Search Results (36,542)

This study investigates the influence of agronomic management on the accumulation of bioactive compounds and the antioxidant capacity of Achillea millefolium L., a medicinal species of increasing relevance for pharmaceutical and nutraceutical applications. Different cultivation strategies were applied, including controlled drought stress, foliar fertilization, and inoculation with plant growth–promoting rhizobacteria (PGPR), in order to evaluate their impact on tissue-specific metabolic responses. The total antioxidant capacity (TAC) of flowers and roots was determined using FRAP, DPPH, and ABTS spectrophotometric assays, while metabolite profiling was performed by UHPLC–MS/MS analysis. Clear differences in antioxidant activity were observed among plant organs and cultivation treatments. Flower extracts showed intermediate antioxidant capacity, with FRAP values ranging from 55.86 to 66.55 mg TE g⁻¹ extract and the highest activity consistently recorded for treatment F_010 (addition of K, P fertilizers under water stress conditions and PGPR absence) across all assays. Root extracts exhibited substantially lower antioxidant values (FRAP 19.40–33.69 mg TE g⁻¹), although samples R_000 (no foliar fertilization, under water stress conditions and PGPR absence) and R_100 (no foliar fertilization, under water stress conditions and presence of PGPR) displayed comparatively higher radical scavenging activity. Metabolic profiling revealed a shared presence of caffeic acid derivatives and flavonoids, including mono- and di-caffeoylquinic acids and apigenin-related compounds, with marked quantitative differences among tissues. Overall, the results demonstrate that agronomic practices significantly influence the accumulation and distribution of antioxidant metabolites in A. millefolium L., highlighting the importance of cultivation strategies for optimizing the production of bioactive phytochemicals. Full article

The aim of this in vitro study was to evaluate the ability of the new strontium-containing composite, Stela (SDI, Victoria, Australia), to induce hydroxyapatite formation and promote remineralization of demineralized dentin, compared to SDR Flow+ (York, PA, USA). Twenty-four dentin slices (1 mm thick) were obtained from extracted wisdom teeth using a microtome and demineralized with 17% EDTA for 2 h. A layer of either Stela or SDR Flow+ was applied to each slice, allowed to set, and preserved in 0.1% thymol solution. Samples were analyzed at 1, 7, 14 and 28 days (n = 3 per group and time). Measurements were taken at baseline, after demineralization, and after application. Apatite formation was assessed using 'Fourier-transform infrared spectroscopy (FTIR), while changes in the Calcium/Phosphate (Ca/P) ratio were evaluated by Energy Dispersive Spectroscopy (EDX). Statistical comparisons were performed using the Wilcoxon test (p < 0.05). Both materials promoted carbonated hydroxyapatite formation and increases in calcium and phosphate. Stela exhibited an apatite peak (1420 cm⁻¹) as early as 24 h and significant increases in calcium and phosphate from day 7. SDR Flow+ reached its peak at 14 days and showed significant increases in the Ca/P ratio. By 28 days, both materials achieved comparable remineralization, confirming their effectiveness in treating demineralized dentine. Full article

Sea buckthorn, a homologue of medicine and food, contains a host of bioactives that can prevent many diseases, especially cardiovascular diseases. The association between oxidative stress (OS) and cardiovascular diseases (CVDs) has been well-established, with OS ultimately leading to CVDs through lipid peroxidation and other mechanisms. In this study, antioxidant components were isolated from sea buckthorn by polyamide medium-pressure chromatography coupled with an HPLC-DPPH activity screening system. Two potential compounds were isolated and identified as Tetrahydroharmol and Isorhamnetin3-O-(6-O-E-sinapoyl)-β-D-glucopyranosyl-(1-2)-β-D-glucopyranoside-7-O-α-L-rhamnopyranoside. Molecular docking technology was used to explore the binding ability of two antioxidant active components to target proteins (LDH, SOD, Nrf2, iNOS, and eNOS). In addition, the antioxidant capacity was determined by EA.hy926 human umbilical vein endothelial fusion cell experiments. The results demonstrate the efficacy of this method for isolating high-purity antioxidants from sea buckthorn. These two activity compounds exhibit potential effects against cardiovascular diseases through antioxidant mechanisms. Full article

