Search Results (391)

Tobacco mosaic virus (TMV) threatens crop yield and quality, while chemical antivirals offer limited efficacy and potential environmental hazards. Marine fungal polysaccharides are promising eco-friendly alternatives due to their biocompatibility and biodegradability. Here, extracellular polysaccharides (EPSs) from the deep-sea fungus Beauveria bassiana T2-2 was isolated, characterized, and produced under optimized conditions (28 °C, 200 rpm, 9 days, pH 8, inoculum 4%) using an L9 (3⁴) orthogonal medium, yielding 3.42 g/L, which is a 48% increase over unoptimized culture. EPSs were glucose-rich, with a molecular weight of 3.56 × 10⁴ Da, containing 90.05% total sugar, 0.28% protein, 1.15% uronic acid, and 1.18% sulfate. In a Nicotiana benthamiana–TMV model, EPSs alleviated viral symptoms, maintained chlorophyll content, enhanced antioxidant enzymes (SOD, POD, CAT), reduced malondialdehyde, and upregulated defense genes in SA, ET, ROS, and phenylpropanoid pathways. EPSs, alone or combined with Ribavirin, activated multi-pathway antiviral immunity, highlighting its potential as a sustainable plant-protective agent. Full article

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) often coexists with obstructive sleep apnea (OSA) due to overlapping metabolic risk factors. Whether continuous positive airway pressure (CPAP) influences hepatic outcomes in MASLD remains uncertain. This systematic review, using updated criteria for MASLD, evaluated the effects of OSA treatment on liver and metabolic outcomes. Methods: PubMed, Web of Science, and CINAHL were searched for randomized controlled trials (RCTs) and observational studies in adults with MASLD and OSA treated with CPAP, lifestyle interventions, pharmacotherapy, or surgery. Outcomes included liver stiffness, fat content, enzymes, fibrosis scores, HbA1c, lipids, and anthropometrics. Risk of bias was assessed with RoB 2 (RCTs) and ROBINS-I (non-randomized studies) and certainty of evidence with GRADE. Results: Eight studies (three RCTs, five observational; n = 1006; 73.5% male) met criteria. Studies evaluated CPAP for from 4 weeks to 3 years, with adherence ≥ 4 h/night in most. CPAP produced modest, inconsistent reductions in alanine aminotransferase and aspartate aminotransferase, small improvements in HbA1c and triglycerides, and minimal changes in liver stiffness, steatosis, weight, or anthropometrics. No RCT demonstrated significant improvement in fibrosis or steatosis. Risk of bias was low in one RCT, “some concerns” in two, and moderate in observational studies; one study had serious confounding risk. Conclusions: CPAP may modestly improve liver enzymes and select metabolic parameters in MASLD with OSA, but evidence for salutary effects on steatosis, fibrosis, and body composition is limited. Level of evidence was low due to methodological limitations, heterogeneity, and imprecision. High-quality, longitudinal trials are needed. Full article

Rare-earth oxide (REO) nanoparticles (NPs)—such as cerium (CeO₂), samarium (Sm₂O₃), neodymium (Nd₂O₃), terbium (Tb₄O₇), and praseodymium (Pr₂O₃)—have demonstrated strong antimicrobial activity against multidrug-resistant bacteria. Their effectiveness is attributed to unique physicochemical properties, including oxygen vacancies and redox cycling, which facilitate the generation of reactive oxygen species (ROS) that damage microbial membranes and biomolecules. Additionally, electrostatic interactions with microbial surfaces and sustained ion release contribute to membrane disruption and long-term antimicrobial effects. REOs also inhibit bacterial enzymes, DNA, and protein synthesis, providing broad-spectrum activity against Gram-positive, Gram-negative, and fungal pathogens. However, dose-dependent cytotoxicity to mammalian cells—primarily due to excessive ROS generation—and nanoparticle aggregation in biological media remain challenges. Surface functionalization with polymers, peptides, or metal dopants (e.g., Ag, Zn, and Cu) can mitigate cytotoxicity and enhance selectivity. Scalable and sustainable synthesis remains a challenge due to high synthesis costs and scalability issues in industrial production. Green and biogenic routes using plant or microbial extracts can produce REOs at lower cost and with improved safety. Advanced continuous flow and microwave-assisted synthesis offer improved particle uniformity and production yields. Biomedical applications include antimicrobial coatings, wound dressings, and hybrid nanozyme systems for oxidative disinfection. However, comprehensive and intensive toxicological evaluations, along with regulatory frameworks, are required before clinical deployment. Full article

