Search Results (11,692)

Agricultural waste poses significant environmental and economic challenges, with the UK generating 135,000 tonnes annually. Upcycling plant-derived waste offers a sustainable approach to enhancing agricultural productivity while producing innovative, health-promoting foods. Cherries, particularly rich in anthocyanins and quercetin, possess antioxidant and anti-inflammatory properties linked to numerous health benefits. In this study researchers and a small agricultural business in Kent, the UK’s largest cherry-producing region, collaborated to quantify the bioactive compounds in products derived from waste cherries and evaluate their health potential. We find that cherry juice, pulp, and pomace retain high anthocyanin content, particularly Cyanidin-3-O-rutinoside, and contain quercetin. Using Caenorhabditis elegans as a model, we demonstrate that cherry pulp supplementation is protective in an Alzheimer’s disease model. Our study highlights the potential to upcycle agricultural waste to produce foods with health benefits while reducing waste. Full article

Cerium oxide nanoparticles (CeO₂NPs) can boost crops’ salt tolerance, yet their regulatory mechanisms in rice cultivars with contrasting salt tolerance remain unclear. This study investigated the regulatory differences in poly (acrylic acid)-coated nanoceria (PNC)-primed in salt-sensitive (Huanghuazhan, H) and salt-tolerant (Xiangliangyou900, X) rice. The results showed that PNC priming improved salt tolerance in two cultivars, but the underlying mechanisms differed. In the H cultivar, the enhanced tolerance was primarily attributed to enhanced photosynthesis (net photosynthesis and transpiration rates were 53.27% and 20.52% higher than the X cultivar); increased abscisic acid (ABA) content (up by 18.80% compared to the X cultivar), and activated stress-responsive signaling. Metabolomics further revealed that the differential metabolites were enriched in galactose metabolism, ascorbate, and aldarate metabolism, synergistically maintaining intracellular redox balance. In the X cultivar, PNC boosted reactive oxygen species’ (ROS) scavenging capacity (catalase (CAT) increased 36.07%, H₂O₂ and malondialdehyde (MDA) decreased 27.31% and 48.61% compared to H); elevated endogenous indole-3-acetic acid (IAA) and gibberellic acid3 (GA3) levels by 9.55% and 9.08%; and specifically activated cellular defense response and glutathione metabolism. Transcriptome analysis further revealed that the expression of IAA/GA3 signal-responsive genes (OsARGOS/OsGASR2) and antioxidant genes (OsCatA, OsAPX1) were significantly higher in the X cultivar than the H cultivar (p < 0.05), whereas the H cultivar showed higher expression of GST and ABA-related genes. This study provides a new perspective for the mechanism of PNC-enhanced salt tolerance in rice. Full article

Ferroptosis is an iron-dependent form of regulated cell death marked by lipid peroxidation in polyunsaturated phospholipids. In head and neck cancer (HNC), where resistance to chemotherapy and immunotherapy is common, ferroptosis offers a mechanistically distinct strategy to overcome therapeutic failure. However, cancer cells often evade ferroptosis via activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key regulator of antioxidant and iron-regulatory genes. HNC remains therapeutically challenging due to therapy resistance driven by redox adaptation. This review highlights the ferroptosis pathway—a form of regulated necrosis driven by iron and lipid peroxidation—and its regulation by Nrf2, a master antioxidant transcription factor. We detail how Nrf2 contributes to ferroptosis evasion in HNC and summarize emerging preclinical studies targeting this axis. The review aims to synthesize molecular insights and propose therapeutic perspectives for overcoming resistance in HNC by modulating Nrf2–ferroptosis signaling. We conducted a structured narrative review of the literature using PubMed databases. Relevant studies from 2015 to 2025 focusing on ferroptosis, Nrf2 signaling, and head and neck cancer were selected based on their experimental design, novelty, and relevance to clinical resistance mechanisms. In HNC, Nrf2 mediates resistance through transcriptional upregulation of GPX4 and SLC7A11, epigenetic stabilization by PRMT4 and ALKBH5, and activation by FGF5 and platelet-derived extracellular vesicles. Epstein–Barr virus (EBV) infection also enhances Nrf2 signaling in nasopharyngeal carcinoma. More recently, loss-of-function KEAP1 mutations have been linked to persistent Nrf2 activation and upregulation of NQO1, which confer resistance to both ferroptosis and immune checkpoint therapy. Targeting NQO1 in KEAP1-deficient models restores ferroptosis and reactivates antitumor immunity. Additionally, the natural alkaloid trigonelline has shown promise in reversing Nrf2-mediated ferroptosis resistance in cisplatin-refractory tumors. Pharmacologic agents such as auranofin, fucoxanthin, carnosic acid, and disulfiram/copper complexes have demonstrated efficacy in sensitizing HNC to ferroptosis by disrupting the Nrf2 axis. This review summarizes emerging mechanisms of ferroptosis evasion and highlights therapeutic strategies targeting the Nrf2–ferroptosis network. Integrating ferroptosis inducers with immune and chemotherapeutic approaches may provide new opportunities for overcoming resistance in head and neck malignancies. Full article

