Search Results (19,889)

Red blood cells (RBCs) are the most abundant cells in peripheral blood and perform critical functions including oxygen and carbon dioxide transport, acid base buffering, regulation of hemorheology, and modulation of immune signaling. Due to their high content of hemoglobin and labile iron, prolonged exposure to high oxygen tension, membrane enrichment with polyunsaturated fatty acids, and the absence of both nucleus and mitochondria, mature RBCs have limited capacity for damage repair and protein re-synthesis, making them highly susceptible to attack by reactive oxygen species (ROS) and reactive nitrogen species (RNS). Hydrogen peroxide (H₂O₂) and 2,2′-azobis(2-methylpropionamidine) dihydrochloride (AAPH) are the two most commonly used inducers in the in vitro models of RBC oxidative injury: H₂O₂ primarily generates hydroxyl radicals via hemoglobin/ferrous ion-dependent Fenton reactions, simulating acute oxidative stress. AAPH releases peroxyl radicals upon thermal decomposition, mimicking persistent lipid peroxidation in cell membranes. Curcumin, a representative polyphenolic compound derived from turmeric, exerts multiple effects including free radical scavenging, metal ion chelation, membrane stabilization, anti-inflammatory activity, and regulation of redox homeostasis. This review systematically summarizes the pathological basis of RBC oxidative damage and the protective effects of curcumin on membrane systems, antioxidant defenses, morphology, and function, based on the core evidence chain “H₂O₂/AAPH—RBCs—curcumin”, integrating recent experimental findings on H₂O₂, AAPH, blood storage-induced injury, and curcumin formulations. It emphasizes that mature RBCs lack nuclei and mitochondria, and therefore mechanisms such as Nrf2/ARE signaling, HO-1 induction, mitochondrial apoptosis, caspase cascades, and inflammasome activation should not be directly equated with transcriptional regulatory pathways within mature RBCs, but rather interpreted as indirect evidence originating from nucleated cells, erythroid progenitors, or the blood microenvironment. The article further proposes that future research should focus on standardized RBC models, physiologically relevant dosages, nanodelivery systems, and translational applications in blood storage, to facilitate the transition of curcumin’s in vitro antioxidant evidence into clinical transfusion medicine and precision nutritional interventions. Full article

Ethanol consumption can modify both drug exposure and drug response. However, the clinical relevance of these interactions depends strongly on the timing and pattern of alcohol intake, the affected pharmacological pathway, the dosage form and organ reserve. This review summarizes current evidence on ethanol–drug interactions, particularly human crossover studies, phenotyping studies, cohort analyses and appropriate case reports. It distinguishes acute ethanol–drug co-exposure, chronic alcohol exposure, drug use during early abstinence after chronic drinking, and pharmacotherapy in alcohol-associated liver disease. Key mechanisms include ADH- and ALDH-dependent ethanol oxidation, acetaldehyde formation, NADH/NAD⁺ redox shift, CYP2E1 induction, carboxylesterase 1 (CES1) modulation, altered intestinal and hepatic first-pass handling, dose dumping from susceptible modified-release products, changes in protein binding in alcohol-associated liver disease, and ALDH inhibition with acetaldehyde accumulation in disulfiram-like reactions. At the molecular level, ethanol may promote acetaldehyde adduct formation with proteins and DNA, CYP2E1-driven reactive oxygen species generation, redox stress, intestinal barrier injury, and CES1-dependent transesterification of selected ester drugs. Acute ethanol intake mainly increases pharmacodynamic toxicity and causes short-term pharmacokinetic disturbances, including enhanced central nervous system depression, delayed gastric emptying, impaired glucose and lactate handling and altered hemodynamic responses. In contrast, chronic exposure, early abstinence and alcohol-associated liver disease are more often associated with hepatic enzyme and transporter remodeling, altered protein binding, reduced hepatic or renal reserve, and greater susceptibility to drug-related organ injury. The highest-risk scenarios involve older adults, polypharmacy, alcohol-associated liver disease, dehydration or acute illness, early abstinence, and the concurrent use of central nervous system depressants, glucose-lowering drugs, NSAIDs, antihypertensives, renally eliminated drugs or warfarin. Hence, ethanol exposure should be treated as a dynamic, context-dependent modifier factor that can acutely exacerbate pharmacodynamic toxicity, alter selected pharmacokinetic pathways and lower organ tolerance to drug-related injury. Full article

Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a promising therapeutic strategy for cervical cancer. However, the mitochondrial factors governing ferroptosis sensitivity in this malignancy remain incompletely understood. PET117, a conserved mitochondrial protein, has been implicated in mitochondrial homeostasis, yet its role in ferroptosis regulation and cervical cancer pathophysiology is unknown. Here, we report a novel role of PET117 in regulating ferroptosis. PET117 expression was significantly elevated in cervical cancer tissues and loss of PET117 in HeLa cells markedly suppressed erastin- and RSL3-induced ferroptosis. Mechanistically, PET117 deficiency attenuated intracellular reactive oxygen species (ROS) accumulation, lipid peroxidation, and iron overload. Mitochondrial proteomics and RNA-seq revealed extensive remodeling of the mitochondrial proteome and ferroptosis-related transcriptional networks upon PET117 depletion. Notably, integrative analysis of mitochondrial and nascent proteomes identified acyl-CoA synthetase family member 2 (ACSF2) as a downstream target of PET117. These findings establish PET117 as a novel regulator of ferroptosis in cervical cancer, thereby linking mitochondrial function to ferroptosis regulation. Full article

Lung cancer is the most common malignant tumor worldwide in terms of both incidence and mortality, and the development of highly effective, low-toxicity therapeutic strategies remains an urgent clinical challenge. Here, we report that Salvianolic acid A (SAA), a natural compound extracted from Salvia miltiorrhiza Bunge, inhibits the proliferation of non-small cell lung cancer (NSCLC) cells and induces ferroptosis. Mechanistically, SAA acts as an SRC kinase inhibitor, blocking SRC autophosphorylation at Tyr416, thereby disrupting the SRC-YAP interaction and preventing YAP nuclear translocation. This leads to GPX4 downregulation and subsequently triggers ferroptosis, characterized by increased reactive oxygen species (ROS), Fe²⁺ accumulation, and lipid peroxidation. Overexpression of YAP abrogates the effects of SAA, while inhibiting SRC or YAP enhances its activity. SAA inhibits tumor growth and downregulates key effector molecules in vivo. In summary, this study reveals a novel mechanism by which SAA induces ferroptosis via the SRC/YAP/GPX4 axis, supporting its further development as a candidate therapeutic agent for NSCLC. Full article

This study investigated the effects of high-lipid diets (HLD) with methionine (Met) supplementations on golden pompano (Trachinotus ovatus). T. ovatus (initial weight 82 ± 0.04 g) were fed with a normal lipid control diet (11.30% crude lipid and 1.04% Met, NLM) and HLDs (18% crude lipid) supplemented with varying Met levels (1.04%, 1.14%, 1.24%, 1.34%, 1.44%, 1.54% and 1.64%) namely HLM1, HLM2, HLM3, HLM4, HLM5, HLM6 and HLM7, respectively. After 56 days of feeding trial, the growth performance such as weight gain rate was significantly elevated in the HLM3 (p < 0.05). The liver lipid droplets area, sum of n-3 and n-6 poly-unsaturated fatty acids and fatty acid synthesis genes were elevated in the HLM1 and HLM7, while the genes for lipid breakdown were elevated in the HLM3. Based on the groups NLM, HLM1, and HLM3, the transcriptome sequence data revealed critical associated lipid metabolism, classic antioxidant pathway nrf2 and ferroptosis markers were influenced by Met and higher lipid. The fish livers in HLD groups with lower or higher Met showed the phenomenon of lipid oxidation obviously, while the reactive oxygen species and malondialdehyde were considerably lowered in the liver of fish in group HLM3 (p < 0.05). The hepatic Met was significantly reduced while cysteine was elevated in the HLM3 compared to HLM7 (p < 0.05). Fe and ferroptosis inducers were significantly upregulated in the liver of HLM1 and HLM7. HLM3 elevated anti-ferroptosis and anti-inflammation markers. In conclusion, Met inclusion in the HLD was associated with nrf2/keap1 and critical anti-ferroptosis-related transcriptional responses and regulated lipid metabolism in T. ovatus. The quadratic regression model revealed the optimal dietary Met in the HLD as 1.32%, which will help formulators make more rational and effective use of dietary lipid to support the better growth of golden pompano. Full article

