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Keywords = antioxidative defenses

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12 pages, 441 KiB  
Article
Cytokine Regulation and Oxidative Stress in Helicobacter Pylori-Associated Gastric Adenocarcinoma at Different Stages: Insights from a Cross-Sectional Study
by Olga Smirnova, Aleksander Sinyakov and Eduard Kasparov
Int. J. Mol. Sci. 2025, 26(15), 7609; https://doi.org/10.3390/ijms26157609 (registering DOI) - 6 Aug 2025
Abstract
Gastric adenocarcinoma is a malignant tumor that develops from the glandular cells of the inner wall of the stomach. The prevalence of this type of disease varies from 90 to 95% of all types of gastric cancer. The aim of our study was [...] Read more.
Gastric adenocarcinoma is a malignant tumor that develops from the glandular cells of the inner wall of the stomach. The prevalence of this type of disease varies from 90 to 95% of all types of gastric cancer. The aim of our study was to investigate the differences in the content of cytokines and oxidative stress markers in patients with gastric adenocarcinoma associated with H. pylori infection depending on the stage. The study included 281 patients with gastric cancer. At stage I of the disease—75 people, stage II—70 people, stage III—69 people, and stage IV of the disease—67 people. The levels of TNF-α, IL-2, IL-8, IFNγ, TNF-β, IL-17A, IL-6, IL-10, and IL-4 in the blood serum of patients and healthy individuals were determined by enzyme immunoassay and plasma oxidative stress scores (MDA, SOD, CAT, GST, GPO, CP). The present study revealed that H. pylori-infected gastric adenocarcinoma at different stages is associated with different plasma levels of cytokines, lipid peroxidation products, and antioxidant defense factors. Further studies are needed to evaluate the effectiveness of therapeutic strategies combining cytokine regulation and oxidative stress to improve clinical outcomes in gastric cancer. Full article
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19 pages, 1080 KiB  
Article
Microplastic Bioaccumulation and Oxidative Stress in Key Species of the Bulgarian Black Sea: Ecosystem Risk Early Warning
by Albena Alexandrova, Svetlana Mihova, Elina Tsvetanova, Madlena Andreeva, Georgi Pramatarov, Georgi Petrov, Nesho Chipev, Valentina Doncheva, Kremena Stefanova, Maria Grandova, Hristiyana Stamatova, Elitsa Hineva, Dimitar Dimitrov, Violin Raykov and Petya Ivanova
Microplastics 2025, 4(3), 50; https://doi.org/10.3390/microplastics4030050 - 6 Aug 2025
Abstract
Plastic pollution in marine environments poses a new global threat. Microplastics (MPs) can bioaccumulate in marine organisms, leading to oxidative stress (OS). This study investigates MP accumulation and associated OS responses in six invertebrate species (Bivalvia, Gastropoda, and Malacostraca) and three key fish [...] Read more.
Plastic pollution in marine environments poses a new global threat. Microplastics (MPs) can bioaccumulate in marine organisms, leading to oxidative stress (OS). This study investigates MP accumulation and associated OS responses in six invertebrate species (Bivalvia, Gastropoda, and Malacostraca) and three key fish species of the Bulgarian Black Sea ecosystems. The target hydrobionts were collected from nine representative coastal habitats of the northern and southern aquatory. MPs were quantified microscopically, and OS biomarkers (lipid peroxidation, glutathione, and antioxidant enzymes) were analyzed spectrometrically in fish liver and gills and invertebrate soft tissues (STs). The specific OS (SOS) index was calculated as a composite indicator of the ecological impact, incl. MP effects. The results revealed species-specific MP bioaccumulation, with the highest concentrations in Palaemon adspersus, Rathke (1837) (0.99 ± 1.09 particles/g ST) and the least abundance in Bittium reticulatum (da Costa, 1778) (0.0033 ± 0.0025 particles/g ST). In Sprattus sprattus (Linnaeus, 1758), the highest accumulation of MPs was present (2.01 ± 2.56 particles/g muscle). The correlation analyses demonstrated a significant association between MP counts and catalase activity in all examined species. The SOS index varied among species, reflecting different stress responses, and this indicated that OS levels were linked to ecological conditions of the habitat and the species-specific antioxidant defense potential to overcome multiple stressors. These findings confirmed the importance of environmental conditions, including MP pollution and the evolutionarily developed capacity of marine organisms to tolerate and adapt to environmental stress. This study emphasizes the need for novel approaches in monitoring MPs and OS to better assess potential ecological risks. Full article
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20 pages, 8344 KiB  
Article
Gum Acacia–Dexamethasone Combination Attenuates Sepsis-Induced Acute Kidney Injury in Rats via Targeting SIRT1-HMGB1 Signaling Pathway and Preserving Mitochondrial Integrity
by Fawaz N. Alruwaili, Omnia A. Nour and Tarek M. Ibrahim
Pharmaceuticals 2025, 18(8), 1164; https://doi.org/10.3390/ph18081164 - 5 Aug 2025
Abstract
Background/Objective: Sepsis-associated acute kidney injury (SA-AKI) is a substantial contributor to mortality in critically ill patients. This study aimed to investigate the impact of gum acacia (GA) and dexamethasone (DEX) combination on lipopolysaccharide (LPS)-induced SA-AKI in rats. Methods: Thirty-six male Sprague Dawley [...] Read more.
