Search Results (496)

Peripheral neuropathy (PN) is a debilitating condition characterized by chronic pain, numbness, and motor dysfunction, with limited treatment options. Ischemic stroke can cause central neuropathy, which may also induce PN. Human mesenchymal stem cells (hMSCs) have shown promise in therapeutic applications, but limitations in cell viability, immune response, and efficacy persist. Extracellular vesicles (EVs), which facilitate cell-free intercellular communication, offer a promising alternative for nerve regeneration. Electrical stimulation (ES) has emerged as a method to enhance EV secretion, and this study investigates its potential for promoting EV production from human adipose tissue-derived mesenchymal stem cells (hASCs) and human Schwann cells (hSCs). In this study, hASCs, hSCs, and lipopolysaccharide (LPS)-induced inflamed hSCs were subjected to one hour of low-frequency direct current (DC) electrical stimulation (100 mV/mL) for 7 days. EVs were isolated using differential ultracentrifugation and characterized through nanoparticle tracking analysis (NTA). Gene expression was analyzed via qRT-PCR to evaluate markers associated with EV biogenesis as well as pro- and anti-inflammatory cytokines. Our results demonstrate that ES significantly increases EV secretion from both hASCs and hSCs, with a notable upregulation of genes involved in both the endosomal sorting complex required for transport (ESCRT)-dependent and ESCRT-independent pathways of EV biogenesis. Additionally, ES modulates inflammation-related markers, promoting anti-inflammatory gene expression and reducing pro-inflammatory gene levels. Notably, LPS-induced hSCs exhibited a phenotype shift from myelinating to non-myelinating cells, producing EVs capable of modulating the inflammatory microenvironment. However, prolonged exposure to ES led to a decrease in EV secretion and changes in EV size distribution, suggesting potential cellular adaptation or membrane stress. This study highlights the potential of ES as a scalable, cell-free strategy to enhance EV production, offering new insights into its therapeutic applications for peripheral neuropathy and nerve regeneration. Full article

In recent years, gentrification has frequently been linked to housing inequality and mass evictions and portrayed in a negative light. This study defines gentrification in terms of neighborhood median household income, income diversity, and their level and trajectories over 14 years (2010–2023), and classifies neighborhood gentrification stages using hierarchical clustering. It then adopts a quantitative, data-driven approach to examine the pairwise statistical and geospatial relationships among gentrification stages, executed evictions (2023–2024), and other housing characteristics (rent, socioeconomic status, and demographics) across New York City neighborhoods. The results demonstrate that pre-gentrifying neighborhoods were 39.08 times more likely to have eviction rates 1.5 standard deviations above the mean, 14.19 times more likely to be geospatial eviction hotspots, and three times more likely to experience evictions per neighborhood than fully gentrified neighborhoods. Income-adjusted regression models indicate that gentrification-stage membership explains variation in eviction severity beyond median household income alone, increasing explained variance from 27.9% to 42.6%; late-stage gentrifying and stable low-change neighborhoods showed significantly lower eviction severity than fully gentrified neighborhoods at comparable income levels. Spatially, the Bronx, the most economically disadvantaged borough, contained 11 of 17 eviction-outlier NTAs and 37 of 48 geospatial eviction hotspots, making it the most eviction-concentrated area in the city. This clustering-based classification framework relies only on widely available Census and administrative data and can be applied to other metropolitan areas or adapted to related urban domains such as land-use and zoning analysis. Targeted, actionable recommendations are offered to direct eviction-prevention resources toward the most vulnerable communities. Full article

Pulmonary delivery of anti-tuberculosis drugs has emerged as a promising alternative for increasing local drug concentrations whilst minimising side effects. Natural polymers—polysaccharides capable of forming polyelectrolyte complexes (PECs) through electrostatic interactions—show great promise in this field. In this study, mucoadhesive chitosan-gellan gum nanoparticles were developed for the controlled release of isoniazid using the polyelectrolyte complex coacervation method. Parameters such as the chitosan-to-gellan gum ratio and the medium pH were investigated to achieve suitable particle size, polydispersity, surface charge, drug loading and encapsulation efficiency. The morphology of the produced nanoparticles was determined using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA), which confirmed the formation of nanoscale spherical particles. The mucoadhesive properties were tested on ovine lung tissue using fluorescence retention analysis, whilst in vitro drug release was studied under physiological conditions. Antimycobacterial activity against Mycobacterium tuberculosis H37Rv was assessed using the Mycobacteria Growth Indicator Tube (MGIT) system, followed by subculturing on Löwenstein–Jensen medium. The produced nanoparticles exhibited high mucoadhesion, maintaining prolonged retention on lung tissue. Drug release showed an initial burst followed by sustained release over 24 h. These results demonstrate that CSGG–INH nanoparticles possess sustained drug release, good mucoadhesion to the lungs and high antimycobacterial activity, supporting their further development as potential carriers for pulmonary delivery of anti-tuberculosis drugs. Full article

