Search Results (898)

Osteoarthritis involves complex interactions between articular joint tissues and the immune system, which is implicated in molecular trafficking via barrier-function modulating cytokines. The current study aims to test effects of an acute spike in TNF-α or TGF-β on vascular barrier function at multiple length scales, from the heart to tissue compartments of the knee, and cellular inhabitants of those respective compartments, in a spontaneous guinea pig model of osteoarthritis. First we quantified the intensity of a fluorescent-tagged 70 kDa tracer, similar in size to albumin, the most prevalent transporter protein in the blood, in tissue compartments of bone (periosteum, marrow space, compact bone, and epiphyseal bone) and cartilage (superficial cartilage, calcified cartilage, and the interface between, i.e., the epiphyseal line), as well as at sites of tendon attachment to bone (entheses). We then examined tracer presence and intensity in the respective pericellular and extracellular matrix zones of bone and cartilage. Acute exposure to TGF-β reduced barrier function (increased permeability) at nearest vascular interfaces in four of eight tissue compartments studied, compared to TNF-α where one of eight tissue compartments showed significant diminishment in barrier function. The increase in permeability associated with reduced barrier function was observed at both tissue compartment and cellular length scales. The observation of pericellular transport of the albumin-sized molecules to osteocytes contrasts with previous observations of barrier function in healthy, untreated animals and is indicative of increased molecular transport in pericellular regions of musculoskeletal tissues in cytokine-treated animals. Understanding age- and disease-related changes in molecular transport within musculoskeletal structures, such as the knee joint, is crucial for elucidating the etiology and pathogenesis of osteoarthritis. Full article

Background: Whether therapeutic albumin (ThHSA) can serve as a defense tool in Candida species (spp.) infections is still a matter of debate, although many physicians are in the habit of infusing ThHSA to restore the physiological concentration of endogenous human serum albumin (HSA). Given the need for innovative anti-Candida strategies, we assessed in vitro the role of ThHSA alone or in combination with voriconazole (VCZ) in combating Candida spp. growth and the role of bovine serum albumin (BSA)—used as a substitute for HSA—with two endogenous bovine antimicrobial peptides in combating C. albicans and other microbes. Results: The combination of ThHSA with VCZ enhanced the antifungal effect on C. albicans, sensitive C. tropicalis, sensitive C. glabrata, and C. lusitaniae. However, for resistant C. tropicalis, the combination of ThHSA with VCZ promoted yeast growth, and VCZ tended to suppress the antimicrobial effect of ThHSA on resistant C. glabrata. As to the possible transposition of ThHSA-type properties to BSA (as regards the growth inhibition of other pathogens), we tested combinations of BSA with two physiological chromogranin A-derived antimicrobial peptides (catestatin and cateslytin). BSA enhanced significantly the activity of catestatin (but not cateslytin) in combating C. albicans, A. fumigatus, and M. luteus, but was inactive against S. aureus and E. coli. Conclusions: Our experiments support the fact that albumins display intrinsic antimicrobial properties, with an unpredictable growth inhibitory effect on various microbes. ThHSA can thus be an adjunctive tool for more efficient care of some, though not all, infections. The interaction of BSA with catestatin and cateslytin is related to their structure, with BSA significantly enhancing the effect of catestatin but not that of cateslytin. Full article

Wider adoption of membrane technology is hindered by fouling and flux/rejection challenges. Recent practice in mitigating these is to incorporate hydrophilic and porous fillers. Herein the addition of hydrophilic graphene oxide (GO) in conjunction with porous mixed ZIFs (ZIF-67/ZIF-8) crystallites were used as inorganic fillers in the preparation of polyphenylenesulfone (PPSU) ultrafiltration (UF) membranes. The morphology of the resultant composite membranes was assessed using atomic force microscopy (AFM) and scanning electron microscopy (SEM) whilst surface hydrophilicity through water contact angle. The pure water flux (PWF) and membrane permeability were found to increase with increasing filler content. This was attributed to the combined hydrophilicity of GO and porous structure of the ZIF materials because of increasing alternative water pathways in the membrane matrix with increasing filler content. Furthermore, the increase in the ZIF component led to increasing bovine serum albumin (BSA) fouling resistance as demonstrated by increasing fouling recovery ratio (FRR). The dye rejection was due to a combination of electrostatic interaction between the fillers and the dyes as well as size exclusion. The chemical interactions between the ZIFs and the dyes resulted in slightly different rejection profiles for the smaller dyes, the cationic methylene blue being rejected less efficiently than the anionic methyl orange, potentially leading to their separation. The larger anionic dye, Congo red was rejected predominately through size exclusion. Full article