Background/Objective: Sepsis-associated acute kidney injury (SA-AKI) is a substantial contributor to mortality in critically ill patients. This study aimed to investigate the impact of gum acacia (GA) and dexamethasone (DEX) combination on lipopolysaccharide (LPS)-induced SA-AKI in rats. Methods: Thirty-six male Sprague Dawley rats were separated into six groups, including the control, GA group, LPS-induced AKI group, DEX + LPS group, GA + LPS group, and GA + DEX + LPS group. AKI was induced in rats using LPS (10 mg/kg, i.p.). GA was administered orally (7.5 g/kg) for 14 days before LPS injection, and DEX was injected (1 mg/kg, i.p.) 2 h after LPS injection. Results: LPS injection significantly (p < 0.05, vs. control group) impaired renal function, as evidenced through increased levels of kidney function biomarkers, decreased creatinine clearance, and histopathological alterations in the kidneys. LPS also significantly (p < 0.05, vs. control group) elevated levels of oxidative stress markers, while it reduced levels of antioxidant enzymes. Furthermore, LPS triggered an inflammatory response, manifested by significant (p < 0.05, vs. control group) upregulation of Toll-like receptor 4, myeloid differentiation primary response 88, interleukin-1β, tumor necrosis factor-α, and nuclear factor-κB, along with increased expression of high-mobility group box 1. Administration of GA significantly ameliorated LPS-induced renal impairment by enhancing antioxidant defenses and suppressing inflammatory pathways (p < 0.05, vs. LPS group). Furthermore, GA-DEX-treated rats showed improved kidney function, reduced oxidative stress, and attenuated inflammatory markers (p < 0.05, vs. LPS group). Conclusions: The GA-DEX combination exhibited potent renoprotective effects against LPS-induced SA-AKI, possibly due to their antioxidant and anti-inflammatory properties. These results suggest that the GA-DEX combination could be a promising and effective therapeutic agent for managing SA-AKI. Full article
(This article belongs to the Section Pharmacology)
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51 pages, 2918 KiB  
Review
Therapeutic Applications and Mechanisms of Superoxide Dismutase (SOD) in Different Pathogenesis
by Shehwaz Anwar, Tarique Sarwar, Amjad Ali Khan and Arshad Husain Rahmani
Biomolecules 2025, 15(8), 1130; https://doi.org/10.3390/biom15081130 - 5 Aug 2025
Abstract
An imbalance between the generation of reactive oxygen species (ROS) and antioxidant defenses is known as oxidative stress, and it is implicated in a number of diseases. The superoxide radical O2– is produced by numerous biochemically relevant redox processes and is thought [...] Read more.