In the pathological process of acute kidney injury (AKI) and its transition to chronic kidney disease, the uric acid (UA) metabolic pathway plays a significant role. UA is produced as the last oxidative product in the metabolism of purine nucleotides. Prolonged organ ischemia promotes the breakdown of nucleotides into adenosine, hypoxanthine, xanthine, and UA. In this study, animal models of ischemia–reperfusion-induced AKI and renal tubular epithelial cells subjected to hypoxia–reoxygenation injury exhibited significantly reduced ATP levels, along with elevated concentrations of purine catabolites, including AMP, hypoxanthine, xanthine, and UA. Concurrently, the expression of xanthine oxidase (XO), a key enzyme in purine catabolism, was upregulated, peaking at 3 h after reoxygenation, accompanied by increased reactive oxygen species (ROS) production. Treatment with the XO inhibitor febuxostat in hypoxia–reoxygenated HK-2 cells led to a marked reduction in UA, inflammatory cytokines, and ROS levels, along with decreased apoptosis and enhanced proliferative capacity. Clinical data analysis revealed that 59.4% of AKI patients presented with hyperuricemia. UA levels demonstrated a linear correlation with the estimated glomerular filtration rate (eGFR) and the tissue necrosis marker lactate dehydrogenase (LDH). A random forest model constructed based on UA, LDH, age, diabetes, and hypertension accurately predicted the eGFR. These findings indicate that patients with I/R-induced AKI exhibit enhanced purine catabolism, and purine metabolic breakdown products are closely associated with the severity of renal injury in I/R AKI. For high-risk AKI populations or patients diagnosed with AKI with significantly elevated UA levels, febuxostat may be considered to prevent AKI onset and improve renal function. Furthermore, in AKI patients where creatinine data are unavailable or not significantly elevated despite markedly increased UA levels, a comprehensive assessment incorporating relevant indicators of glomerular filtration function is recommended. Full article

Background: Vascular calcification is a strong predictor of cardiovascular morbidity and mortality. Oxidative stress plays a key role in promoting vascular calcification. Glutathione (GSH), as a major cellular antioxidant, is produced in response to oxidative stress and is regulated by the enzyme glutamate-cysteine ligase (GCL). In this study, we examined the role of the GCL modifier subunit (GCLm) in regulating vascular smooth muscle cell (VSMC) calcification. Methods: Human coronary artery VSMCs were exposed to phosphate-rich media to induce calcification. Results: Calcification led to a decrease in the GSH:GSSG ratio (reduced glutathione to oxidized glutathione), and elevated GCLm expression, coincident with mobilization of osteogenic genes and loss of contractile phenotype. KEGG pathway analysis of human unstable atherosclerotic plaques similarly showed increased GCLm expression and activation of reactive oxygen species (ROS)-related pathways. Notably, forced overexpression of GCLm in murine VSMCs (MOVAS cells) significantly accelerated calcification. These findings implicate GCLm upregulation in promoting VSMC calcification, potentially by disrupting redox homeostasis and driving phenotypic switching. Further mechanistic studies are warranted to evaluate GCLm as a potential therapeutic target in vascular calcification. Full article

