Search Results (7,971)

Developing fungus-resistant grape varieties is essential to reduce phytosanitary inputs in viticulture. This study presents the first comprehensive oenological characterization of Divona, a new disease-resistant white grape variety developed by Agroscope. Musts and wines were produced over three contrasting vintages (2019, 2020, 2022) at the Pully experimental vineyard (Switzerland). Chemical analyses, sensory evaluations, and quantification of key aroma compounds (volatile thiols, monoterpenes) were conducted. A split-plot ANOVA and multiple factor analysis (MFA) separated vintage variability from winemaking effects (pre-fermentation maceration, fermentation temperature), which were treated exploratorily. The results indicate that vintage was the primary driver of variability. Lacking technical replicates within vintages, the study relies on biological replication across years to assess treatment robustness, interpreting winemaking effects as exploratory trends. Pre-fermentation maceration tended to enhance color intensity and certain aromatic precursors in the must. Under these specific conditions, the effects of fermentation temperature and maceration treatment appear modest relative to the dominant influence of vintage. Divona wines demonstrated high aromatic potential with a fruity expression. These findings establish a foundational oenological profile for Divona, validating its suitability for temperate climates and low-input viticulture, while offering preliminary technical guidelines to optimize sensory quality. Full article

Marine macroalgae constitutes an important source of structurally diverse secondary metabolites with significant pharmaceutical potential. In the present study, an untargeted liquid chromatography–mass spectrometry (LC-MS)-based metabolomic approach was integrated with biological screening to investigate the relationship between metabolite composition and antiproliferative activity in eight Mediterranean macroalgal species. Crude organic extracts were evaluated against the human colorectal cancer cell lines HT-29 and HCT-116, while the most active extracts were further investigated by flow cytometry to explore their cellular effects. Comparative metabolomic analysis revealed marked interspecific differences, with the brown algae Dictyota dichotoma and Rugulopteryx okamurae exhibiting metabolomes enriched in lipophilic diterpenoids and showing the highest cytotoxic activity. Although the bioactive compounds were not isolated, the antiproliferative effects were associated with diterpene-rich metabolite profiles containing tentatively annotated compounds such as dictyodial- and dilkamural-related diterpenoids tentatively. D. dichotoma displayed potent activity against both HT-29 and HCT-116 cells (GI₅₀ ≈ 4.5–5 μg mL⁻¹), whereas R. okamurae was markedly more active against HT-29 than HCT-116 cells, demonstrating that tumour genetic background substantially influences cellular susceptibility to macroalgal extracts and highlighting the importance of evaluating multiple cancer cell models during preliminary screening. Flow cytometry demonstrated increased intracellular reactive oxygen species (ROS), reduced metabolic viability, and decreased cell concentration following treatment with the most active extracts, whereas Annexin V/propidium iodide staining showed no detectable increase in apoptotic cell populations. These findings suggest that oxidative stress-associated metabolic impairment, rather than classical apoptosis, contributes to the observed antiproliferative activity. Overall, this study demonstrates the value of integrating untargeted metabolomics with comparative biological screening to identify promising marine macroalgae and metabolite classes for future bioassay-guided isolation and development of marine-derived anticancer agents. Full article