For critical-sized bone defects, bioactive implants are indispensable. Although advanced three-dimensional (3D) printing technology enables the precise manufacturing of customized bone scaffolds, implant-associated infections (IAIs) remain a significant clinical challenge. Moreover, traditional passive antibacterial coatings often face problems such as uncontrolled release of antibacterial agents and insufficient long-term antibacterial efficacy. This review elaborates on the transformation of antibacterial strategies in the field of bone tissue engineering (BTE) from “passive” to “smart responsive” modes. We summarize the endogenous (such as pH, temperature, reactive oxygen species (ROS), and enzyme) and exogenous (such as light, microwave, and ultrasound) response systems. Notably, the ultrasound-driven strategy is highly emphasized due to its outstanding deep tissue penetrability and dual functional characteristics: it can not only eliminate stubborn biofilms through the sonodynamic effect by generating ROS, but also promote osteogenesis through the piezoelectric effect. Additionally, we also discuss the recent progress of artificial intelligence (AI) in the field of bone scaffold manufacturing. AI-driven algorithms help to rapidly optimize complex scaffold structures and accurately predict their mechanical properties, thereby effectively avoiding the inefficiencies brought about by the traditional “trial and error” method. In conclusion, combining AI-assisted manufacturing technology with smart responsive antibacterial strategies opens up a highly promising frontier field for the development of personalized and infection-free bone implants. Full article

Cardiovascular diseases remain the top cause of death worldwide, with atherosclerosis as a key underlying factor. Natural bioactive ingredients from functional foods are increasingly sought after for preventing chronic metabolic and heart conditions due to their safety and suitability for long-term use. Octacosanol is a naturally occurring long-chain fatty alcohol primarily isolated from plant waxes, including rice bran wax and sugarcane wax. Emerging evidence indicates that octacosanol exhibits promising antioxidant properties and may exert protective effects against atherosclerosis through modulation of lipid metabolism and endothelial function. Unlike statins, which can cause side effects over time, octacosanol works gently through several pathways: it protects blood vessel lining by clearing reactive oxygen species and activating endothelial nitric oxide synthase (eNOS); reduces vascular inflammation by blocking nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling; moderates lipid metabolism by lowering 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity and proprotein convertase subtilisin/kexin type 9 (PCSK9) expression; and suppresses excessive platelet aggregation to reduce thrombotic risk. When taken alongside statins, it boosts lipid control while easing statin-related side effects. With its excellent safety profile, octacosanol is an ideal natural ingredient for functional foods, offering a novel multi-target dietary approach to support long-term cardiovascular health. Full article

Rust, caused by the fungus Uromyces pisi, is the most harmful disease of peas in temperate regions. It is necessary to search for sources of resistance with different defense mechanisms in the pea gene pool. A set of 38 Pisum sativum accessions of various origin was studied in Western Siberia in 2021–2024. The aim of the research was to assess the accessions in the field and under controlled conditions using seedlings and adult plants, as well as to study the interaction of U. pisi with resistant varieties, and to determine genetic control of rust resistance. All accessions showed partial (incomplete) resistance to rust in the field. A set of 10 resistant varieties was used for studying U. pisi interaction with peas using cytological methods. The protective mechanisms of Russian varieties led to the inhibition of 50–90% spores on leaf surfaces before penetration into the stomata, and a part of the small colonies died without hypersensitive reaction in the tissues. Hydrogen peroxide and phenolic compounds with red and green autofluorescence appeared by the stage of sporogenesis. Five varieties showed adult resistance to rust. A hybridological analysis revealed monogenic dominant control of resistance in two varieties, and digenic control in two others. The information obtained expands the understanding of the partners’ interaction in the pathosystem ‘U. pisi–P. sativum’, and can also be used for breeding pea varieties with different resistance mechanisms. Full article