Population aging in Asia is arriving before the institutions to support it. Assessments of social protection usually treat sustainability, adequacy and fairness separately, obscuring how they trade off within one system. This study introduces NTA-SAFE, five indicators derived from the National Transfer Accounts lifecycle identity, applied to Japan, South Korea, Thailand, the Philippines and Indonesia. Base-year per capita profiles are combined with UN World Population Prospects 2024 populations through 2050, so all movement reflects age structure alone; results are reported across all five WPP series as a demographic sensitivity range. An explicit two-part rule classifies each economy by who provides net transfers to its elderly and by demographic stage. Japan and South Korea are state-led; the Philippines and Indonesia are family-asset-led, retaining the fiscal headroom of young populations. Thailand is transitional and the substantive case, carrying the demographic and fiscal exposure of a state-led system while families supply 78% of net transfer support to its elderly. Thai elderly consumption sits near working-age parity: the exposure lies not in current living standards but in the institutional basis on which they rest. Direction of change is robust in 24 of 25 country-indicator combinations. Higher benefit generosity is consistently associated with a narrower fiscal base, as a budget constraint implies, though five cases cannot establish universality. Whether family-mediated support reproduces life-course inequality into old age is a hypothesis the framework can pose but not test, the accounts carrying no distributional data. Indonesia’s classification is provisional, its profile predating the 2014 health insurance reform. NTA-SAFE is replicable wherever National Transfer Accounts exist. Full article

Extracellular vesicles (EVs) from Gram-positive bacteria are gaining more interest as potential biotechnological systems for vaccines and drug delivery. However, scalable production protocols remain poorly defined. Here, we evaluated upstream and downstream processes for the controlled production of extracellular vesicles from Staphylococcus epidermidis. Bacterial growth and vesicle release were compared between shake-flask cultures and a controlled stirred-tank bioreactor (STBR), and vesicles were isolated using either ultracentrifugation (UC) or ultrafiltration (UF). STBR cultivation significantly increased biomass accumulation during the exponential phase while preserving the same growth observed in shake flasks. Nanoparticle tracking analysis (NTA) showed time-dependent particle accumulation in both systems, with UF consistently yielding higher particle recovery than UC. Despite differences in yield, vesicles isolated by both methods displayed comparable size distributions and TEM imaging confirmed the spherical morphology. Protein quantification revealed greater protein recovery in UF preparations, whereas particle-to-protein ratios indicated similar sample composition between isolation methods. Together, these results suggest that controlled STBR fermentation combined with UF enables a reproducible, scalable production of S. epidermidis EVs without compromising vesicle integrity. This work provides an integrated framework for Gram-positive EV manufacturing and supports future translational applications. Full article

Enterotoxigenic Escherichia coli F18 (E. coli F18) ranks as the leading bacterial cause of diarrhea in piglets. Exosomes and other extracellular vesicles ferry diverse RNA species, among them mRNAs and non-coding RNAs, and act as central intermediaries in intercellular communication. Their contribution to the biology of E. coli F18-infected IPEC-J2 cells, however, has received no attention. In this study, we characterized the morphology, particle dimensions, and output of exosomes secreted by control and E. coli F18-infected cells, then profiled their circRNA cargo by RNA-seq. Nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blotting verified that the vesicle-like particles recovered from IPEC-J2 cultures were bona fide exosomes. We then catalogued the circRNAs within IPEC-J2-derived exosomes during E. coli F18 infection. Comparing the two groups yielded 280 differentially expressed circRNAs (DECs), of which circCHUK displayed the largest shift. circCHUK abundance rose sharply in E. coli F18-treated IPEC-J2 cells. Knocking down or overexpressing circCHUK markedly altered the adherence of E. coli F18 to IPEC-J2 cells. ceRNA network construction pinpointed the exo-circCHUK/ssc-miR-339-3p/FUT2 as candidate axis. Collectively, we speculated that exo-circCHUK is a new biomarker that regulates E. coli F18 susceptibility, offering a conceptual framework for tackling bacterial diarrhea in piglets. Full article

