Search Results (993)

Objective: Posaconazole, a second-generation triazole antifungal used for the prevention or treatment of invasive fungal infections, has been shown to markedly increase tacrolimus exposure in vivo when co-administered, potentially leading to clinically significant adverse events. A physiologically based pharmacokinetic (PBPK) model was developed to predict tacrolimus–posaconazole interactions in renal transplant recipients with different CYP3A5 genotypes, to inform tacrolimus dose adjustment in clinical practice. Methods: First, to obtain the critical inhibition parameters, in vitro enzyme kinetic studies were conducted. Based on these data, a whole-body physiologically based pharmacokinetic (PBPK) model for TAC was developed and validated in PK-Sim. A published, validated posaconazole PBPK model was applied concurrently. Model performance was evaluated against published pharmacokinetic data in healthy volunteers receiving tacrolimus with posaconazole. A virtual Chinese renal transplant recipient was generated by incorporating population-specific physiological parameters, including CYP3A5 genotype-dependent enzyme expression. Results: In vitro experimental results demonstrated that POSA acts as a potent reversible competitive inhibitor of CYP3A4/5-mediated TAC metabolism. The tacrolimus PBPK model adequately captured pharmacokinetics across CYP3A5 genotypes, and tacrolimus pharmacokinetics during co-administration with posaconazole were also predicted. Compared with CYP3A5 expressers, nonexpressers showed greater variability in tacrolimus whole-blood concentrations and greater susceptibility to posaconazole-mediated interactions. The CYP3A5*3*3 genotype was associated with higher C_max and AUC. Dose optimization simulations predicted that after 6–7 days of posaconazole co-administration, nonexpressers would require the reduction of tacrolimus dosing frequency from every 12 h to every 24 h to maintain trough concentrations within 8–15 ng/mL, whereas a 50% dose reduction was predicted to be optimal for expressers. Conclusions: A tacrolimus–posaconazole PBPK drug–drug interaction model was developed for the population of renal transplant recipients and used to simulate tacrolimus trough concentrations across CYP3A5 genotypes and dosing regimens, supporting genotype-informed co-administration in clinical practice. Full article

Bowl-shaped gold nanoparticles (BAuNPs) are of significant interest due to their tunable localized surface plasmon resonance (LSPR) properties. This report presents a new synthesis method that uses hemispherical hydrogen nanobubbles on planar, non-conducting surfaces as templates for gold shell deposition. Initial synthesis under stagnant conditions yielded non-uniform sub-micron particles, attributed to localized hydrogen concentration gradients. The cyclonic flow was introduced aiming to reduce these gradients, although simultaneously inducing significant particle aggregation, obscuring the open structure. To overcome these challenges, an electrochemical microfluidic system was implemented to create a laminar flow environment. This configuration optimizes ion distribution and introduces shear forces that promote particle detachment, successfully limiting particle dimensions to below 200 nm, and preventing the accumulation. Systematic optimization identified optimal parameters: an ideal channel length of 7.5 mm, an applied potential of −0.6 V, and a flow rate of 0.028 µL s⁻¹. These parameters that strike a balance between nanobubble growth and gold deposition kinetics can produce highly uniform BAuNPs with a well-defined open structure and thin solid gold shells, with an outer diameter of 105.3 ± 12.1 nm and a core diameter of 80.1 ± 11.9 nm. These structural parameters successfully shift the plasmonic resonance to 760 nm, which responds perfectly with the first biological window for potential in vivo biomedical applications. Full article