An imbalance between the generation of reactive oxygen species (ROS) and antioxidant defenses is known as oxidative stress, and it is implicated in a number of diseases. The superoxide radical O2– is produced by numerous biochemically relevant redox processes and is thought to play role in diseases and pathological processes, such as aging, cancer, membrane or DNA damage, etc.; SOD, or superoxide dismutase, is essential for reducing oxidative stress. As a result, the elimination of ROS by SOD may be a useful disease prevention tactic. There have been reports of protective effects against neurodegeneration, apoptosis, carcinogenesis, and radiation. Exogenous SODs’ low bioavailability has drawn criticism. However, this restriction might be removed, and interest in SOD’s medicinal qualities increased with advancements in its formulation. This review discusses the findings of human and animal studies that support the benefits of SOD enzyme regulation in reducing oxidative stress in various ways. Additionally, this review summarizes contemporary understandings of the biology of Cu/Zn superoxide dismutase 1 (SOD1) from SOD1 genetics and its therapeutic potential. Full article
(This article belongs to the Topic Enzymes and Enzyme Inhibitors in Drug Research)
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18 pages, 1602 KiB  
Article
Interacting Effects of Heat and Nanoplastics Affect Wheat (Triticum turgidum L.) Seedling Growth and Physiology
by Debora Fontanini, Stefania Bottega, Monica Ruffini Castiglione and Carmelina Spanò
Plants 2025, 14(15), 2426; https://doi.org/10.3390/plants14152426 - 5 Aug 2025
Abstract
Nano- and microplastic pollution, together with the ongoing rise in global temperatures driven by climate change, represent increasingly critical environmental challenges. Although these stressors often co-occur in the environment, their combined effects on plant systems remain largely unexplored. To test the hypothesis that [...] Read more.
Nano- and microplastic pollution, together with the ongoing rise in global temperatures driven by climate change, represent increasingly critical environmental challenges. Although these stressors often co-occur in the environment, their combined effects on plant systems remain largely unexplored. To test the hypothesis that their interaction may exacerbate the effects observed under each stressor individually, we investigated the response of seedlings of Triticum turgidum to treatments with fluorescent polystyrene nanoplastics under optimal (25 °C) and elevated (35 °C) temperature conditions. We evaluated seedling growth, photosynthetic pigment content, and oxidative stress markers using both biochemical and histochemical techniques. In addition, we assessed enzymatic and non-enzymatic antioxidant responses. The use of fluorescently labeled nanoplastics enabled the visualization of their uptake and translocation within plant tissues. Elevated temperatures negatively affect plant growth, increasing the production of proline, a key protective molecule, and weakly activating secondary defense mechanisms. Nanoplastics disturbed wheat seedling physiology, with these effects being amplified under high temperature conditions. Combined stress enhances nanoplastic uptake in roots, increases oxidative damage, and alters antioxidant responses, reducing defense capacity in leaves while triggering compensatory mechanisms in roots. These findings underscore a concerning interaction between plastic pollution and climate warming in crop plants. Full article
(This article belongs to the Section Plant Physiology and Metabolism)
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18 pages, 8203 KiB  
Article
Puerarin Enhances Eggshell Quality by Mitigating Uterine Senescence in Late-Phase Laying Breeder Hens
by Zhenwu Huang, Guangju Wang, Mengjie Xu, Yanru Shi, Jinghai Feng, Minhong Zhang and Chunmei Li
Antioxidants 2025, 14(8), 960; https://doi.org/10.3390/antiox14080960 (registering DOI) - 5 Aug 2025
Abstract
The deterioration of uterine calcium transport capacity induced by aging is a common problem for late-laying period hens, causing decline in eggshell quality. This study aimed to investigate the effects and possible regulatory mechanisms of dietary puerarin (PU) on calcium transport and eggshell [...] Read more.
