Search Results (2,453)

Background: Effective regenerative therapeutics for acute and chronic wounds remain a critical unmet need in biomedicine. Objectives: This study aimed to develop novel collagen–cerium oxide nanoparticle hydrogels designed to enhance cellular metabolism, proliferation, and antioxidant/antimutagenic activity, accelerating wound regeneration in vivo. Methods: Collagen–nanocerium composites were synthesized by combining a collagen extract with cerium oxide nanoparticles at defined concentrations. In vitro assays using human fibroblasts identified two formulations that enhanced proliferation and metabolic activity by 42–50%. FTIR spectroscopy confirmed chemical interactions within the composite matrix. Toxicity, antioxidant, and antigenotoxic effects were evaluated using Escherichia coli MG1655 lux-biosensors to assess their general toxicity, antioxidant and pro-oxidant activities, and antigenotoxic and promutagenic effects. In vivo efficacy was tested in Wistar rats with full-thickness skin wounds. Treated groups were compared to untreated controls and Dexpanthenol-treated positive controls. On days 3, 7, and 14, healing was assessed clinically, histologically, and morphometrically. Results: Biosensor analysis demonstrated non-toxicity and antigenotoxic activity of the nanocomposites, reduced DNA damage by up to 45%, providing 31–49% protection against H₂O₂ and 15–23% against O₂⁻ radicals. The animal study results demonstrated significantly accelerated healing with both nanocomposites versus control and comparison groups, evidenced by improved tissue regeneration, reduced inflammation, and increased fibroblast infiltration. Conclusions: The developed hydrogels exhibit promising pharmacological profiles, including antioxidant, antimutagenic, anti-inflammatory, and pro-regenerative effects validated across in vitro and in vivo models. Full article

Background/Objectives: A comparative study of silver (Ag), titanium nitride (TiN), zirconium nitride (ZrN), and copper (Cu) coatings on titanium (Ti) disks, considering the specifications of a microporous skin- and bone-integrated titanium pylon (SBIP), was performed to assess their biocompatibility, osseointegration, and mechanical properties. Methods: To assess cytotoxicity and biocompatibility, Ti disks with various metal coatings were co-cultured with FetMSCs and MG-63 cells for 1, 3, 7, and 14 days and subsequently evaluated using a cell viability assay, as supported by SEM and confocal microscopy studies. The antimicrobial activity of the selected four materials coating the implants was tested against S. aureus by mounting Ti disks onto the surface of LB agar dishes spread with a bacterial suspension and measuring the diameter of the growth inhibition zones. Quantitative Real-Time Polymerase Chain Reaction (RT-PCR) analysis of the relative gene expression of biomarkers that are associated with extracellular matrix components (fibronectin, vitronectin, type I collagen) and cell adhesion (α2, α5, αV integrins), as well as of osteogenic markers (osteopontin, osteonectin, TGF-β1, SMAD), was performed during the 14-day follow-up period. Additionally, the activity of matrix metalloproteinases (MMP-1, -2, -8, -9) was assessed. Results: All samples with metal coatings, except the copper coating, demonstrated a good cytotoxicity profile, as evidenced by the presence of a cellular monolayer on the sample surface on the 14th day of the follow-up period (as shown by SEM and inverted confocal microscopy). All metal coatings enhanced MMP activity, as well as cellular adhesion and osteogenic marker expression; however, TiN showed the highest values of these parameters. Significant inhibition of bacterial growth was observed only in the Ag-coated Ti disks, and it persisted for over 35 days. Conclusions: The silver-based coating, due to its high antibacterial activity, low cytotoxicity, and biointegrative capacity, can be recommended as the coating of choice for microporous titanium implants for further preclinical studies. Full article