Background/Objectives: Natural multi-component nutraceutical formulations may modulate interconnected pathways involved in metabolic and bone health. This study evaluated, using in vitro models, the effects of a standardized botanical–vitamin formulation on intestinal barrier integrity, osteoblastic activity, and osteoclast differentiation, focusing on intestinal-bone crosstalk, redox-inflammatory signalling, and potential synergistic interactions among components. Methods: A combined in vitro approach using intestinal, osteoblastic, and osteoclastic cell models was applied to assess a formulation containing characterized plant extracts and vitamin D₃. The study evaluated cytocompatibility, intestinal barrier function, cellular uptake, and the modulation of markers related to osteogenesis and osteoclastogenesis, using biochemical, molecular, and enzymatic assays, as well as oxidative stress measurements and synergy analysis. Results: The formulation maintained intestinal barrier integrity and bioavailability without cytotoxicity, promoted osteoblastic differentiation and reduced oxidative stress, while inhibiting osteoclast differentiation and resorptive activity. These effects were associated with modulation of inflammatory and redox-related signalling pathways and showed additive to synergistic interactions among components. Conclusions: These findings support a multi-target nutraceutical approach that can concurrently influence intestinal barrier and bone remodelling in vitro, offering mechanistic evidence for its role in modulating the gut–bone axis, and highlight the need for further studies in advanced models and clinical trials. Full article

Physalis peruviana L., a South American species, has been increasingly cultivated because of its bioactive compounds and high commercial value. This study evaluated the biochemical responses and fruit quality of physalis plants subjected to different water availability regimes (40%, 70%, and 100% of field capacity), followed by recovery periods. The experiment was conducted at São Paulo State University in a randomized block design with split plots. Plants were exposed to different irrigation regimes and subsequently rewatered over a 120-day period. Leaf and fruit analyses showed that water stress at 40% field capacity significantly increased both enzymatic and non-enzymatic antioxidant levels, thereby mitigating oxidative damage, as indicated by lower lipid peroxidation and reduced reactive oxygen species accumulation. However, this defense response was accompanied by marked reductions in fruit yield, fruit number, fresh mass, and fruit quality. Notably, although rewatering reversed several biochemical stress markers at the leaf level, fruit yield and commercial quality did not recover, suggesting irreversible damage to reproductive development during the stress period. These findings indicate that controlled water deficit may enhance antioxidant accumulation, highlighting the potential of stressed plants for pharmaceutical or nutraceutical applications. However, prolonged water stress, even when followed by a recovery period, impairs commercial fruit production. Therefore, irrigation management should be aligned with the intended production objective. Full article

Type 2 diabetes mellitus (T2DM) affects approximately 10–25% of patients undergoing orthopedic procedures and is associated with impaired tissue healing, increased complication rates, and reduced responsiveness to orthobiologic therapies, including platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), and mesenchymal stem cell (MSC) preparations. The underlying mechanisms include advanced glycation end-product accumulation, NF-κB-driven chronic inflammation, Nrf2 pathway impairment, mitochondrial dysfunction, and epigenetic diabetic memory, collectively compromising both orthobiologic product quality and the tissue microenvironment. Emerging, predominantly mechanistic evidence suggests that targeted nutritional interventions, including bioactive compounds targeting mitochondrial biogenesis pathways, anti-inflammatory dietary patterns, and specific micronutrients, may modulate these pathological processes and potentially improve orthobiologic outcomes. This narrative review synthesizes evidence from diabetic pathophysiology, orthobiologic outcomes research, and nutritional science to propose a conceptual clinical framework for regenerative medicine optimization in T2DM patients. Critical knowledge gaps are identified, and a research agenda is proposed. The proposed framework, based primarily on mechanistic and preclinical evidence, should be interpreted as a foundation for research prioritization and hypothesis generation rather than as a clinical protocol. Rigorous randomized trials directly evaluating nutritional optimization in orthobiologic therapy for diabetic patients are required before evidence-based recommendations can be established. Full article

Graft-versus-host disease (GVHD) remains the most severe complications following allogeneic hematopoietic cell transplantation (allo-HCT). Mesenchymal stromal cells (MSCs) have shown therapeutic potential in GVHD due to their immunomodulatory properties. However, their clinical application is constrained by safety concerns, including ectopic engraftment, microvascular obstruction, rejected by host, and potential tumor-supportive effects. Increasing evidence suggests that MSC-derived exosomes (MSC-Exos), as cell-free mediators, retain many of the beneficial effects of MSCs while exhibiting improved safety and stability profiles. MSC-Exos carry diverse bioactive cargo, including nucleic acids, lipids, and proteins, and can modulate immune responses, promote tissue repair, and restore barrier integrity. In this review, we place particular emphasis on both immunoregulation and tissue barrier protection as dual mechanisms underlying MSC-Exos efficacy in GVHD. We further discuss emerging preclinical and clinical evidence, as well as key challenges in translation. Full article