To sustain egg production and gut health in aging flocks, the poultry industry seeks alternative synbiotic feed supplements. This study aimed to optimize Pediococcus acidilactici V202-fermented rice bran (PFR) and evaluate its effects on nutrient digestibility and cecal microbial populations in aged laying hens. In experiment 1, solid-state fermentation conditions (substrate particle size, moisture, and temperature) were optimized for viable lactic acid bacteria (LAB) counts. In experiment 2, in vitro assays were used to assess cecal fermentation kinetics. Subsequently, an in vivo trial involving twenty 80-week-old Hy-Line Brown hens evaluated the impact of PFR supplementation on nutrient digestibility and microbial profiles compared to a control diet. For experiment 1, the optimized fermentation conditions consisted of 40-mesh rice bran, a 30:70 bran-to-water ratio, incubation at 39 °C for 12 h, and drying at 40 °C, which produced the highest viable LAB counts. For experiment 2, PFR enhanced in vitro cumulative cecal gas production. In vivo, compared to the control, PFR supplementation significantly increased the apparent digestibility of dry matter (82.69% vs. 77.03%; p = 0.014), crude protein (82.75% vs. 75.38%; p = 0.016), crude fiber (36.30% vs. 23.10%; p = 0.015), ether extract (86.70% vs. 82.91%; p = 0.016), and gross energy (78.31% vs. 74.99%; p = 0.026). Furthermore, PFR beneficially modulated cecal microbial populations, increasing LAB while reducing Salmonella spp. In conclusion, these findings suggest that optimized PFR could be a promising synbiotic supplement to improve digestive efficiency and support beneficial cecal microbial populations in aged laying hens. Full article

The current study illustrates the modeling of a biocompatible poly γ-glutamic acid (PGA)–chitosan–rGO nanocomposite hydrogel scaffold, which showed a promising novel scaffold for stimulating central nerve regeneration that addresses the shortcomings of recent therapies and improves tissue engineering, controls inflammation, and restores lost functions after spinal cord injuries (SCIs). In the implementation part of the study, the COMSOL program’s top-notch modeling of a detailed investigation of how a scaffold’s in vivo diffusion affects injured neurons. Michaelis–Menten kinetics is used to characterize the enzyme process of releasing the outer covering shell of the scaffold, PGA, from a biomaterial matrix to the nerve cell. Results suggested that the injectable hydrogel scaffold theoretically reduces extracellular glutamate concentrations, presenting a potential mechanism to mitigate localized excitotoxicity. Future in vivo experimental validation is required to determine if this reduction prevents neural cell death Full article

Background/Objectives: Advanced renal cell carcinoma (aRCC) remains incurable, with no established optimal sequence of targeted therapies due to interpatient heterogeneity and acquired resistance. We developed a luciferase-enabled patient-derived orthotopic xenograft (PDOX) avatar platform to evaluate sequential targeted therapies in individualized aRCC models that recapitulate tumor architecture, proliferation, angiogenesis, metastasis, and PD-L1 expression. Methods: Tumor specimens from two renal cell carcinoma (RCC) patients were expanded subcutaneously in NOD/SCID mice, transduced with luciferase/red fluorescent protein (Luc/RFP), and orthotopically implanted into mouse kidneys (KiCa-Pt58: sarcomatoid RCC, pT3aN1M1, Fuhrman grade 4; KiCa-Pt118: clear cell RCC with sarcomatoid component, pT3aNxM0, Fuhrman grade 4, respectively). Tumor growth and metastasis were monitored weekly by bioluminescence imaging (BLI). Mice were randomized into vehicle control or four sequential treatment groups (Everolimus→Sunitinib [E→S], Sunitinib→Everolimus [S→E], Pazopanib→Sunitinib [P→S], Pazopanib→Everolimus [P→E]). Drugs were administered orally three times weekly until resistance (>200% BLI increase), with one switch. At necropsy, tumor burden, ex vivo BLI metastasis, weights, H&E histology, and immunohistochemistry (Ki67, CD44, CD31, PD-L1) were assessed. Results: Two independent experiments were performed. In dosing optimization, PDOX tumors recapitulated parental histology and proliferative indices, mirroring patient trajectories. KiCa-Pt58 (metastatic sarcomatoid RCC; deceased 1-month post-nephrectomy) showed aggressive features: rapid engraftment at low doses, early growth (week 2), and lung metastases in 78% of mice (sacrifice day 34), reflecting a fulminant course. KiCa-Pt118 (non-metastatic; patient recurrence-free >8 years post nephrectomy) exhibited indolent behavior: delayed engraftment requiring higher doses plus lymph node stromal (HK) support, slower growth (week 4), no metastases, and later sacrifice (day 78), consistent with remission. In sequential therapy evaluation, for KiCa-Pt58, P→E yielded greatest reductions in tumor weight (p < 0.01), lung metastases (p < 0.01), Ki67+ proliferation, CD31+ angiogenesis, and PD-L1 expression versus control; E→S and S→E were also effective. For KiCa-Pt118, S→E and P→E reduced tumor burden (p < 0.01) and Ki67⁺ proliferation; S→E lowered CD31 and PD-L1. Conclusions: This RCC PDOX platform faithfully preserves patient-specific biology—including metastatic propensity, engraftment efficiency, growth kinetics, and stromal dependency—while enabling real-time evaluation of sequential targeted therapies. Given the limited number of models tested, these findings provide proof-of-concept for individualized treatment exploration in advanced RCC and support future investigation of rational combinations with immune checkpoint blockade in humanized or immunocompetent systems. Full article

