Search Results (6,730)

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

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

In response to the water loss, shrivelling, and oxidative ageing commonly observed in Golden passion fruit after harvest, this study systematically evaluated the regulatory effects of short-wave ultraviolet (UV-C) treatment. The results showed that UV-C treatment at 3.6 kJ m⁻² significantly curtailed the increases in weight loss and shrivelling index during storage. Low-field nuclear magnetic resonance (LF-NMR) analysis revealed that this treatment effectively maintained the stability of water distribution in fruit tissues by delaying the conversion of free water to bound water. Regarding antioxidant regulation, UV-C treatment significantly increased the activities of key antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and glutathione reductase (GR), while promoting the accumulation of non-enzymatic antioxidants, such as total phenols, total flavonoids, and ascorbic acid (AsA). These changes synergistically enhanced reactive oxygen species (ROS)-scavenging capacity, leading to significant reductions in H₂O₂ content and malondialdehyde (MDA) levels, thereby alleviating lipid peroxidation damage to cell membranes. Overall, UV-C treatment effectively maintained cell membrane integrity and regulated water migration through the coordinated regulation of enzymatic and non-enzymatic antioxidant defence systems, thereby delaying passion fruit shrivelling and improving postharvest quality and storage stability. Full article

Chronic rhinosinusitis (CRS) is an inflammatory disease of the sinonasal mucosa whose pathogenesis is characterized by complex interactions of immunological and environmental factors. The maintenance of normal sinonasal function requires a balance of sinus ostial patency, mucociliary clearance, and mucus secretion, and disruption of this balance can lead to CRS. Although many studies have examined the pathophysiology of CRS, the role of reactive oxygen species (ROS) remains incompletely understood. In this review, we analyzed 22 studies of CRS that examined the effects of ROS on epithelial barrier function, local immune responses, and tissue remodeling. The results from in vitro studies, animal models, and human tissue analyses suggest that ROS are not merely by-products of inflammation, but appear to function as key mediators in the pathophysiology of CRS, particularly in the formation and persistence of the CRS phenotype with nasal polyps (CRSwNP). In particular, CRSwNP is characterized by increased activity of enzymes in the dual oxidase (DUOX) and NADPH oxidase (NOX) families, mitochondrial dysfunction, and decreased activity of superoxide dismutase (SOD) and peroxiredoxin 2 (PRDX2). At the molecular level, these alterations increase the generation of ROS and impair antioxidant defense. At the cellular level, these alterations disrupt the epithelial barrier, activate inflammasomes, increase pyroptosis, and induce the formation of neutrophilic and eosinophilic extracellular traps. These changes culminate in the epithelial–mesenchymal transition (EMT), with the formation of nasal polyps and tissue remodeling. Increased oxidative stress can also occur in CRS without nasal polyps (CRSsNP), but this phenotype appears to have relatively preserved antioxidant defense systems, which may partly explain the more limited structural remodeling. External stimuli, such as fungal proteases, bacterial toxins, and certain antibiotics, can also increase the production of ROS and may contribute to disease chronicity. Taken together, the level and pathophysiological roles of ROS differ in the two primary phenotypes of CRS. Further mechanistic studies are needed to clarify the specific alterations of redox pathways in these two phenotypes and to develop novel therapeutic strategies that target ROS. Full article

Background/Objectives: Filipendula ulmaria (L.) Maxim. (meadowsweet) is a medicinal plant traditionally used for its antioxidant and anti-inflammatory effects. There is also some data indicating its anticancer potential; however, its impact on colorectal cancer cells remains poorly understood. Here we investigated the cytotoxic and pro-apoptotic effects of an aqueous F. ulmaria extract on human LoVo colorectal cancer cells and analyzed some of the mechanisms underlying it. Methods: LoVo colorectal cancer cells were treated with the aqueous extract and analyzed for intracellular reactive oxygen species (ROS), mitochondrial membrane potential, DNA damage, lysosomal alterations, apoptosis-related mechanisms, and antioxidant activity. Phytochemical profiling was performed by HPLC-TOF/MS. Results: The extract elevated intracellular ROS levels, disrupted mitochondrial membrane potential, and induced DNA damage in LoVo cells. Activation of crucial caspases, along with increased p53 levels, confirmed engagement of both extrinsic and intrinsic apoptotic pathways. Changes in lysosomal fluorescence were also observed, indicating alterations in lysosomal properties. In chemical assays (FRAP, TAC, DPPH, ABTS, and superoxide scavenging), the extract demonstrated robust antioxidant capacity comparable to or exceeding that of ascorbic acid. Phytochemical profiling by HPLC-TOF/MS revealed a rich presence of bioactive flavonoids, phenolic acids, and coumarins. Altogether, our findings indicate that the extract’s cytotoxicity against colon cancer cells arises from a multifaceted mechanism involving oxidative stress, organelle dysfunction, and apoptosis induction. Conclusions: These results highlight F. ulmaria aqueous extract as a promising candidate for colorectal cancer phytotherapy as a form of supportive treatment and warrant further preclinical validation. Full article

