Search Results (1,764)

White-nose syndrome (WNS), caused by the psychrophilic fungus Pseudogymnoascus destructans, poses a severe threat to wild bat populations. Caves serve as unique microecosystems. Exploring antagonistic microorganisms and their volatile antifungal compounds within these native environments has emerged as a promising ecological control strategy. In this study, we isolated four antagonistic bacterial strains from bat cave soil that completely inhibit P. destructans. Additionally, we identified benzaldehyde (BzH) and 2,5-dimethylpyrazine (2,5-DMP) as their primary antifungal volatile organic compounds (VOCs). Combined physiological, biochemical, and multi-omics analyses revealed that these two VOCs disrupt the structural integrity of the fungal cell wall and membrane. This disruption triggers abnormal energy metabolism and compensatory ATP accumulation, leading to a significant intracellular burst of reactive oxygen species and the impairment of primary antioxidant defenses. This sustained oxidative stress causes irreversible DNA damage, endoplasmic reticulum stress, and basal metabolic dysfunction. Consequently, this cascade induces apoptosis and significantly downregulates the expression of essential virulence genes. In conclusion, this study systematically elucidates the molecular network through which VOCs released by cave soil microorganisms antagonize P. destructans. These findings provide a theoretical foundation and candidate intervention molecules for the contactless biocontrol of WNS. Full article

Pregnancy involves profound metabolic, hormonal, and immunological adaptations essential for fetal development; however, disturbances may lead to complications such as preeclampsia (PE), pre-gestational diabetes, and gestational diabetes mellitus (GDM). These conditions are closely linked to oxidative stress, inflammation, endothelial dysfunction, impaired placentation, and metabolic dysregulation. Consequently, dietary strategies capable of modulating these pathways are of increasing interest. Edible and medicinal mushrooms are widely studied as functional food due to the content of bioactive compounds with antioxidant, anti-inflammatory, immunomodulatory, and metabolic regulatory effects. This review summarizes the nutritional composition of mushrooms and highlights key bioactive constituents with antioxidant and metabolic regulatory properties. Among them, ergothioneine has emerged as a key molecule due to its potent redox-buffering capacity and its potential involvement in the activation of the Nrf2 signaling pathway, a master regulator of cellular antioxidant defense. Through modulation of Nrf2-dependent gene expression, mushroom-derived compounds may contribute to improved cellular resilience against oxidative damage relevant to PE and GDM pathophysiology. Mushroom consumption has additionally been associated with improved glycemic control and enhanced antioxidant defenses in experimental and limited clinical studies, although evidence regarding the prevention or management of hypertensive and metabolic pregnancy complications remains insufficient. Although preclinical findings are promising, clinical evidence remains limited. Further well-designed prospective studies and randomized controlled trials are required to determine efficacy, safety, optimal intake, and active compounds responsible for these effects. Nevertheless, current evidence supports the biological plausibility that edible and medicinal mushrooms are promising dietary modulators of the ergothioneine–Nrf2 axis with potential relevance for maternal–fetal health. Full article

The natural stilbene resveratrol is a widely researched molecule, owing to its antioxidant activity and abundance of pharmacological effects. However, its application is still hindered due to its low aqueous solubility, bioavailability and photostability. Therefore, in the current study, resveratrol was loaded in two types of polymeric nanoparticles, namely mixed Pluronic F127 and P123 micelles, and bovine serum albumin nanospheres. The loaded micelles and nanospheres possessed mean diameters of 33 nm and 145 nm, zeta potentials of −4 mV and −22.6 mV, and encapsulation efficiency levels of 89.4% and 76.2%, respectively. The aqueous solubility of resveratrol increased after loading, especially in the albumin nanospheres. A sustained release was observed, more pronounced for the micelles. The photostability of the encapsulated and pure resveratrol was evaluated under daylight exposure and UV irradiation. The micelles showed superior protective effect compared to the nanospheres. The antioxidant potentials of the formulations were examined through ABTS radical scavenging activity assay and in vitro cell model of oxidative stress in L929 fibroblasts. The resveratrol-loaded albumin nanospheres showed a more enhanced antioxidant effect. Thus, the encapsulation of resveratrol in both types of nanoparticles could be considered an advantageous approach due to improvements in solubility, stability and antioxidant activity. Full article