Carbon-fiber-reinforced plastic (CFRP) machining by ultrashort-pulse lasers promises high precision but is limited due to the heterogeneous epoxy–carbon fiber structure, which creates heat-affected zones and variable kerf quality. This work investigates synthesized copper hydroxyphosphate as a laser-absorbing additive to improve femtosecond (1030 nm) laser ablation of CFRP. Copper hydroxyphosphate particles were synthesized hydrothermally and incorporated into an epoxy matrix to produce single-ply CFRP laminates. Square patterns (0.5 × 0.5 mm) were ablated with a pulse energy of 0.5–16 μJ. Then, ablated volumes were profiled and materials characterized by SEM and EDS. In neat epoxy the copper additive reduced optimum ablation efficiency and decreased penetration depth, while producing smoother, less porous surfaces. In contrast, CFRP with copper hydroxyphosphate showed increased efficiency and higher penetration depth. SEM and EDS analyses indicate more uniform matrix removal and retention of resin residues on fibers. These results suggest that copper hydroxyphosphate acts as a local energy absorber that trades volumetric removal for improved surface quality in epoxy and enhances uniformity and process stability in CFRP femtosecond laser machining. Full article

The development of advanced drug delivery systems is essential for improving therapeutic efficacy, particularly in the treatment of neurodegenerative disorders such as Alzheimer’s disease. This study investigates zinc-modified mordenite zeolite (MR-ZN) as a novel platform for the controlled delivery of donepezil (DPZ), a cholinesterase inhibitor. Natural mordenite was modified with zinc, enhancing its surface area from 62.1 to 85.4 m²/g and improving its adsorption properties. Donepezil was successfully loaded at two doses (10 mg and 23 mg), achieving high loading efficiencies of 95% and 94%, respectively. Adsorption kinetics followed a pseudo-second-order model (R² > 0.99), indicating that chemisorption predominates through coordination between DPZ functional groups and Zn²⁺ sites, while complementary physisorption via hydrogen bonding and van der Waals interactions also contributes to molecular stabilization within the zeolite framework. In vitro release studies under simulated gastrointestinal conditions demonstrated sustained and pH-responsive release profile with 80% and 82% of donepezil released after 24 h for 10 mg and 23 mg formulations, respectively. Density Functional Theory (DFT) calculations revealed favorable adsorption energy (−26.4 kJ/mol), while Bader and Electron Localization Function (ELF) analyses confirmed hydrogen bonding and electrostatic interactions without compromising the zeolite framework. These findings validate MR-ZN as structurally stable, efficient, cost-effective and biocompatible matrix for oral drug delivery. The combination of experimental data and theoretical modeling supports its potential to improve bioavailability and therapeutic performance in neurodegenerative treatment. Full article

Background: Mechanical processing techniques are commonly employed to prepare adipose tissue for clinical applications in reconstructive and aesthetic procedures. However, their histological and immunohistochemical impact on adipose tissue remains incompletely characterized. Purpose: This systematic review aims to investigate the impact of mechanical processing on the histological and immunohistochemical properties of adipose tissue. Methods: A systematic search was conducted using PubMed, Ovid, and Cochrane Library databases, with publications up to December 2024, employing Boolean operators (“mechanically processed” OR “lipoaspirate” OR “fat graft” OR “gauze rolling” OR “decantation” OR “coleman fat” OR “celt” OR “nanofat” OR “lipofilling” OR “human fat”) AND (“histol*”). Included were English-language studies or studies with a recognized English translation which had been subject to peer review and reported quantitative or qualitative markers of mechanically processed human adipose tissue with histology or immunohistochemistry. Risk of Bias was assessed with the OHAT score. Results: A total of 15 studies (n = 15) were included. In 13 of 15 studies (87%), mechanically processed adipose tissue demonstrated an increased stromal vascular fraction (SVF) cell density compared to unprocessed fat. Twelve studies (80%) reported improved preservation of the extracellular matrix (ECM), while 11 studies (73%) observed a reduction in mature adipocytes. Immunohistochemical analyses in 10 studies (67%) revealed elevated expression of vascular markers (CD31, CD34) and perilipin. Adverse histological features such as oil cysts, fibrosis, and inflammatory infiltrates were reduced in 9 studies (60%). Considerable heterogeneity in processing techniques and staining protocols precluded meta-analysis. Conclusions: Mechanical processing of adipose tissue is associated with favorable histological and immunohistochemical profiles, including increased SVF cell density, improved ECM preservation, and reduced inflammatory and fibrotic features. These findings support the potential of mechanical processing to enhance graft quality; however, standardization of techniques and evaluation protocols is needed to strengthen clinical translation. Full article

