (except for IL-8). This effect of mucin is not anion-specific since particles of powdered kidney stone (mainly calcium oxalate) in the present study or calcium phosphate nanowires in our previous report also activated Lum-CL and Luc-CL response of neutrophils after mucin sorption. Full article