Background: Current Alzheimer’s disease (AD) treatments primarily focus on symptom management and offer limited potential to arrest disease progression. To address this limitation, we developed baicalin–myricetin (BM) functionalized selenium nanoparticles (SeNPs), termed BMSe@BSA, aimed at multi-targeted neuroprotection. Materials and Methods: BMSe@BSA nanoparticles were synthesized via a gel–sol technique using bovine serum albumin (BSA), ascorbic acid, selenous acid, and BM. Interactions among BSA, BM, and SeNPs were characterized by microscopy and spectrometry. Cytotoxicity was assessed on RAW 264.7 and PC12 cells to determine biocompatibility. Neuroinflammation and cognitive function were evaluated in C57BL6/J mice challenged with Aβ1-42. Recognition memory was tested through open-field exploration, novel object recognition (NOR), and T-maze assays. Inflammatory markers (IL-1β and TNF-α) and microglial changes in the cerebral cortex were quantified, while amyloid fibril morphology was assessed using atomic force microscopy (AFM). Results: Spectroscopic analysis verified successful BM functionalization. Transmission electron microscopy revealed a spherical morphology with an average particle size of 90.57 nm, zeta potential of 27.2 mV, and a polydispersity index (PDI) of 0.270. BM entrapment efficiency reached approximately 90%. Cytotoxicity assays confirmed the nanoparticles’ safety, with no toxicity observed at concentrations up to 400 µg/mL after 4 h of incubation. BMSe@BSA effectively inhibited amyloid fibril formation, downregulated pro-inflammatory cytokine expression, preserved neuronal integrity, and significantly enhanced cognitive performance in AD mouse models. Conclusion: BMSe@BSA appear as a potential nanotherapeutic approach for targeted brain delivery and multi-pathway intervention in Alzheimer’s disease. Full article

The inherent hydrophobicity of poly(vinylidene fluoride) (PVDF) ultrafiltration membranes leads to severe membrane fouling when processing proteinaceous solutions and organic contaminants, significantly limiting their practical applications. This study presents a novel metal-ion mediated co-deposition strategy for fabricating high-performance antifouling poly(vinylidene fluoride) (PVDF) hollow fiber ultrafiltration membranes. Through Zn²⁺ coordination-driven self-assembly, a uniform and stable composite coating of dopamine (DA), tannic acid (TA), and ZIF-8 nanoparticles was successfully constructed on the membrane surface under mild conditions. The modified membrane exhibited significantly enhanced hydrophilicity, with a water contact angle of 21° and zeta potential of −29.68 mV, facilitating the formation of a dense hydration layer that effectively prevented protein adhesion. The membrane demonstrated exceptional separation performance, achieving a pure water permeability of 771 L/(m²∙h∙bar) and bovine serum albumin (BSA) rejection of 97.7%. Furthermore, it showed outstanding antifouling capability with flux recovery rates exceeding 83.6%, 74.7%, and 71.5% after fouling by BSA, lysozyme, and ovalbumin, respectively. xDLVO analysis revealed substantially increased interfacial free energy and stronger repulsive interactions between the modified surface and protein foulants. The antifouling mechanism was attributed to the synergistic effects of hydration layer formation, optimized pore structure, additional water transport pathways from ZIF-8 incorporation, and electrostatic repulsion from negatively charged surface groups. This work provides valuable insights into the rational design of high-performance antifouling membranes for sustainable water treatment and protein separation applications. Full article

We aimed to investigate the interaction mechanism of transport protein Human serum albumin (HSA) with a synthesized compound, QP-11, with tested antimalarial properties to monitor the changes in the protein because of QP-11 binding. The interaction between the antimalarial compound QP-11 and HSA was thoroughly investigated through a multidimensional approach, utilizing UV-VIS spectroscopy, fluorescence, time-resolved fluorescence, and CD (Circular dichroism), alongside molecular docking techniques. Our findings unveiled a robust 1:1 binding pattern, signifying a strong affinity between QP-11 and HSA. Employing static quenching, evidenced by time-resolved fluorescence spectroscopy, QP-11 was observed to induce fluorescence quenching of HSA, particularly binding to subdomain IIA. Thermodynamic parameters indicated that van der Waals forces and hydrogen bonding predominantly facilitated the binding, with increased temperature compromising complex stability. The 3D fluorescence and CD results demonstrated QP-11-induced conformational changes in HSA. Both experimental and in silico analyses suggested a spontaneous, exothermic binding reaction. The profound impact of the QP-11–HSA interaction underscores the potential for QP-11 in antimalarial drug development, encouraging further exploration for dose design and enhanced pharmacodynamic and pharmacokinetic properties. Full article

