Search Results (475)

The development of ceria (CeO_2−x)-based nanoantioxidants requires fine-tuning of structural and surface properties for enhancing antioxidant behavior in biological environments. In this contest, here ultrasmall water-dispersible CeO_2−x nanoparticles (NPs), characterized by a high Ce³⁺/Ce⁴⁺ ratio, were synthesized in a non-polar solvent and phase-transfer to an aqueous environment through ligand-exchange reactions using citric acid (CeO_2−x@Cit) and post-treatment with dopamine hydrochloride (CeO_2−x@Dopa). The concept behind this work is to enhance via surface engineering the intrinsic antioxidant properties of CeO_2−x NPs. For this purpose, thanks to electron transfer reactions between dopamine and CeO_2−x, the CeO_2−x@Dopa was obtained, characterized by increased surface Ce³⁺ sites and surface functionalized with polydopamine bearing o-quinone structures as demonstrated by complementary spectroscopic (UV–vis, FT-IR, and XPS) characterizations. To test the antioxidant properties of CeO_2−x NPs, the scavenging activity before and after dopamine treatment against artificial radical 1,1-diphenyl-2-picrylhydrazyl (DPPH^·) and the ability to reduce the reactive oxygen species in Diencephalic Immortalized Type Neural Cell line 1 were evaluated. CeO_2−x@Dopa demonstrated less efficiency in DPPH^· scavenging (%radical scavenging activity 13% versus 42% for CeO_2−x@Cit before dopamine treatment at 33 μM DPPH^· and 0.13 mg/mL loading of NPs), while it markedly reduced intracellular ROS levels (ROS production 35% compared to 66% of CeO_2−x@Cit before dopamine treatment with respect to control—p < 0.001 and p < 0.01, respectively). While steric hindrance from the dopamine-derived polymer layer limited direct electron transfer from CeO_2−x NP surface to DPPH^·, within cells the presence of o-quinone groups contributed with CeO_2−x NPs to break the autoxidation chain of organic substrates, enhancing the antioxidant activity. The functionalization of NPs with o-quinone structures represents a valuable approach to increase the inherent antioxidant properties of CeO_2−x NPs, enhancing their effectiveness in biological systems by promoting additional redox pathways. Full article

Alcohol dependency is a complex and chronic condition that negatively impacts multiple organ systems, including the skin. A key pathological factor in this process is oxidative stress, leading to progressive cellular damage, chronic inflammation, and accelerated cutaneous aging. Alcohol metabolism generates reactive oxygen species (ROS), which overwhelm endogenous antioxidant defenses and contribute to a range of skin alterations, including nonspecific changes such as xerosis, erythema, and wrinkle formation, as well as inflammatory and neoplastic skin disorders. Additionally, alcohol-induced alterations of the skin microbiome may further exacerbate skin barrier dysfunction and inflammatory responses. This review explores the biochemical mechanisms and skin microbiome alterations linking alcohol-induced oxidative stress to skin damage and disease. Furthermore, it evaluates the therapeutic potential of antioxidant-based interventions, both natural and synthetic. Antioxidants may offer protective and regenerative effects by scavenging free radicals, modulating inflammatory responses, and enhancing skin barrier function. The paper aims to provide a comprehensive overview of the molecular and microbial interplay between alcohol, oxidative stress, and skin health, while identifying future directions for targeted antioxidant therapy in individuals with alcohol dependency. Full article