Ferroptosis, a regulated cell death pathway driven by iron-dependent lipid peroxidation, is modulated by cellular antioxidant systems, particularly the glutathione (GSH)–glutathione peroxidase 4 (GPX4) axis. NAD kinase (NADK), the only enzyme converting NAD⁺ to NADP⁺ located in cytoplasm, fuels NADPH-dependent antioxidant defenses. However, its role in ferroptosis regulation remains not fully explored. Using ferroptosis-sensitive HT1080 cells, we employed pharmacological inhibition (thioNAM), siRNA-mediated knockdown, and plasmid-driven overexpression of NADK to dissect its impact on ferroptosis. Complementary interventions with nicotinamide mononucleotide (NMN), glucose-6-phosphate dehydrogenase (G6PD) and malic enzyme 1 (ME1) were used to map metabolic interactions. Cell viability, redox metabolites (NADPH and GSH), oxidative stress markers (ROS, MDA), and protein expression were quantified. ThioNAM depleted NADP(H) and sensitized cells to RSL-3-induced ferroptosis, which was reversible with Ferrostatin-1. NADK knockdown produced similar results, reducing NADP(H) levels and amplifying lipid peroxidation. Conversely, NADK overexpression restored NADPH/GSH levels and rescued ferroptosis. NADK was essential for G6PD- and ME1-mediated NADPH production and ferroptosis resistance. Administration of ThioNAM or knockdown of NADK abolished the ferroptosis-rescuing effects of NMN, whereas NADK overexpression enhanced NMN’s ability to rescue ferroptosis by maintaining redox homeostasis. NADK is a metabolic hub in ferroptosis regulation, bridging NMN-driven NAD⁺ salvage to NADPH synthesis via G6PD/ME1. Targeting NADK offers novel strategies for diseases associated with ferroptosis. Full article

Melatonin, a key regulator of the circadian rhythm, exerts strong antioxidant effects by scavenging reactive oxygen species (ROS) and modulating enzymatic redox balance. Xanthine oxidoreductase (XOR), a molybdenum- and iron–sulfur-containing enzyme, catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid—the final steps of purine catabolism—serving as an important enzymatic source of ROS under physiological conditions. XOR exists in three interconvertible isoforms: xanthine dehydrogenase (XDH), which uses NAD⁺ as an electron acceptor; xanthine oxidase (XO), which transfers electrons to oxygen, producing superoxide and hydrogen peroxide; and an intermediate form (XDO) that reflects the redox-dependent interconversion between the two. This study aimed to evaluate temporal and sex-dependent variations in XOR isoforms and their relationship with melatonin levels in healthy individuals. Sixty-six volunteers (33 women aged 24–38 and 33 men aged 24–44) were examined. Blood samples were collected at 02:00, 08:00, 14:00, and 20:00. Serum melatonin was measured using ELISA, and XOR isoform activities were determined spectrophotometrically. Melatonin exhibited a precise 24 h rhythm with a nocturnal peak at 02:00 (~98 pg/mL) and a daytime nadir at 14:00 (~9 pg/mL). XO activity varied significantly (p < 0.01), showing an inverse correlation with melatonin in men (ρ = −0.52, p = 0.006), while XDO activity correlated positively with melatonin in women at 14:00 (ρ = 0.48, p = 0.01). These findings indicate sex-specific and time-dependent regulation of XOR isoforms, suggesting that redox homeostasis is modulated differently in men and women throughout the day. Understanding these dynamics may refine the interpretation of oxidative stress biomarkers and help optimize diagnostic and chronotherapeutic approaches in redox-related disorders. Full article

The reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) is a primary electron donor for both antioxidant enzymes, such as glutathione reductase, and pro-oxidant enzymes, such as NADPH oxidases that produce reactive oxygen species (ROS) and nitric oxide synthases that generate nitric oxide which act as signaling molecules. Monitoring NADPH levels, NADPH/NADP⁺ ratio, and especially distinguishing from NADH, provides vital information about cellular redox status, energy generation, survival, lineage specification, and death pathway selection. NADPH detection is key to understanding metabolic reprogramming in cancer, aging, and cardiovascular, hormonal, neurodegenerative, and autoimmune diseases. Liquid chromatography combined with mass spectrometry (LC-MS) is crucial for NADPH detection in redox signaling because it offers the high sensitivity, specificity, and comprehensive profiling needed to quantify this vital but labile redox cofactor in complex biological samples. Using hepatoma cell lines, liver tissues, and primary hepatocytes from mice lacking transaldolase or nicotinamide nucleotide transhydrogenase, or having lupus, this study demonstrates that accurate measurement of NADPH depends on its preservation in reduced form which can be optimally achieved by extraction of metabolites in alkaline solution, such as 0.1 M potassium hydroxide (KOH) in comparison to 80% methanol (MeOH) alone or 40:40:20 methanol/acetonitrile/formic acid solution. While KOH extraction coupled with hydrophilic interaction liquid chromatography (HILIC) and mass spectrometry most reliably detects NADPH, NADP, NADH, NAD, polyamines, and polyols, MeOH extraction is best suited for detection of glutathione and overall discrimination between complex metabolite extracts. This study therefore supports performing parallel KOH and MeOH extractions to enable comprehensive metabolomic analysis of redox signaling. Full article

Background/Objectives: Biochemical processes such as the glycolytic pathway and Kreb’s cycle are important in producing ATP for the brain. Without a sufficient supply of glucose for energy metabolism, the brain cannot efficiently regulate or coordinate the actions and reactions of the body. It is well documented that traumatic brain injury (TBI) is associated with reduced energy metabolism through the production of reactive oxygen/nitrogen species. Antioxidants, such as glutathione (GSH), have been shown to combat the deleterious effects of oxidation by scavenging ROS/RNS, inhibiting propagation, and removing neurotoxic byproducts. Gamma-glutamylcysteine ethyl ester (GCEE), an ethyl ester moiety of gamma-glutamylcysteine, exhibits antioxidant activity by increasing GSH production. This therapeutic has protective effects against oxidative stress through the elevation of glutathione. Methods: This study investigates the enzymatic activities of several key energy-related proteins that have been identified as nitrated in treated Wistar rats with moderate TBI. To test the hypothesis that the elevation of GSH production upon administration of GCEE will normalize enzymatic activity post-TBI, adult male Wistar rats were equally divided into three groups: sham, saline, and GCEE. Rats were treated with 150 mg/kg saline or GCEE at 30 and 60 min post-TBI. Upon sacrifice, brains were harvested and enzymatic activity was measured spectrophotometrically. Results: An increase in enzymatic activity upon GSH elevation via GCEE administration in several key enzymes was observed. Conclusions: GCEE is a potential therapeutic strategy to restore energy-related proteins in the brain post-TBI via GSH elevation. Full article

During the grain and cereal production process, whether during harvesting, processing, or storage, errors can occur, compromising product quality and potentially leading to contamination by fungi, which produce toxic substances known as mycotoxins. When fed to animals, these contaminated grains and cereals can cause several negative effects on animal health, impacting their production performance, including immunosuppression, hepatotoxicity, nephrotoxicity, and reproductive problems. To minimize the problems caused by mycotoxins, anti-mycotoxin additives, also known as adsorbents, are used. These are inert materials that bind to mycotoxins and are excreted in feces, preventing their action within the animal’s body. Therefore, the objective of this study was to evaluate the effectiveness of an anti-mycotoxin product based on bentonite, activated charcoal, milk thistle extract, and yeast cell wall in the diet of mycotoxin-contaminated lambs on animal health and performance. Thirty lambs were divided into three homogeneous groups: control (without mycotoxins or additives), mycotoxin (with mycotoxins), and anti-mycotoxin (mycotoxins and additive). The mycotoxins used for feed contamination were aflatoxin (AFLA) (200 ppb), fumonisin (FUMO) (15 ppm), zearalenone (ZEA) (500 ppb), and deoxynivalenol (DON) (1.5 ppm). The anti-mycotoxin additive was used at a dose of 1 kg/ton of concentrate. Parameters of zootechnical performance, hematological profile, serum biochemistry, and oxidative status were evaluated. The group that ingested the contaminated concentrate with mycotoxin had a lower average daily weight gain (ADG) when compared to the control and anti-mycotoxin groups. Ingestion of a mycotoxin-contaminated diet increased the activity of aspartate aminotransferase and gamma-glutamyltransferase, which are indicators of liver damage. However, when the anti-mycotoxin additive was used, the increase in these enzymes was modest and lower than in the mycotoxin group. Ingestion of a mycotoxin-containing concentrate increased levels of oxidative stress biomarkers such as reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), myeloperoxidase (MPO), and reduced glutathione (GST), demonstrating that the mycotoxin challenge was effective in causing oxidative stress. However, when the diet was contaminated with mycotoxins and supplemented with the anti-mycotoxin additive, the levels of ROS and TBARS were similar to those of the negative control group. We concluded that adding the anti-mycotoxin product to the lambs’ diets prevented or minimized the problems caused by mycotoxin consumption, allowing these lambs to have ADG, and feed efficiency similar to the control group. Full article