The deterioration of uterine calcium transport capacity induced by aging is a common problem for late-laying period hens, causing decline in eggshell quality. This study aimed to investigate the effects and possible regulatory mechanisms of dietary puerarin (PU) on calcium transport and eggshell quality in aged hens. Two hundred eighty-eight Hubbard Efficiency Plus broiler breeder hens (50-week-old) were randomly allocated to three dietary treatments containing 0, 40, or 200 mg/kg puerarin (PU), with 8 replicates of 12 birds each, for an 8-week trial. The results demonstrated that dietary PU ameliorated the eggshell thickness and strength, which in turn reduced the broken egg rate (p < 0.05). Histological analysis showed that PU improved uterus morphology and increased epithelium height in the uterus (p < 0.05). Antioxidative capacity was significantly improved via upregulation of Nrf2, HO-1, and GPX1 mRNA expression in the uterus (p < 0.05), along with enhanced total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-PX) activity, and decreased levels of the oxidative stress marker malondialdehyde (MDA) (p < 0.05). Meanwhile, PU treatment reduced the apoptotic index of the uterus, followed by a significant decrease in expression of pro-apoptotic genes Caspase3 and BAX and the rate of BAX/BCL-2. Additionally, calcium content in serum and uterus, as well as the activity of Ca2+-ATPase in the duodenum and uterus, were increased by dietary PU (p < 0.05). The genes involved in calcium transport including ERα, KCNA1, CABP-28K, and OPN in the uterus were upregulated by PU supplementation (p < 0.05). The 16S rRNA gene sequencing revealed that dietary PU supplementation could reverse the age-related decline in the relative abundance of Bacteroidota within the uterus (p < 0.05). Overall, dietary PU can improve eggshell quality and calcium transport through enhanced antioxidative defenses and mitigation of age-related uterine degeneration. Full article
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34 pages, 9516 KiB  
Article
Proteus sp. Strain JHY1 Synergizes with Exogenous Dopamine to Enhance Rice Growth Performance Under Salt Stress
by Jing Ji, Baoying Ma, Runzhong Wang and Tiange Li
Microorganisms 2025, 13(8), 1820; https://doi.org/10.3390/microorganisms13081820 - 4 Aug 2025
Abstract
Soil salinization severely restricts crop growth and presents a major challenge to global agriculture. In this study, a plant-growth-promoting rhizobacterium (PGPR) was isolated and identified as Proteus sp. through 16S rDNA analysis and was subsequently named Proteus sp. JHY1. Under salt stress, exogenous [...] Read more.
Soil salinization severely restricts crop growth and presents a major challenge to global agriculture. In this study, a plant-growth-promoting rhizobacterium (PGPR) was isolated and identified as Proteus sp. through 16S rDNA analysis and was subsequently named Proteus sp. JHY1. Under salt stress, exogenous dopamine (DA) significantly enhanced the production of indole-3-acetic acid and ammonia by strain JHY1. Pot experiments revealed that both DA and JHY1 treatments effectively alleviated the adverse effects of 225 mM NaCl on rice, promoting biomass, plant height, and root length. More importantly, the combined application of DA-JHY1 showed a significant synergistic effect in mitigating salt stress. The treatment increased the chlorophyll content, net photosynthetic rate, osmotic regulators (proline, soluble sugars, and protein), and reduced lipid peroxidation. The treatment also increased soil nutrients (ammoniacal nitrogen and available phosphorus), enhanced soil enzyme activities (sucrase and alkaline phosphatase), stabilized the ion balance (K+/Na+), and modulated the soil rhizosphere microbial community by increasing beneficial bacteria, such as Actinobacteria and Firmicutes. This study provides the first evidence that the synergistic effect of DA and PGPR contributes to enhanced salt tolerance in rice, offering a novel strategy for alleviating the adverse effects of salt stress on plant growth. Full article
(This article belongs to the Section Plant Microbe Interactions)
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24 pages, 4384 KiB  
Article
Untargeted Metabolomic Identifies Potential Seasonal Biomarkers of Semen Quality in Duroc Boars
by Notsile H. Dlamini, Serge L. Kameni and Jean M. Feugang
Biology 2025, 14(8), 995; https://doi.org/10.3390/biology14080995 (registering DOI) - 4 Aug 2025
Abstract
High semen quality is vital for reproductive success in the swine industry; however, seasonal fluctuations often compromise this quality. The molecular mechanism underlying these seasonal effects on semen quality remains largely unclear. This study employed untargeted metabolomic profiling of boar seminal plasma (SP) [...] Read more.
