Search Results (10,837)

Background/Objectives: Myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide, driven largely by underlying coronary artery disease (CAD). Reactive oxygen species (ROS) and reactive nitrogen species (RNS) play pivotal mechanistic roles in endothelial dysfunction, atherosclerotic plaque progression, and subsequent cardiac injury. Excessive production of these reactive species disrupts cellular redox balance, promotes mitochondrial dysfunction, and accelerates vascular inflammation, ultimately contributing to plaque rupture and MI. This study aimed to investigate the mechanistic associations and clinical correlations of individual ROS and RNS markers in patients with MI. Methods: We conducted a case–control study including 86 patients with MI and 60 age- and sex-matched controls without cardiovascular disease, recruited from the Medina Cardiac Center in Saudi Arabia. The MI cohort was subdivided into ST-elevation MI (STEMI, n = 62) and non-ST-elevation MI (NSTEMI, n = 24) to explore potential differences in oxidative and nitrosative stress profiles. Serum levels of multiple ROS (including hydrogen peroxide, hydroxyl radical, and superoxide anion) and RNS (including nitric oxide and peroxynitrite) were quantified using validated fluorescence-based assays. Clinical and biochemical parameters, including lipid profiles, troponin, and left ventricular ejection fraction, were also assessed. Results: Most ROS and RNS markers were significantly elevated in MI patients compared to controls (p < 0.05), except for nitrogen dioxide. Moderate to strong positive correlations were observed between ROS/RNS levels and serum total cholesterol and LDL-cholesterol (p < 0.001). In contrast, weak or non-significant correlations were found between ROS/RNS markers and serum troponin or left ventricular ejection fraction. Both STEMI and NSTEMI subgroups demonstrated significantly higher oxidative and nitrosative stress levels compared to controls, with distinct patterns between the subtypes. Conclusions: This study underscores a mechanistic link between elevated ROS/RNS levels and myocardial infarction, supporting the importance of targeting oxidative and nitrosative pathways as potential therapeutic strategies. Full article

Parkinson’s disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra, and key pathways such as neuroinflammation, oxidative stress, and autophagy are believed to significantly contribute to the mechanisms of neurodegeneration. Calpain activation plays a critical role in neuroinflammation and neurodegeneration, as demonstrated by its impact on microglial activation, reactive oxygen species (ROS) production, and neuronal survival. In this study, we investigated the effects of calpain inhibition using calpeptin (CP) and calpain-2-specific inhibitors in cellular and murine models of neuroinflammation and PD. In BV2 microglial cells, LPS-induced production of pro-inflammatory cytokines (TNF-α, IL-6) and chemokines (MCP-1, IP-10) were significantly reduced by CP treatment with a concomitant decrease in ROS generation. Similarly, in VSC-4.1 motoneuron cells, calpain inhibition attenuated IFN-γ-induced ROS production and improved cell viability, demonstrating its neuroprotective effects. Moreover, in a murine MPTP model of PD, calpain inhibition reduced astrogliosis, ROCK2 expression, and levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-7, and IL12p70) and chemokines (MCP-1 and IP-10) in the dorsal striatum and plasma. The specific role of calpain-2 in immune modulation was further highlighted in human microglia, SV-40 cells. With respect to immune modulation in these cells, siRNA-mediated knockdown of calpain-2, but not calpain-1, significantly reduced antigen presentation to CD4+ T cells. Thus, calpain-2 is likely involved in regulating antigen presentation and activation of inflammatory CD4+ T cells. These findings underscore the therapeutic potential of calpain-2 inhibition in mitigating neuroinflammation and neurodegeneration, particularly in PD, by targeting microglial activation, ROS production, and neuronal survival pathways. Full article

Background: Reactive oxygen species (ROS) generated due to mitochondrial dysfunction are one of the primary causes of the initiation and progression of senescence. Although reducing mitochondrial ROS production is known as an effective strategy for the treatment of aging, effective components that reduce mitochondrial ROS production or effective treatments that utilize them have not yet been developed. Methods: Screening of plant-generated secondary metabolites to overcome ROS-mediated stress found that ε-viniferin, a dimer of resveratrol, effectively reduces mitochondrial ROS production. Results: ε-viniferin induced efficient electron transport and reduced mitochondrial ROS, a consequence of inefficient electron transport. In addition, ε-viniferin acted as a senolytic that selectively eliminates senescent fibroblasts, thereby restoring mitochondrial function and senescence-associated phenotypes. RNA sequencing analysis revealed that regulator of G protein signaling 16 (RGS16) was an important gene for ε-viniferin-mediated senescence rejuvenation. Upregulation of RGS16 showed similar effects as ε-viniferin in reducing mitochondrial ROS production and restoring mitochondrial function. Conclusions: This study discovered a novel mechanism by which ε-viniferin rejuvenates senescence by lowering ROS production in mitochondria. The novel mechanism will serve as a basis for developing therapeutics that regulate mitochondrial ROS production to treat aging. Full article