One of the main limitations of photodynamic therapy (PDT) is hypoxia, which is caused by increased tumour proliferation creating a hypoxic tumour microenvironment (TME), as well as oxygen consumption by PDT. Hypoxia-activated prodrugs (HAPs), such as molecules containing aliphatic or aromatic N-oxide functionalities, are non-toxic prodrugs that are activated in hypoxic regions, where they are reduced into their cytotoxic form. The (oxido)pyridylporphyrins tested in this work were synthesised as potential HAPs from their AB₃ pyridylporphyrin precursors, using m-chloroperbenzoic acid (m-CPBA) as an oxidising reagent. Their ground-state and excited-state spectroscopic properties, singlet oxygen (¹O₂) production by the photodegradation of 1,3-diphenylisobenzofurane (DPBF) and theoretical lipophilicity were determined. In vitro analyses included cellular uptake, localisation and (photo)cytotoxicity under normoxia and CoCl₂-induced hypoxia. The CoCl₂ hypoxia model was used to reveal their properties, as related to HIF-1 activation and HIF-1α accumulation. (Oxido)pyridylporphyrins showed promising properties, such as the long lifetime of the excited triplet state, a high quantum yield of intersystem crossing, and high production of ROS/¹O₂. Lower cellular uptake resulted in an overall lower phototoxicity of these N-oxide porphyrins in comparison to their N-methylated analogues, and both porphyrin series were less active on CoCl₂-treated cells. (Oxido)pyridylporphyrins showed higher selectivity for pigmented melanoma cells, and the antioxidant activity of melanin pigment seemed to have a lower impact on their PDT activity compared to their N-methylated analogues in both CoCl₂-induced hypoxia and normoxia. Their potential HAP activity will be evaluated under conditions of reduced oxygen concentration in our future studies. Full article

Danshen polysaccharide (DSPS) is the main natural compound extracted from the traditional Chinese herb Danshen. Although DSPS is well-known for its antioxidant and anti-inflammatory properties, its impact on aflatoxin B1 (AFB1)-induced damage has not been explored. This study aims to investigate the potential protective mechanisms of DSPS against AFB1-induced liver damage and immune disorders. The experiment lasted a total of three weeks, during which 120 rabbits were randomly assigned to six groups (n = 20). AFB1 and DSPS were incorporated into the diets of each group. We found that DSPS significantly inhibited AFB1-induced hepatocyte edema, inflammatory cell infiltration, and increased serum aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) levels (p < 0.05). DSPS alleviated oxidative damage by downregulating CYP1A1/A2 mRNA, enhancing liver total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and glutathione (GSH) levels, and reducing the production of reactive oxygen species (ROS) and malondialdehyde (MDA) (p < 0.05). DSPS inhibits the expression of cytochrome c (cyt.c), caspase 9, and caspase 3, significantly reducing the apoptosis rate of hepatocytes (p < 0.05). Additionally, DSPS elevates the levels of immunoglobulins (IgA, IgG, IgM) and interferon-gamma (IFN-γ), while decreasing the concentration of IL-4 (p < 0.05). This study demonstrates that DSPS can alleviate AFB1-induced damage, with the underlying mechanisms likely related to enhanced antioxidant capacity, inhibition of oxidative stress, and intrinsic apoptotic pathways, as well as improved immune responses. Full article