Sophorolipids (SLs) constitute a group of unique biosurfactants in light of their unique properties, among which their physicochemical characteristics and antimicrobial activity stand out. SLs can exist mainly in acidic and lactonic forms, both of which display inhibitory activity. This study explores the interaction of non-acetylated acidic SL with bovine serum albumin (BSA). SL significantly enhances BSA’s thermal stability, increasing its midpoint unfolding temperature from 61.9 °C to approximately 76.0 °C and ΔH from 727 to 1054 kJ mol⁻¹ at high concentrations, indicating cooperative binding. Fourier-Transform Infrared Spectroscopy (FTIR) analysis confirms SL’s protective effect against thermal unfolding, enabling BSA to maintain its helical structure at 70 °C, distinguishing it from other surfactants that cause denaturation. Furthermore, SL fundamentally alters the sequence of thermal unfolding events; β-aggregation precedes helical domain unfolding, suggesting protective binding to BSA’s helical regions. Computational docking reveals high-affinity binding (Kd = 14.5 μM). Uniquely, SL binds between BSA domains IB and IIIA, establishing hydrophobic interactions, salt bridges, and hydrogen bonds, thus stabilizing the protein’s 3D structure. This distinct binding site is attributed to SL’s amphipathic character. This work deepens the understanding of the molecular characteristics of SL–protein interactions and contributes to improving the general knowledge of this outstanding biosurfactant. Full article

Nitrosamines, including N-nitroso diethylamine (NDEA) have emerged as pharmaceutical impurities and carcinogenic environmental contaminants of grave public health safety concerns. This study reports on the preparation and first use of cysteine–gold nanoparticles (CysAuNPs) for colorimetric detection of NDEA in human serum albumin (HSA) under physiological conditions. Molecular docking (MD) and molecular dynamic simulation (MDS) were performed to probe the interaction between NDEA and serum albumin. UV–visible absorption and fluorescence spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM) imaging were used to characterize the synthesized CysAuNPs. These CysAuNPs show a UV–visible absorbance wavelength maxima (λ_max) at 377 nm and emission λ_max at 623 nm. Results from DLS measurement revealed the CysAuNPs’ uniform size distribution and high polydispersity index of 0.8. Microscopic imaging using TEM showed that CysAuNPs have spherical to nanoplate-like morphology. The addition of NDEA to HSA in the presence of CysAuNPs resulted in a remarkable increase in the absorbance of human serum albumin. The interaction of NDEA–CysAuNPs–HSA is plausibly facilitated by hydrogen bonding, sulfur linkages, or by Cys–NDEA-induced electrostatic and van der Waal interactions. These are due to the disruption of the disulfide bond linkage in Cys–Cys upon the addition of NDEA, causing the unfolding of the serum albumin and the dispersion of CysAuNPs. The combined use of molecular dynamic simulation and colorimetric experiment provided complementary data that allows robust analysis of NDEA in serum samples. In addition, the low cost of the UV–visible spectrophotometer and the easy preparation and optical sensitivity of CysAuNPs sensors are desirable, allowing the low detection limit of the CysAuNPs sensors, which are capable of detecting as little as 0.35 µM NDEA in serum albumin samples, making the protocol an attractive sensor for rapid detection of nitrosamines in biological samples. Full article

Electric fields are emerging as powerful tools to actively regulate biomolecular interactions at biointerfaces. In this study, we investigated how varying electric field strengths (0–100 mV/mm) influence the interfacial interaction between human serum albumin (HSA) and six tyrosine kinase inhibitors (TKIs): imatinib, bosutinib, dasatinib, nilotinib, ponatinib, and radotinib. Using atomic force microscopy (AFM), we quantified changes in adhesion force, specific (F_i) and non-specific (F₀) force, friction behavior, and protein morphology. Increasing field strength led to significant reductions in adhesion force (22–47%), F_i (27–44%), F₀ (38–53%), friction force (38–67%) and constant-load friction force (43–54%), along with decreased protein average surface height and roughness, indicating electric field-induced molecular compaction and interface smoothing. Notably, more hydrophobic TKIs showed greater responsiveness. These findings highlight the potential of electric fields to modulate protein–drug interactions in a controllable manner, offering a new strategy for the development of electrically tunable drug delivery systems and smart biomedical interfaces. Full article