The functional role of MAPKK genes in potato (Solanum tuberosum L.) under high-temperature stress remains unexplored, despite their critical importance in stress signaling and yield protection. We characterized StMAPKK1, a novel group D MAPKK localized to plasma membrane/cytoplasm. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed cultivar-specific upregulation in potato (‘Atlantic’ and ‘Desiree’) leaves under heat stress (25 °C, 30 °C, and 35 °C). Transgenic lines overexpressing (OE) StMAPKK1 exhibited elevated antioxidant enzyme activity, including ascorbate peroxidase (APX), catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD), mitigating oxidative damage. Increased proline and chlorophyll accumulation and reduced oxidative stress markers, hydrogen peroxide (H₂O₂) and malondialdehyde (MDA), indicate improved cellular redox homeostasis. The upregulation of key antioxidant and heat stress-responsive genes (StAPX, StCAT1/2, StPOD12/47, StFeSOD2/3, StMnSOD, StCuZnSOD1/2, StHSFA3 and StHSP20/70/90) strengthened the enzymatic defense system, enhanced thermotolerance, and improved photosynthetic efficiency, with significant improvements in net photosynthetic rate (Pn), transpiration rate (E), and stomatal conductance (Gs) under heat stress (35 °C) in StMAPKK1-OE plants. Superior growth and biomass (plant height, plant and its root fresh and dry weights, and tuber yield) accumulation, confirming the positive role of StMAPKK1 in thermotolerance. Conversely, RNA interference (RNAi)-mediated suppression of StMAPKK1 led to a reduction in enzymatic activity, proline content, and chlorophyll levels, exacerbating oxidative stress. Downregulation of antioxidant-related genes impaired ROS scavenging capacity and declines in photosynthetic efficiency, growth, and biomass, accompanied by elevated H₂O₂ and MDA accumulation, highlighting the essential role of StMAPKK1 in heat stress adaptation. These findings highlight StMAPKK1’s potential as a key genetic target for breeding heat-tolerant potato varieties, offering a foundation for improving crop resilience in warming climates. Full article

Air pollution acts as a pervasive oxidative stressor, disrupting global crop production and ecosystem health through the overproduction of reactive oxygen species (ROS). Hazardous pollutants impair critical physiological processes—photosynthesis, respiration, and nutrient uptake—triggering oxidative damage and yield losses. This review synthesizes current knowledge on plant defense mechanisms, emphasizing the integration of enzymatic (SOD, POD, CAT, APX, GPX, GR) and non-enzymatic (polyphenols, glutathione, ascorbate, phytochelatins) antioxidant systems to scavenge ROS and maintain redox homeostasis. We highlight the pivotal roles of transcription factors (MYB, WRKY, NAC) in orchestrating stress-responsive gene networks, alongside MAPK and phytohormone signaling (salicylic acid, jasmonic acid, ethylene), in mitigating oxidative stress. Secondary metabolites (flavonoids, lignin, terpenoids) are examined as biochemical shields against ROS and pollutant toxicity, with evidence from transcriptomic and metabolomic studies revealing their biosynthetic regulation. Furthermore, we explore biotechnological strategies to enhance antioxidant capacity, including overexpression of ROS-scavenging genes (e.g., TaCAT3) and engineering of phenolic pathways. By addressing gaps in understanding combined stress responses, this review provides a roadmap for developing resilient crops through antioxidant-focused interventions, ensuring sustainability in polluted environments. Full article

Inflammatory bowel disease (IBD) is characterized by oxidative stress imbalance and intestinal barrier disruption. Reducing excessive ROS has become a promising therapeutic strategy. Compared with conventional polyphenols, nanomaterials offer greater stability and bioavailability for ROS scavenging. Here, ellagic acid (EA) was converted into uniform nanoparticles (EAs) with reactive oxygen scavenging capacity through horseradish peroxidase (HRP)-mediated oxidative polymerization and subsequently encapsulated in the anti-gastric acid hydrogel F-DP to obtain the hybrid system F-DP@EAs. EAs reduced ROS, MDA, NO, IL-1β, and TNF-α levels in vitro, while increasing IL-4 and IL-10 expression, thus alleviating inflammation. Herein, F-DP@EAs prolonged intestinal retention time and exerted superior protective effects in the DSS-induced colitis model. Oral F-DP@EAs lowered DAI, preserved colon length, increased glutathione (GSH) and superoxide dismutase (SOD), decreased NO and MDA, restored zonula occludens-1 (ZO-1), and reduced mucosal lesions. These findings demonstrate that combining nanoparticle and hydrogel technologies markedly enhances the preventive and protective efficacy of EA, highlighting F-DP@EAs as a promising candidate for future IBD therapy. Full article