High semen quality is vital for reproductive success in the swine industry; however, seasonal fluctuations often compromise this quality. The molecular mechanism underlying these seasonal effects on semen quality remains largely unclear. This study employed untargeted metabolomic profiling of boar seminal plasma (SP) to identify metabolites and metabolic pathways associated with semen quality during the summer and winter months. Semen samples were collected from mature Duroc boars at a commercial boar stud and classified as Passed or Failed based on motility and morphology. SP from five samples per group was analyzed using ultra-high-performance liquid chromatography–mass spectrometry (UHPLC-MS). In total, 373 metabolites were detected in positive ion mode and 478 in negative ion mode. Several differentially expressed metabolites (DEMs) were identified, including ergothioneine, indole-3-methyl acetate, and avocadyne in the summer, as well as LysoPC, dopamine, and betaine in the winter. These metabolites are associated with key sperm functions, including energy metabolism, antioxidant defense, and capacitation. KEGG pathway analysis indicated enrichment in starch and sucrose metabolism, pyrimidine metabolism, and amino acid metabolism across the seasons. Overall, the results reveal that SP metabolomic profiles vary with the season, thereby influencing semen quality. The identified metabolites may serve as potential biomarkers for assessing semen quality and enhancing reproductive efficiency in swine production. Full article
(This article belongs to the Special Issue Reproductive Physiology and Pathology in Livestock)
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15 pages, 1820 KiB  
Article
Ozone Treatment Modulates Reactive Oxygen Species Metabolism Regulation and Enhances Storage Quality of Kiwifruit During Cold Storage
by Ziyu Jin, Jin Tan, Xinyu Zhang, Xin Li, Wenqiang Guan, Pu Liu and Aiqiang Chen
Horticulturae 2025, 11(8), 911; https://doi.org/10.3390/horticulturae11080911 (registering DOI) - 4 Aug 2025
Abstract
Fresh fruit are highly perishable commodities, facing significant postharvest losses primarily due to physiological deterioration and microbial spoilage. Conventional preservation methods often face limitations regarding safety, residue, and environmental impact. Because of its rapid decomposition and low-residue-impact characteristics, ozone has proven superior as [...] Read more.
Fresh fruit are highly perishable commodities, facing significant postharvest losses primarily due to physiological deterioration and microbial spoilage. Conventional preservation methods often face limitations regarding safety, residue, and environmental impact. Because of its rapid decomposition and low-residue-impact characteristics, ozone has proven superior as an efficient and eco-friendly solution for preserving fruit quality after harvest. The maturation and aging processes of kiwifruit are closely linked to the involvement of reactive oxygen species (ROS) metabolism. This study aimed to investigate the effects of intermittent ozone treatment (21.4 mg/m3, applied for 0, 1, 3, or 5 h weekly) on ROS metabolism, the antioxidant defense system, and storage quality of kiwifruit during cold storage (0.0 ± 0.5 °C). The results showed ozone treatment slowed the decline in titratable acid (TA) content and fruit firmness, inhibited increases in total soluble solids (TSSs) and weight loss, and maintained the storage quality. Additionally, ozone treatment enhanced the activities of antioxidant-related enzymes. This includes superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX). Furthermore, it delayed the reduction in ascorbate (ASA), glutathione (GSH), total phenolic compounds, and flavonoid content, while also preventing the accumulation of ROS and the rise in malondialdehyde (MDA) levels. In summary, the results indicate that ozone treatment enhances the antioxidant capacity of kiwifruit by increasing the structural integrity of cell membranes, preserving the structural integrity of cell membranes, and effectively maintaining the storage quality of the fruit. Full article
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12 pages, 1094 KiB  
Review
DJ-1 Serves as a Central Regulator of Diabetes Complications
by Feng Zhou, Jia-Bin Zhou, Tian-Peng Wei, Dan Wu and Ru-Xing Wang
Curr. Issues Mol. Biol. 2025, 47(8), 613; https://doi.org/10.3390/cimb47080613 - 4 Aug 2025
Viewed by 39
Abstract
Diabetes mellitus poses a significant global health challenge, primarily due to its chronic metabolic dysregulation, leading to widespread tissue and organ damage. This systemic impact results in a range of complications that markedly reduce patients’ quality of life. Therefore it is critical to [...] Read more.