Pre-eclampsia and foetal growth restriction (FGR) are major pregnancy complications primarily driven by placental dysfunction, and remain leading causes of maternal and perinatal morbidity. Ultrasound imaging, Doppler studies, and angiogenic biomarkers like placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) constitute the main diagnostic modalities; however, these predominantly reflect established disease rather than early molecular disturbances underlying placentation. The identification of biomarkers directly associated with trophoblast signalling pathways has the potential to improve early risk stratification and enable mechanistic classifications. Kisspeptin signalling via its receptor (KISS1R) regulates trophoblast invasion, extracellular matrix remodelling, ERK1/2 activation, and angiogenic balance, thereby modulating spiral artery transformation. Kisspeptin-10 (KP-10), the minimal bioactive fragment of KISS1, is highly expressed in placental syncytiotrophoblasts and exerts its effects through the G-protein-coupled receptor KISS1R. Core features of early-onset FGR and pre-eclampsia (PE)—including defective placentation, maternal vascular malperfusion, and angiogenic imbalance—have been linked to dysregulation of this pathway. During normal gestation, maternal circulating kisspeptin concentrations rise exponentially. In contrast, pregnancies subsequently complicated by FGR or PE, particularly in the early gestation, are associated with reduced levels. However, the comparability of existing studies and their translational applicability are limited by a substantial methodological heterogeneity, including assay variability, gestational age dependence, and inadequate adjustment for maternal confounders. These limitations hinder robust conclusions regarding the role of kisspeptin in placental pathology. This review critically integrates molecular, pathophysiological, and clinical evidence relating to the role of KP-10 in placental dysfunction. The key question is whether KP-10 represents a mechanistic biomarker of trophoblast signalling dysfunction or merely a secondary marker of reduced placental mass; resolving this distinction is essential. Full article

Background/Objectives: Dietary antioxidants are frequently utilized by breast cancer (BC) patients to mitigate treatment-related toxicities and enhance quality of life. However, their clinical efficacy remains highly controversial due to conflicting epidemiological and clinical data. This review aims to critically evaluate the molecular mechanisms, clinical outcomes, and translational challenges of antioxidant supplementation in BC management. Methods: A comprehensive evaluation of current literature—encompassing observational cohorts, randomized controlled trials, and mechanistic in vitro/in vivo models—was conducted. The analysis focused on the pharmacological interactions of diverse bioactive compounds (polyphenols, vitamins, carotenoids) with BC progression and standard antineoplastic regimens. Results: Current evidence demonstrates a paradoxical, double-edged role of antioxidants in oncology. While specific interventions (e.g., Coenzyme Q10, melatonin) effectively ameliorate treatment-induced toxicities without compromising therapeutic efficacy, the concurrent administration of antioxidants during cytotoxic chemotherapy can inadvertently neutralize essential reactive oxygen species (ROS), correlating with increased disease recurrence and mortality. Furthermore, clinical translation is severely hindered by the intrinsic hydrophobicity of natural compounds, the lack of whole-food matrix standardization, and dose-dependent hepatotoxicity. Emerging targeted delivery systems, such as lipid nanoformulations, show significant potential in overcoming these pharmacokinetic barriers. Conclusions: The therapeutic viability of antioxidant supplementation in BC is not universal; it is heavily dictated by intrinsic tumor biology, specific treatment modalities, and chronopharmacology. These findings underscore a critical biological imperative to transition from generalized dietary guidelines toward a rigorous paradigm of precision nutritional oncology, strictly avoiding concurrent antioxidant supplementation during active oxidative therapies. Full article

Background: Oxidative liver damage, fibrosis, cirrhosis and liver failure are caused by reactive oxygen species and inflammatory responses triggered by bile retention during prolonged cholestasis. Pomegranate and persimmon fruits, which are loaded with bioactive compounds that have anti-inflammatory and antioxidant properties, were evaluated separately for their efficacy in preventing oxidative stress and inflammation in cholestasis. Methods: Pomegranate and persimmon juices were analyzed for their vitamin C, carotenoids and organic acid levels, phenolic profile, and antioxidant activity. Liver protection against oxidative stress and inflammation brought on by cyclosporine-induced cholestasis in rats was verified by biochemical measurements, metabolite identification, and histopathologic examination. To forecast the mechanism of pomegranate and persimmon anti-inflammatory action, an in silico assessment was also carried out. Results: Vitamin C levels in pomegranate and persimmon juices were 99.55 and 51.75 µg/g, respectively. In both pomegranate and persimmon juices, gallic acid was the most prevalent phenolic compound (123.20 and 50.69 µg/g, respectively). Pomegranate and persimmon juices significantly (p < 0.05) reduced the rise in liver values of MDA, NO, TNF-α, IL-6, IL-1β, and TLR4, as well as serum values of total and direct bilirubin caused by cyclosporine. Additionally, the alteration of metabolites, particularly amino acids, demonstrated the inhibitory effect of pomegranate and persimmon juices on liver damage. Gallic acid’s and catechin’s substantial binding affinities with target inflammatory cytokines (TNF-α and TLR4) were further validated by molecular docking. Conclusions: These results showed that pomegranate and persimmon juices mainly modulated inflammation and oxidative stress to provide hepato-protective benefits against cyclosporine-induced cholestatic liver injury. Full article