Male infertility is a pathological condition that affects many subjects and for which a progressive increase in cases has been observed in recent years. The mechanisms underlying male reproductive system dysfunction are not fully understood and the specific drugs use has not produced optimal results. Therefore, the focus on developing new therapeutic options to prevent or treat this dysfunction is continuously growing. Defective sperm function has been associated with oxidative stress (OS) due to reactive oxygen species (ROS) excessive production. OS is related to mitochondrial dysfunction, lipid peroxidation, DNA damage and fragmentation, and ultimately sperm cell death. Many defense mechanisms to protect from ROS injuries have been developed; natural antioxidants, such as vitamin C and E are able to interact with oxidizing radicals, neutralizing them. Interestingly, resveratrol (RSV), a natural polyphenol with proven health-promoting actions, has been found to be an effective free radical scavenger in several in vitro and in vivo models, providing protection against OS. In this review, we discussed mechanisms related to the modulation of redox homeostasis in the testis and how the alteration of these processes can determine a damage in testicular function; particularly, we focused on the antioxidant properties of RSV that could give beneficial effects in preserving male fertility. Full article

Melatonin (MT) can enhance plant stress tolerance by activating the internal defense system, but its application in rubber trees has been barely reported up to now. In this study, we found that the relative electrical conductivity (REC), H₂O₂, and malondialdehyde (MDA) contents were significantly higher in the leaves of rubber tree seedlings under drought stress compared to the control (water treatment), whereas chlorophyll contents were obviously lower in the leaves under drought stress compared to the control. MT partly relieves the aforementioned drought-induced adverse effects by dramatically reducing chlorophyll degradation, H₂O₂ accumulation, MDA content, and REC. Comparative transcriptomes among the PEG (P), MT (M), and PEG + MT (PM) treatments against the control showed that 213, 896, and 944 genes were differently expressed in rubber tree seedlings treated with M, P, and PM in contrast to the control. Among the 64 differently expressed genes (DEGs) being common among the three comparisons, the expression profiles of 25 were opposite in MH compared with PH. Intriguingly, all the KEGG pathways of the DEGs mentioned above belonged to metabolism including energy metabolism, carbohydrate metabolism, amino acid metabolism, and the metabolism of cofactors and vitamins. Exogenous application of MT mainly regulated the genes associated with photosynthesis and the anti-oxidative defense system, thereby enhancing the antioxidant protection of rubber tree seedlings under drought stress. These results suggest that exogenous melatonin application can effectively enhance drought tolerance by heightening ROS scavenging to decrease H₂O₂ accumulation in rubber tree seedlings. Our results elucidate the molecular mechanisms of MT’s roles in drought stress, which help to employ exogenous MT to boost drought tolerance in the rubber tree. Full article

Toxoplasma gondii is an Apicomplexan parasite that possesses a well-developed system of scavengers of reactive oxygen species (ROS). Among its components, T. gondii mitochondrial superoxide dismutase (TgSOD2) is essential, as predicted by the CRISPR phenotype index and evidenced by the non-viability of its constitutive knockouts. As an obligate intracellular parasite, TgSOD2 is upregulated during extracellular stages. Herein, we generated a viable TgSOD2 knockdown mutant using an inducible auxin–degron system to explore the biological role of TgSOD2 in T. gondii. Depletion of TgSOD2 led to impaired parasite growth and replication, reduced mitochondrial membrane potential (MMP), abnormalities in the distribution of ATP synthase within its mitochondrial electron transport chain (mETC), and increased susceptibility to mETC inhibitors. Through a proximal biotinylation approach, we identified the interactions of TgSOD2 with complexes IV and V of its mETC, suggesting that these sites are sensitive to ROS. Our study provides the first insights into the role of TgSOD2 in maintaining its mitochondrial redox homeostasis and subsequent parasite replication fitness. Significance: Toxoplasma gondii infects nearly a third of the world population and can cause fetal miscarriages or life-threatening complications in vulnerable patients. Current therapies do not eradicate the parasite from the human hosts, rendering them at risk of recurrence during their lifetimes. T. gondii has a single mitochondrion, which is well-known for its susceptibility to oxidative damage that leads to T. gondii’s death. Therefore, targeting T. gondii mitochondrion remains an attractive therapeutic strategy for drug development. T. gondii’s mitochondrial superoxide dismutase is an antioxidant protein in the parasite mitochondrion and is essential for its survival. Understanding its biological role could reveal mitochondrial vulnerabilities in T. gondii and provide new leads for the development of effective treatments for T. gondii infections. Full article

