Search Results (1,190)

This study aimed to provide the first comprehensive seed-based phytochemical and biological investigation of Onosma onur-koyuncui Sezer, a species endemic to Türkiye, by characterizing its chemical composition and evaluating its in vitro antioxidant and enzyme inhibitory potential. A multi-technique approach combining SPME-GC-FID/MS, GC-FID/MS after silylation, ICP-OES, and UHPLC-HRMS/MS was applied to n-hexane and 70% aqueous methanol seed extracts, together with total phenolic and flavonoid determinations, complementary antioxidant assays, and α-amylase inhibition. p-Cymene (15.00%) was the major volatile, octadecatrienoic acid (27.77%) predominated in the fatty acid profile, and calcium (28.50 mg/g_dw) was the most abundant mineral. UHPLC-HRMS/MS revealed chlorogenic acid (51.29 mg/g_dw) and diosmetin (42.95 mg/g_dw) as major constituents of the 70% aqueous methanol extract. This extract showed the highest phenolic and flavonoid contents and notable antioxidant activity, particularly in the DPPH assay (IC₅₀ = 0.043 mg/mL), exceeding that of BHA (IC₅₀ = 0.118 mg/mL), and exhibited α-amylase inhibition (IC₅₀ = 0.40 mg/mL). These findings provide the first integrated characterization of O. onur-koyuncui seeds and highlight their phytochemical diversity and antioxidant potential. Full article

Doxorubicin hydrochloride (DX) is a widely used chemotherapeutic agent whose severe side effects can be attenuated by suitably designing drug delivery systems. The complexation between DX and the biocompatible and biodegradable sodium alginate (ALG) results in the formation of DX@ALG nanoparticles under conditions where neither the drug nor the polymer tends to form nanoscopic structures. DX@ALG complex formation leads to the quenching of DX intrinsic fluorescence, and the drug shows chiroptical properties characteristic of supramolecular gels of DX. The association of DX and ALG into supramolecular nanoparticles takes place at low DX concentration and without salt addition. More than 99% of the moles of DX complexed with ALG form a gel-like phase, and DX@ALG nanoparticles show a high DX loading efficiency. Nanoparticle formation is revealed by Dynamic Light Scattering (DLS) and Atomic Force Microscopy (AFM). Quantum Mechanics (QM) calculations support the formation of supramolecular DX-ALG aggregates by π–π stacking and hydrogen bonds. DX@ALG nanoparticles have been fully characterized by several spectroscopic techniques. Preliminary in vitro evaluation of DX@ALG toxicity revealed an antiproliferative activity against selected cancer cell lines. Full article

Background/Objectives: The development of new metallodrugs has represented an important milestone in recent years for their potential application in different therapeutic approaches. Therefore, the objective of this study was to synthesize a series of P^N iminophosphine Pd(II) complexes (1Pd–3Pd) incorporating different aliphatic amines. Methods: All complexes were characterized using several spectroscopic and analytical techniques, including ¹H, ¹³C{¹H}, and ³¹P{¹H} NMR spectroscopy, mass spectrometry, FT-IR spectroscopy, and elemental analysis. In addition, complex 3Pd was unambiguously characterized by single-crystal X-ray diffraction. Results: Supramolecular studies allowed the main noncovalent interactions responsible for stabilizing the crystal lattice of complex 3Pd to be identified. These interactions were analyzed using Hirshfeld surface analysis, which revealed that C-H···π and C-H···Cl interactions contributed most significantly to the stabilization of the crystal lattice. All complexes exhibited stability in different solvents and positive lipophilicity values, with complex 3Pd displaying the highest hydrophobicity. Through in vitro studies, the minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) of all complexes were determined against different Gram-positive and Gram-negative bacterial strains, as well as fungal strains of Candida species. Complex 3Pd exhibited the highest activity, particularly against L. monocytogenes (1.17 µg/mL), P. aeruginosa (4.68 µg/mL), and all fungal strains (18.75 µg/mL), displaying both bactericidal and fungicidal activity. Furthermore, in silico studies enabled the identification of the potential modes of action of the complexes against different molecular targets present in the bacterial and fungal strains. Conclusions: These results demonstrate the efficacy of the three synthesized complexes against different virulent strains exhibiting resistance to broad-spectrum drugs. Furthermore, the presence of the metal center, together with the incorporation of increasingly longer aliphatic chains, appears to enhance the antibacterial and antifungal activity of the complexes. Full article