Heavy metal pollution has become a major environmental challenge limiting agricultural productivity worldwide. Copper (Cu), although an essential micronutrient, becomes phytotoxic at elevated concentrations, primarily by inducing oxidative stress. Among the most widespread metabolic adjustments triggered by abiotic stress is the accumulation of proline, which is a compatible osmolyte that stabilizes proteins and membranes and helps maintain cellular redox homeostasis. This paper demonstrates that the heterologous expression of TsPAP1, a triticale gene encoding a prolyl aminopeptidase, enhances proline accumulation and confers increased Cu tolerance in Arabidopsis thaliana. Under Cu stress, transgenic lines maintained superior physiological performance relative to the wild type (WT), as evidenced by the reduced biomass loss and lower accumulation of malondialdehyde and reactive oxygen species. Cu exposure activated antioxidant defenses; however, the induction of catalase (CAT), class III peroxidases (POD), ascorbate peroxidase (APX), and glutathione reductase (GR) activities was more pronounced in transgenic lines. Transcriptomic analysis revealed a higher expression of genes encoding antioxidant isoforms localized to chloroplasts (sAPX, CSD2), the cytosol (APX1), peroxisomes (CAT1), and the apoplast (Prx02, Prx51), indicating targeted reinforcement of the multi-compartmental redox defense system. Together, these findings identify TsPAP1 as a potential regulator of proline-dependent redox homeostasis that contributes to enhanced Cu tolerance through the coordinated activation of antioxidant networks. The results further suggest that PAP-dependent peptide turnover contributes to proline-mediated stress adaptation, linking peptide metabolism with antioxidant regulation and highlighting TsPAP1 as a promising target for engineering heavy metal-resilient crops. Full article

Low-molecular-weight collagen peptides from food processing byproducts offer a sustainable approach to mitigating intestinal inflammation, yet their mechanistic roles remain incompletely understood. We evaluated red fish scale collagen peptides-I (LSCP-I), a <3 kDa collagen peptide fraction derived from Lutjanus erythropterus scales, in cellular and murine models of colitis. In Caco-2 cells subjected to macrophage-mediated inflammatory injury, LSCP-I (50 µg/mL) increased proliferation by 35%, enhanced migration by 40%, preserved barrier integrity, reduced reactive oxygen species (ROS) by 45%, decreased lipid peroxidation by 30%, and restored glutathione (GSH) and superoxide dismutase (SOD) activity. In mice with dextran sulfate sodium (DSS)-induced colitis, oral administration of LSCP-I at 200, 400 and 800 mg/kg/day attenuated weight loss and diarrhea, lowered intestinal permeability by 38%, enhanced colon histology, and restored the balance between pro- and anti-inflammatory cytokines. Mechanistically, LSCP-I activated the Nrf2 antioxidant pathway and partially restored gut microbiota composition. These results demonstrate that LSCP-I reinforces intestinal barrier function, restores redox homeostasis, and modulates host–microbiota interactions, establishing its potential as a functional food ingredient for the prevention and management of inflammatory bowel disease. Full article