Natural polymer-based nanoparticles have emerged as promising stabilizers for Pickering emulsions, offering biocompatibility, environmental sustainability, and improved protection of active compounds. This study developed chitosan/gum arabic (CH/GA) nanoparticles as solid stabilizers for quercetin-loaded Pickering emulsions to enhance the stability and antioxidant bioactivity of quercetin (QE), a plant-derived flavonoid known for its potent radical-scavenging activity but limited by oxidative degradation. A systematic formulation strategy was employed to evaluate the effects of CH/GA concentration (0.5–2.0% w/v), oil type (olive, soybean, sunflower, and coconut), and oil volume fraction (ϕ = 0.5–0.7) on emulsion stability. The formulation containing 1.5% CH/GA and olive oil at ϕ = 0.6 exhibited optimal physical and interfacial stability. Quercetin (0.1% w/w) was incorporated into the optimized emulsions and characterized for long-term stability, particle size, droplet morphology, rheology, antioxidant activity (DPPH), cytocompatibility, and intracellular reactive oxygen species (ROS) protection using HaCaT keratinocytes. The olive oil-based formulation (D1-QE) exhibited greater viscosity retention and antioxidant stability than its soybean-based counterpart (E2-QE) under both room temperature (RT) and accelerated heating–cooling (H/C) storage conditions. Confocal microscopy confirmed the accumulation of CH/GA nanoparticles at the oil–water interface, forming a dense interfacial barrier and enhancing emulsion stability. HPLC analysis showed that D1-QE retained 92.8 ± 0.5% of QE at RT and 82.8 ± 1.5% under H/C conditions after 30 days. Antioxidant activity was largely preserved, with only 4.7 ± 1.7% and 14.9 ± 4.8% loss of DPPH radical scavenging activity at RT and H/C, respectively. Cytotoxicity testing in HaCaT keratinocytes confirmed that the emulsions were non-toxic at 1 mg/mL QE and effectively reduced H₂O₂-induced oxidative stress, decreasing intracellular ROS levels by 75.16%. These results highlight the potential of CH/GA-stabilized Pickering emulsions as a polymer-based delivery system for maintaining the stability and functional antioxidant activity of QE in bioactive formulations. Full article

Alzheimer’s disease (AD) is characterized by β-amyloid plaques, neurofibrillary tangles, neuroinflammation, and oxidative stress—pathological features that pose significant challenges for the development of therapeutic interventions. Given these challenges, this review comprehensively evaluates the neuroprotective mechanisms of bioactive compounds derived from red algae, including polysaccharides and phycobiliproteins, which are considered a promising source of natural therapeutics for AD. Red algal constituents exhibit neuroprotective activities through multiple mechanisms. Sulfated polysaccharides (e.g., carrageenan, porphyran) suppress NF-κB-mediated neuroinflammation, modulate mitochondrial function, and enhance brain-derived neurotrophic factor (BDNF) expression. Phycobiliproteins (phycoerythrin, phycocyanin) and peptides derived from their degradation scavenge reactive oxygen species (ROS) and activate antioxidant pathways (e.g., Nrf2/HO-1), thus mitigating oxidative damage. Carotenoids (lutein, zeaxanthin) improve cognitive function through the inhibition of acetylcholinesterase and pro-inflammatory cytokines (TNF-α, IL-1β), while phenolic compounds (bromophenols, diphlorethol) provide protection by targeting multiple pathways involved in dopaminergic system modulation and Nrf2 pathway activation. Emerging extraction technologies—including microwave- and enzyme-assisted methods—have been shown to optimize the yield and maintain the bioactivity of these compounds. However, the precise identification of molecular targets and the standardization of extraction techniques remain critical research priorities. Overall, red algae-derived compounds hold significant potential for multi-mechanism AD interventions, providing novel insights for the development of therapeutic strategies with low toxicity. Full article