Scutellaria barbata D. Don (SBD) has been widely investigated for antitumor activity, but its immune- and tumor microenvironment (TME)-related mechanisms remain fragmented. This study synthesized preclinical evidence on SBD and contextualized the findings using network pharmacology. A scoping review was conducted according to established scoping review methodology and PRISMA-ScR guidance. Preclinical in vitro and in vivo cancer studies published between January 2016 and December 2025 were searched in PubMed, Embase, CENTRAL, and OASIS. Network pharmacology analysis was performed using TCMSP, SwissTargetPrediction, ImmPort, GeneCards, STRING, Cytoscape, MCODE, DAVID, GO, and KEGG analyses. Fifty-six preclinical studies were included. SBD extracts, fractions, polysaccharides, diterpenoids, flavonoids, and isolated constituents suppressed cancer cell proliferation, induced cell-cycle arrest, promoted apoptosis and ferroptosis, modulated autophagy, induced endoplasmic reticulum stress-associated cell death, inhibited migration, invasion, angiogenesis, and metastasis, and enhanced chemosensitivity across diverse cancer models. Immune- and TME-related effects included activation of natural killer cells and CD8⁺ T cells, reduction in regulatory T cells, T helper 17 cells, myeloid-derived suppressor cells, and M2-like tumor-associated macrophage polarization, modulation of cytokine and inflammatory signaling, and regulation of epithelial–mesenchymal transition, matrix remodeling, angiogenesis, and metastatic niche formation. Network pharmacology identified 32 active candidate compounds, 408 predicted targets, and 152 immune/TME-overlapping targets. Protein–protein interaction and enrichment analyses highlighted AKT1, TNF, SRC, EGFR, and BCL2 as candidate hub targets and implicated PI3K-Akt, MAPK, Ras, EGFR tyrosine kinase inhibitor resistance, and proteoglycans in cancer. SBD-derived interventions showed antitumor, immunomodulatory, and TME-remodeling activities across diverse preclinical models. The integrated findings identify recurrent biological processes and candidate molecular targets, while differences in preparation, chemical characterization, dose, and experimental design limit direct comparison across studies. This framework supports further mechanistic, pharmacokinetic, and translational evaluation of chemically characterized SBD preparations and candidate compounds. Full article

Ruscus aculeatus L. (butcher’s broom) is traditionally used in the management of chronic venous disorders; however, the molecular mechanisms underlying its vascular activity remain insufficiently characterized. This study investigated the effects of an 80% ethanolic rhizome extract on human cerebral microvascular endothelial hCMEC/D3 cells under normoxic and hypoxic conditions. The extract was phytochemically characterized using ultra-high-performance liquid chromatography–diode array detection–high-resolution mass spectrometry (UHPLC–DAD–HRMS), while its biological effects were evaluated by assessing cell viability and the secretion of selected cytokines, including transforming growth factor beta (TGF-β) isoforms, using Bio-Plex multiplex assays. Phytochemical analysis confirmed steroidal saponins as the predominant constituents and also revealed minor phenolic compounds, including hydroxycinnamic acid amides. The extract (10 and 50 μg/mL) was well tolerated by hCMEC/D3 cells and did not significantly reduce cell viability under either normoxic or hypoxic conditions. Its effects on cytokine secretion depended on oxygen availability and the mediator examined. Under hypoxia, the extract partially shifted interleukin-6 (IL-6) and interleukin-8 (IL-8) secretion toward normoxic levels and attenuated interferon alpha (IFN-α)-induced tumor necrosis factor alpha (TNF-α) production, whereas a significant increase in granulocyte-macrophage colony-stimulating factor (GM-CSF) relative to the untreated control was observed only with the combination of 50 μg/mL extract and IFN-α. Hypoxia also differentially affected TGF-β isoforms, increasing TGF-β1 and decreasing TGF-β2, while treatment with the extract shifted both responses toward the profile observed under normoxia; TGF-β3 remained largely unchanged. Overall, these findings indicate that R. aculeatus rhizome extract does not exert a uniform anti-inflammatory effect but rather modulates endothelial secretory responses in an oxygen- and mediator-dependent manner. These observations provide new insights into the endothelial effects of R. aculeatus that may contribute to its vascular activity. Full article

Functional foods containing antioxidants and anti-inflammatory compounds are a promising nutritional intervention. However, significant gaps remain in the literature on the development and evaluation of functional snacks for improving health outcomes. This systematic literature review (SLR) aimed to summarize the existing evidence on the development of enriched functional snacks containing bioactive ingredients, with a particular focus on their potential relevance to mental health. The review also examined food technologies, consumer acceptance, current knowledge gaps, and priorities for future research. The SLR was conducted in accordance with the PRISMA guidelines. PubMed, Scopus, and Web of Science were searched for studies on snacks and functional foods published between 2020 and 2025. Original studies evaluating functional snacks and/or bioactive compounds with neuroprotective, anti-inflammatory, or antioxidant properties were included. The initial search yielded 281,118 records. Following screening and quality assessment, 22 articles were selected through a three-author consensus process. Among the included studies, 12/22 focused on product development and antioxidant activity. Three studies included in vivo evaluations, while four included in vitro assessments of anti-inflammatory or antioxidant effects. Technologies such as extrusion, nanoencapsulation, and freeze-drying were employed to protect bioactive compounds and preserve bioactivity. Only two studies included sensory evaluation, with both reporting preliminary evidence of high acceptability. Overall, the SLR revealed limited evidence on functional snacks, particularly regarding their effects on mental health. Significant gaps remain in biological, neuroprotective, and sensory validation. Further studies are needed to establish the efficacy, biological effects, and consumer acceptability of enriched functional snacks, as well as consumer acceptability across diverse, relevant target populations. Full article