The personal care product market has expanded rapidly in recent years, along with growing consumer awareness of chemical exposures and increasing demand for “clean” products. Consumer perceptions of product safety and potential health impacts are commonly based on ingredient labels, intended use, and certifications, rather than the full chemical composition of finished products. In this study, we conducted a targeted review of certification and ingredient-evaluation programs in the United States and European markets. Eighteen programs were identified and characterized based on their evaluation approaches, data sources, and whether they incorporate analytical measurement of finished products. We also evaluated the current U.S. and EU regulatory frameworks. Across both certification and regulatory systems, evaluation was found to rely primarily on ingredient-based approaches and supporting documentation, with limited incorporation of analytical measurement. As a result, contaminants, impurities, and incidentals/non-intentionally added substances (which have previously been identified in many consumer products) may not be consistently identified or evaluated for safety. These findings highlight a fundamental gap between intended formulation and actual product composition. Incorporating analytical measurement, particularly non-targeted approaches, provides a complementary groundwork for identifying previously unrecognized chemical exposures and improving the accuracy of product safety certification programs and hazard assessments. Aligning evaluation with measured chemical composition may enhance transparency and better reflect real-world exposure, support more credible sustainability claims, enhance consumer trust, support growing market demand, support consumer safety, and contribute to more effective regulation in the personal care industry. Full article

AgaDcat is a promising β-agarase for the production of functional neoagarooligosaccharides (NAOSs), but its limited thermal stability and poor reusability as a free enzyme increase enzyme consumption and production cost during repeated agarose hydrolysis. In this study, β-agarase AgaDcat was immobilized on nickel-nitrilotriacetic acid magnetic nanoparticles (Ni-NTA-MNPs) through His-tag/Ni-NTA affinity interactions. The successful preparation of Ni-NTA-MNPs and the immobilization of AgaDcat were verified by SEM, EDS, VSM, FT-IR, XRD, and TGA. Following optimization, the immobilized enzyme exhibited an activity retention of 80.47%. Thermal stability assays showed that the immobilized enzyme was more thermostable than the free enzyme. After incubation at 50 °C for 60 min, the immobilized enzyme retained 59.4% of its initial activity, whereas the free enzyme retained only 29.1%. Moreover, the immobilized enzyme displayed good reusability, retaining 90.59% and 58.71% of its activity after 3 and 7 cycles, respectively. HPAEC-PAD analysis showed that the immobilized enzyme reached reaction equilibrium within 4–8 h, with neoagarotetraose (NA4) and neoagarohexaose (NA6) identified as the major degradation products, whereas the free enzyme required 20 h, indicating significantly improved catalytic efficiency. These results indicate that IMAC-based immobilization improves the stability, reusability, and catalytic efficiency of β-agarase, providing a promising reusable biocatalytic strategy for the efficient production of functional neoagarooligosaccharides. Full article

A strategy based on the hyperbranched polyol process (HB-polyol process) is presented for the synthesis of hemocompatible cobalt nanocomposites Co/G_nOH with controlled morphology and predictable functional properties. Third-generation (G₃OH) and fourth-generation (G₄OH) hyperbranched polyester polyols were used as smart polyol nanoreactors. We establish, for the first time, the fundamental physicochemical principles of the HB-polyol process based on a comprehensive analysis of FT-IR, UV-Vis, NMR, NTA, and TEM data. These principles encompass the stages of pre-organization, nucleation, polyol oxidation and the stabilization of cobalt-loaded metallopolymer nanocomposites within the binary [CoCl₂–G_nOH] system (n = 3, 4). Magnetic measurements revealed that the samples exhibit paramagnetic properties at 5 K. The size of the magnetic cores in the Co/G₃OH samples was estimated by fitting the field-dependent magnetization curves to the Langevin function and was found to range from 1.4 nm to 7.2 nm, indicating the superparamagnetic behavior of the nanocomposites. In vitro biological tests of the Co/G_nOH nanocomposites demonstrated high hemocompatibility, as well as pronounced modulatory and antimycotic activity across all samples. The obtained results hold promise for the development of simple design technologies for multifunctional “intelligent” materials based on metal and dendritic nanoparticles for biomedical applications. Full article