In this study, we investigated the potential of a three-mushroom complex extract (GMK) to inhibit neuronal cell death induced by the activation of AMPA and NMDA receptors following glutamate treatment in NGF-differentiated PC12 neuronal cells. GMK significantly mitigated glutamate-induced excitotoxic neuronal apoptosis by reducing the elevated expression of BAX, a critical regulator of apoptosis, and restoring BCL2 levels. These neuroprotective effects were associated with redox regulation, as evidenced by the upregulation of SOD, CAT, and GSH levels, and the downregulation of MDA levels. Mechanistic studies further revealed that GMK effectively scavenged ROS by downregulating NOX1, NOX2, and NOX4, while upregulating NRF1, P62, NRF2, HO1, and NQO1. Additionally, in the same model, GMK treatment increased acetylcholine, choline acetyltransferase, and GABA levels while reducing acetylcholinesterase activity. These effects were also attributed to the regulation of redox balance. Furthermore, we investigated the antioxidant and anti-inflammatory mechanisms of GMK in LPS-stimulated BV2 microglia. GMK inhibited the activation of IκB and MAPK pathways, positively regulated the BCL2/BAX ratio, suppressed TXNIP activity, and upregulated NQO1 and NOX1. In conclusion, GMK improved neuronal excitotoxicity and microglial inflammation through the positive modulation of the redox regulatory system, demonstrating its potential as a natural resource for pharmaceutical applications and functional health foods. Full article

This study designed a polyurethane core–shell fiber (PU CSF) wound dressing, which achieved unique redox catalytic function by loading nanoceria (n-CeO₂) nanozyme and effectively reduced potential side effects. The stability of ceria nanoparticles with superoxide dismutase (SOD) mimetic activity was optimized. Engineered PU CSFs with different doses of citrate-modified nanospheres (CeO₂@PU CSFs) were successfully fabricated via electrospinning and showed excellent SOD-mimetic activity in reducing oxidative stress both in vitro and in vivo. Notably, low-dose nanoceria PU CSFs demonstrated advantages in promoting wound healing and reducing scar formation compared to high-dose and SOD-loaded groups (p < 0.05), despite lower reactive oxygen species (ROS) scavenging capacity (p < 0.001). Transcriptome analysis revealed distinct mechanisms in rat skin studies: the CeO₂-loaded dressing systemically downregulated cell activation- and innate immunity-related genes (Fos, Trpm2, Cybb, and Nlrc4), while the SOD-loaded group specifically regulated inflammation mediated by oxidative stress (IL17a and Ccl20). The optimized core–shell structure and low-dose nanoceria provided balanced redox modulation, effectively protecting cells from oxidative damage while providing a multifunctional therapeutic platform for damaged wound healing. Full article