Exercise-induced reactive oxygen and nitrogen species (RONS) serve as crucial signaling molecules for training adaptation, mitochondrial biogenesis, and inflammatory resolution, rather than being mere markers of oxidative damage. Chronic or excessive high-dose antioxidant supplementation may suppress these vital redox-sensitive pathways. Consequently, this narrative review examines food-based antioxidant strategies as approaches for redox modulation, meaning support for recovery and redox homeostasis without indiscriminately suppressing exercise-induced redox signals that may contribute to training adaptation, while emphasizing the distinction between whole-food matrices and isolated supplements. A structured literature search was conducted across major electronic databases, including PubMed, Web of Science, Scopus, and SPORTDiscus. The search focused on intersecting themes of exercise physiology, redox biology, and sports nutrition. The reviewed evidence includes short-term human intervention studies, systematic reviews, meta-analyses, and mechanistic studies examining tart cherry, berries, pomegranate, cocoa, green tea, beetroot, extra virgin olive oil, and Mediterranean-style dietary patterns. Overall, the evidence suggests that these food-based strategies may influence recovery-related outcomes through mechanisms extending beyond direct radical scavenging, including inflammatory regulation, vascular function, and gut-derived metabolism; however, the strength and consistency of findings vary by food source, outcome, dose, timing, study population, dietary matrix, and bioavailability. Current literature does not support universal, fixed daily antioxidant use. Food-based strategies appear most appropriate during periods of elevated recovery demands, such as heavy training blocks, congested competition, muscle damage, or environmental stress. Food-based antioxidant nutrition should therefore be interpreted as a conceptual, evidence-informed approach to periodized and context-specific recovery support, rather than as a universal or evidence-graded guideline, because much of the available evidence derives from short-term and heterogeneous intervention studies. These strategies should complement foundational sports nutrition practices (energy availability, macronutrient distribution, hydration, and sleep) when balancing the preservation of long-term training adaptations with the need for acute recovery. Full article

Shiga toxin-producing Escherichia coli (STEC) infections are a major cause of hemolytic uremic syndrome (HUS), a thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. The pathogenesis of STEC-HUS is primarily driven by Shiga toxins (Stx), which induce endothelial injury, inflammation, platelet activation, and microvascular thrombosis. Hemolysis associated with thrombotic microangiopathy leads to the release of hemoglobin and free heme into the circulation. Free heme, an iron-containing molecule with potent pro-oxidative, pro-inflammatory, and cytotoxic properties, contributes to oxidative stress, endothelial dysfunction, complement activation, and further tissue injury. Oxidative stress plays a crucial role in both host and bacterial cells, influencing disease progression and the expression of bacterial virulence factors, including Shiga toxin. N-acetyl-L-cysteine (NAC), a precursor of glutathione (GSH) and a well-established antioxidant, has attracted attention as a potential adjunctive therapeutic agent due to its antioxidant, anti-inflammatory, antiplatelet, and cytoprotective properties. In addition, NAC may influence iron- and heme-mediated oxidative damage and improve erythrocyte resistance to oxidative stress. This review summarizes current knowledge regarding the roles of oxidative stress and free heme in STEC-HUS and examines the mechanistic rationale and current evidence supporting NAC as a potential adjunctive strategy. The available evidence remains largely indirect and preclinical; therefore, the potential role of NAC in STEC-HUS should be considered hypothesis-generating and requires further investigation in clinical studies. Full article