Background/Objectives: Naegleria fowleri is a free-living protozoan that causes primary amoebic meningoencephalitis, a rapidly progressing central nervous system infection with high mortality rates and limited treatment options. Targeting virulence-associated proteins is essential for effective drug development. Fowlerpain-1 (FWP1), a papain-like cysteine protease (CP) implicated in extracellular matrix degradation and host–cell cytotoxicity, has been investigated as a therapeutic target. This study aimed to evaluate the FWP1 pocket geometry and stefin binding using an integrated in silico structural biology approach. Methods: A computational pipeline was used, including AlphaFold2-Multimer modeling of FWP1–stefin complexes, 20-ns molecular dynamics simulations under NPT conditions for conformational sampling, and molecular mechanics Poisson–Boltzmann surface area free energy calculations. Three natural CP inhibitors (stefins) were investigated. Structural stability was assessed using root mean square deviations, and binding profiles were characterized using protein–protein interaction analysis. Results: Stable FWP1–stefin interaction interfaces were predicted, with human stefin A showing favorable binding free energy. Two conserved motifs (PG and QVVAG) were identified as critical mediators of active-site recognition. Druggability analysis revealed a concave pocket with both hydrophobic and polar characteristics, consistent with a high-affinity ligand-binding site. Conclusions: This computational study supports a structural hypothesis for selective FWP1 inhibition and identifies stefins as promising scaffolds for developing structure-guided protease-targeted therapeutics against N. fowleri. Full article

Aquaporin-4 (AQP4) is expressed in ependymal cells bordering the ventricles, the glia limitans, and pericapillary astrocyte endfeet forming the blood–brain barrier. The sporadic occurrence of obstructive congenital hydrocephalus (OH) has been observed in the offspring of AQP4⁻/⁻ mice generated in the CD1 strain background. Here, we used microarray analysis to explore gene expression profiles in the periaqueductal area from littermate AQP4⁻/⁻ pups at postnatal day 12. We compared wild-type (WT) animals with AQP4⁻/⁻ animals that developed OH (AQP4⁻/⁻-OH) and those that did not (AQP4⁻/⁻-NH). Bioinformatic analysis identified gene sets associated with proliferation and migration of microglia, ependymal cell adhesion, extracellular matrix components, axon myelination, and neuronal synapsis. Among the differentially expressed genes, Spp1—expressed by neonatal CD11c⁺ microglia—was highlighted in the triple comparison. Spp1 was significantly upregulated in AQP4⁻/⁻-NH and downregulated in AQP4⁻/⁻-OH mice. These findings suggest that CD11c⁺ microglia, via Spp1 expression, play a key morphogenic role in the aqueduct of Sylvius and their absence, occurring in a small subset of AQP4⁻/⁻-CD1 animals, leads to obstructive hydrocephalus. Full article

The present study investigates the hypothesis that green plantain peel (GPP) could be used as a functional ingredient to enrich fermented milk, thus improving its nutritional profile and bioactive content. The objective of the present study was to develop a fermented milk product with added GPP and to evaluate its physical–chemical, technological, microbiological, and sensory characteristics, as well as the bioaccessibility of bioactive compounds after in vitro digestion (INFOGEST). The methodological strategy involved the formulation of four treatments: one control (Fermented Milk Control, FMC) and three with different concentrations of cooked plantain peel (5%—FM5, 10%—FM10, and 20%—FM20). The results demonstrated that the incorporation of peel had a significant impact on the technological properties, resulting in increased syneresis and color change. In contrast, pH and acidity were more influenced by storage duration. Lactic acid bacteria demonstrated viability at probiotic concentrations (≥10⁶ CFU/mL) for a duration of up to 11 days. The incorporation of GPP resulted in a substantial increase in the phenolic compound content and antioxidant activity of the product, with the FM20 treatment showing the highest antioxidant activity (DPPH: 1555 ± 16 µmol TE/mL, ABTS: 576 ± 29 µmol TE/mL, FRAP: 2427 ± 58 µmol Fe²⁺/mL) compared to FMC. Sensory analysis revealed that texture and color were the most influential attributes, with formulations FM5 and FM10 being the most accepted, as indicated by an acceptability index above 82%. The simulated in vitro digestion led to an increase in the measurable phenolic content and a corresponding enhancement of antioxidant activity. This suggests that the digestive process enhances the release of these compounds from the food matrix, thereby increasing their bioaccessibility. Full article