Zearalenone (ZEA) is a widely distributed estrogenic mycotoxin that can disrupt intestinal barrier integrity by inducing ferroptosis, thereby posing serious risks to animal health. Curcumin (CUR), as a natural polyphenolic compound with multi-target regulatory properties, has attracted increasing attention for its antioxidative and cytoprotective effects; however, its role in ZEA-induced ferroptosis remains poorly understood. In this study, the protective effects of curcumin (CUR) were evaluated in IPEC-J2 cells by co-treating the cells with zearalenone (ZEA) at its LC₅₀ (75.23 μM) and curcumin (5 or 15 μM) for 24 h. CCK-8 assays showed that CUR significantly (p < 0.05) and highly significantly (p < 0.01) improved cell viability in the 5 μM and 15 μM groups, respectively, compared with ZEA alone. CUR co-treatment significantly (p < 0.01) restored glutathione (GSH) levels, and markedly (p < 0.01) reduced Fe²⁺ accumulation, reactive oxygen species (ROS) production, malondialdehyde (MDA) content, and lipid peroxidation (LPO). Transmission electron microscopy revealed pronounced mitochondrial cristae loss and membrane collapse in ZEA-treated cells, which were visibly alleviated by CUR. At the molecular level, ZEA downregulated GPX4 and SLC7A11 and upregulated ACSL4, FTH1, and p53 (all p < 0.01), whereas these changes were significantly reversed (p < 0.05 or p < 0.01) by CUR. In conclusion, CUR exerts cytoprotective effects against ZEA-induced ferroptosis, likely via modulation of the p53/SLC7A11/GPX4 signaling pathway. Full article

Rheumatoid arthritis (RA) is one of the most common chronic autoimmune diseases which global prevalence is approximately 0.3–2%. Numerous studies provide evidence that the elevated levels of reactive oxygen species (ROS) contribute to the pathogenesis and progression of RA. In response to redox imbalance, several intrinsic antioxidant defence mechanisms are activated to counteract oxidative stress and scavenge ROS. The aim of the present study is to analyse whether the levels of lactoferrin and thioredoxin, two proteins which are part of the antioxidant defence of the body, are associated with fibrinogen and other acute phase proteins such as CRP and ferritin in RA. Serum lactoferrin, thioredoxin, ferritin, and CRP levels were measured using ELISA. Significant positive correlations of lactoferrin and thioredoxin with fibrinogen were observed in RA patients, r = 0.394, p < 0.0001 and r = 0.410, p = 0.002, respectively. These positive correlations were also observed in females, r = 0.375, p < 0.0001 and r = 0.447, p = 0.001, in the subgroup of patients with DAS28 < 5.1, r = 0.689, p < 0.0001 and r = 0.604, p = 0.001 and in the subgroup of patients with normal CRP, r = 0.488, p < 0.0001 and r = 0.414, p = 0.005, respectively. These findings help clarify the pathogenetic interplay between oxidative stress, inflammation, and coagulation in RA and indicate the need for further studies to elucidate the potential of lactoferrin and thioredoxin as biomarkers that capture pathological disease changes. Full article

Ultrahigh dose rate (UHDR) radiotherapy, also known as FLASH radiotherapy (FLASH-RT), has shown potential for increasing tumor control while sparing normal tissue. In parallel, gold nanoparticles (GNPs) have been extensively explored as radiosensitizers due to their high atomic number and ability to enhance the generation of reactive oxygen species (ROS) through water radiolysis. In this study, we investigate the synergistic effects of UHDR electron beams and GNP-mediated radiosensitization using Monte Carlo (MC) simulations based on the Geant4-DNA code. A spherical water phantom with embedded GNPs of varying sizes (5–100 nm) was irradiated using pulsed electron beams (100 keV and 1 MeV) at dose rates of 60, 100, and 150 Gy/s. The chemical yield of ROS near the GNPs was quantified and compared to an equivalent water nanoparticle model, and the yield enhancement factor (YEF) was used to evaluate radiosensitization. Results demonstrated that YEF increased with smaller GNP sizes and at lower UHDR, particularly for 1 MeV electrons. A maximum YEF of 1.25 was observed at 30 nm from the GNP surface for 5 nm particles at 60 Gy/s. The elevated ROS concentration near GNPs under FLASH conditions is expected to intensify DNA damage, especially double-strand breaks, due to increased hydroxyl radical interactions within nanometric distances of critical biomolecular targets. These findings highlight the significance of nanoparticle size and beam parameters in optimizing ROS production for FLASH-RT. The results provide a computational basis for future experimental investigations into the combined use of GNPs and UHDR beams in nanoparticle-enhanced radiotherapy. Full article