Supplements are widely perceived as safe and beneficial; yet in oncology, this assumption is questionable. Clinical trials over the past few decades have often produced disappointing results, raising a critical question: are these agents used correctly, or could they inadvertently cause harm? This review examines supplements frequently used in cancer care—such as oral vitamin C, berberine, N-acetylcysteine, vitamin D, vitamin E, melatonin, polyphenols, alpha-lipoic acid, selenium, and coenzyme Q10—which can act as tumor suppressors or promoters depending on dose, route, and disease stage. We examine their dual antioxidant and pro-oxidant properties, revealing that therapeutic outcomes are shaped not only by the molecule itself, but also by bioavailability, dosing thresholds, and the tumor redox environment. Building on these insights, we propose that four factors may be considered to guide clinical use: ensure that anticancer effects are not overshadowed by antioxidant activity, achieve sufficient bioavailability, confirm pro-oxidant concentrations where possible, and prioritize supplements that target the respiration-supported non-OxPhos pathways. By framing supplements as context-dependent redox modulators rather than universally beneficial agents, this review provides a mechanistically grounded framework for informing future research and safer, more effective integrative oncology strategies. Full article

Numerous adverse effects caused by oxidative stress are commonly observed in preterm infants. This stress is caused by the oxidative burden resulting mainly from supplemental oxygen and parenteral nutrition (PN), and by their precarious antioxidant defense. The natural antioxidant defense against these oxidant molecules relies on glutathione, levels of which are low in preterm infants. Given that several short- and long-term biological complications are associated with this oxidative stress, the aim of this narrative review was to discuss glutathione supplementation as a method for reducing it. Consequently, after briefly discussing the effectiveness of partially reducing oxidative stress through adequate photoprotection of PN, it is proposed to correct premature infants’ glutathione deficiency by adding glutathione to PN. To justify the proposed intervention, this article will discuss the scientific evidence related to the (1) importance of glutathione, (2) causes of glutathione deficiency and ways to prevent it, (3) reasons why the disulfide form (GSSG) is recommended over the reduced form (GSH) for PN supplementation, (4) efficacy of parenteral GSSG in preventing oxidative stress, and (5) safety profile of glutathione infusion. In conclusion, we believe that the time has come to improve the health of premature infants by providing GSSG-supplemented PN. Full article

Cellulose nanocrystals (CNCs) are renewable and biodegradable nanomaterials that can stabilize Pickering emulsions through steric hindrance and electrostatic repulsion. However, pristine CNCs show limited interfacial anchoring because of their strong hydrophilicity and high surface charge density, making the emulsions susceptible to coalescence, phase separation, and structural instability under environmental stresses. This review summarizes two major strategies for stabilizing and functionally regulating CNC-based Pickering emulsions: chemical modification and synergistic stabilization. Chemical modification regulates CNC surface charge, wettability, interfacial anchoring, and functional group composition through oxidation, amination, esterification, graft copolymerization, desulfation, and etherification, whereas synergistic stabilization constructs composite interfacial films or continuous-phase networks through noncovalent interactions between CNCs and proteins, polysaccharides, cyclodextrins, surfactants, inorganic nanomaterials, or functional molecules. The ability of these emulsion systems to compartmentalize oil-soluble bioactives within structured droplets also provides a basis for improving bioactive stability and release behavior in food-related formulations. These strategies improve emulsion stability and introduce antibacterial, antioxidant, responsive, and controlled-release properties, highlighting the potential of CNC-based Pickering emulsions in active food systems, including food preservation, active packaging, and the stabilization, protection, and release regulation of food bioactives. Remaining challenges in green preparation, structural regulation, release mechanisms, scalable production, and practical evaluation are also discussed. Full article