High-grade serous carcinoma (HGSC) of the ovary is characterized by two major histological patterns: a classic papillary/micropapillary architecture and a solid pseudo-endometrioid transitional (SET) variant. We investigated whether the distinct morphologic subtypes are underpinned by transcriptomic differences in the tumor microenvironment (TME). We profiled 21 HGSC tumors (7 SET, 14 classic) using a 770-gene NanoString PanCancer Progression panel. Differential expression analysis revealed ~20 genes with significantly different expression (>4-fold, adjusted p < 0.01) between SET and classic tumors. Unsupervised clustering partially separated SET and classic tumors, suggesting that global gene expression patterns correlate with histologic subtype. SET tumors exhibited upregulation of cell-cycle and epithelial genes (e.g., PTTG1, TRAIL, HER3) and downregulation of genes involved in epithelial–mesenchymal transition (EMT), extracellular matrix (ECM) organization, and angiogenesis (e.g., TWIST2, FGF2, decorin) relative to classic tumors. Notably, PTTG1 and TRAIL were upregulated ~6–9-fold in SET tumors, whereas TWIST2 was ~7-fold downregulated, consistent with reduced EMT in SET tumors. Pathway analysis indicated that SET tumors appear to have an immune-active, stroma-poor microenvironment, in line with an “immunoreactive” phenotype, whereas classic tumors showed a mesenchymal, stroma-rich profile. These molecular distinctions could have diagnostic utility and may inform therapeutic stratification, with key dysregulated genes (e.g., HER3, TRAIL, FGF2) representing potential prognostic or predictive biomarkers. For example, high HER3 expression in SET tumors might predict sensitivity to ERBB3/PI3K inhibitors, whereas stromal factors (e.g., FGF2) enriched in classic HGSC could be targeted with microenvironment-modulating therapies. These preliminary findings require validation before translation into pathology practice via immunohistochemical (IHC) assays (e.g., for HER3 or TRAIL), potentially enabling improved classification and personalized treatment of HGSC. We report effect sizes as log₂ fold change with 95% confidence intervals and emphasize FDR-adjusted q-values. Given the small sample size and the absence of outcome data (OS/PFS/PFI), results are preliminary and hypothesis-generating. Orthogonal protein-level validation and replication in larger, independent cohorts are required before any translational inference. Full article

Background/Objectives: This study investigated how selected functionality-related characteristics (FRCs) of hypromellose (HPMC)—namely viscosity, hydroxypropoxy substitution, particle size, and the ratio of water-soluble (FlowLac^® 100) to water-insoluble (Avicel^® PH-102) fillers— affect the release of carvedilol from matrix tablets. Methods: Using a Central Composite Design (CCD) Design of Experiments (DoE), mixtures of HPMC QbD samples were prepared to achieve target HPMC FRC levels. Within the CCD, levels of FlowLac^® 100 and Avicel^® PH-102 were also varied. The mean and standard deviation of carvedilol release at each analyzed time point of the release profile were used as target variables for individual multiple linear regression (MLR) models. Results: Lactose, the water-soluble filler, significantly accelerated carvedilol release, whereas the water-insoluble MCC slowed and stabilized release by improving gel integrity. Among the HPMC FRCs, particle size had the strongest influence during the early release phase, while HPMC viscosity and hydroxypropoxy substitution degree became more important in later phases. Analysis of the results using optimized multiple linear regression (MLR) models revealed key interaction effects, particularly between HPMC viscosity and lactose content, and between viscosity and particle size, demonstrating their combined role in modulating release kinetics. Conclusions: These findings provide valuable insight into how controlling HPMC’s FRCs and filler composition can reduce interbatch variability in drug release and support the rational design of robust controlled release formulations. Full article