Ellagic acid (EA) is a natural polyphenol found in various fruits, nuts, and mushrooms. It exhibits a variety of biological activities, including potent antioxidant, anti-inflammatory, anti-obesity, and neuroprotective properties. EA exerts hepatoprotective effects through multiple mechanisms, including (1) scavenging reactive oxygen species (ROS) and enhancing endogenous antioxidant defenses (e.g., by activating Nrf2/ARE), (2) modulating inflammatory signaling pathways (e.g., inhibiting NF-κB, TNF-α, and IL-6), and (3) regulating apoptosis (e.g., downregulating the Bax/Bcl-2 ratio) and fibrosis (e.g., inhibiting TGF-β/Smad signaling). Despite its promising preclinical efficacy, the clinical applicability of EA is currently limited by its poor bioavailability. This could potentially be overcome by advanced delivery systems or by directly administering its active microbial metabolites, known as urolithins. EA and its derivatives also modulate the gut microbiota, promoting the growth of beneficial species and reducing gut permeability and hepatic inflammation. Preliminary clinical trials and other emerging evidence suggest that EA may reduce liver inflammation, oxidative stress, and metabolic dysregulation. However, more extensive human studies are needed to confirm its efficacy and safety in managing liver disease. This review highlights the therapeutic potential of EA in the treatment of liver diseases, particularly metabolic-dysfunction-associated steatotic liver disease (MASLD). Full article

Strawberry (Fragaria × ananassa Duch.) is an important fruit worldwide whose growth, development, and productivity are threatened by salinity. The WRKY transcription factors (TFs) were reported to play an important role in regulating abiotic stresses response. However, research on their roles to regulate salt stress tolerance in strawberry remains limited. In current study, the FvWRKY75 gene was isolated and characterized from the Ruegen strawberry, and induced by various stress treatment. The results showed that the FvWRKY75 transcription factor was a transcriptional activator and localized in the nucleus. Phenotypic and physiological analysis revealed that ectopic expression of FvWRKY75 in Arabidopsis improved salt tolerance by enhancing the antioxidant system activities, modulating ROS scavenging and upregulating stress-related genes. Y1H and dual luciferase assays revealed that FvWRKY75 can directly bind to the promoter of the FvCRK5 gene by recognizing the W-box element. Compared with the WT, ectopic expression of FvCRK5 gene in Arabidopsis enhanced salt tolerance characterized by the reduced ROS accumulation, higher chlorophyll content, lower MDA content, and enhanced SOD and POD activity. Herein, the FvWRKY75 gene acted as a positive regulator in salt stress resistance, at least in part, via the WRKY-CRK network to regulate the antioxidant enzyme defense system and stress-related genes to regulate salt stress tolerance in strawberry. Full article

Pyrus bretschneideri ‘Xinli No.7’, a progeny of Pyrus sinkiangensis ‘Korla Fragrant Pear’, is an early-maturing, high-quality pear (Pyrus spp.) cultivar. As a dominant variety in China’s pear-producing regions, it holds significant agricultural importance. Investigating its male sterility (MS) mechanisms is critical for hybrid breeding and large-scale cultivation. Integrated cytological, physiological, and transcriptomic analyses were conducted to compare dynamic differences between male sterility (MS, ‘Xinli No.7’) and male-fertile (MF, ‘Korla Fragrant Pear’) plants during anther development. Cytological observations revealed that, compared with ‘Korla Fragrant Pear’, the tapetum of ‘Xinli No.7’ exhibited delayed degradation and abnormal thickening during the uninucleate microspore stage. This pathological alteration compressed the microspores, ultimately leading to their abortion. Physiological assays demonstrated excessive reactive oxygen species (ROS) accumulation, lower proline content, higher malondialdehyde (MDA) levels, and reduced activities of antioxidant enzymes (peroxidase and catalase) in MS plants. Comparative transcriptomics identified 283 co-expressed differentially expressed genes (DEGs). Functional enrichment linked these DEGs to ROS-scavenging pathways: galactose metabolism, ascorbate and aldarate metabolism, arginine and proline metabolism, fatty acid degradation, pyruvate metabolism, and flavonoid biosynthesis. qRT-PCR validated the expression patterns of key DEGs in these pathways. A core transcriptome-mediated MS network was proposed, implicating accelerated ROS generation and dysregulated tapetal programmed cell death. These findings provide theoretical insights into the molecular mechanisms of male sterility in ‘Xinli No.7’, supporting future genetic and breeding applications. Full article