Steroid hormones constitute a group of emerging contaminants with high biological activity; their presence in aquatic systems is primarily linked to municipal wastewater, animal production, aquaculture, and pharmaceutical use. Their environmental significance lies in the fact that they can induce biological responses at very low concentrations, even within ranges considered environmentally low. This review synthesizes and analyzes the available evidence on the presence, environmental distribution, treatment, fate, and ecotoxicological effects of natural and synthetic steroid hormones in different aquatic matrices. The compiled results show wide variability in environmental concentrations, with estrone (E1) values of up to 3050 ng L⁻¹ in effluents from wastewater treatment plants, 17α-ethinylestradiol (EE2) of 4608 ng L⁻¹ in effluents, and progesterone of up to 16,687 ng L⁻¹ in treated effluents. In surface waters, concentrations of up to 4152 ng L⁻¹ for E1 and 1200 ng L⁻¹ for EE2 were recorded. From an ecotoxicological perspective, reproductive, developmental, molecular, metabolic, and physiological alterations were documented at exposure concentrations as low as 0.4 ng L⁻¹ for EE2 and 0.5 ng L⁻¹ for levonorgestrel (LNG). However, the concentration associated with each response varied widely depending on the species, the compound, the developmental stage, the duration of exposure, and the experimental conditions. The available evidence indicates that conventional wastewater treatment may not completely remove these compounds, thereby facilitating their transfer to receiving ecosystems, while sediments may act as potential environmental reservoirs. Taken together, the findings highlight the need to assess steroid hormones using an integrated approach that simultaneously considers concentration, exposure, biological response, environmental persistence, and the specific characteristics of each compound, particularly in studies aimed at evaluating their ecological relevance. Full article

Background: Diabetes mellitus (DM) is an extremely complex metabolic disorder, with many factors contributing to persistent hyperglycaemia, redox dysregulation, and micro- and macrovascular damage over time. There is growing evidence that oxidative stress is one of the main mechanisms of β-cell damage, insulin resistance, and consequent tissue damage, pointing to the need for therapies to modulate metabolic and redox responses. The extensive nature of quinones has revealed that they can be potential dual-acting redox-active compounds that may have antioxidant and antidiabetic activities. Objectives: This review aims to evaluate quinones from a pharmaceutical perspective, considering the chemical diversity and structure–activity relationships, the physicochemical parameters pertinent to drug development, and the mechanisms of action in terms of glucose homeostasis, insulin signalling, mitochondrial protection, and glycoxidative damage. Methods: Narrative review of the evidence from medicinal chemistry, experimental pharmacology, pharmacokinetics, formulation research, and clinical studies of the potential role of quinones in diabetes and its complications. The paper addresses the relationship between chemical structure and biological activity, redox-dependent mechanisms of action, tissue-protective actions, challenges associated with delivery, toxicity, and recent approaches to formulation. Results: Quinones influence several processes implicated in diabetes, including mitochondrial dysfunction, oxidative stress, pancreatic β-cell injury, insulin signalling impairment, AGE-RAGE activation, and chronic inflammation. Currently, CoQ10 has the strongest evidence in humans, while thymoquinone (TQ), pyrroloquinoline quinone (PQQ), anthraquinones, and mitochondria-targeted derivatives have mainly cellular and animal studies to support them. Low solubility, variable systemic exposure, rapid metabolism, and the potential for pro-oxidant effects at high concentrations continue to hamper therapeutic development of these compounds. Conclusions: Future research scopes will rely on rational derivatisation, precision delivery technologies, and clinically validated safety frameworks to translate redox pharmacology into effective therapeutic interventions. Full article