Gastric ulcer (GU) is a common gastrointestinal disorder that impacts quality of life. Currently, several drugs are available for GU treatment, including proton pump inhibitors like omeprazole (OMP); however, their use is limited by numerous potential adverse effects. Glycyrrhizic acid (GLY), a natural anti-inflammatory agent, exhibits promising gastroprotective properties; however, its use is likewise limited by numerous potential adverse effects. This study aimed to synthesize GLY nanoparticles (GLY-NPs) to enhance their therapeutic potential and to comparatively evaluate their efficacy against OMP in an ethanol-induced GU in male Wistar rats. GLY-NPs were synthesized via a hydrothermal method and characterized using TEM, XRD, FTIR, and zeta potential analyses. In vivo, GLY-NPs significantly attenuated gastric mucosal damage compared to OMP, as evidenced by macroscopic and histopathological analyses. Biochemical assays revealed that GLY-NPs markedly improved antioxidant defenses by elevating SOD, catalase, and glutathione peroxidase activities while reducing MDA levels, surpassing the effects of OMP. Furthermore, GLY-NPs modulated inflammatory responses by downregulating p38 MAPK, NF-κB, and TNF-α expression, concomitant with upregulation of the anti-inflammatory cytokine IL-10. Mechanistic insights indicated that GLY-NPs favorably regulated key signaling pathways implicated in gastric mucosal protection, including suppression of the JAK2/STAT3 and TGF-β1/Smad3 pathways, alongside activation of the SIRT1/FOXO1/PGC-1α axis. In conclusion, these findings indicate that GLY-NPs offer higher gastroprotective effects relative to traditional OMP therapy through comprehensive modulation of oxidative stress, inflammation, and molecular signaling pathways. This study highlights GLY-NPs as a potent nanotherapeutic candidate for the effective management of GU. Full article

Chronic venous disease (CVD) and its major manifestation, varicose veins (VV) of the lower limbs, is a common, multifactorial disease that affects a significant percentage of adult and elderly people worldwide. Its prevalence has been constantly increasing with the aging of the population and, particularly, with the obesity pandemic (hence, the term ‘phlebesity’). The major pathophysiological mechanisms that are potentiating each other in a vicious cycle, leading to chronic venous hypertension, are represented by endothelial dysfunction, chronic inflammation, impaired hemodynamics, and venous wall remodeling. Oxidative stress is another pathomechanism responsible for CVD and its complications, with the increased generation of reactive oxygen species and decreased antioxidant defense being reported to contribute to VV formation. Herein, we present evidence for the role of impaired redox homeostasis as pathophysiological mechanism responsible for chronic local and systemic oxidative stress in patients with CVD. Full article

Cellular senescence, a state of permanent cell cycle arrest, represents a double-edged sword in biology—providing tumor-suppressive functions while contributing to tissue degeneration, chronic inflammation, and age-related diseases when senescent cells persist. A key driver of senescence is oxidative stress, primarily mediated by excessive reactive oxygen species that damage mitochondrial DNA, modulate redox-sensitive signaling pathways, and trigger the senescence-associated secretory phenotype. Emerging evidence highlights the pathogenic role of SASP in promoting local inflammation, immune evasion, and senescence propagation. This review explores the intricate interplay between redox imbalance and cellular senescence, emphasizing mitochondrial dysfunction, SASP dynamics, and their implications in aging and cancer. We discuss current senotherapeutic strategies—including senolytics, senomorphics, antioxidants, gene therapy, and immunotherapy—that aim to eliminate or modulate senescent cells to restore tissue homeostasis. Understanding the heterogeneity and context-specific behavior of senescent cells remains crucial for optimizing these therapies. Future research should focus on addressing key knowledge gaps, including the standardization of senescence biomarkers such as circulating miRNAs, refinement of predictive preclinical models, and development of composite clinical endpoints. These efforts are essential to translate mechanistic insights into effective senotherapeutic interventions and enable the safe integration of senescence-targeting strategies into routine clinical practice. Full article