Background: Regional heterogeneity of the macula and peripheral retinas contributes to the differences in retinal physiology, metabolic demand and susceptibility to macular diseases such as age-related macular degeneration (AMD), diabetic macular oedema (DME) and Macular telangiectasia type 2 (MacTel). Extracellular vesicles (EVs) released from the retinal pigment epithelium (RPE)-choroid are increasingly recognised as mediators of extracellular communication and correlate with the molecular biological states of their tissue of origin. However, regional variation in EV composition in human RPE-Choroid tissues remains poorly characterised. Methods: Human macular and peripheral RPE-choroid explants from non-diseased donor eyes (n = 4) were cultured ex vivo using a transwell system. EV and EV-depleted conditioned media were collected by differential ultracentrifugation, respectively. EVs were characterised by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Proteomic profiling was performed using LC-MS/MS followed by multivariate, pathway, and differential expression analyses. Results: TEM and NTA confirmed the presence of vesicle-like particles in a 119–140 nm size range, indicating small EVs in both regions. Proteomic analysis demonstrated a region-associated separation between the macular and peripheral samples in both EV proteome and EV-depleted soluble secretome datasets. GO enrichment analysis revealed that macular EV proteomes were enriched for wound healing, cell–substrate adhesion, and focal adhesion-related terms with a high abundance of integrin and annexin family members, whereas peripheral EV proteomes were enriched for retinoid- and vitamin-binding terms. In the EV-depleted soluble secretome, macular-enriched proteins were associated with actin binding and extracellular matrix-related terms, while peripheral-enriched proteins were correlated with RNA localisation and nuclear compartment terms. Comparative analysis identified EV-specific, secretome-specific, and shared extracellular protein pools. Several EV-specific markers and membrane proteins such as annexins and integrins, showed a relatively high enrichment in macular EV proteomes, whereas CD63 is more abundant in peripheral EV proteomes. In contrast, EV-depleted soluble secretome contains cytokine- and ligand-associated proteins, including MIF, SPP1, and IL6, which may suggest that EVs and soluble secreted proteins represent partially distinct extracellular signalling compartments. Conclusions: Human macular and peripheral RPE-choroid explants released secretory proteins in a regional differentiated manner, supported by PLS-DA and GO enrichment analyses of both EV proteomes and EV-depleted soluble secretome. Further analysis of the EV proteomes may show that such differences were also able to be reflected in protein categories such as EV-specific markers, mitochondrial and membrane proteins. These findings provide a foundation for future investigations into the role of EV-mediated communication in macular diseases and may support the development of region-specific extracellular biomarkers and therapeutic targets. Full article

Background/Objectives: Psoriasis is a chronic, immune-mediated inflammatory skin disorder affecting millions of individuals worldwide. It remains a therapeutic challenge due to the limited skin penetration of many drugs, adverse systemic effects, and the need for long-term management. Transferosomal nanoformulations containing natural products were proposed as a potential therapeutic tool. Methods: Transferosomes containing 20-hydroxyecdysone and resveratrol were prepared using the thin-film hydration method followed by probe ultrasonication, generating several formulation variants differing in composition. The vesicles were characterized by dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) to determine size, polydispersity index (PDI), and zeta potential. Furthermore, time-domain nuclear magnetic resonance (TD-NMR) relaxation measurements were employed to evaluate local molecular dynamics and membrane fluidity, providing deeper insights into the structural integrity and elasticity of the transferosomal systems. The stability of the nanoformulations was assessed for one month in water and phosphate-buffered saline (PBS). Viability was evaluated in vitro using the MTS assay on human epidermal keratinocyte (HEK) and psoriasis-patient derived human epidermal keratinocyte (PHEK) cell lines, alongside antimicrobial profiling against four representative human skin microbiome strains. Acute toxicity was further examined in vivo using the Danio rerio FET test. Results: The formulations demonstrated high physicochemical stability over the tested period, maintained desirable particle sizes within 100–200 nm, and showed no cytotoxicity toward skin-associated bacteria or in the zebrafish model. Conclusions: The developed nanoformulations present suitable properties in terms of safety and stability and can be considered for potential use in psoriasis treatment. Full article