Annona amazonica R. E. Fries (Annonaceae) is a tropical species native to Central and South America whose phytochemical profile remains poorly investigated. In the present study, the bark of A. amazonica was subjected to phytochemical investigation using conventional chromatographic techniques, leading to the isolation and identification of 18 metabolites comprising a diterpene, sesquiterpenes, steroids, ketosteroids, and alkaloids. Attention was given to N-formylactinodaphnine (16), which was isolated and comprehensively characterized by high-resolution electrospray ionization mass spectrometry (HRESIMS), infrared spectroscopy (IR), and one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR) spectroscopy. The present study provides a complete spectroscopic dataset for this compound and documents its occurrence in A. amazonica. The other isolated metabolites further expand the known phytochemical profile of the species. The effects of the isolated compounds on cellular viability were evaluated against HepG2, HCT116, MDA-MB-231, MCF-7, and U-87 MG human cancer cell lines and MRC-5 fibroblasts using the Alamar Blue assay after 72 h of incubation. Actinodaphnine (14) activity was detected across all five evaluated cancer cell lines, with IC₅₀ values ranging from 5.59 to 11.73 μg/mL. N-Methylactinodaphnine (cassythicine) (15) had an IC₅₀ value of 4.27 μg/mL against HCT116 cells; because of the limited amount of isolated material, compound 15 was evaluated only against HCT116 and MRC-5 cells. Overall, the results expand the phytochemical knowledge of A. amazonica, provide comprehensive spectroscopic documentation of N-formylactinodaphnine (16) from this species, and identify alkaloids with measurable in vitro activity in the cell-based viability assay. Full article

Background/Objectives: The deterioration of maxillofacial silicone elastomers is caused by microbial colonization and mechanical failure. Traditional inorganic nanofillers influence the elasticity of materials and their surface hygiene. This study provides a two-phase evaluation of mechanically milled pumpkin (Cucurbita pepo) extract nanoparticles (PE-NPs) to evaluate the in vitro anti-adhesion efficacy, mechanical properties, and surface characteristics of VST-50 maxillofacial silicone. Methods: In Phase I (Screening Phase), a comparison was made between conventional direct mixing and a newly developed multi-step catalyst-mediated mixing method. The preliminary assessment of anti-adhesion activity against Staphylococcus epidermidis (S. epidermidis), Shore A hardness, and tear strength was carried out at concentrations of 0, 0.5, 1.0, 1.5, and 2.0 wt.%. In Phase II (Characterization Phase), using the optimized fabrication protocol, final assessment of ultimate tensile strength (UTS), percentage elongation, profilometer surface roughness (Ra), and optical contact angle (Wettability) was carried out. Microstructural characterization was executed using FTIR, FE-SEM/EDX, XRD, and 3D Atomic Force Microscopy (AFM). Results: Phase I displays that the catalyst-mediated mixing effectively facilitated processing within the siloxane matrix, resulting in homogeneous nanoparticle dispersion. PE-NPs exhibited a concentration-dependent anti-adhesion response, achieving 95.7% anti-adhesion activity at 2.0 wt.% while improving tear strength and balancing hardness. Phase II demonstrated that 1.5 wt.% represented the concentration providing the most favorable overall balance, significantly enhancing tensile strength (10 [10–10.25] MPa) and elongation percentage (592.26 ± 47.97%). Macro-roughness and contact angles remained statistically unchanged (p > 0.05), maintaining baseline surface wettability. However, AFM nanomorphology revealed that 1.5 wt.% PE-NPs effectively filled matrix micro-voids, decreasing nanoscale roughness to 18.88 nm. Agglomeration was captured at 2.0 wt.%, resulting in suboptimal mechanical performance. Conclusions: Incorporating 1.5 wt.% organic PE-NPs via a multi-step catalyst integration technique provides an eco-friendly, strong strategy among the evaluated concentrations to enhance initial in vitro mechanical and anti-adhesion properties among the evaluated concentrations without altering baseline surface roughness. Full article