The fungal pathogen Colletotrichum jiangxiense has a broad host range and high destructive potential. It is a major causal agent of brown spot disease in diverse plants. Antifungal mechanisms used by biocontrol fungi against plant pathogens include disruption of cellular structures and cell wall damage, which can lead to protoplast leakage and hyphal lysis. In this study, we investigated the antifungal mechanism of the endophytic fungus Diaporthe novem DJ13 against C. jiangxiense, the causal agent of rhododendron brown spot. DJ13 is an effective biocontrol strain previously isolated by our research group from healthy leaves of Rhododendron pulchrum. Physiological assays showed that treatment with DJ13 fermentation broth increased membrane permeability, elevated MDA content, reduced TCA cycle enzyme activities, and increased AKP activity. These findings suggest impaired membrane integrity, disrupted energy metabolism, and cell wall damage. Transcriptomic analysis of the treated pathogen identified 1680 significantly differentially expressed genes (DEGs), including 961 up-regulated and 719 down-regulated genes. Among these genes, ABC transporter genes were significantly up-regulated, whereas genes involved in membrane structure metabolism were significantly down-regulated. Chitinase genes were up-regulated, whereas α-glucanase genes were down-regulated. DASH family cryptochrome genes were significantly down-regulated, while genes related to reactive oxygen species (ROS) production, including xanthine dehydrogenase, were significantly up-regulated. In addition, FAD-dependent oxidoreductase genes were up-regulated, while respiratory-metabolism-related genes, including trimethyllysine dioxygenase, were down-regulated. Together, the physiological and transcriptomic data provide a correlative framework supporting the hypothesis that the antifungal mechanism of DJ13 fermentation broth may involve the coordinated action of four processes: cell membrane damage, cell wall disruption, oxidative stress, and inhibition of energy metabolism. These findings also identify candidate genes for future functional validation. Full article

Mononuclear nonheme iron(IV)–oxo species supported by mixed nitrogen–sulfur (N/S) ligands remain scarce, despite the prevalence of sulfur donors in biological iron sites and their expected impact on ferryl reactivity and catalyst design. In this work, a seven-coordinate iron(II) complex, [(N₃S₂)Fe^II(ClO₄)₂], bearing a rigid 15-membered N₃S₂ macrocycle, is shown to rapidly generate a mononuclear nonheme Fe^IV=O intermediate upon reaction with m-chloroperbenzoic (m-CPBA) acid in acetonitrile. The Fe^IV=O species forms within ≤2 s and is thermally persistent (t₁/₂ = 4.3 h at 25 °C), albeit in partial yield (~39% Fe^IV=O by Mössbauer spectroscopy), placing it in an intermediate regime between highly reactive but short-lived ferryl species and more inert, long-lived analogues. The intermediate is characterized by Mössbauer spectroscopy (δ = 0.35 mm s⁻¹, ΔE_Q = 0.90 mm s⁻¹, Γ_FWHM = 0.30 mm s⁻¹, relative area = 39.4%), EPR silence, a UV–vis absorption band at 428 nm, and cryogenic high-resolution ESI–MS (m/z 223.510, (N₃S₂)Fe^IV=O²⁺). Stopped-flow kinetic studies reveal saturation behavior that is well described by a pre-equilibrium oxidant-association model and subsequent O–O bond activation, with apparent activation parameters of ΔH^‡ = 17.7 kJ mol⁻¹ and ΔS^‡ = −155 J mol⁻¹ K⁻¹, indicating a highly ordered transition state within the seven-coordinate N₃S₂ framework under the conditions employed. Functionally, the Fe^IV=O species mediates clean oxygen-atom transfer to triphenylphosphine (k₂ = 8.1 × 10⁻² M⁻¹ s⁻¹) with an effective turnover number of ~12 after correction for the Fe^IV=O yield, establishing that this mixed N/S platform is catalytically competent under mild conditions, though less reactive than state-of-the-art all-nitrogen systems. Collectively, these findings identify the seven-coordinate N₃S₂ macrocycle as a mixed-donor platform that moderately extends ferryl lifetime while retaining measurable oxo-transfer reactivity, providing mechanistic guidance for the development of nonheme iron oxidation catalysts that incorporate sulfur donors. Full article