Acetaminophen (APAP) overdose is a major cause of drug-induced liver injury and remains a widely used model of xenobiotic-induced hepatotoxicity. Oxidative stress, mitochondrial dysfunction, and ferroptosis are key events in APAP-mediated liver damage. In this study, we investigated whether L-menthol pretreatment protects against APAP-induced acute liver injury and explored the underlying mechanisms in vivo and in vitro. Male C57BL/6 mice were pretreated with L-menthol (100 mg/kg/day) for 7 days before APAP challenge (300 mg/kg). L-menthol markedly attenuated hepatic necrosis, inflammatory infiltration, and hepatocyte injury, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, suppressed IL-1β, IL-6, and TNF-α production, restored hepatic glutathione and superoxide dismutase levels, and decreased malondialdehyde accumulation. Transcriptomic analysis revealed significant enrichment of differentially expressed genes in reactive oxygen species- and ferroptosis-related pathways. In APAP-challenged HepG2 cells, L-menthol improved cell viability, preserved mitochondrial ultrastructure, reduced ferrous iron accumulation, was associated with upregulation of Keap1/Nrf2/HO-1/NQO1 pathway-related proteins, and restored GPX4 expression. Collectively, these findings indicate that L-menthol pretreatment attenuates APAP-induced hepatotoxicity, possibly through enhancement of antioxidant defenses and attenuation of ferroptosis-associated changes, supporting its potential as a preventive hepatoprotective small molecule against xenobiotic-induced liver injury. Full article

The pineal gland regulates circadian physiology through the periodic production of melatonin (MLT). In addition to its established role as a chronobiotic agent, MLT regulates redox homeostasis and mitochondrial physiology. Mitochondria and redox-active molecules, particularly reactive oxygen species (ROS), play essential roles in reproduction, including gamete physiology, fertilization, and early embryonic development. Although excessive oxidative stress (OS) impairs fertility, controlled ROS signaling is necessary for normal reproductive function. This comprehensive review synthesizes current evidence regarding MLT as a key intermediary linking circadian signaling with mitochondrial physiology and redox homeostasis. We discuss molecular pathways through which MLT regulates mitochondrial function, including activation of the Nrf2 signaling pathway, modulation of mitochondrial permeability transition, regulation of electron transport chain (ETC) efficiency, and apoptotic signaling. Furthermore, this study investigates MLT’s ability to scavenge free radicals and activate antioxidant defense mechanisms. Moreover, we review novel findings regarding the effects of MLT in experimental animals and humans, assisted reproductive technologies (ART) such as in vitro fertilization (IVF), and consider the translational significance of the hormone as an enhancer of fertility. We also highlight gaps in the literature, including methodological inconsistencies, supraphysiologic doses, and insufficient data from large human cohorts. Lastly, we discuss an integrative model whereby MLT may function as an important regulator of mitochondrial redox balance, with potential implications for reproductive physiology and reproductive outcomes, and propose new avenues for investigation. Full article