This study evaluated the effect of vitamin C (L-ascorbyl-2-polyphosphate) on the physiological condition, biochemical antioxidant activity, immune responses, and gene expression in the reproductive tract, as well as on sperm quantity and quality in male white shrimp Penaeus vannamei broodstock. Four diets containing 42.5% protein, 11.5% lipids, and 23.5% carbohydrates were formulated with L-ascorbyl-2-polyphosphate as a source of vitamin C at the following concentrations: 0.016 g/kg (Basal), 0.322 g/kg (A), 0.628 g/kg (B), and 0.934 g/kg (C). Shrimp fed diet C exhibited the highest SOD and CAT activity and serum cholesterol levels, but the lowest expression of hemocyanin (Hemo) mRNA transcripts (p ˂ 0.05). Shrimp fed diet A showed the highest Hemo mRNA expression and phenoloxidase (PO) activity, while those fed diet B had the highest serum triglyceride levels (p ˂ 0.05). In contrast, shrimp fed diets A and B exhibited the lowest serum cholesterol levels (p ˂ 0.05). There were no differences in sperm quality between the diets. In relation to sperm quantity, the shrimp fed diet B had the highest sperm cell count (2,750,000 cel/mL), and those fed diet A had the lowest (585,000 cel/mL) (p ˂ 0.05). These results indicate that vitamin C influences the reproductive aspects of male P. vannamei broodstock. A dietary inclusion level of 0.628 g/kg promotes optimal physiological, oxidative stress, and immunological conditions for increased sperm cell production, whereas an excessive level may promote oxidative stress. Full article

Ionizing radiation (IR) as a stress inducer has a significant impact on various normal stem cells differentiation through activation of various signaling pathways. Low levels of oxidative stress of IR may preserve or even enhance cell differentiation. In response to IR, reactive oxygen species (ROS) can activate various signaling pathways that promote cell differentiation, notably through the involvement of nuclear factor erythroid 2–related factor 2 (NRF2). NRF2 interacts with multiple pathways, including Wnt/β-catenin (osteogenesis), PPARγ (adipogenesis), and BDNF/TrkB (neurogenesis). This response is dose-dependent: low doses of IR activate NRF2 and support differentiation, while high doses can overwhelm the antioxidant system, resulting in cell death. However, the quality of various types of IR, such as proton and carbon ion radiation, may have a varied impact on stem cells (SCs) differentiation compared to X-rays. Hence, activation of the NRF2 signaling pathway in SCs and cell differentiation depends on the level of stress and the quality and quantity of IR. This review is an update to explore how IR modulates SCs fate toward osteogenic, adipogenic, and neurogenic lineages through the NRF2 signaling pathway. We highlight mechanistic insights, dose-dependent effects, and therapeutic implications, bridging gaps between experimental models and clinical translation. Full article

Since 2000, antioxidant research in Chile has shown steady growth, from the chemical sciences to their application in biomedical sciences, functional foods, reproduction, and environmental studies. This study presents a bibliometric analysis of Chilean scientific output in the field of antioxidants from 2000 to 2024, organized into five-year intervals. A total of 3190 research articles indexed in the Web of Science (WoS) database were analyzed. Bibliometric indicators—including Price’s, Bradford’s, and Zipf’s laws—were applied to assess literature growth, authorship concentration, journal dispersion, and keyword evolution. Key findings include (i) high productivity from institutions such as the Universidad de Chile, Pontificia Universidad Católica de Chile, Universidad de Santiago de Chile, and Universidad de Concepción; (ii) the identification of leading authors such as Dr. Antonio Vega-Gálvez, Dr. Guillermo Schmeda-Hirschman, and Dr. Mario J. Simirgiotis; and (iii) the consolidation of three main research areas: biomedical applications (e.g., cancer, cardiovascular, and neurodegenerative diseases), food science and technology (e.g., antioxidant properties, and agro-industrial waste revalorization), and ethnopharmacology (e.g., native plant use). This study made it possible to map the state of the art of antioxidant research in Chile and identify key players and research lines, consolidating a comprehensive vision of scientific development in this field. Full article