The valorization of agro-industrial by-products is of increasing importance within circular economy strategies. Aronia melanocarpa pomace, a by-product of juice production, represents a valuable source of polyphenols with potential applications in food, nutraceutical, and cosmetic formulations. This study aimed to evaluate the effect of different preservation methods on the polyphenolic composition of Aronia pomace and to optimize accelerated solvent extraction (ASE). Pomace samples were subjected to drying, freeze-drying, freezing (−18 °C), and deep freezing (−80 °C). UAE was applied as a rapid screening method for polyphenol extraction, while ASE was used as an advanced technique for efficient recovery of target compounds. ASE parameters, including temperature (40–120 °C), methanol concentration (40–100%), and number of extraction cycles (1–3), were optimized using response surface methodology (RSM) based on a Box–Behnken design. Qualitative and quantitative analyses were performed using UHPLC–MS and HPLC–DAD. The developed models were statistically significant (p < 0.01) with high coefficients of determination (R² = 0.88–0.97). Temperature had a positive effect on phenolic acid extraction but negatively affected anthocyanins due to thermal degradation. Optimal extraction conditions differed between compound groups: phenolic acids were maximized at 120 °C and 75% methanol (two cycles), while anthocyanins required milder conditions (82 °C, 92% methanol, three cycles). Moreover, our study showed that drying significantly reduced the content of several compounds, particularly anthocyanins, whereas low-temperature methods had minimal impact. The results highlight the importance of tailored extraction strategies and support the sustainable utilization of Aronia pomace as a source of bioactive compounds. Full article

Marine biofouling is a major global concern affecting the marine industry, the environment, and public health. The accumulation of organisms on submerged surfaces causes significant economic losses, including increased fuel consumption, higher pollutant emissions, and accelerated corrosion. Antifouling (AF) coatings with biocides are widely used to prevent this problem. However, many conventional biocides have been banned due to toxicity, creating an urgent need for environmentally friendly alternatives. In previous studies, we synthesized a gallic acid derivative and three flavonoids that showed AF activity against the settlement of mussel larvae (Mytilus galloprovincialis) together with low ecotoxicity. In the present work, to further assess their potential in marine coatings and exploit the advantages of nanocarriers in protecting and prolonging bioactive effects, these compounds were loaded into halloysite nanotubes (HNTs) and incorporated into epoxy coatings. Coatings containing the same AF compounds in free form were also prepared for comparison. HNTs were characterized by scanning electron microscopy (SEM), and compound loading was quantified by thermogravimetric (TG) analysis. The resulting composites were analyzed by SEM and dynamic water contact angle measurements. Laboratory bioassays with M. galloprovincialis larvae showed that coatings containing HNT-loaded synthetic compounds generally reduced larval settlement more effectively than the corresponding coatings containing the same compounds directly dispersed in the epoxy matrix, with values below 20% after both 15 and 40 h of exposure for the best-performing formulation. These findings highlight the novelty of the proposed HNT-based delivery strategy for nature-inspired synthetic antifoulants and support its potential for the development of effective and environmentally safer AF coatings. Full article