The use of nanoparticles has revolutionized drug delivery by enabling targeted and controlled therapeutic release. However, their interactions with intracellular organelles, particularly lysosomes, are not yet fully understood. This study delineates the differential effects of two widely used nanocarriers—mesoporous silica (MSNs) and albumin (ANPs) nanoparticles—on lysosomal biology, with a focus on the expression and activity of cathepsins (CtsB and CtsD), which are key proteases involved in protein degradation and maintaining cellular balance. These two types of nanoparticles, differing in their material and degradability, exhibit distinct behaviors inside the cell. We demonstrate that inorganic MSNs cause significant changes in lysosomal function by altering lysosomal content and cathepsin levels, without triggering lysosomal membrane permeabilization—a typical response to organic particle stress. In contrast, ANPs—which are susceptible to lysosomal cathepsin degradation—induce milder changes in cathepsin expression and maintain lysosomal integrity. Our results highlight that the composition of nanocarriers plays a pivotal role in modulating lysosomal protease activity and maintaining overall cellular homeostasis, highlighting the importance of these parameters in the rational design of drug delivery platforms. Full article

Background: Trimetazidine is a clinically established cardioprotective agent with anti-ischemic and antioxidant properties, widely used in the management of coronary artery disease. Combining its metabolic and cytoprotective effects with the potent anti-inflammatory activity of profens presents a promising therapeutic strategy. Methods: Five novel trimetazidine–profen hybrid compounds were synthesized using N,N′-dicyclohexylcarbodiimide-mediated coupling and structurally characterized by NMR and high-resolution mass spectrometry. Their antioxidant activity was evaluated by hydroxyl radical scavenging assays (HRSA), and the anti-inflammatory potential was assessed via the inhibition of albumin denaturation (IAD). Lipophilicity was determined chromatographically. Molecular docking and 100 ns molecular dynamics simulations were performed to investigate the binding modes and stability in human serum albumin (HSA) binding sites. The acute toxicity of the hybrid molecules was predicted in silico using GUSAR software. Results: All synthesized hybrids demonstrated varying degrees of biological activity, with compound 3c exhibiting the most potent antioxidant (HRSA IC₅₀ = 71.13 µg/mL) and anti-inflammatory (IAD IC₅₀ = 108.58 µg/mL) effects. Lipophilicity assays indicated moderate membrane permeability, with compounds 3c and 3d showing favorable profiles. Docking studies revealed stronger binding affinities of S-enantiomers, particularly 3c and 3d, to Sudlow sites II and III in HSA. Molecular dynamics simulations confirmed stable ligand–protein complexes, highlighting compound 3c as maintaining consistent and robust interactions. The toxicity results indicate that most hybrids, particularly compounds 3b–3d, exhibit a favorable safety profile compared to the parent trimetazidine. Conclusion: The hybrid trimetazidine–profen compounds synthesized herein, especially compound 3c, demonstrate promising dual antioxidant and anti-inflammatory therapeutic potential. Their stable interaction with serum albumin and balanced physicochemical properties support further development as novel agents for managing ischemic heart disease and associated inflammatory conditions. Full article

The structures of the developing eye may be damaged as a result of the impact of reactive oxygen species (ROS) interacting with different cellular components. The antioxidant molecules found in the eye, especially in the vitreous body—the largest component of the eye, playing a crucial role in the formation of structures and functions of the developing eye—provide protection to the eye tissues from ROS. This review considers various antioxidant molecules (ascorbic acid, lutein, bilirubin, uric acid, catecholamines, erythropoietin, albumin, and alpha-fetoprotein) that have been found in the human vitreous body during the early stages of pregnancy (10–31 weeks of gestation) and their functions in the development of the eye. The presence of some molecules is transient (lutein, AFP), whereas a temporal decrease (albumin, bilirubin) or increase (ascorbic acid, erythropoietin) in the concentrations of other antioxidants is observed. Since the actual overall content of antioxidants in the developing vitreous body is probably much higher than that found to date, further research is needed to study antioxidants there. It is especially important to study the antioxidant status of the vitreous body at the earliest stages of its development. Antioxidants found suggest their use for the prophylactic of ocular diseases during pregnancy and finding new antioxidants could create an additional opportunity in this regard. Full article