Methylglyoxal (MG), a reactive carbonyl species, is now recognized as a novel signaling molecule regulating abiotic stress tolerance and plant growth. Using tolerant (BHL-25 and BHL-27) and susceptible (BARI Barley-6 and BHL-26) genotypes, the study aimed to reveal the detailed mechanisms of MG-priming-induced salt stress tolerance in barley (Hordeum vulgare L.). Seeds were primed with MG, and seven-day-old seedlings were transferred to hydroponic solution. After one week of seedling growth in hydroponic solutions, the salinity stress was imposed. The five treatments were as follows: control (0 salt + 0 mM MG), salt (16 dS m⁻¹) + 0 mM MG, salt + 0.25 mM MG, salt + 0.5 mM MG, and salt + 1 mM MG. Significant genotype-dependent changes were observed in response to salt stress based on morphological, physiological and biochemical traits. Salt stress significantly impaired shoot length, shoot dry weight, root volume, root dry weight, relative water content, leaf Na⁺ content and K⁺/Na⁺ ratio. Salinity stress caused a significant increase in oxidative indices in all genotypes; however, the tolerant genotypes showed a lower increase. Importantly, in plants grown from MG-primed seeds, the negative effects of salt stress were reversed by modulating the K⁺/Na⁺ ratio, the activities of antioxidative and glyoxalase pathway enzymes as well as the redox state of ascorbate and glutathione. In conclusion, MG-mediated salt tolerance was linked to a reduction in reactive oxygen species (ROS) and activation of ROS and MG detoxification processes as well as favorable regulation of the K⁺/Na⁺ ratio, glutathione and ascorbate redox state that improved the growth of the barley plants under salinity. Full article

Inflammation contributes to the rapid progression of high-grade gliomas, indicating that anti-inflammatory strategies targeting NF-κB signaling may offer therapeutic benefit. Cannabidiol (CBD) and celecoxib (CELE) are hydrophobic pharmacological agents whose formulation in lipid carriers may support their combined biological evaluation. In this proof-of-concept study, we investigated liposomal formulations containing CBD, CELE, or both compounds in U-87 MG high-grade glioma cells and in a subcutaneous xenograft model. We assessed cytotoxicity, apoptosis, oxidative stress, Nrf2-dependent responses, NF-κB-centered inflammatory networks, tumor cell invasive properties, and Wnt/β-catenin pathway activity. The nanoformulations induced reactive oxygen species generation by 1.8-fold, which was accompanied by Nrf2 activation. Cationic formulations loaded with the compounds produced more pronounced pro-apoptotic effects (up to 39%) than POPC liposomes, although both types reduced the nuclear translocation of the NF-κB p65 subunit. The CBD + CELE-containing formulation showed a trend toward reduced tumor progression in mice. It is important to note that the in vitro and in vivo nanoformulations were physicochemically related, but not identical, and the in vivo experiment should be interpreted as a preliminary assessment after intratumoral administration. Overall, cationic liposomes co-loaded with CBD + CELE represent a promising platform for further optimization aimed at coordinated modulation of inflammatory, oxidative, and proliferative pathways in glioma. However, additional studies, including tissue distribution, release kinetics, and efficacy in orthotopic glioma models, are needed to fully verify their translational potential. Full article

Drug resistance remains a significant challenge in the clinical treatment of acute myeloid leukemia (AML). Therefore, there is an urgent need to develop a novel combinatorial therapy strategy, aiming to overcome drug resistance and improve therapeutic outcomes in AML. Herein, we developed a covalent organic framework bispecific nanosystem, namely glucose oxidase-loaded iron porphyrin covalent organic framework coated with bone marrow stromal cell membrane and functionalized with anti-CD3 and anti-PD-L1 antibodies (abbreviated FeC-G@M-C&P). The fabricated FeC-G@M-C&P displayed good cascade catalytic activity. The bone marrow stromal cell membrane endowed the nanosystem with robust targeting ability, which further triggered abundant reactive oxygen species (ROS) production for chemodynamic therapy. Moreover, bone marrow stromal cell membrane component suppressed the migration and adhesion of C1498 cells by interfering with the CXCR4/CXCL12 axis. Meanwhile, anti-CD3 and anti-PD-L1 antibodies improved T cell activation, relieved immune suppression, and jointly enhanced T cell-mediated immune responses against leukemia cells. Experimental results indicated that the FeC-G@M-C&P plus T cells group showed better anti-leukemia effects compared with other groups, which can be attributed to the integration of chemodynamic therapy, CXCR4/CXCL12 axis blockade therapy and immunotherapy. Collectively, the fabricated nanosystem provided a promising approach for the combined treatment of AML. Full article