Amazonian bufonid toads represent an important source of bioactive compounds with promising pharmacological potential. Among them, Rhaebo guttatus and Rhinella marina produce complex cutaneous and parotoid gland secretions composed mainly of bufadienolides, indole alkaloids, antimicrobial peptides, biogenic amines, and other secondary metabolites that play essential roles in chemical defense. This narrative review summarizes current knowledge regarding the ecology, chemical composition, biological activities, toxicological profile, and therapeutic potential of secretions from these two Amazonian species. A literature search was conducted using PubMed, Scopus, Web of Science, SciELO, and Google Scholar, covering publications from 2005 to 2025. The reviewed evidence demonstrates that these secretions exhibit a broad spectrum of biological activities, including antiproliferative, antimicrobial, antiparasitic, antiviral, immunomodulatory, antioxidant, anti-inflammatory, analgesic, and larvicidal effects. These pharmacological properties are primarily associated with the modulation of molecular targets such as Na⁺/K⁺-ATPase, intracellular signaling pathways, oxidative stress, and inflammatory mediators. Despite their remarkable therapeutic potential, the clinical application of crude secretions remains limited by their significant systemic toxicity and narrow therapeutic window. Overall, the secretions of R. guttatus and R. marina constitute a valuable natural reservoir of bioactive molecules with considerable potential for drug discovery and the development of innovative therapeutic agents. Full article

Plant extracts remain an important source of antiviral agents, while nanocarrier-based delivery systems have emerged as a promising strategy for improving their therapeutic safety and efficacy. Building on previous findings indicating that nanoliposomal encapsulation improved the anti-coronavirus activity of Aesculus hippocastanum seed extract against human coronavirus strain OC43 (HCoV-OC43), the present study evaluated whether encapsulation reduces the genotoxic effects of the extract and explored a potential molecular basis for the previously observed antiviral activity. Genotoxicity assessment using the alkaline comet assay in MRC-5 human lung fibroblasts demonstrated that at 1 mg/mL, liposomal encapsulation was associated with an approximately 86.0% reduction in %Tail DNA, from 21.301 ± 0.368% for the free extract to 2.984 ± 1.523% for the liposome-encapsulated extract. In parallel, chemical profiling by high-performance liquid chromatography coupled with high-resolution tandem mass spectrometry (HPLC–HRMS/MS) enabled the identification and tentative annotation of 46 metabolites, including triterpenoid saponins, flavonoids, indole-3-acetic acid glycosides, and organic acids. Based on this phytochemical profile, representative constituents were subjected to molecular docking against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nonstructural proteins Nsp5 and Nsp12 to investigate their potential contribution to the previously demonstrated antiviral activity of the extract. Among the evaluated compounds, hesperidin exhibited the most favorable predicted binding affinity toward both targets, while quercetin also showed favorable interactions, suggesting that flavonoid constituents may contribute to the antiviral activity of the extract. These findings indicate that liposomal encapsulation improves the biological safety profile of A. hippocastanum seed extract, while phytochemical characterization and molecular docking provide preliminary insights into the constituents that may contribute to its previously demonstrated anti-coronavirus activity. Full article

Modern agrochemicals support crop productivity and food security, yet their residues, transformation products and formulation components can move through the agro-food chain and affect plants, soil organisms, wildlife, livestock and people. This review addresses a persistent gap in the literature: most existing assessments examine single compounds, single organisms or single environmental compartments in isolation, whereas real-world exposure spans the entire agro-food chain and connects plant, animal, environmental and human health. To address this gap, this review was designed as an integrative, One-Health-oriented synthesis of the original evidence assembled on organophosphate, neonicotinoid and glyphosate-based products, covering environmental fate, exposure pathways, molecular toxicity, non-target effects and ecosystem consequences. The main body of work consists of a structured literature research and comparative evidence assessment across laboratory, mesocosm and field studies, from which a cross-level evaluation was constructed: oxidative stress, neurotoxocity, endocrine and immune disruption, soil microbiome alteration, pollinator and aquatic biodiversity loss, food and feed residues, antimicrobial-resistance pathways and insecticide resistance affecting disease vectors. Particular attention is given to formulation effects, mixtures, chronic low-dose exposure and the distinction between contaminant removal, transformation, detoxification and mineralisation. Finally, the review evaluates integrated pest management, precision application, biological control, phytoremediation, nanotechnology-assisted treatment and synthetic-biology-enabled bioremediation. The synthesis identifies evidence gaps in field-scale validation, mixture toxicity, One Health surveillance and regulatory integration and proposes priorities for safer agrochemical use, environmental monitoring and ecosystem-based risk reduction. Full article