Background/Objectives: Boron neutron capture therapy (BNCT) relies on the selective delivery of boron-10 to tumor cells. Although 4-[¹⁰B]borono-L-phenylalanine (BPA) is currently the only clinically approved BNCT agent, it is limited by poor L-type amino acid transporter 1 (LAT1)/LAT2 selectivity and aqueous solubility. We previously developed 3-borono-5-fluoro-α-methyl-L-phenylalanine (5F-αMe-3BPA), a novel BPA derivative designed to be a LAT1-targeted BNCT/positron emission tomography theranostic agent. This study comprehensively characterizes its pharmacological profile and explores its pharmacokinetic optimization by modulating renal organic anion transporter 1 (OAT1). Methods: Transport kinetics of BPA, related analogs, and 5F-αMe-3BPA were analyzed in HEK293 cells stably expressing LAT1 or LAT2 using Michaelis–Menten analysis. Time-dependent cellular uptake and intracellular retention of BPA and 5F-αMe-3BPA were evaluated in T3M-4 pancreatic cancer cells with or without the LAT1 inhibitor JPH203. In vivo biodistribution was examined in T3M-4 tumor-bearing mice after intravenous administration of 5F-αMe-3BPA or BPA, with assessment of probenecid pretreatment. Results: 5F-αMe-3BPA retained LAT1 affinity comparable to that of BPA while showing markedly reduced LAT2-mediated transport, indicating improved LAT1/LAT2 selectivity. In T3M-4 cells, 5F-αMe-3BPA showed stronger LAT1 dependence, higher steady-state accumulation, and better intracellular retention than BPA under amino acid-containing conditions. Although 5F-αMe-3BPA achieved favorable tumor-to-plasma and tumor-to-muscle ratios in vivo, it was rapidly cleared from circulation. Probenecid pretreatment increased plasma exposure, reduced early renal accumulation, and significantly enhanced tumor boron accumulation, reaching approximately twofold higher levels than control. Conclusions: These findings establish 5F-αMe-3BPA as a highly LAT1-selective BNCT candidate and identify probenecid pretreatment as a clinically translatable pharmacokinetic strategy for maximizing therapeutic boron delivery. Full article