This study systematically explored the interaction mechanisms between two KRAS G12C inhibitors (Sotorasib and Adagrasib) and human serum albumin (HSA) via UV-vis spectroscopy, fluorescence spectroscopy, three-dimensional fluorescence spectroscopy, and molecular docking methods. The experimental findings demonstrated that both drugs caused static quenching of HSA fluorescence, with binding constants of 13.64 × 10³ M⁻¹ (Sotorasib) and 63.67 × 10³ M⁻¹ (Adagrasib), demonstrating significant selectivity differences in their binding affinities. UV spectral analysis demonstrated distinct microenvironmental perturbations: Sotorasib and Adagrasib induced a shift (∆λ = 7 nm and ∆λ = 8 nm, respectively) at 211 nm, consistent with altered polarity in HSA’s binding pockets. Fluorescence spectroscopy confirmed a 1:1 binding stoichiometry, with Stern-Volmer analysis validating static quenching as the dominant mechanism. Three-dimensional fluorescence spectra further highlighted Adagrasib’s stronger conformational impact, reducing tyrosine and tryptophan residue fluorescence intensities by 16% (Peak 1) and 10% (Peak 2), respectively, compared to Sotorasib. Molecular docking revealed divergent binding modes: Sotorasib occupied Sudlow Site I via three hydrogen bonds and hydrophobic interactions (∆G = −24.60 kJ·mol⁻¹), whereas Adagrasib bound through one hydrogen bond and hydrophobic forces (∆G = −30.92 kJ·mol⁻¹), with stability differences attributed to structural characteristics. This study uses multispectral technology and molecular docking to reveal the binding mechanism of Sotorasib and Adagrasib with HSA, providing a theoretical basis for designing highly targeted albumin nanocarriers. The strong binding properties of Adagrasib and HSA may reduce the toxicity of free drugs, providing direction for the development of long-acting formulations. Full article

This study investigates key factors affecting the adsorption behavior of proteins on the multimodal chromatographic adsorbent Capto MMC, aiming to enhance selective protein separation strategies. Batch equilibrium experiments were conducted using six model proteins to explore the combined effects of pH, ionic strength, and the nature of salts (kosmotropic and chaotropic) on protein–ligand interactions. Given that the Capto MMC ligand supports multiple interaction modes beyond cation exchange, particular focus was placed on acidic proteins (pI 4–5), which exhibited binding even at moderately elevated pH values—conditions ineffective for conventional cation exchangers. Hydrophobic interactions were identified as critical for stable binding of proteins like BSA and fetuin, while hydrophilic proteins such as ovalbumin showed minimal adsorption. Chromatographic column experiments were performed to evaluate elution performance under various buffer conditions, revealing that prolonged adsorption phases can reduce recovery yields for proteins with less stable tertiary structures. The findings highlight how salt type, pH, and protein hydrophobicity interplay to modulate multimodal binding mechanisms, providing practical insights for the design of tailored purification protocols. Full article

A polyelectrolyte (PE) chain in the vicinity of an oppositely charged surface can exhibit a discontinuous transition from the adsorbed to the desorbed state once the electrostatic attractive interactions are not strong enough to overcome the entropic losses caused by the PE-surface adsorption. In the context of PE–protein interactions, the heterogeneity of the charge distribution and the effects of a low dielectric permittivity underneath the surface are crucial. Studies of the combined effects of these two properties are very sparse, especially in the spherical geometry; we thus fill this gap here. We study the adsorption of PE chains onto spherical particles with heterogeneously charged surfaces, with the main focus on the critical-adsorption conditions and the effects of a low-dielectric core. Metropolis Monte Carlo simulations are employed, with the PE exploring the phase-space around the binding particle in the canonical ensemble. Two adsorption–desorption transitions are observed when the particle possesses a net charge of the same sign as that of the PE, resulting in nonmonotonic behavior of the critical charge density required for the PE–particle electrostatically driven adsorption. An increased affinity between the PEs and low-dielectric particles with variable heterogeneous charge distributions is observed, in contrast to the behavior detected for homogeneous low-dielectric particles. This higher affinity occurs when the Debye screening length in the solution becomes comparable to the dimensions of a patch of the opposite sign to the PE. A number of real-life applications of the considered PE–particle system is presented in the discussion, in particular regarding the properties of the complex formation between various PEs and globular proteins featuring a dipolar-type distribution of electric charges on their surfaces, such as insulin and bovine serum albumin. Full article