Diabetes mellitus poses a significant global health challenge, primarily due to its chronic metabolic dysregulation, leading to widespread tissue and organ damage. This systemic impact results in a range of complications that markedly reduce patients’ quality of life. Therefore it is critical to understand the mechanisms underlying these complications. DJ-1 (also known as PARK7) is a highly conserved multifunctional protein involved in antioxidative defense, metabolic equilibrium, and cellular survival. Recent studies have highlighted that DJ-1 is critically involved in the pathogenesis and progression of diabetic complications, including macrovascular issues like cardiovascular disease and microvascular conditions such as diabetic nephropathy, retinopathy, and neuropathy, suggesting that it may serve as a promising therapeutic target. Importantly, drugs targeting DJ-1 have shown therapeutic effects. This review provides a comprehensive overview of the current under-standing of DJ-1’s role in diabetes-related complications, emphasizing recent research advances. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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33 pages, 938 KiB  
Review
Exploring the Antioxidant Roles of Cysteine and Selenocysteine in Cellular Aging and Redox Regulation
by Marta Pace, Chiara Giorgi, Giorgia Lombardozzi, Annamaria Cimini, Vanessa Castelli and Michele d’Angelo
Biomolecules 2025, 15(8), 1115; https://doi.org/10.3390/biom15081115 - 3 Aug 2025
Viewed by 419
Abstract
Aging is a complex, universal biological process characterized by the progressive and irreversible decline of physiological functions across multiple organ systems. This deterioration is primarily driven by cumulative cellular damage arising from both intrinsic and extrinsic stressors. The free radical theory of aging, [...] Read more.
Aging is a complex, universal biological process characterized by the progressive and irreversible decline of physiological functions across multiple organ systems. This deterioration is primarily driven by cumulative cellular damage arising from both intrinsic and extrinsic stressors. The free radical theory of aging, first proposed by Denham Harman in 1956, highlights the role of reactive oxygen species (ROS), byproducts of normal metabolism, in driving oxidative stress and age-related degeneration. Emerging evidence emphasizes the importance of redox imbalance in the onset of neurodegenerative diseases and aging. Among the critical cellular defenses against oxidative stress are sulfur-containing amino acids, namely cysteine (Cys) and selenocysteine (Sec). Cysteine serves as a precursor for glutathione (GSH), a central intracellular antioxidant, while selenocysteine is incorporated into key antioxidant enzymes such as glutathione peroxidases (GPx) and thioredoxin reductases (TrxR). These molecules play pivotal roles in neutralizing ROS and maintaining redox homeostasis. This review aims to provide an updated and critical overview of the role of thiol-containing amino acids, specifically cysteine and selenocysteine, in the regulation of redox homeostasis during aging. Full article
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16 pages, 5537 KiB  
Article
Different Light Wavelengths Differentially Influence the Progression of the Hypersensitive Response Induced by Pathogen Infection in Tobacco
by Bao Quoc Tran, Anh Trung Nguyen and Sunyo Jung
Antioxidants 2025, 14(8), 954; https://doi.org/10.3390/antiox14080954 (registering DOI) - 3 Aug 2025
Viewed by 115
Abstract
Using light-emitting diodes (LEDs), we examined how different light wavelengths influence the hypersensitive response (HR) in tobacco plants infected with Pseudomonas syringae pv. tomato (Pst). Pst-infiltrated plants exhibited greater resistance to Pst infection under green and blue light compared to white and red [...] Read more.