Iron oxide-based nanomaterials have attracted considerable interest owing to their unique magnetic properties and potential biomedical and environmental applications. In this study, starch-coated superparamagnetic Fe₃O₄ nanoparticles (Sta-MNP) were synthesized and comprehensively characterized using electron microscopy (TEM, SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), vibrating sample magnetometry (VSM), attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR), and nanoparticle tracking analysis (NTA). The results confirmed the formation of a magnetite-based iron oxide nanoparticles sample with a median physical diameter of 12.24 nm, superparamagnetic behavior with a saturation magnetization of 59.81 emu/g, and effective starch coating on the nanoparticle surface. The biological effects of Sta-MNP were assessed in Triticum aestivum L. using the mitotic index (MI) and aberration index (AI) as cytogenetic endpoints, respectively. Exposure-induced concentration-dependent increases in both parameters across the tested volume fractions (0–200 µL/L), suggesting a significant interaction between Sta-MNP and dividing cells. Overall, this study provides a comprehensive physicochemical profile of starch-coated magnetite nanoparticles and demonstrates their potential cytogenetic impact in a plant model system, supporting further investigation of their environmental interactions and potential agricultural applications. Full article

This work analyzes protocol-dependent effects on the colloidal characterization and drug loading/release analysis of model thermosensitive PNIPAM-co-COOH microgels and shows how they can be quantified or minimized through targeted methodological refinements. Findings reveal that standard single-beam DLS underestimates the collapsed hydrodynamic radius by 18% at 43 °C due to thermal convection. After drift correction, 3D-DLS combined with SLS provides a consistent description of thermally induced collapse, pH-dependent swelling and core–corona structure. Regarding drug delivery, loading efficiency for Doxorubicin and 5-Fluorouracil is maximized near the volume phase transition temperature, where hydrophobic interactions are strongest. For release studies, dialysis is recommended, but free-drug blanks are required to account for membrane-induced delay and ensure accurate early kinetic profiles. By integrating TEM, AFM, SLS, DLS, NTA and LDE, this study establishes a robust framework for the colloidal characterization of thermosensitive microgels. These refinements reduce experimental bias and may be extended to related soft nanocarriers. Full article

A strong seismic swarm occurred in the south Aegean Sea from late January to March 2025. Here, we apply natural time analysis (NTA), which can identify the critical stage before strong earthquakes, and find that all earthquakes of magnitude five or larger have been preceded by criticality. Moreover, we study the frequency–magnitude distribution of the seismic swarm and suggest a generalization of the Gutenberg–Richter law, which is compatible with Tsallis nonextensive statistical mechanics. This suggestion is tested for different earthquake catalogs available for this seismic swarm with successful results. Since NTA has already been applied to the strongest seismic swarm ever recorded in Japan, observed in 2000 in the Izu Islands region, we apply the present suggestions to the case of another swarm observed during June 1980, which was the strongest seismic swarm in the same region since 1979. The strongest magnitude class M7 earthquake of that swarm was also preceded by criticality in the NTA. Finally, we show that earthquake nowcasting could be applied to predict in advance that no earthquake exceeding magnitude 6.5 would occur during the south Aegean seismic swarm. Full article

Safflower (Carthamus tinctorius L.) is a cash crop grown worldwide. Its seeds and flowers are primarily processed for edible oil and medicinal raw materials, while stems and leaves are discarded as agricultural waste. Recently, plant-derived exosome-like nanoparticles (PELNs) have gained growing research interest in food nutrition owing to their exceptional biocompatibility and relatively low cost for large-scale production. This study aimed to explore the potential functional value of safflower leaf agricultural waste by isolating safflower-derived PELNs. Firstly, a protocol was established for the isolation and purification of safflower (Carthamus tinctorius L.)-derived exosome-like nanoparticles (Ct-ELNs) from safflower leaves using sucrose density gradient ultracentrifugation. NTA analysis revealed that the 30–45% sucrose fraction enriched with Ct-ELNs exhibited the most uniform particle size, highest particle concentration, and optimal purity. Transmission electron microscopy confirmed typical PELNs ultrastructure: disc- or cup-shaped vesicles surrounded by bilayer lipid membranes. FM4-64 fluorescence suggests time-dependent association and likely cellular uptake of labeled Ct-ELNs by IPEC-J2 cells. Cellular assays demonstrated that Ct-ELNs elevated IPEC-J2 cell metabolic activity under matched protein-normalized dosing conditions. The 30–45% sucrose fraction showed the most favorable physicochemical profile and preliminary in vitro protective effects, including improved IPEC-J2 cell metabolic activity and modulation of Enterotoxigenic Escherichia coli (ETEC)-induced inflammation-related gene expression. Overall, this study established an optimized isolation protocol for Ct-ELNs derived from safflower leaves. These data indicate that safflower-derived Ct-ELNs confer preliminary cytoprotective transcriptional regulatory effects on intestinal epithelial cells under in vitro culture conditions. Full article