Polygonum equisetiforme Sm. is traditionally used in the Mediterranean region as a medicinal plant and herbal tea ingredient. This study aimed to characterize its phenolic constituents and evaluate its in vitro potential against metabolic targets associated with obesity and diabetes. Methanolic and defatted aqueous extracts of the aerial parts were prepared, and the aqueous extract was fractionated using chromatographic techniques. The isolated compounds were characterized by one- and two-dimensional NMR spectroscopy, supported by mass spectrometry where available, and compared with published spectroscopic data. Antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide anion radical (O₂•⁻), nitric oxide (NO), cupric ion reducing antioxidant capacity (CUPRAC), ferric reducing antioxidant power (FRAP), and Trolox equivalent antioxidant capacity (TEAC) assays. Inhibitory effects against α-amylase, α-glucosidase, and pancreatic lipase were determined, and glucose uptake was assessed in 3T3-L1 cells. Seven phenolic compounds were identified: 3-O-acetyl-(−)-epicatechin, liquiritin, catechin, tamarixetin, quercetin, quercetin-3-O-glucoside, and quercetin-3-O-galactoside. Among these, 3-O-acetyl-(−)-epicatechin and tamarixetin are reported for the first time in the genus Polygonum. The phenolic-rich fractions exhibited pronounced antioxidant activity, with Fr. E showing the strongest DPPH radical-scavenging activity (IC₅₀ = 6.00 µg/mL). The methanolic and aqueous extracts inhibited α-amylase (IC₅₀ = 310.95 and 285.00 µg/mL), α-glucosidase (IC₅₀ = 374.04 and 362.82 µg/mL), and pancreatic lipase (IC₅₀ = 519.20 and 868.50 µg/mL), respectively. At 100 µg/mL, both extracts enhanced glucose uptake in 3T3-L1 cells, with a further significant increase observed in the presence of insulin. These findings expand the phytochemical knowledge of P. equisetiforme and demonstrate its multi-target in vitro potential against metabolic processes associated with obesity and diabetes. Full article

Panax ginseng-derived EV-like particles (PG-EVLPs) are nanoscale lipid bilayer vesicles extracted from ginseng roots, stems, leaves, or cell cultures, with diameters typically between 50 and 200 nm. Available preclinical studies have demonstrated that PG-EVLPs exhibit favorable in vitro and in vivo biocompatibility and short-term safety, without obvious hemolysis, cytotoxicity or organ damage, making them an active area of research at the intersection of traditional Chinese medicine and nanomedicine. This review covers separation and purification methods, physicochemical characterization techniques, bioactive component composition, and pharmacological mechanisms of PG-EVLPs. It also evaluates several delivery strategies, including natural nanocarrier delivery, engineering modification, and hydrogel composite systems, and discusses current challenges in standardization, safety assessment, and clinical translation. Full article