The growing consumer demand for plant-based, protein- and fiber-enriched foods has encouraged the incorporation of novel functional ingredients into bakery products. Hemp flour (HF), obtained from cold-pressed hemp seeds, represents a sustainable ingredient rich in proteins, dietary fibers, lipids, and bioactive compounds, making it suitable for nutritional fortification. This study investigated the impact of HF addition (5–40%) on the quality of muffins prepared with wheat flour (WF) and whole wheat flour (WWF). An initial hedonic sensory evaluation identified 5–20% HF as the most acceptable substitution range, which was then subjected to detailed physicochemical, sensory, textural, colorimetric, and microbiological analyses. Incorporation of HF significantly increased protein (up to +44%), fiber (up to +172%), and ash (up to +76%) contents, while decreasing moisture (−39%). Both WF and WWF muffins darkened with HF incorporation, with a greater lightness reduction in WF. Texture changes (increased firmness and gumminess) were more pronounced in WF muffins. Sensory analysis revealed that WF muffins were best accepted at 10–15% HF, whereas WWF muffins maintained good acceptability up to 20% HF, indicating better integration of HF in the whole grain matrix. All samples complied with microbiological safety requirements. Overall, the optimal substitution level was 10–15% HF in WF muffins and 20% HF in WWF muffins, demonstrating that HF can enhance the nutritional profile of muffins while maintaining acceptable technological and sensory properties in a matrix-dependent manner. Full article

Accurate determination of opacity is critical for understanding radiation transport in both astrophysical and laboratory plasmas. We employ atomic data from R-Matrix calculations to investigate radiative properties in high-energy-density (HED) plasma sources, focusing on opacity variations under extreme plasma conditions. Specifically, we analyze environments such as the base of the convective zone (BCZ) of the Sun ($2\times {10}^6$ K, $N_e={10}^{23}$/cc), and radiative opacity data collected using the inertial confinement fusion (ICF) devices at the Sandia Z facility ($2.11\times {10}^6$ K, $N_e=3.16\times {10}^{22}$/cc) and the Lawrence Livermore National Laboratory National Ignition Facility. We calculate Rosseland Mean Opacities (RMO) within a range of temperatures and densities and analyze how they vary under different plasma conditions. A significant factor influencing opacity in these environments is line and resonance broadening due to plasma effects. Both radiative and collisional broadening modify line shapes, impacting the absorption and emission profiles that determine the RMO. In this study, we specifically focus on electron collisional and Stark ion microfield broadening effects, which play a dominant role in HED plasmas. We assume a Lorentzian profile factor to model combined broadening and investigate its impact on spectral line shapes, resonance behavior, and overall opacity values. Our results are relevant to astrophysical models, particularly in the context of the solar opacity problem, and provide insights into discrepancies between theoretical calculations and experimental measurements. In addition, we investigate the equation-of-state (EOS) and its impact on opacities. In particular, we examine the “chemical picture” Mihalas–Hummer–Däppen EOS with respect to level populations of excited levels included in the extensive R-matrix calculations. This study should contribute to improving opacity models of HED sources such as stellar interiors and laboratory plasma experiments. Full article

Diabetic nephropathy (DNR) remains a major complication of type 2 diabetes with limited options to halt progression. We evaluated whether DNR (a sulfur-rich extract from Hongsan garlic) confers renoprotection in a db/db mouse model. Seventy male C57BLKS/J mice were randomized into seven groups (db/m control, db/db control, metformin 250 mg/kg, DNR 100/300/900 mg/kg, and metformin 250 mg/kg + DNR 300 mg/kg) and treated orally for eight weeks. Physiological, biochemical, urinary, histological, and immunohistochemical(IHC) endpoints were assessed, including serum creatinine, blood urea nitrogen(BUN), lipids, glucose, urinary microalbumin/albumin-to-creatinine ratio(ACR), glomerular area, mesangial expansion, and renal KIM-1 and TGF-β1 expression. Chemical profiling of the DNR extract by HPLC and LC–MS/MS identified allicin as a principal sulfur-containing constituent, exhibiting a distinct retention peak at 2.90 min and a protonated molecular ion at m/z 162.1 [M]⁺ with diagnostic fragment ions at m/z 145.1, 120.1, and 99.0. Allicin was qualitatively confirmed as a characteristic component of DNR, serving as a representative chemical marker for compositional characterization. DNR produced dose-dependent improvements: reductions in serum creatinine and BUN, improved lipid and glycemic profiles, decreased urinary microalbumin and ACR, and amelioration of glomerular hypertrophy and mesangial matrix expansion. IHC showed lower KIM-1 and TGF-β1 staining in treated groups. Effects at higher DNR doses were comparable to or additive with metformin for several endpoints. These findings indicate that DNR has promising renoprotective effects in this preclinical model. Full article