Environmental stressors such as heavy metals and pesticides pose significant threats to honeybee health by inducing oxidative stress. Enhancing nutritional supply has emerged as a potential strategy for honeybees to enhance stress resistance. However, the underlying molecular mechanisms remain poorly understood. This study investigated the role of leucine (Leu) in regulating antioxidant responses in honeybees (Apis mellifera L.), with a focus on the involvement of sestrin and the Target of Rapamycin (TOR) signaling pathway. The results showed that Leu supplementation activated the TOR signaling pathway and upregulated sestrin expression, leading to enhanced antioxidant capacity and reduced reactive oxygen species (ROS) levels. Silencing sestrin disrupted antioxidant homeostasis, increased stress susceptibility, and caused midgut damage, confirming its essential role in oxidative stress resistance. Notably, inhibition of TOR did not prohibit the protective effects of Leu, suggesting that sestrin, rather than TOR, serves as a key mediator. Furthermore, Leu fine-tuned antioxidant responses under different stress conditions through sestrin. Overall, this study demonstrates that Leu and sestrin play a central role in maintaining antioxidant homeostasis and provide a theoretical basis for nutritional strategies to improve honeybee health and stress resilience. Full article

Tetrabromobisphenol A mono(2-hydroxyethyl) ether (TBBPA-MHEE) is an important byproduct during the production of tetrabromobisphenol A (TBBPA) and its related derivatives. Although it has been detected in aquatic environments, its in vivo developmental toxicity and underlying mechanisms remain poorly understood. In this study, zebrafish were used as a model organism to evaluate the early developmental toxicity, neurobehavioral toxicity, and candidate molecular responses associated with TBBPA-MHEE. The 96 h median lethal concentration (96 h-LC₅₀) of TBBPA-MHEE for zebrafish embryos/larvae was 1.684 mg/L. Sublethal nominal exposure concentrations (2, 20, and 200 μg/L) caused developmental abnormalities, including reduced body length, pericardial edema, impaired swim bladder development, and significantly inhibited spontaneous motor activity as well as the response to light–dark transition and mechanical stimulation. Transgenic reporter assays further showed shortened motor neuron projections, reduced brain-region fluorescence in Tg(gad1b:mCherry) larvae, and downregulated the expression of neurodevelopment-related genes. Network toxicology analysis suggested that MTOR, SRC, MAPK3, and GSK3B were identified as candidate targets potentially associated with TBBPA-MHEE-induced neurotoxicity, with significant enrichment of the ErbB signaling pathway and possible perturbation of PI3K/Akt/mTOR-related responses. In addition, TBBPA-MHEE exposure increased the accumulation of reactive oxygen species (ROS) in the larval brain and induced inflammatory and apoptotic responses. Quercetin intervention partially alleviated ROS accumulation and inflammation and improved the developmental and motor phenotypes. Collectively, these findings indicate that TBBPA-MHEE induces neurodevelopmental toxicity in zebrafish, possibly associated with altered transcriptional responses related to ErbB signaling and the PI3K/Akt/mTOR axis, accompanied by oxidative stress, inflammatory responses, and apoptosis-related events. Because exposure concentrations were not analytically verified, all treatment levels are reported as nominal concentrations. This study provides experimental evidence for the toxicological assessment and environmental risk evaluation of TBBPA derivative pollutants. Full article

Vitiligo is a multifactorial depigmentation disorder involving complex interactions among oxidative stress, immune dysregulation, inflammatory signaling, and programmed cell death pathways, which act as a central driver of melanocyte dysfunction and loss, interacting with immune-mediated cytotoxicity and intrinsic cellular susceptibility. Excessive reactive oxygen species (ROS) disrupt mitochondrial integrity, impair redox homeostasis, suppress microphthalmia-associated transcription factor (MITF)-dependent melanogenesis, and induce melanocyte apoptosis. Concomitant dysfunction of the nuclear factor erythroid 2-related factor 2 (NRF2)/antioxidant response element (ARE) axis further exacerbates oxidative injury by limiting endogenous antioxidant capacity. Current therapeutic approaches, including corticosteroids, phototherapy, and targeted immunomodulators, achieve partial repigmentation but do not adequately resolve melanocyte-intrinsic redox imbalance. This structured narrative review comprehensively integrates mechanistic and translational evidence to define phytocompounds as redox-active, multi-target modulators in vitiligo. Plant-derived polyphenols, flavonoids, terpenoids, and related metabolites are shown to attenuate ROS accumulation, preserve mitochondrial function, activate NRF2-dependent antioxidant signaling, and restore MITF-mediated expression of tyrosinase and associated melanogenic enzymes. Furthermore, coordinated modulation of MAPK, PI3K/Akt, and JAK/STAT pathways highlights their capacity to regulate immune–oxidative crosstalk and promote melanocyte survival. Despite promising preclinical and emerging clinical evidence of repigmentation efficacy, translational progress remains limited by poor phytochemical standardization, insufficient transcriptional and proteomic validation, suboptimal stability and dermal bioavailability, and a lack of rigorously designed clinical trials. Collectively, this review provides a mechanistic framework linking redox dysregulation to melanocyte failure and positions phytocompounds as rational candidates for adjunctive or stand-alone antioxidant-based therapies, while defining critical priorities for clinical translation. Full article