Diabetes mellitus is a long-term metabolic disease associated with elevated glucose levels in blood and still constitutes one of the major public health issues worldwide. Inhibition of carbohydrate-digesting enzymes like α-amylase and α-glucosidase has been found to be effective in controlling postprandial hyperglycemia. The current study focused on designing, synthesis, characterization, and evaluation of novel 2,4-thiazolidinedione derivatives (D1–D5) as potent antidiabetic drugs utilizing combined in silico, in vitro, and in vivo techniques. Results from drug-likeness and ADME analyses indicated that all synthesized derivatives met Lipinski’s rule of five and had desirable pharmacokinetics properties along with reduced toxicity. Molecular docking against maltase-glucoamylase (human; PDB ID: 3TOP) protein showed good binding affinities of both D1 and D5 derivatives (−7.74 and −7.40 kcal/mol respectively) due to stable interactions with catalytic residues of enzymes. Inhibition of enzymes in vitro showed that D1 and D5 had the highest inhibitory activities of all synthesized derivatives, with IC₅₀ of 33.86 ± 2.1 and 37.55 ± 1.7 μM against α-amylase and 29.81 ± 3.2 and 32.43 ± 1.2 μM against α-glucosidase, respectively. Cytocompatibility tests on L6 myoblast cells proved that the lead compounds were well tolerated. In addition, studies in a model of Drosophila melanogaster induced by a high-sugar diet revealed a significant decrease in the level of glucose concentration depending on the dose, especially for D1 and D5, indicating their antihyperglycemic activity in vivo. Thus, these data confirm that D1 and D5 can be regarded as promising lead compounds for the development of new antidiabetics acting via inhibition of carbohydrate-metabolizing enzymes. Full article

The continual spermatogenesis throughout adulthood is ensured by a rare and unique cell group named spermatogonial stem cells (SSCs), which undergo self-renewal and/or differentiate into sperm cells. SSCs also become a promising genetic source for the protection of animal biodiversity. However, the isolation and culture of SSCs in vitro is still a big challenge and poorly explored in rabbits. The main objective of this study was to isolate, culture, and deeply characterize SSCs obtained from rabbit testes. Briefly, rabbit testicular tissue was mechanically and enzymatically dissociated, and obtained testicular somatic and germ cells were cultured for a short term in culture media supplemented with specific molecular factors maintaining SSC self-renewal and proliferation (GDNF, GFRα-1, FGF2, etc.). Immunofluorescent and PCR techniques were used for molecular profiling of cultured SSCs, while TEM analysis revealed their ultrastructure. After a few weeks, round and grape-like SSC colonies emerged, growing on the feeder cell layer. Rabbit SSCs showed positive staining for DBA, GFRA1, PLZF, RET, PGP9.5, DAZL, and DDX4. Increased expression of additional SSC markers was noticed using RT-qPCR and dd PCR (RET, PLZF, PGP9.5, DAZL, DDX4, CDH1, CD9, CD14, CD90, c-kit, ALDH, SSEA-4, SALL4, OCT4, and SOX2), while ultrastructure typical for primitive undifferentiated cells was observed under TEM. In conclusion, we successfully established a method for rabbit SSC isolation, culture, and phenotyping, which might facilitate their collection for further cryopreservation. However, the self-renewal, proliferative, and differentiation capacities of cultured SSCs still need to be confirmed through an in vivo SSC transplantation experiment. Full article

Introduction: Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disorder involving ROS and ferroptosis. MXene, a 2D material, functions as both a drug carrier and ROS scavenger. Butylphthalide (NBP), a neuroprotective agent, suffers from poor aqueous solubility and bioavailability. This study synthesized Ti₂C@BSA-NBP, a novel MXene nanocomposite, to enhance NBP delivery and therapeutic efficacy for AD. Materials and Methods: Ti₂C@BSA-NBP was synthesized via self-assembly and amidation reaction, and characterized by multiple techniques. In vitro, ROS-scavenging capacity, mitochondrial function, and ferroptosis markers were assessed in H₂O₂-injured cells. In vivo efficacy was evaluated in an AD mouse model via behavioral, histopathological, and biochemical analyses. Results: The nanocomposite exhibited robust ROS-scavenging activity in vitro, significantly attenuating ROS, restoring mitochondrial function, and reversing ferroptosis markers. In vivo, Ti₂C@BSA-NBP ameliorated learning/memory deficits, partially repaired neuronal morphology, and suppressed neuroinflammation. Mechanistically, it downregulated ACSL4 and Aβ overexpression while restoring GPX4 inhibition. Discussion: Ti₂C@BSA-NBP exerts synergistic neuroprotection through MXene-mediated ROS clearance and NBP-mediated multi-target regulation, counteracting oxidative stress, ferroptosis, and neuroinflammation. Conclusions: Ti₂C@BSA-NBP is a promising multifunctional nanoplatform integrating antioxidant activity, enhanced drug delivery, and ferroptosis modulation for AD therapy. Full article