Combining biological treatment with electrochemical oxidation (EO) may provide an effective strategy for high-strength livestock wastewater by coupling biodegradable organic compounds removal with oxidation of more persistent contaminants. This study compared activated-sludge biological treatment (B) and boron-doped diamond EO in both sequences (EO + B and B + EO) using livestock wastewater with a chemical oxygen demand (COD) of approximately 16 g O₂ L⁻¹. B treatment was evaluated at different hydraulic retention times and EO at predefined COD removal targets. EO + B achieved 87–94% COD removal with lower specific energy consumption, whereas B + EO consistently achieved approximately 99% COD removal and greater removal of dissolved organic carbon, phosphorus, several metals, and solids. Lowering the organic load before EO did not reduce the stage-specific energy demand of EO polishing. Process order also altered nitrogen speciation: EO + B resulted in lower final ammonium and nitrate concentrations but nitrite accumulation, whereas B + EO promoted nitrate formation. Salmonella spp. and Escherichia coli were not detected after either sequence. B + EO provided deeper physicochemical polishing but promoted substantial chlorate and perchlorate formation, whereas EO + B was less energy demanding and avoided final oxychlorine accumulation. These distinct water-quality profiles support fit-for-purpose selection of treatment sequences according to the intended reuse application. Full article

Pharmaceutical residues, particularly anticancer compounds, are persistent aquatic contaminants that require efficient treatment strategies. This study developed a UV-LED-assisted peroxymonosulfate (PMS)/zero-valent iron (ZVI) advanced oxidation system for the degradation and toxicity reduction of daunorubicin in aqueous solution. The effects of key operational parameters were optimized using response surface methodology. Under optimal conditions (pH 3, PMS 1.5 mM, ZVI 0.3 g/L, and daunorubicin 10 mg/L), nearly complete degradation was achieved within 15 min, following pseudo-first-order kinetics (R² > 0.95). LC–MS analysis revealed the formation of transformation products and suggested oxidative fragmentation pathways of daunorubicin. The process achieved 65% total organic carbon removal after 6 h, indicating substantial but incomplete mineralization. Fe²⁺ evolution and ESR analysis demonstrated that ZVI-mediated PMS activation generated reactive species, with sulfate radicals playing a major role and hydroxyl radicals contributing to oxidation. Toxicity and mutagenicity assays confirmed significant reductions in biological effects after treatment. These findings demonstrate that the UV-LED/PMS/ZVI system is a promising approach for the treatment of daunorubicin-containing wastewater. Full article

Selenium (Se) exerts essential biological functions via selenoprotein-mediated antioxidant defense and redox homeostasis. Selenium-enriched yeast (SEY) is a high-bioavailability organic Se source widely used in aquaculture. However, its effects on flesh quality in adult common carp (Cyprinus carpio) remain unclear. This study investigated the effects of graded dietary SEY on growth, muscle quality, Se deposition, antioxidant status, and associated metabolic responses in adult common carp. Results demonstrate that SEY supplementation (1.84 and 2.56 mg Se/kg) significantly improved growth performance without impairing physiological homeostasis. Mechanistically, SEY dose-dependently strengthened muscular antioxidant defense, with glutathione peroxidase activity increased by up to 7-fold, alongside elevated superoxide dismutase and catalase activities and reduced malondialdehyde content. This enhanced antioxidant capacity may maintain myofibrillar and membrane integrity, potentially contributing to the improvement of water-holding capacity and textural properties. SEY elevated umami amino acids and flavor nucleotides. Furthermore, in the 2.56 mg Se/kg supplemented group, SEY also increased muscle crude protein as well as organic Se deposition, with >99.99% of selenium present as selenocystine and selenomethionine. Untargeted metabolomics revealed that SEY reshaped the metabolome, enriching nucleotide metabolism and arginine biosynthesis pathways, which may partly account for the observed changes in umami-associated compounds. In conclusion, dietary SEY supplementation is an effective strategy for producing high-quality, Se-biofortified common carp. Full article