In producing docosahexaenoic acid (DHA) with Schizochytrium sp., the production yield of DHA can be effectively increased through using hydrogen peroxide (H₂O₂) and controlling its concentration at the desired level, since H₂O₂ is a common regulatory mediator for lipid accumulation in oleaginous microorganisms. However, when exposed to the environment of oxidative stress induced by the long-term exogenous addition of H₂O₂ over an extended time span, cells’ metabolic activity would be gradually decreased or even stopped, which ultimately results in a limited duration for producing DHA efficiently. In fact, the severe accumulation of ROS cannot be avoided when implementing the normal DHA fermentation batch without the use of exogenous H₂O₂ because of the necessity of supplying a mass of oxygen for cell respiration. Aiming to overcome these issues, a novel periodic feeding strategy for H₂O₂ and p-aminobenzoate was proposed, and the underlying principle of this strategy is that the substantial harm inflicted on cells due to their continuous exposure to the oxidative stress environment can be effectively alleviated through the implementation of a recovery treatment (p-aminobenzoate, reducing agent) subsequent to the environmental stimulus. When using this strategy, it was achieved that, concurrently, activities of the vital enzymes participating in lipid biosynthesis were maintained at their maximum levels and the maintenance coefficient of glucose reduced to its minimum level (0.0034 1/h vs. 0.0027 1/h) by controlling ROS concentration at lower and desired levels, and thus DHA concentration reached the maximum value of 1.49 ± 0.20 g/L, with a 49% increase compared to the control group. Full article

Effective intervention on oxidative damage of bovine mammary epithelial cells (bMECs) is particularly important for reducing the incidence rate of mastitis. As a natural antioxidant, resveratrol (RES) can scavenge ROS, protecting cells from oxidative damage. However, the role of RES in bMECs and its potential protective mechanism have not been fully elucidated. Our results indicated that RES alleviated oxidative damage and enhanced antioxidant capacity in bMECs. Furthermore, RES increased SIRT5 expression and interacted with SIRT5, which attenuated cellular oxidative stress, inflammatory response and autophagy activity. Interestingly, SIRT5 and RES further improved mitochondrial dysfunction by increasing intracellular NADPH and GSH levels. Meanwhile, RES activated SIRT5 to regulate enzymatic activity of SDH and IDH2, which were important enzymes for producing intracellular ATP and antioxidants. RES specifically activated SIRT5 to attenuate the succinylation levels of intracellular IDH2 associated with interacting with SIRT5. Collectively, these outcomes revealed that RES might function as an activator of SIRT5 to attenuate oxidative damage of bMECs via activating SIRT5-IDH2 axis, resulting in increased GSH and NADPH production. Therefore, RES may be useful to prevent and control bovine mastitis by relieving oxidative damage. Full article