The structures of the developing eye may be damaged as a result of the impact of reactive oxygen species (ROS) interacting with different cellular components. The antioxidant molecules found in the eye, especially in the vitreous body—the largest component of the eye, playing a crucial role in the formation of structures and functions of the developing eye—provide protection to the eye tissues from ROS. This review considers various antioxidant molecules (ascorbic acid, lutein, bilirubin, uric acid, catecholamines, erythropoietin, albumin, and alpha-fetoprotein) that have been found in the human vitreous body during the early stages of pregnancy (10–31 weeks of gestation) and their functions in the development of the eye. The presence of some molecules is transient (lutein, AFP), whereas a temporal decrease (albumin, bilirubin) or increase (ascorbic acid, erythropoietin) in the concentrations of other antioxidants is observed. Since the actual overall content of antioxidants in the developing vitreous body is probably much higher than that found to date, further research is needed to study antioxidants there. It is especially important to study the antioxidant status of the vitreous body at the earliest stages of its development. Antioxidants found suggest their use for the prophylactic of ocular diseases during pregnancy and finding new antioxidants could create an additional opportunity in this regard. Full article

This review aims to provide a comprehensive overview of how oxidative stress drives inflammation, structural remodeling, and clinical expression of childhood asthma, while critically appraising emerging redox-sensitive biomarkers and antioxidant-focused preventive and therapeutic strategies. Oxidative stress arises when reactive oxygen species (ROS) and reactive nitrogen species (RNS) outpace airway defenses. This surplus provokes airway inflammation: ROS/RNS activate nuclear factor kappa-B (NF-κB) and activator protein-1 (AP-1), recruit eosinophils and neutrophils, and amplify type-2 cytokines. Normally, an antioxidant network—glutathione (GSH), enzymes such as catalase (CAT) and superoxide dismutase (SOD), and nuclear factor erythroid 2-related factor 2 (Nrf2)—maintains redox balance. Prenatal and early exposure to fine particulate matter <2.5 micrometers (µm) (PM_2.5), aeroallergens, and tobacco smoke, together with polymorphisms in glutathione S-transferase P1 (GSTP1) and CAT, overwhelm these defenses, driving epithelial damage, airway remodeling, and corticosteroid resistance—the core of childhood asthma pathogenesis. Clinically, biomarkers such as exhaled 8-isoprostane, hydrogen peroxide (H₂O₂), and fractional exhaled nitric oxide (FeNO) surge during exacerbations and predict relapses. Therapeutic avenues include Mediterranean-style diet, regular aerobic exercise, pharmacological Nrf2 activators, GSH precursors, and mitochondria-targeted antioxidants; early trials report improved lung function and fewer attacks. Ongoing translational research remains imperative to substantiate these approaches and to enable the personalization of therapy through individual redox status and genetic susceptibility, ultimately transforming the care and prognosis of pediatric asthma. Full article

Drought stress poses a significant threat to tree growth, making the development of drought-resistant species essential for ecological restoration. WRKY transcription factors are critical regulators of plant drought responses; however, the role of WRKY22 in the woody species Populus ussuriensis K. remains unclear. In this study, the PuWRKY22 gene was cloned from P. ussuriensis via homologous cloning and was found to be highly expressed in leaves and responsive to abscisic acid (ABA) signaling. Subcellular localization confirmed that PuWRKY22 is a nuclear protein. Using fluorescein enzyme complementation assays, PuWRKY22 was shown to bind specifically to W-box cis-elements, indicating its function as a transcriptional regulator. Under ABA and osmotic (sorbitol) stress, the seed germination rate, root growth, and biomass of tobacco and Populus davidiana × Populus bolleana strains overexpressing PuWRKY22 were significantly increased. Additionally, these overexpressed strains exhibited a reduction in reactive oxygen species (ROS) accumulation and a decrease in membrane lipid peroxidation. Transcriptomic analyses revealed that PuWRKY22 activates expression of the ABA receptor gene Ptr.PYL4 (Potri.006G104100.v4.1), which regulates stomatal closure to minimize water loss. Consistent with this, stomatal observations and photosynthetic measurements demonstrated that PuWRKY22 enhances drought tolerance by protecting photosystem II and preserving chlorophyll content. Collectively, this study elucidates the molecular mechanism by which PuWRKY22 enhances drought resistance in woody plants through ABA signaling, providing a foundation for breeding drought-tolerant forest species. Full article