Using light-emitting diodes (LEDs), we examined how different light wavelengths influence the hypersensitive response (HR) in tobacco plants infected with Pseudomonas syringae pv. tomato (Pst). Pst-infiltrated plants exhibited greater resistance to Pst infection under green and blue light compared to white and red light, as indicated by reduced HR-associated programmed cell death, lower H2O2 production, and up to 64% reduction in membrane damage. During the late stage of HR, catalase and ascorbate peroxidase activities peaked under green and blue LEDs, with 5- and 10-fold increases, respectively, while superoxide dismutase activity was higher under white and red LEDs. Defense-related genes CHS1, PALa, PR1, and PR2 were more strongly induced by white and red light. The plants treated with green or blue LEDs during Pst infection prompted faster degradation of phototoxic Mg-porphyrins and exhibited smaller declines in Fv/Fm, electron transport rate, chlorophyll content, and LHCB expression compared to those treated with white or red LEDs. By contrast, the induction of the chlorophyll catabolic gene SGR was 54% and 77% lower in green and blue LEDs, respectively, compared to white LEDs. This study demonstrates that light quality differentially affects Pst-mediated HR, with green and blue light more effectively suppressing HR progression, mainly by reducing oxidative stress through enhanced antioxidative capacity and mitigation of photosynthetic impairments. Full article
(This article belongs to the Special Issue Oxidative Stress and Antioxidant Defense in Crop Plants, 2nd Edition)
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59 pages, 1351 KiB  
Review
The Redox Revolution in Brain Medicine: Targeting Oxidative Stress with AI, Multi-Omics and Mitochondrial Therapies for the Precision Eradication of Neurodegeneration
by Matei Șerban, Corneliu Toader and Răzvan-Adrian Covache-Busuioc
Int. J. Mol. Sci. 2025, 26(15), 7498; https://doi.org/10.3390/ijms26157498 - 3 Aug 2025
Viewed by 131
Abstract
Oxidative stress is a defining and pervasive driver of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). As a molecular accelerant, reactive oxygen species (ROS) and reactive nitrogen species (RNS) compromise mitochondrial function, amplify lipid peroxidation, induce [...] Read more.
Oxidative stress is a defining and pervasive driver of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). As a molecular accelerant, reactive oxygen species (ROS) and reactive nitrogen species (RNS) compromise mitochondrial function, amplify lipid peroxidation, induce protein misfolding, and promote chronic neuroinflammation, creating a positive feedback loop of neuronal damage and cognitive decline. Despite its centrality in promoting disease progression, attempts to neutralize oxidative stress with monotherapeutic antioxidants have largely failed owing to the multifactorial redox imbalance affecting each patient and their corresponding variation. We are now at the threshold of precision redox medicine, driven by advances in syndromic multi-omics integration, Artificial Intelligence biomarker identification, and the precision of patient-specific therapeutic interventions. This paper will aim to reveal a mechanistically deep assessment of oxidative stress and its contribution to diseases of neurodegeneration, with an emphasis on oxidatively modified proteins (e.g., carbonylated tau, nitrated α-synuclein), lipid peroxidation biomarkers (F2-isoprostanes, 4-HNE), and DNA damage (8-OHdG) as significant biomarkers of disease progression. We will critically examine the majority of clinical trial studies investigating mitochondria-targeted antioxidants (e.g., MitoQ, SS-31), Nrf2 activators (e.g., dimethyl fumarate, sulforaphane), and epigenetic reprogramming schemes aiming to re-establish antioxidant defenses and repair redox damage at the molecular level of biology. Emerging solutions that involve nanoparticles (e.g., antioxidant delivery systems) and CRISPR (e.g., correction of mutations in SOD1 and GPx1) have the potential to transform therapeutic approaches to treatment for these diseases by cutting the time required to realize meaningful impacts and meaningful treatment. This paper will argue that with the connection between molecular biology and progress in clinical hyperbole, dynamic multi-targeted interventions will define the treatment of neurodegenerative diseases in the transition from disease amelioration to disease modification or perhaps reversal. With these innovations at our doorstep, the future offers remarkable possibilities in translating network-based biomarker discovery, AI-powered patient stratification, and adaptive combination therapies into individualized/long-lasting neuroprotection. The question is no longer if we will neutralize oxidative stress; it is how likely we will achieve success in the new frontier of neurodegenerative disease therapies. Full article
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17 pages, 1724 KiB  
Article
Effects of Eriobotrya japonica (Thunb.) Lindl. Leaf Extract on Zebrafish Embryogenesis, Behavior, and Biochemical Pathways
by Jorge Barros, Irene Gouvinhas, Carlos Venâncio, Daniel Granato, Ana Novo Barros and Luís Félix
Molecules 2025, 30(15), 3252; https://doi.org/10.3390/molecules30153252 - 3 Aug 2025
Viewed by 107
Abstract
Eriobotrya japonica (Thunb.) Lindl. leaves are rich in polyphenolic compounds, yet their toxicological effects in aquatic models remain poorly understood. This study evaluated the impact of a hydroethanolic E. japonica leaf extract on zebrafish embryos through the use of morphological, behavioral, and biochemical [...] Read more.