Background: Oral colon-targeted delivery for inflammatory bowel disease (IBD) faces significant challenges, including limited gastrointestinal stability, premature drug release, and insufficient mucosal retention. Methods: To address these limitations, a mucoadhesive polysaccharide-based composite hydrogel incorporating prednisolone-loaded polymeric micelles was developed to enhance colonic delivery and promote mucosal repair. Amphiphilic oxidized dextran–oleylamine (ODEX-OA) copolymers were synthesized to self-assemble into prednisolone-loaded micelles. These micelles were subsequently embedded within a thiolated chitosan (CSSH) hydrogel through a Schiff base reaction, yielding the ODEX-OA-Pred-CSSH composite. The resulting system was comprehensively characterized for particle size, mucoadhesion, degradation, and pH/ROS dual-responsive drug release. Its colon-targeting capability and therapeutic efficacy were subsequently assessed in a dextran sulfate sodium (DSS)-induced colitis mouse model. Results: In vitro, the composite hydrogel demonstrated nanoscale micellar size, enhanced drug release kinetics under simulated inflammatory colonic conditions, and prolonged colonic retention for up to 24 h following oral administration. In vivo, studies confirmed that ODEX-OA-Pred-CSSH significantly alleviated colitis, evidenced by a reduced disease activity index, diminished pro-inflammatory cytokine levels, restored colon length, decreased spleen index, and improved histological mucosal repair. Conclusions: These findings collectively suggest that this mucoadhesive micelle–hydrogel composite represents a promising and effective oral colon-targeted platform for the treatment of IBD. Full article

Background: TV-44749 is a subcutaneous (sc) long-acting injectable (LAI) formulation of olanzapine that recently demonstrated efficacy and safety as a treatment for schizophrenia in adults without the occurrence of post-injection delirium/sedation syndrome (PDSS) in the phase 3 SOLARIS trial (NCT05693935). TV-44749’s sc route of administration and formulation were designed to provide prolonged olanzapine release over a monthly dosing interval and to avoid the risk of post-injection delirium/sedation syndrome (PDSS). It was designed as a copolymer in situ-forming depot technology to provide a LAI formulation that could withstand physiological and environmental factors that could affect controlled-release kinetics. Methods: To evaluate the robustness of the TV-44749 formulation, an in vitro release (IVR) study in human plasma was conducted, comparing TV-44749 to the commercially available intramuscular (im) long-acting injection formulation of olanzapine pamoate monohydrate. In addition, in vivo studies in rats were conducted to assess the effect of injection site manipulation following TV-44749 sc injection on olanzapine release from the depot. Results: The IVR study showed that upon contact with human plasma, copolymers comprising TV-44749 formulation instantly precipitate and form a solid matrix that entraps olanzapine particles. This prevents an uncontrolled release of olanzapine. Additionally, in vivo rat studies found that manipulation of the injection site after TV-44749 administration, by either heating or rubbing at different time-points, resulted in no meaningful effect on overall olanzapine exposure. Conclusions: The presented findings support the robustness of the TV-44749 formulation in maintaining controlled-release properties, even under conditions that could otherwise compromise release performance. Full article

Background: UVA-induced photoaging is driven by a self-reinforcing cycle of persistent oxidative stress, inflammation, and extracellular matrix (ECM) degradation. Quercetin (Que) offers potent photoprotective potential, yet its clinical utility is hindered by poor aqueous solubility and low skin permeability. Objective: To develop a stable quercetin delivery system and evaluate its protective efficacy against UVA-induced photoaging via the NRF2/NF-κB signaling axis. Methods: Network pharmacology and molecular docking identified potential targets. An oil-in-water (O/W) nano-emulsion was formulated and characterized. Its effects were evaluated in UVA-irradiated human skin fibroblasts (HSFs; 1.2 J/cm²/day for 5 days) and a BALB/c mouse model (20 J/cm²/day for 8 weeks). Results: Network pharmacology identified 85 shared targets between Quercetin and photoaging. Molecular docking confirmed high affinities (binding energies < −7.0 kcal/mol) for NRF2, NF-κB p65, SOD2, and MMP-1. The optimized O/W nano-emulsion (144–154 nm, Zeta potential −38 to −43 mV) enhanced Quercetin solubility by 175-fold and followed Higuchi release kinetics. In HSFs, 30 μm Quercetin reduced SA-β-Gal positivity from 45.8% to 12.5% (73% inhibition), decreased ROS by 66%, and restored Type I collagen intensity to 82 ± 3 a.u. In vivo, topical 0.3% Que emulsion significantly attenuated skin-fold thickening (reducing thickness from 3135 μm to 2170 μm; 30.6% reduction) and achieved a 91% collagen retention rate. Mechanistically, Quercetin treatment significantly upregulated NRF2 and SOD2 expression while suppressing the NF-κB p65/MMP-1/3 inflammatory axis at both mRNA and protein levels (p < 0.01). Conclusions: Topical Quercetin emulsion effectively facilitates dermal delivery and alleviates UVA-induced photoaging by rebalancing the NRF2/NF-κB axis, thereby enhancing antioxidant defenses and preserving ECM integrity. This formulation represents a robust strategy for skin photoprotection and functional cosmetic intervention. Full article