Glucose functions as both an essential energy source and a critical signaling molecule, playing pivotal roles in regulating plant growth, development, and stress responses. Here, we report that AtCHYR1, a previously characterized RING-type ubiquitin E3 ligase involved in drought tolerance, also participates in glucose signaling. Exposure to high glucose levels significantly inhibits AtCHYR1 expression, particularly in root tips, while low glucose conditions, such as osmotic stress, sugar starvation, and dark conditions, induce its expression. Importantly, analysis of chyr1 mutants and plants overexpressing AtCHYR1 revealed that AtCHYR1 positively regulated the high glucose-mediated inhibition of germination and root growth, as well as starvation-induced growth retardation, through enhanced reactive oxygen species (ROS) accumulation in root tips. Additionally, transcriptional levels of glucose-activated pathogenesis-related (PR) and defense-related genes were reduced, while hypoxia-associated and ROS-inducing genes were significantly upregulated in AtCHYR1-overexpressing plants. Collectively, our findings provide novel insights into the role of AtCHYR1 in plant responses to fluctuating sugar availability and its control of ROS homeostasis during seed germination and plant growth. Full article

Antioxidants have drawn much interest owing to their capacity to shield the human body from reactive oxygen species (ROS). Therefore, it is essential to develop a quick and easy assay for the evaluation of antioxidants and for imaging their distribution in food. Herein, we describe a fluorescence measurement platform for assessing and visualizing antioxidant capacity. Our method is based on using the composite of graphene quantum dots (GQDs) with Fe³⁺ (Fe³⁺-GQDs) as a reagent for evaluating and imaging the antioxidant capacity in foods using a fluorescence turn-off–on strategy. The fluorescence of GQDs was found to be selectively quenched with Fe³⁺ at pH 3.5. Upon addition of an antioxidant, Fe³⁺ is reduced to Fe²⁺, and the fluorescence of GQDs is regained. Next, we investigated the fluorescence intensity after the reaction of Fe³⁺-GQDs with seven typical antioxidants, and it showed excellent sensitivity down to 0.60 µM of antioxidant. Next, using Fe³⁺-GQDs as a reagent, we developed a paper-based fluorescence imaging method for antioxidants in foods. Furthermore, we analyzed the distribution of antioxidant capacity on cucumber and carrot slices (tips, central parts, and shoulders). Next, the antioxidant capacity of cucumber and carrot slice extracts was measured, and the results were consistent with the fluorescence imaging results of the intact slices. Full article

Green mold formed by Penicillium digitatum is a major disease that limits the yield and overall value of postharvest citrus fruits. The antifungal activity of sodium cuminate (SC) against P. digitatum and the corresponding mechanism were explored in this research. The minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) of SC against P. digitatum were 0.4 and 0.8 g L⁻¹, respectively. SC (8 × MFC) reduced the incidence of disease in Ponkan fruits without compromising their quality. The results of CFW staining and extracellular alkaline phosphatase assays revealed that 1/2MIC SC for 30 min had no impact on the cell wall integrity of P. digitatum. In contrast, 1/2MIC SC apparently destroyed cell membrane integrity, as shown by the increase in the content of reactive oxygen species (ROS), malondialdehyde, and H₂O₂. The addition of exogenous cysteine (Cys) or diphenyleneiodonium chloride (DPI) significantly mitigated the cytotoxic effects of SC. At the same time, mitochondrial membrane potential was significantly decreased by 1/2MIC SC, and the addition of exogenous Cys or DPI restored it to normal levels. In summary, the antifungal capacity of SC might be attributable to membrane damage in P. digitatum caused by oxidative stress. Full article