To realize the high-value valorization of cold-pressed walnut meal, walnut oligopeptides were fabricated via synchronous dual-enzyme hydrolysis combined with activated carbon decolorization and membrane separation purification. We optimized the overall preparation process and systematically characterized the products, including their amino acid profile, in vitro antioxidant capacity, cytoprotective effects against H₂O₂-triggered oxidative injury in PC12 cells, and regulatory activity toward acetylcholinesterase (AChE). The optimal hydrolysis conditions were identified as pH 10.0, total enzyme dosage of 11,000 U/g, a trypsin-to-alkaline protease ratio of 2.1:1, solid–liquid ratio of 1:26, temperature of 51 °C and reaction duration of 4 h, which produced a hydrolysis degree of 33.02%. The optimized decolorization parameters were pH 5.2, activated carbon dosage of 2.3%, treatment at 58 °C for 43 min, with a peptide recovery rate reaching 83.35%. Cold-pressed walnut meal is rich in glutamic acid, arginine and aspartic acid, which lay the molecular foundation for the bioactive properties of the derived oligopeptides. In vitro tests demonstrated that the oligopeptides possessed strong scavenging ability against hydroxyl, DPPH and superoxide anion radicals (clearance rates of 90.18%, 81.72% and 85.80%, respectively), and maintained 73.21% of antioxidant activity after simulated gastrointestinal digestion. Moreover, walnut oligopeptides at 0.8 mg/mL showed no cytotoxicity and afforded a 79.88% protective effect against oxidative damage. The peptides significantly boosted SOD and GSH-Px activities, lowered MDA accumulation, and strongly suppressed AChE activity, performing better than donepezil hydrochloride. This efficient, eco-friendly technique achieves high-value utilization of walnut processing by-products. The obtained oligopeptides possess great potential as natural antioxidants and neuroprotective ingredients for functional food development. Full article

Background/Objectives: Shape-memory biodegradable scaffolds (4D scaffolds) represent promising platforms for minimally invasive tissue engineering and localized drug delivery. This study investigated how two different fabrication techniques, electrospinning (ES) and extrusion-based direct ink writing (DIW), influence the structural, thermal, mechanical, shape-memory, and drug-release properties of poly(L-lactide-co-caprolactone) (PLA/PCL 70:30) scaffolds loaded with dexamethasone (DXM). Methods: DXM-loaded PLA/PCL 70:30 scaffolds were fabricated by ES and DIW. The resulting matrices were characterized in terms of morphology, mass, thickness, drug-loading efficiency, thermal properties by differential scanning calorimetry, shape-memory performance, tensile mechanical properties, and in vitro DXM release. Results: Both fabrication techniques produced DXM-loaded matrices with comparable mass and thickness and high loading efficiencies (>82%). Glass transition temperatures ranged between 33 and 39 °C, supporting thermally induced shape recovery under physiologically relevant conditions, while ES processing was associated with higher polymer crystallinity. All scaffolds exhibited shape-memory behavior, with recovery ratios exceeding 90%. ES scaffolds displayed a microporous nanofibrous architecture, whereas DIW scaffolds showed a more open and highly porous structure. These morphological differences were reflected in their mechanical behavior: ES scaffolds exhibited higher tensile strength (up to 16.5 MPa vs. 1.9 MPa) and elongation at break (up to 320% vs. 243%). Drug-release profiles were also fabrication-dependent, with ES scaffolds reaching a plateau at approximately 80% DXM release, whereas DIW scaffolds showed near-complete release within 48 h. Conclusions: Both fabrication approaches preserved the thermoresponsive shape-memory behavior of PLA/PCL 70:30 but generated distinct scaffold architectures that strongly influenced mechanical performance and DXM-release kinetics. Full article