Natural products display exceptional chemical diversity and a broad range of mechanisms of action that are not adequately captured by traditional classifications based on target class, pharmacological phenotype, or chemical scaffold. Such classification schemes often lead to fragmented understanding of mechanisms of action, obscuring the unified principles underlying different target systems while failing to recognize the stage-dependent mechanisms exhibited by the same molecule in varying contexts. Here, we propose a unified “space–interface–time” framework to classify the mechanisms of action by examining the physical principles through which natural products reshape the functions of different biomolecules. Within this framework for unifying the classification of natural product mechanisms of action, geometry-driven binding site occupancy and conformational constraints are assigned to the spatial dimension; induction or stabilization of multicomponent complexes and kinetic regulation of state lifetimes are assigned to the interfacial and temporal dimensions, respectively. Finally, we discuss the conceptual and technical challenges of bridging static structural snapshots with dynamic in vivo pharmacology, and highlight emerging opportunities offered by time-resolved structural methods and the integration of molecular dynamics, machine learning, and biophysical workflows for mechanism-guided drug discovery. Full article

HIV-1 integrase (IN) strand transfer inhibitors (INSTIs) are central to modern antiretroviral therapy (ART) because of their high potency and durable effect on viral suppression. However, drug resistance mutations (DRMs) within HIV-1 IN emerge, which can compromise long-term treatment efficacy. Many distinct DRMs that arise under INSTI therapy have been extensively tabulated in public repositories and literature. However, the timelines over which they emerge, accumulate, and consolidate in patients have not been systematically integrated across clinical and experimental studies. In this review, we synthesize current evidence on the temporal evolution of DRMs within HIV-1 IN by examining mutational kinetic data from viruses derived from people living with HIV/AIDS (PLWH) and from in vitro selection experiments. We compare experimental timelines to recent computational predictions derived from Potts-based fitness landscapes coupled with kinetic Monte Carlo simulations and identify reproducible kinetic classes that distinguish fast-, intermediate-, and slow-emerging DRMs. Rapidly emerging DRMs such as E92Q and N155H typically appear early under drug pressure and often represent low-barrier adaptive responses, whereas the most clinically consequential mutations, such as Q148H/K/R, G140A/S, and E138K, arise only after extended therapy and generally require compensatory mutational backgrounds to persist. Although absolute emergence times vary substantially between in vivo and in vitro systems, consistent temporal trends across datasets support the existence of underlying epistatic constraints that shape drug resistance evolution. Understanding DRM timelines is clinically relevant because it provides a framework for interpreting resistance detected at virological failure, informs optimal timing of resistance testing, and may enable earlier identification of high-risk evolutionary trajectories before durable resistance is established. Full article