Imines, commonly known as Schiff bases, are widely investigated compounds because of their structural versatility and biological properties. In this study, we aimed to evaluate the antioxidant potential of salicylaldehyde-derived imines and to determine how their reduction to the corresponding secondary amines affects their radical-scavenging activity and mechanism of action. Two series of phenolic derivatives, imines I1–I6 and amines A1–A6, were synthesized and assessed using an integrated experimental and theoretical strategy combining five in vitro antioxidant assays with density functional theory calculations. Antioxidant evaluation by DPPH, ABTS, FRAP, phenanthroline, and CUPRAC assays revealed distinct activity profiles for the two series. The imine derivatives were more effective in electron-transfer-based assays, whereas the reduced amines showed stronger DPPH radical-scavenging activity. Compound A6 exhibited the highest overall antioxidant activity, with IC₅₀ values (e.g., DPPH IC₅₀ = 26.7 ± 0.97 µM; ABTS IC₅₀ = 11.69 ± 0.43 µM) lower than BHT (DPPH IC₅₀ = 85.85 ± 3.69 µM) and BHA (DPPH IC₅₀ = 59.39 ± 1.9 µM) in most assays. DFT calculations in aqueous medium indicated that the phenolic OH groups govern antioxidant reactivity and identified SPLET as the dominant mechanism for A6, supported by a remarkably high rate constant (k = 1.40 × 10⁵ M⁻¹s⁻¹) and a 100% branching ratio (G), completely outcompeting the HAT mechanism (k = 2.28 × 10⁻² M⁻¹s⁻¹). In addition to the antioxidant investigation, cytotoxicity was assessed in MDA-MB-231 breast cancer cells and Vero normal cells, revealing that the chlorinated derivatives such as I5 combine moderate anticancer activity (MDA-MB-231 IC₅₀ = 122.6 ± 2.23 µM) with lower toxicity toward non-tumor cells (Vero IC₅₀ > 400 µM). Molecular docking studies were conducted to elucidate the binding modes of the active derivatives within the active sites of EGFR, Tubulin, and Topoisomerase IIβ, while subsequent 100 ns molecular dynamics simulations validated the structural stability and sustained interaction energies of these predicted complexes. Full article

Pecan (Carya illinoinensis) is an edible nut rich in phytochemicals with potential health-promoting properties; however, the bioactive constituents responsible for its neuroprotective effects remain insufficiently characterized. This study aimed to identify bioactive constituents from pecan through bioactivity-guided fractionation and to evaluate the protective effects of pecan extract and the identified compound against oxidative stress and amyloid beta (Aβ)_1–42-induced cognitive impairment. Pecan ethanolic extract exhibited antioxidant and cytoprotective activities in PC12 cells exposed to hydrogen peroxide-induced oxidative stress. Sequential liquid–liquid fractionation, silica gel open-column chromatography, and preparative thin-layer chromatography, coupled with repeated bioactivity screening, progressively tracked the active fractions and led to the identification of ethyl gallate as a bioactive constituent of pecan extract by high-performance liquid chromatography and gas chromatography–mass spectrometry. The biological relevance of these findings was further evaluated in Aβ_1–42-injected male mice. Dietary administration of pecan extract significantly improved spontaneous alternation performance in the Y-maze test, whereas ethyl gallate improved Y-maze performance and memory retention in the passive avoidance test, without apparent systemic toxicity under the experimental conditions. Although brain malondialdehyde levels showed a numerical decrease following ethyl gallate administration, the differences were not statistically significant. Collectively, these findings demonstrate the bioactivity-guided linkage of ethyl gallate to an active pecan fraction and provide preclinical evidence supporting further investigation of pecan-derived bioactives as food-derived functional ingredients relevant to cognitive health. Full article