Eriobotrya japonica (Thunb.) Lindl. leaves are rich in polyphenolic compounds, yet their toxicological effects in aquatic models remain poorly understood. This study evaluated the impact of a hydroethanolic E. japonica leaf extract on zebrafish embryos through the use of morphological, behavioral, and biochemical parameters. The 96 h LC50 was determined as 189.8 ± 4.5 mg/L, classifying the extract as practically non-toxic, according to OECD guidelines. Thereby, embryos were exposed for 90 h to 75 and 150 mg/L concentrations of the E. japonica leaf extract. While no significant effects were noted at the lowest concentration of 150 mg/L, significant developmental effects were observed, including reduced survival, delayed hatching, underdevelopment of the swim bladder, and retention of the yolk sac. These malformations were accompanied by marked behavioral impairments. Biochemical analysis revealed a concentration-dependent increase in superoxide dismutase (SOD) and catalase (CAT) activity, suggesting the activation of antioxidant defenses, despite no significant change in reactive oxygen species (ROS) levels. This indicates a potential compensatory redox response to a pro-oxidant signal. Additionally, the acetylcholinesterase (AChE) activity was significantly reduced at the highest concentration, which may have contributed to the observed neurobehavioral changes. While AChE inhibition is commonly associated with neurotoxicity, it is also a known therapeutic target in neurodegenerative diseases, suggesting concentration-dependent dual effects. In summary, the E. japonica leaf extract induced concentration-dependent developmental and behavioral effects in zebrafish embryos, while activating antioxidant responses without triggering oxidative damage. These findings highlight the extract’s potential bioactivity and underscore the need for further studies to explore its safety and therapeutic relevance. Full article
(This article belongs to the Special Issue Biological Activities of Traditional Medicinal Plants, 2nd Edition)
18 pages, 1812 KiB  
Review
Nanocarriers for Medical Ozone Delivery: A New Therapeutic Strategy
by Manuela Malatesta and Flavia Carton
Nanomaterials 2025, 15(15), 1188; https://doi.org/10.3390/nano15151188 - 3 Aug 2025
Viewed by 203
Abstract
Ozone (O3) occurs in nature as a chemical compound made of three oxygen atoms. It is an unstable, highly oxidative gas that rapidly decomposes into oxygen. The therapeutic use of O3 dates back to the beginning of the 20th century [...] Read more.
Ozone (O3) occurs in nature as a chemical compound made of three oxygen atoms. It is an unstable, highly oxidative gas that rapidly decomposes into oxygen. The therapeutic use of O3 dates back to the beginning of the 20th century and is currently based on the application of low doses, inducing a moderate oxidative stress that stimulates the antioxidant cellular defenses without causing cell damage. Low O3 doses also induce anti-inflammatory and regenerative effects, and their anticancer potential is under investigation. In addition, the oxidative properties of O3 make it an excellent antibacterial, antimycotic, and antiviral agent. Thanks to these properties, O3 is currently widely used in several medical fields. However, its chemical instability represents an application limit, and ozonated oil is the only stabilized form of medical O3. In recent years, novel O3 formulations have been proposed for their sustained and more efficient administration, based on nanotechnology. This review offers an overview of the nanocarriers designed for the delivery of medical O3, and of their therapeutic applications. The reviewed articles demonstrate that research is active and productive, though it is a rather new entry in the nanotechnological field. Liposomes, nanobubbles, nanoconstructed hydrogels, polymeric nanoparticles, and niosomes were designed to deliver O3 and have been proven to exert antiseptic, anticancer, and pro-regenerative effects when administered in vitro and in vivo. Improving the therapeutic administration of O3 through nanocarriers is a just-started challenge, and multiple prospects may be foreseen. Full article
(This article belongs to the Section Biology and Medicines)
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