Background: The current study uses a computational technique to investigate synthesized thiazine compounds that exhibit potential interactions with the GABA_A receptor. A series of novel thiazine derivatives was synthesized via the cyclization reaction of chalcone with thiourea. Methods: For the synthesized compounds, spectroscopic characterization, namely FT-IR, ¹H NMR, ¹³C NMR, and mass spectrometry, was carried out. In addition, the AutoDock Vina 4.2 software was applied to carry out an in silico docking study. Results: The synthesized compounds C3 and C6 exhibited comparable predicted docking scores (−9.0 and −9.1 kcal/mol, respectively), with favorable predicted interactions at the GABAA receptor binding site. Furthermore, in silico ADMET analysis provided insights into the drug-likeness and pharmacokinetic profiles of the synthesized compounds; however, potential safety liabilities, including Ames positivity, hERG II liability, and hepatotoxicity, were predicted for some derivatives. Conclusions: It was determined that the synthesized compounds’ various physiologically significant and physiologically relevant parameters fell within the range of Lipinski’s rule of five. The synthesized compounds (C1–C10) were tested for anxiolytic activity by the elevated plus maze test, and compound C6 was found to be the most potent. Additionally, the in vitro GABA-AT enzyme activity assay showed that compound C6 had the highest inhibitory potential, with an IC50 of 13.29 ± 1.622 µM. Full article

Introduction: White spot lesions (WSLs) are early enamel demineralization lesions associated with increased surface roughness and plaque retention. Profilometry is commonly used to evaluate these surface changes, although methodological variability remains significant. Objective: To critically evaluate the available evidence regarding the validity and reproducibility of profilometry for assessing surface roughness in experimentally induced WSL models and treatment-modified surfaces and to identify methodological factors influencing its application across in vitro studies. Methods: A systematic review of 27 in vitro studies published between 2021 and 2026 was conducted. Methodological characteristics of contact and non-contact profilometry were synthesized, and evidence relevant to validity and reproducibility was qualitatively assessed based on complementary analytical methods and the reporting of standardized measurement procedures. Results: Considerable heterogeneity was identified in specimen sample and preparation, demineralization protocols, profilometric systems, acquisition settings, roughness parameters, and experimental conditions. Both contact and non-contact profilometry detected treatment- and demineralization-related surface changes, with Ra being the most frequent reported parameter. Complementary analytical techniques provided supporting evidence for the interpretation of profilometric findings but did not constitute formal validation. Methodological details relevant to reproducibility were inconsistently reported, and formal repeatability or reproducibility testing was generally lacking, Conclusion: Profilometry appears useful for quantitatively characterizing surface topography in experimentally demineralized enamel as a model of WSLs and treatment-modified enamel; however, substantial methodological variability and limited formal validation and reproducibility testing prevent definitive conclusions regarding its validity and reproducibility. Greater standardization of methodologies of measurement and reporting protocols is required to improve comparability and strengthen the evidence base. Full article

Background/Objectives: Matrix pellet formulations enable homogeneous incorporation of the active ingredient and advanced control of release depending on the excipients added. The aim of this study was to develop, characterize, and assess the drug release profiles of microcrystalline cellulose (MCC) and isomalt-based matrix pellets with direct drug incorporation, advancing beyond the earlier concept of isomalt as a mere inert core with layered drug application, under simulated physiological conditions in vitro. Methods: Matrix pellets with varying MCC–isomalt ratios (90:10, 70:30, and 50:50) were produced by extrusion/spheronization and subsequently coated with film-forming polymers. Dissolution experiments were performed under varying osmolarity to characterize release profiles. The experimental design data were statistically evaluated. Results: The extrusion/spheronization technique yielded uniform, robust matrix pellets with acceptable sphericity and mechanical integrity, even at high isomalt levels. Release from coated pellets was significantly influenced by the polymer coating and osmolarity of the dissolution medium. However, with increasing isomalt content in the matrix, the dependence of drug release kinetics on medium osmolarity was substantially reduced. Conclusions: The production of MCC–isomalt matrix pellets in which isomalt acts as a functional matrix component reduced the effect of osmolarity of dissolution medium on the release of ibuprofen sodium salt in in vitro experiments. Full article