A series of silver-polygalacturonate complexes with improved structure and activity against bacterial infections was developed. Pure sodium polygalacturonate was obtained by saponification of a pectin precursor and identified by NMR as predominantly homogalacturonan (uronide content 95%). Polygalacturonate complexes with ionic and borohydride-reduced silver with a controllable metallic component were synthesized; the role of spontaneous Ag⁺ reduction was revealed. The presence of uniform 5 nm nanoparticles and negligible particulate by-products in the reduced complexes was verified. The complexes showed similar silver-normalized activity against non-resistant bacteria, irrespective of complex stoichiometry/silver state. Pharmaceutical silver proteinate with a similar nanoparticle profile exhibited the same silver-normalized activity, indicating the lack of a ligand effect. The Ag⁺ complex was more effective against some hospital drug-resistant strains. The cytotoxicity of the complexes depended on fibroblast type, silver state, ligand type, exposure time, presumably in association with cellular availability and glutathione depletion. The complexes were administered to rats with excisional wounds persistently infected with S. aureus. Swab/histological analyses of the treated wounds revealed decreased bacterial burden/tissue damage, along with promotion of wound contraction/closure and matrix formation. The nanoparticle complexes that were compared had similar antibacterial/regenerative effects, while the Ag⁺ complex demonstrated higher efficacy in vivo. These results encourage the use of the developed silver-polygalacturonate complexes as antibacterial substances. Full article

Although total knee replacements have an insignificant impact on patients’ mobility and quality of life, real-time performance monitoring remains a challenge. Monitoring the load over time can improve surgery outcomes and early detection of mechanical imbalances. Triboelectric nanogenerators (TENGs) present a promising approach as a self-powered sensor for load monitoring in TKR. A TENG was fabricated with dielectric layers consisting of Kapton tape and 3D-printed thermoplastic polyurethane (TPU) matrix incorporating CNT and BTO fillers, separated by an air gap and sandwiched between two copper electrodes. The sensor performance was optimized by varying the concentrations of BTO and CNT to study their effect on the energy-harvesting behavior. The test results demonstrate that the BTO/TPU composite that has 15% BTO achieved the maximum power output of 11.15 μW, corresponding to a power density of 7 mW/m², under a cyclic compressive load of 2100 N at a load resistance of 1200 MΩ, which was the highest power output among all the tested samples. Under a gait load profile, the same TENG sensor generated a power density of 0.8 mW/m² at 900 MΩ. By contrast, all tested CNT/TPU-based TENG produced lower output, where the maximum generated apparent power output was around 8 μW corresponding to a power density of 4.8 mW/m², confirming that using BTO fillers had a more significant impact on TENG performance compared with CNT fillers. Based on our earlier work, this power is sufficient to operate the ADC circuit. Furthermore, we investigated the durability and sensitivity of the 15% BTO/TPU samples, where it was tested under a compressive force of 1000 N for 15,000 cycles, confirming the potential of long-term use inside the TKR. The sensitivity analysis showed values of 37.4 mV/N for axial forces below 800 N and 5.0 mV/N for forces above 800 N. Moreover, dielectric characterization revealed that increasing the BTO concentration improves the dielectric constant while at the same time reducing the dielectric loss, with an optimal 15% BTO concentration exhibiting the most favorable dielectric properties. SEM images for BTO/TPU showed that the 10% and 15% BTO/TPU composites showed better morphological characteristics with lower fabrication defects compared with higher filler concentrations. Our BTO/TPU-based TENG sensor showed robust performance, long-term durability, and efficient energy conversion, supporting its potential for next-generation smart total knee replacements. Full article