Background/Objectives: Triptolide (TP), a potent natural diterpenoid, exhibits anti-glioma activity, but faces significant clinical translation challenges, including poor water solubility, systemic toxicity such as hepatotoxicity, and inadequate tumor targeting. This study aimed to develop a novel epidermal growth factor receptor (EGFR)-targeted liposomal formula-tion, designated as TP-CTX-Lip (where CTX denotes cetuximab), to enhance the deliv-ery efficiency and therapeutic window of TP. Methods: The formulation was optimized using a uniform design approach (four factors, six levels) and prepared via thin-film hydra-tion–ultrasonication. The encapsulation of TP was supported by Fourier transform in-frared spectroscopy (FTIR) and thermal analysis (DSC/TGA), which revealed molecu-lar interactions (e.g., hydrogen bonding) with lipid components and a marked en-hancement in thermal stability, consistent with successful incorporation into the lipo-somal bilayer. The physicochemical properties, including the size, polydispersity index (PDI), zeta potential, encapsulation efficiency, and drug loading, were characterized. In vitro release kinetics were evaluated in phosphate buffer (pH 7.4), and cytotoxicity was assessed in high-EGFR (U87-MG) and low-EGFR (SW1088) glioma cells. In vivo efficacy and developmental toxicity were investigated using zebrafish models. The op-timized TP-CTX-Lip demonstrated favorable characteristics: size = 131.3 ± 4.5 nm, PDI = 0.24 ± 0.006, zeta potential = −23.37 ± 0.27 mV, encapsulation efficiency = 85.83% ± 1.81%, and drug loading = 13%. In vitro release followed first-order kinetics dominated by Higuchi diffusion (79.0% ± 4% at 24 h). After 48 h of treatment, TP-CTX-Lip exhib-ited significantly enhanced cytotoxicity in U87-MG cells (IC50 = 10.4 ± 0.2 nM), com-pared with IC50 values of 42.8 nM in SW1088 cells and 45.3 nM for non-targeted lipo-somes. In the 3T3-L1 non-cancerous cell line, the 48 h IC50 value of TP-CTX-Lip (8.433 ± 0.954µM) was higher than that of the TP solution (2.173 ± 0.181µM) but lower than that of TP-Lip (25.78 ± 2.691µM). Specifically, in 3T3-L1 cells, the 48 h IC50 of TP-CTX-Lip (8.43 µM) was approximately 4-fold higher than that of free TP (2.17 µM), confirming its substantially reduced cytotoxicity against non-cancerous cells. Results: In comparison to TP-Lip and free FITC solution, the uptake rate of TP-CTX-Lip in U87-MG cells exhibited a significantly higher level. Specifically, the uptake rate for the TP-CTX-Lip group (57.46 ± 5.44%) was statistically significantly higher than that of TP-Lip (13.7 ± 2.33%) and the free FITC solution group (20.97 ± 1.60%) (p < 0.01). In zebrafish, TP-CTX-Lip reduced developmental toxicity, with LC50 increased 1.26 times to 5.733 μg/mL, and suppressed orthotopic U87-MG xenograft growth (p < 0.001), in-dicating an improved therapeutic window as reflected by the LC50/IC50 ratio. Conclusions: the EGFR-targeted TP-CTX-Lip significantly enhances the tumor selectivity and safety of TP, providing a promising strategy for targeted glioma therapy. Full article

This study formulated and characterized metformin-loaded chitosan nanoparticles (NPs) using the ionic gelation technique and evaluated the drug release kinetics. Characterization confirmed successful drug encapsulation, with Fourier-transform infrared spectroscopy (FTIR) indicating compatibility, and X-ray diffraction (XRD) showing attenuation of characteristic metformin reflections consistent with reduced crystalline contribution after encapsulation. Particle sizes ranged from 74.28 to 86.82 nm. The NPs exhibited stable zeta potentials (+42.38 to +49.06 mV) and high entrapment efficiencies (68.42–81.26%). In vitro drug release studies at pH 7.4 and pH 2.0 demonstrated an initial burst release, followed by sustained release over 24 h. The cumulative drug release ranged from 81.92% to 97.72% at pH 7.4 and 89.4% to 98.1% at pH 2.0, with a faster release at pH 2.0. Drug release kinetics followed first-order for batch MN1, while batches MN2 and MN3 best fitted into the Higuchi model, indicating diffusion-controlled release through the chitosan polymeric network. The formulated metformin nanoparticles demonstrated significant potent dose-related and time-dependent cytotoxic effect against ovarian cancer cell lines and in vivo blood glucose lowering effect compared to the conventional dosage forms and control (p < 0.05). These findings highlight the potential of metformin-loaded chitosan NPs for sustained drug delivery, which may enhance patient compliance by reducing dosing frequency. Future studies should further explore their clinical applications. Full article