The internal mammary arteries (IMAs) and coronary arteries share many common characteristics. The inner layer (tunica intima, or intima) of both arteries is lined with a smooth, longitudinally orientated monolayer of endothelial cells (ECs), connective tissue, and an internal elastic lamina that separates the tunica intima from the tunica media (middle layer). The intima of IMAs is lined with an additional protective layer, the neointima, containing vascular smooth muscle cells (VSMCs). The neointima, located between the intima and internal elastic lamina, protects IMAs from damage by assisting in the remodeling of VSMCs. Coarse longitudinal folds in the internal elastic lamina of IMAs partially prevent the infiltration of VSMCs into damaged IMAs, and intimal thickening is thus less likely to occur. Inflamed IMAs resist the migration of monocytes across the endothelial layer and prevent the formation of lipid-rich macrophages (foam cells) within the subintimal or medial layers of arteries. IMAs are thus less likely to form plaques and develop atherosclerosis (AS). Higher levels of prostacyclin (PGI2) in IMAs prevent blood clotting. The anti-thrombotic agents, and production of tumor necrosis factor α (TNF-α), interferon-γ (INF-γ), and visfatin render IMAs more resistant to inflammation. An increase in the production of nitric oxide (NO) by ECs of IMAs may be due to small ubiquitin-like modifier (SUMO) proteins that alter the nuclear factor kappa B (NF-κB) and TLR pathways. The production of reactive oxygen species (ROS) in IMAs is suppressed due to the inhibition of NADPH oxidase (NOX) by a pigment epithelium-derived factor (PEDF), which is a serine protease inhibitor (SERPIN). In this review, a comparison is drawn between the anatomy of IMAs and coronary arteries, with an emphasis on how ECs of IMAs react to immunological changes, rendering them more suited for coronary artery bypass grafts (CABGs). This narrative review covers the most recent findings published in PubMed and Crossref databases. Full article

Bovine endometritis can be caused by Escherichia coli (E. coli), from which the lipopolysaccharide (LPS) triggers TLR4/NF-κB-mediated inflammation and reactive oxygen species (ROS) overproduction, resulting in impaired reproductive performance. While NADPH oxidase (NOX) is a critical source of ROS generation, its role in bovine endometrial epithelial cells (BEEC) and modulation by selenium remains unexplored. In this study, primary BEEC was challenged by LPS to assess NOX2/4 expression kinetics. Inhibitors of NOX and NF-κB were applied to observe the role of NOX-derived ROS in BEEC inflammation and in selenomethionine (SeMet)-modulated anti-inflammation. ROS levels were measured by flow cytometry. The changes in inflammatory cytokines, and the proteins related to NOX4 and NF-κB, were analyzed via qPCR and Western blot. As a result, the inhibition of NOX decreased LPS-induced proinflammatory cytokine expression, ROS accumulation, NOX4 level, and the phosphorylation of NF-κB P65 and IκBα. Conversely, the suppression of NF-κB downregulated the levels of ROS and NOX4. Cotreatment with SeMet and a NOX inhibitor further suppressed the inflammatory response, ROS level, and NF-κB pathway activation compared to individual treatment, but had no additive effect on the NOX4 protein level. In conclusion, the NOX4/ROS/NF-κB axis forms a proinflammatory feedback loop in LPS-stimulated BEEC. SeMet mitigates oxidative stress and inflammation partially through NOX4 inhibition. Full article

In the pursuit of novel anticancer therapies, assessing their selectivity and safety profile towards healthy cells is crucial. This study investigated chlorochalcones, derivatives of 2′-hydroxychalcone containing a chlorine atom, for their impact on human breast cancer cells (MCF-7 and MDA-MB-231), healthy blood cells (erythrocytes, peripheral blood mononuclear cells (PBMCs), platelets), and microvascular endothelial cells (HMEC-1). Our findings demonstrated that chlorochalcones did not detrimentally affect erythrocytes, showing no hemolysis or preserving osmotic resistance and transmembrane potential. They also exhibited minimal impact on normal PBMC viability and varying effects on platelet metabolic activity at therapeutic concentrations. Importantly, these derivatives displayed lower toxicity towards HMEC-1 endothelial cells than towards breast cancer cells, indicating a degree of selectivity. Chlorochalcones have high antiproliferative activity against cancer cells, primarily by inducing apoptosis with virtually no significant impact on cell cycle progression. Their mechanism of action involves the modulation of reactive oxygen species (ROS) levels and induction of mitochondrial dysfunction, including membrane depolarization and reduced mitochondrial mass. Biological activity, including toxicity and ROS modulation, is dependent on the position and number of chlorine atoms. In conclusion, this study highlights the ability of chlorochalcones to effectively target malignant cells while sparing normal circulatory and endothelial cells, thus positioning them as a promising class of candidates for further anticancer drug development. Full article