The safety profile for bio-derived phenols post-oxidation and their related antioxidant/redox potential remain largely under-explored. Oxidation by fungi, in terms of environmental impacts via fungal oxidation by enzymes, remains an attractive strategy under milder conditions, since it is one route by which many naturally occurring lignocellulosic phenols are modified; thus, an immediate need still exists for characterizing the effects that these modified phenolic compounds may have. Methodology: We examined four different biomass-derived phenolics—vanillin, ferulic acid, syringaldehyde and guaiacol—that were oxidized with fungal laccase and characterized their effects on normal human lung fibroblasts and levels of cellular oxidative stress. Laccase activity was evaluated via the ABTS method and through simple observation and UV-Vis spectroscopic scanning of the phenolics in question, and compared with the untreated version of each phenolic. In addition to assessing the cytotoxic effect and oxidative stress generated by the phenols alone, an ELISA-based measurement assay was used to investigate the relative abundance of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) in the human normal lung fibroblast cell line under varying treatment regimes, complemented by phase-contrast microscopy. Scores integrating the biomarkers were analyzed via clustering, PCA, radar and Pearson correlation analyses, to discern distinct trends in antioxidant potential after laccase conversion. Observations: Each of the four tested phenolics demonstrated the presence of laccase activity, leading to substantial differences in visible appearance compared with the control and characteristic absorbance shifts at differing wavelengths from the original molecule. Cell viability dropped dramatically as phenol concentration was increased and the untreated phenolics resulted in diminished confluence and induced greater levels of oxidative damage, from guaiacol and syringaldehyde. Laccase treatment resulted in higher MTT reduction activity and improved cellular morphology compared with the corresponding untreated phenolic compounds. Untreated phenols induced the highest levels of MDA, while decreasing SOD, CAT, GPx and GSH levels. Post-oxidation with laccase, there were lower amounts of lipid peroxidation, along with improved levels of antioxidant activity compared with the control phenol. Multi-technique analyses show clear distinctness between the untreated and laccase-converted phenolic groups. Clustering with multivariate techniques separated all cell groups in line with control samples, grouping the laccase-converted treatments towards the middle and displaying an inverse relationship between MDA and the antioxidant markers. Conclusions: Laccase conversion markedly decreases the adverse effects that bio-derived phenols have on normal cell viability and induces fewer detrimental effects on the cellular redox balance. This is a critical discovery in terms of finding greener methods by which to upgrade bio-derived substances as we research these lignocellulosic phenols. By employing ELISA-based measurements along with multiple analysis techniques, we present a suitable paradigm for studying biological effects in all bio-based goods intended for pharmaceuticals, packaging materials, nutraceuticals or a host of different applications. Full article

Global warming exacerbates high-temperature stress, disturbing the growth, metabolic homeostasis and quality formation of tea plants (Camellia sinensis L.). Trehalose, a multifunctional osmolyte, can enhance abiotic stress tolerance, but its systematic metabolic mechanism against heat damage in tea remains unclear. Here, we applied integrated gas chromatography–mass spectrometry (GC-MS) and liquid chromatography–mass spectrometry (LC-MS) non-targeted metabolomics to compare control (CK), heat-stressed (T), and trehalose-treated heat-stressed (TT) tea leaves. We identified 163 differential volatile metabolites in GC-MS and 1619 differential non-volatile metabolites in LC-MS. Metabolite classification showed that organic oxygen compounds dominated differential volatile metabolites, while lipids and lipid-like molecules dominated differential non-volatile metabolites. The Kyoto Encyclopedia of Genes and Genomes enrichment showed that alanine, aspartate and glutamate metabolism, arginine biosynthesis, aminoacyl-tRNA biosynthesis, and flavone and flavonol biosynthesis were core shared pathways. Quantitatively, exogenous trehalose under heat stress significantly increased carbohydrate accumulation, restored lipid homeostasis, and elevated alanine, arginine, and related intermediates, thereby maintaining carbon–nitrogen balance. Trehalose also remodeled the amino acid substrate pool for aminoacyl-tRNA biosynthesis. In flavonoid metabolism, trehalose enhanced high-antioxidant flavonoid aglycones while reducing most glycosides and inhibiting excessive hydroxylation of flavonols. Although total flavonoid content decreased in TT relative to T, this reflected alleviated oxidative damage and reduced dependence on flavonoid-based defense. Combined with total amino acid and flavonoid quantifications, we conclude that exogenous trehalose enhances tea plant thermotolerance by coordinately regulating primary amino acid metabolism and secondary flavonoid metabolism. These findings provide a theoretical basis for using trehalose in heat-resistance cultivation and quality improvement of tea plants. Full article