Hypertension is a severe global public health issue. Food-derived angiotensin-converting enzyme (ACE)-inhibitory peptides have shown great potential as safe and effective alternatives to synthetic antihypertensive drugs. Camel milk is rich in bioactive peptides. This study aimed to screen for ACE-inhibitory peptides from hydrolyzed camel casein, explore their inhibitory mechanisms and endothelial protective effects in vitro, and reveal their potential antihypertensive pathways using network pharmacology. This study screened three peptides with angiotensin-converting enzyme (ACE) inhibitory activity from enzymatically hydrolyzed camel casein components: MVPFLQPK, VPFLQPKVM, and QKWKFL, with IC₅₀ values of 277.1, 396.9, and 486.9 μmol/L, respectively. Enzyme inhibition kinetics analysis indicated that MVPFLQPK exhibited a non-competitive inhibition pattern, VPFLQPKVM exhibited a mixed inhibition pattern, and QKWKFL exhibited a competitive inhibition pattern. Molecular docking revealed that all three peptides formed hydrogen bond interactions with ACE, and QKWKFL and VPFLQPKVM directly bound to the enzyme’s active site to inhibit substrate catalysis. Molecular dynamics simulation further confirmed the high stability of the three peptide–ACE complexes, with binding free energies from −34.24 to −51.19 kcal/mol. The primary contributing forces include hydrogen bonds, van der Waals interactions, electrostatic forces, and nonpolar solvation effects. Network pharmacology analysis suggested that these peptides may exert synergistic antihypertensive effects by regulating multiple blood pressure-related pathways, including the renin–angiotensin system, renin secretion, and calcium signaling pathways, by acting on key targets such as ACE, REN, SRC, and MMP9. Cell experiments demonstrated that all three peptides exhibited no cytotoxicity in the Ang II-induced HUVEC injury model, significantly promoted NO release, inhibited ET-1 secretion, and possessed endothelial protective potential. This study investigated the in vitro ACE-inhibitory mechanism of peptides derived from camel milk and their potential role in blood pressure regulation, providing experimental evidence for subsequent in vivo activity validation and the development of functional camel milk protein products. Full article

The development of efficient and biocompatible sorbent nanomaterials for cesium removal is critical for environmental and biomedical decontamination. Here, hybrid composites based on ultra-small Prussian blue or Zn Prussian blue-type nanoparticles confined within porous chitosan beads are proposed for Cs⁺ extraction. Nanoparticle confinement ensures homogeneous dispersion and improved accessibility of ion-exchange sites, while preserving the porous polymeric network, as confirmed by physicochemical characterization. Cs⁺ adsorption was investigated under neutral and acidic conditions (pH 7.2 and 1.2), at concentrations of 0–9 mmol/L and contact times of 0–50 h, showing efficient uptake and favorable kinetics, with confirmed stability in simulated gastric fluid. In vivo performance was assessed in a mouse model of cesium contamination (70 mg Cs⁺/kg). Treatment with nanocomposites (225 mg/kg) was compared to bulk Prussian blue (75 mg/kg), revealing enhanced detoxification efficiency. Histological analysis of liver, spleen, and kidney tissues showed no detectable structural damage, consistent with unchanged systemic biomarkers. Overall, the proposed chitosan-confined Prussian blue-type nanocomposites combine high Cs⁺ removal efficiency, kinetic accessibility, and in vivo safety, highlighting their potential for decorporation applications. Full article