Reductive stress (RS) results from the overactivity of the enzymatic and non-enzymatic antioxidant systems and from excess antioxidant agents that neutralize reactive oxygen species. Hibiscus sabdariffa Linnaeus (HSL) is a natural source of antioxidant molecules that can overload the antioxidant system. Twenty-one Wistar rats were divided into three groups: group 1 (G) G1: rats that consumed a 6% HSL infusion for one month (HSL + 6%), G2: rats that consumed a 6% HSL infusion for one month and were then given natural water for another month (HSL ± 6%), and G3: rats with natural drinking water. Renal vascular resistance (RVR) was evaluated through their responses to norepinephrine (Ne), acetylcholine (Ach), super oxide (O₂⁻), hydrogen peroxide (H₂O₂)_, and peroxynitrite (ONOO⁻). The activity of antioxidant enzymes and oxidative stress markers was evaluated. RVR was increased by Ne and H₂O₂ (p = 0.03), but it was decreased by Ach, O₂⁻, and ONOO⁻ (p = 0.01). The reduced glutathione / oxidized glutathione (GSH/GSSG) ratio and nitrates/nitrites ratio, the total antioxidant capacity, the activities of superoxide dismutase, catalase, peroxidases, glutathione peroxidase, glutathione reductase, glucose-6-phosphate, and the expression of phosphorylated NrF2 were increased (p ≤ 0.04). However, the thiol groups, adenochrome, and glutathione-S-transferase were decreased (p = 0.01) in G1 vs. G2 and G3. The excessive consumption of antioxidants provided by a 6% HSL infusion results in RS contributing to a decrease in ROS. Full article

The objective of the present study was to develop injectable solutions of curcumin (CUR) and resveratrol (RES) for intravenous administration as a strategy to increase their solubility and stability, as well as to evaluate their cytotoxic potential, individually and in combination, on human lung non-small adenocarcinoma cells (A549 cells) and non-tumoral cells isolated from normal human bronchial epithelium (BEAS cells) to establish possible synergistic effects and potential therapeutic alternatives for lung cancer. Using factorial experimental designs, the components of the injectable CUR and RES solutions were selected, and their hemolytic potential was evaluated by a static method. In addition, combinations of injectable CUR:RES solutions (25:75, 50:50 and 75:25) were prepared from the individual ones, and their stability under refrigeration conditions and cytotoxic potential on A549 and BEAS cells were evaluated. The stability of the injectable solutions of CUR, RES and their different combinations was maintained for 3 months, except for the 25:75 combination of CUR:RES. Furthermore, the cytotoxic potential of CUR and RES on tumoral cells (A549) and non-tumoral (BEAS) cells was evaluated, indicating a dose-dependent effect; the combination of CUR:RES 50:50 and the combination of CUR:RES 75:25 presented synergistic effects in reducing cell viability. This study suggests that injectable solutions of CUR, RES and their combination for intravenous administration could be potential viable candidates and should be evaluated for their efficacy in animal models of lung cancer to establish new possible treatments. Full article