Background: Type 2 diabetes mellitus (T2DM) is a global health challenge characterized by chronic hyperglycemia and oxidative stress. Pithecellobium dulce root has long been recognized for its antidiabetic potential; however, its specific bioactive constituents and mechanisms of action remain poorly defined. This study aimed to evaluate the antidiabetic and antioxidant properties of extracts and isolated molecules from P. dulce root bark. Methods: The DCM/MeOH crude extract of P. dulce root bark was fractionated with n-hexane (PDEH) and ethyl acetate (PDAE), followed by chromatographic purification and spectroscopic characterization, yielding seventeen compounds (1–17). The antioxidant activity (DPPH, ABTS, FRAP) and antidiabetic potential of PDEH, PDAE, and 1–17 were assessed in vitro using yeast-derived enzymes and in silico (targeting human α-glucosidase [PDB: 2QLY] and human α-amylase [PDB: 4GQR]). The in vitro α-glucosidase experiments used saccharomyces cerevisiae enzyme, which varies from the human target. Therefore, these results should be taken as preliminary screening data that needs confirmation with human enzymes. Results: Compound 1 was identified as new, while 2 was isolated for the first time from a natural source. The cell-free chemical tests DPPH, ABTS, and FRAP measured antioxidant capability. These tests quantify radical-scavenging and electron-transfer capabilities in vitro and are preliminary chemical screening methods. They do not directly represent biological antioxidant activity in cells or organisms. PDEH demonstrated strong radical scavenging against DPPH (IC₅₀ = 15.30 μg/mL) and ABTS (IC₅₀ = 12.80 μg/mL), while pristriol (16) showed ferric reducing power (EC₅₀ = 4200 μM FeSO₄/g). Enzyme inhibition assays demonstrated activity against α-amylase (IC₅₀ 53.88–112.24 µg/mL; acarbose IC₅₀ = 91.20 µg/mL) and α-glucosidase (IC₅₀ 18.38–136.88 µg/mL; acarbose IC₅₀ = 11.31 µg/mL). Compounds 15, 1, and 2 showed superior activity compared to acarbose for α-amylase, with effect sizes (Cohen’s d) of 2.15, 0.94, and 0.82, respectively, and IC₅₀ values of 53.88, 88.15, and 92.62 µg/mL; for α-glucosidase, IC₅₀ values were 18.38, 39.25, and 36.40 µg/mL, respectively. Docking studies supported these findings, revealing binding energies of −9.08, −8.34, and −7.22 kcal/mol for compounds 1, 2, and 15 with α-amylase, and −10.35 and −9.79 kcal/mol for compounds 1 and 2 with α-glucosidase. ADME profiling further identified 1 and 2 as promising lead candidates for dual-enzyme inhibition. Conclusions: P. dulce root bark represents a potent source of bioactive molecules with both antioxidant and dual-enzyme-inhibitory properties. These findings validate its traditional use and highlight its potential in the development of multitarget therapies for T2DM management. Full article

The skin serves as the body’s first line of defense against environmental threats, acting as a barrier between external aggressors and internal systems. Current evidence regarding the roles of sulfur dioxide (SO₂) in biology and medicine is limited. Environmental pollutants, including SO₂, can increase the production of reactive oxygen species in the skin, leading to oxidative damage that may worsen various dermatological conditions. Endogenous SO₂, proposed as the fourth member of the gasotransmitter family, functions as a biological signaling molecule. It is generated in various human skin cells, including vascular smooth muscle cells, endothelial cells, mast cells, keratinocytes, macrophages, adipocytes, fibroblasts, dermal immune cell population, etc, where it performs multiple functions at physiologically relevant concentrations. Endogenous SO₂ plays a crucial role in regulating cell signaling and maintaining skin homeostasis through its antioxidant, anti-inflammatory, and cytoprotective effects. Abnormal generation and metabolism of SO₂ are linked to several critical processes in the skin, including vascular biology, immune response, cell proliferation, pigmentation, malignancy, protective barriers, senescence, and resistance to stress. This paper provides a narrative review of the significant roles of SO₂ in skin health and disease. A comprehensive understanding of the complex molecular effects and mechanisms mediated by SO₂ in human skin, along with the development of gas therapy, will be essential for translating fundamental research into clinical applications. Full article