Bone tissue plays a vital role in the human body and possesses intrinsic self-repair mechanisms; however, large defects or pathological fractures may exceed its natural healing capacity. Bone tissue engineering provides promising strategies to restore bone integrity through the use of scaffolds, growth factors, and stem cells. While calcium phosphate (CaP)-based ceramics, such as hydroxyapatite (HAp) and tricalcium phosphate (TCP), represent the current benchmark, their limitations, including slow degradation (HAp) and limited osteoinductivity (TCP), have driven the development of alternative biomaterials. In this context, magnesium phosphate (MgP)-based materials have gained increasing attention due to their tunable resorption rate, improved biodegradability, and ability to stimulate osteogenesis and angiogenesis through the release of magnesium (Mg²⁺) ions. This study reports on composite scaffolds based on electrospun poly(ε-caprolactone) (PCL) fibres coated with MgP layers doped with lithium (Li) and zinc (Zn), designed to mimic the nanofibrous architecture of the extracellular matrix. Lithium and zinc were selected due to their known ability to modulate cellular response, with lithium promoting osteogenic activity and zinc contributing to improved cell proliferation and antibacterial potential. The phosphate phases obtained by coprecipitation were deposited onto the PCL fibres using Matrix-Assisted Pulsed Laser Evaporation (MAPLE), enabling controlled surface functionalization. Following thermal treatment, the formation of the crystalline magnesium pyrophosphate (Mg₂P₂O₇) phase was confirmed by chemical and structural characterization. The combination of a slowly degrading PCL matrix, providing sustained structural support, and a bioactive MgP coating, enabling rapid and controlled ion release, results in improved scaffold performance in terms of biocompatibility, biodegradability, and bioactivity. While the slow degradation rate of PCL ensures mechanical stability over an extended period, the surface-deposited MgP phase allows immediate interaction with the biological environment, facilitating faster ion release and enhancing cell–material interactions. These findings highlight the potential of the developed composites as promising candidates for trabecular bone regeneration and as viable alternatives to conventional CaP-based scaffolds in regenerative medicine. Full article

Autophagy dysfunction is implicated in the pathogenesis of Alzheimer’s disease (AD), and enhancing autophagic flux has been proposed as a potential strategy for addressing neurodegenerative diseases. To expand the structural diversity of ingenol esters and systematically evaluate their autophagic flux activation activity, a systematic phytochemical investigation of ingenane diterpenoids from Euphorbia peplus was conducted. A total of 13 ingenane-type compounds were isolated and identified, including two previously undescribed compounds, euphingenol A and B (1–2), together with 11 known analogs (3–13). Their structures were elucidated by extensive spectroscopic analyses (HRESIMS and NMR) and comparison with literature data. The compounds were evaluated for their bioactivity with flow cytometry in assays of autophagic flux in HM Cherry-GFP-LC3 (human microglia cells stably expressing the tandem monomeric mCherry-GFP-tagged LC3) cells. 17-O-benzoyl-20-deoxyingenol (3) significantly activated autophagic flux at concentrations of 10 μM and 40 μM, while euphingenol A (1) induced a dose-dependent increase, with structure-activity relationship analysis indicating that C-17 acylation enhances this bioactivity. These findings suggest that compound 3 warrants further investigation as a potential modulator of autophagic flux, possibly through binding to PKCδ (protein kinase C), with relevance to autophagy-related neurodegenerative conditions. Full article

Exopolysaccharides (EPSs) are emerging as sustainable polymers for biomedical hydrogels. Here, we report hydrogels from sulfated EPSs produced by Porphyridium cruentum and ionically crosslinked with Ca²⁺, Ce³⁺, or Cu²⁺ to generate tunable networks with bioactive potential. Rheological analysis showed viscoelastic behavior was primarily governed by cation nature and accessible binding site density, with diminishing gains above 2.5 wt% EPS and limited benefit beyond 10 wt% crosslinker. Ce³⁺ produced the most solid-like gel, Ca²⁺ yielded more thixotropic networks, and Cu²⁺ promoted rapid, heterogeneous crosslinking consistent with fast surface complexation. These network signatures showed distinct in vitro performances. Cation selection tuned antibacterial activity against Staphylococcus aureus and Escherichia coli, with Cu²⁺ achieving rapid bactericidal effects and Ce³⁺ enabling an 8-log reduction after 24 h. The ABTS assay showed that Ca²⁺- and Ce³⁺-crosslinked gels had antioxidant potential (≥40 µM Trolox eq.mg⁻¹); however, antioxidant capacity was assay dependent. Conditioned-medium assays showed ≥75% viability at day 3 for Ca²⁺- and Ce³⁺-crosslinked gels against human dermal fibroblasts (HDFs), while only Ce³⁺-crosslinked gels were cytocompatible against human keratinocytes (HaCaTs). Cu²⁺-crosslinked gels were highly cytotoxic across all tested conditions. Macrophage cytokine readouts (TNF-α and IL-6) indicated formulation-dependent immunobiological response. This work establishes microalgal EPSs as versatile polymers and links crosslinking chemistry to rheological modulation and multifunctional biomedical performance, while direct wound-healing efficacy remains to be demonstrated in future in vivo or wound repair functional models. Full article