There is an urgent need for new approaches and strategies for the introduction of antioxidant drugs in medicine. Despite hundreds of clinical trials with potential antioxidants, no antioxidant drugs have so far been developed for clinical use; this is mainly as a result of commercial reasons, but also due to insufficient data for regulatory authority approval. Antioxidant activity is a physiological process essential for healthy living. However, increased production of toxic free radicals and reactive oxygen species is observed in many clinical conditions, which are associated with serious and sometimes irreversible damage. Antioxidant drug strategies may involve short- to long-term therapeutic applications for the purpose of prevention, treatment, or post-treatment effects of a disease. These strategies are different for each disease and may include the design of protocols for the inhibition of oxidative damage through iron chelation, enhancing antioxidant defences by increasing the production of endogenous antioxidants, and activating antioxidant mechanisms, as well as the administration of synthetic and natural antioxidants. Both the improvement of antioxidant biomarkers and clinical improvement or disease remission are required to suggest effective therapeutic intervention. More concerted efforts, including new academic strategies, are required for the development of antioxidant drugs in clinical practice. Such efforts should be similar to the fulfilment of orphan or emergency drug regulatory requirements, which, in most cases, involve the treatment or clinical improvement of rare or severe diseases such as neurodegenerative diseases and cancer. Promising results of antioxidant therapeutic interventions include mainly the repurposing of the iron chelating/antioxidants drugs deferiprone (L1) and deferoxamine, and also the iron-binding drug N-acetylcysteine (NAC). In some clinical trials, the lack of pharmacodynamic and ferrikinetic data, wrong posology, and insufficient monitoring have resulted in inconclusive findings. Future strategies involving appropriate protocols and drug combinations, such as L1 and NAC, appear to improve the prospect of developing antioxidant drug therapies in different diseases, including those associated with ferroptosis. New strategies may also involve the use of pro-drugs such as aspirin, which is partly biotransformed into iron chelating/antioxidant metabolites with chemopreventive properties in cancer, and also in other therapeutic interventions. A consortium of expert academics on regulatory drug affairs and clinical trials could increase the prospects for antioxidant drug development in medicine. Full article

Lipid peroxidation driven by polyunsaturated fatty acid (PUFA) oxidation compromises feed quality and animal health. Single antioxidants (e.g., ethoxyquin (EQ), butylated hydroxytoluene (BHT)) face limitations including dose-dependent toxicity, bioaccumulation risks, and inadequate protection against multistage oxidation. Composite systems leveraging complementary mechanisms offer a promising alternative. This study evaluated synergistic efficacy of rationally formulated composite antioxidants (combining synthetic radical scavengers and metal chelators) versus single-component systems in enhancing lipid oxidative stability in high-fat animal feed. The basal diet containing oxidized oil served as the control group (CON). Seven groups were supplemented with the basal diet as follows: Treatment A, 36 g/ton Butylated Hydroxytoluene (BHT); Treatment B, 60 g/ton Ethoxyquin (EQ); Treatment C, 132 g/ton EQ; Treatment D, 10 g/ton EQ + 12 g/ton BHT; Treatment E, 10 g/ton EQ + 12 g/ton BHT + 6 g/ton Citric acid (CA); Treatment F, 20 g/ton EQ + 6 g/ton BHT + 6 g/ton CA; and treatment G, 2 g/ton EQ + 25 g/ton BHT + 6 g/ton CA. Oxidative stability was assessed over a 10-week period under natural storage (T0-T10) and acute thermal stress (120 °C drying for 2 h followed by ambient storage; HT0 to HT10). Oxidative stability was assessed via: antioxidant capacity (DPPH (2,2-Diphenyl-1-picrylhydrazyl)/ABTS (2,2′-Azinobis (3-ethylbenzothiazoline-6-sulfonic acid) scavenging, total antioxidant capacity), physical indices: Color (L*, a*, b*), and chemical oxidation markers: conjugated dienes (CD), peroxide value (PV), p-anisidine value (p-AV), malondialdehyde (MDA), acid value (AV), total oxidation (TOTOX). Superior synergistic performance of the ternary blend (Treatment E) was demonstrated versus singles (A/B/C). Retention of radical scavenging capacity was significantly enhanced, with greater stability observed under accelerated storage. Primary oxidation (PV) and secondary oxidation (MDA, p-AV) were most effectively suppressed by Treatment E. Superior color stability (minimal L* change) was maintained under thermal stress. The lowest TOTOX values were achieved across all conditions by Treatment E. Stage-specific vulnerabilities were shown by single antioxidants (BHT volatilization; pro-oxidative effects of EQ at high doses). Comprehensive, temperature-resilient protection was delivered collectively by the synergistic EQ+BHT+CA system (Treatment E) via combined radical quenching and metal chelation. The inherent limitations of individual antioxidants were effectively overcome by the optimized composite, enabling reduced total dosage while substantially extending the lipid oxidative stability period. Full article