Hydrogen sulfide (H₂S), nitric oxide (NO), and carbon monoxide (CO) are now recognized as key gasotranmitters that regulate vascular function, contributing to vasodilation, angiogenesis, inflammation control, and oxidative balance. Initially regarded as toxic gases, they are produced on demand by specific enzymes, including cystathionine γ-lyase (CSE), endothelial nitric oxide synthase (eNOS), and heme oxygenase-1 (HO-1). Their activity is tightly controlled by redox-sensitive pathways. Reactive oxygen species (ROS), particularly superoxide and hydrogen peroxide, modulate gasotransmitter biosynthesis at the transcriptional and post-translational levels. Moreover, ROS affect gasotransmitter availability through oxidative modifications, including thiol persulfidation, nitrosative signaling, and carbonylation. This redox regulation ensures a tightly coordinated response to environmental and metabolic cues within the vascular system. This review synthesizes the current understanding of redox–gasotransmitter interactions, highlighting how ROS modulate the vascular roles of H₂S, NO, and CO. Understanding these interactions provides critical insights into the pathogenesis of cardiovascular diseases and offers potential redox-targeted therapies. Full article

Oxidative stress, a state resulting from an imbalance between the generation of reactive oxygen species (ROS) and the body’s antioxidant capacity, is a significant contributor to the development of various human pathologies, including malignancies, cardiovascular conditions, neurodegenerative disorders, and the aging process. Antioxidants, both enzymatic and non-enzymatic, are vital in neutralizing free radicals and protecting against cellular damage. Given the limitations of synthetic antioxidants, such as potential toxicity and variable effectiveness, there has been a growing focus on biotechnological methods for producing these essential compounds. This review, titled “Engineering Antioxidants with Pharmacological Applications: Biotechnological Perspectives”, explores the latest developments in this field by examining how biological systems are being utilized to create a wide range of antioxidants. We discuss key production strategies, including the use of microbial cell factories, enzyme-driven synthesis, plant cell cultures, and metabolic engineering. The review provides specific examples of biotechnologically derived antioxidants, such as enzymatic defenses like superoxide dismutase, catalase, and glutathione peroxidase, as well as non-enzymatic molecules like carotenoids, polyphenols, and vitamins. We also evaluate the therapeutic potential of these bio-engineered antioxidants, analyzing preclinical and clinical data on their effectiveness in disease prevention and treatment. The mechanisms by which these compounds combat oxidative stress are also discussed. Finally, we address the current hurdles in scaling up production and managing costs while also outlining future research avenues, such as the creation of new production systems, advanced delivery technologies, and the discovery of novel antioxidant compounds through bioprospecting and synthetic biology. This comprehensive review highlights the potential of biotechnology to offer sustainable and impactful solutions for managing oxidative stress and enhancing overall health. Full article

Drought is one of the major abiotic stresses threatening maize production globally. Under drought stress, maize plants produce excessive reactive oxygen species (ROS), leading to oxidative damage. The apoplast, as the site of substance and signal exchange between plant cells and the external environment, is an important location for the production of ROS under drought stress. Elucidating the ROS scavenging mechanisms in the apoplast is crucial for understanding plant stress responses. However, there is still a lack of research on the ROS scavenging enzymes in maize apoplast and their mediated signaling pathways. We verified that maize peroxidase Prx25 (ZmPrx25) is localized in the apoplast, it scan scavenge hydrogen peroxide (H₂O₂), and we systematically investigated the responses of the apoplastic ZmPrx25-ROS system to osmotic stress. ROS accumulate in the apoplast of maize mesocotyl in response to osmotic stress and transmit the external osmotic stress signals from the apoplast to the inner cellular compartments. The expression of ZmPrx25 is highly upregulated in the meristematic regions of maize seedlings under osmotic and oxidative stress. Overexpression of ZmPrx25 in Arabidopsis promoted seed germination and plant growth, significantly enhancing tolerance to osmotic and oxidative stress. This study provides a new perspective on the role of Prx25 in scavenging ROS under drought stress. Full article