Pediatric inflammatory diseases, such as neonatal necrotizing enterocolitis (NEC), juvenile idiopathic arthritis (JIA), and asthma, pose numerous challenges in clinical treatment due to their complex pathogenesis and the still-developing stage of children’s immune systems. These challenges include poor precision, strong toxic and side effects, and unclear long-term biological safety. In recent years, the development of nanozymes has provided new opportunities to address these issues. This review systematically summarizes the latest research progress of nanozymes in the diagnosis and treatment of pediatric inflammatory diseases. Firstly, we focus on the rational design principles of nanozymes tailored to the physiological characteristics of children, including the regulation of their catalytic activity and strategies for optimizing biocompatibility. Subsequently, we deeply analyze the core roles of these antioxidant nanozymes in breaking the vicious cycle of oxidative stress and reshaping the inflammatory microenvironment through multiple mechanisms, such as scavenging reactive oxygen species (ROS), regulating macrophage polarization, and inhibiting the pro-inflammatory protein (NLRP3 inflammasome). Moreover, we detail the successful applications of nanozymes in various typical pediatric inflammatory disease models and emphasize their potential as a multifunctional theranostic platform in achieving synergistic antioxidant, antibacterial, and targeted drug delivery. Finally, this article prospectively discusses the key challenges that nanozymes must address in the process of clinical translation for children, including long-term biological safety, precise dose control, and individualized drug delivery, and looks forward to the development of intelligent responsive and biodegradable nanozymes. This review aims to provide theoretical basis and reference ideas for the in-depth exploration and clinical application of nanozymes as innovative nanomedicines in the field of pediatric precision medicine in the future. Full article

Eukaryotic genomic DNA is packaged into chromatin as nucleosomes, where it remains susceptible to reactive oxygen species (ROS) that generate the mutagenic lesion 8-oxo-7,8-dihydroguanine (8oxoG). While 8-oxoguanine DNA glycosylase 1 (OGG1) can initiate repair of 8oxoG base paired with C within the nucleosome core particle (NCP) in a position- dependent manner, it is unknown whether MutY homolog (MUTYH), the DNA glycosylase that excises misincorporated A opposite 8oxoG, can initiate repair of 8oxoG:A base pairs within NCPs. To address this, we combined cryo-EM, molecular dynamics (MD) simulations, and biochemical assays. We determined that MUTYH activity on nucleosomal 8oxoG:A is strongly suppressed, with detectable excision limited to the entry/exit region. Cryo-EM structures at four superhelical locations reveal that 8oxoG adopts the syn conformation and Hoogsteen base pairs with A, as in non-nucleosomal DNA, indicating that lesion presentation is not altered by the histone octamer. MD simulations further reveal that 8oxoG:A base pair dynamics and local DNA backbone perturbations are similar in nucleosomal and non-nucleosomal DNA. Together, these data establish that the NCP sterically excludes MUTYH from 8oxoG:A base pairs, making them largely inaccessible to MUTYH processing. This work ultimately provides mechanistic insight for the elevated G to T transversion rate observed in histone-bound DNA following oxidative stress. Full article

Background: Cardiometabolic syndrome is a cardiovascular disease characterized by metabolic dysregulation, with obesity triggering overactivation of the cardiac Renin–Angiotensin System (RAS). This leads to pathological cardiac changes and dysfunction. Empagliflozin (EMPA) modulates local RAS components in the kidney and liver, but its role in regulating cardiac RAS needs further study. Methods: Twenty-four male Wistar rats were separated into the following two groups: (1) control and (2) metabolic syndrome (MS) fed a high-fat diet, and after 8 weeks, half of each group was treated with EMPA (10 mg/kg) for 8 subsequent weeks. Finally, the animals underwent echocardiography, and under sodium thiopental anesthesia, blood samples were taken for FBS and lipid profile measurement. Finally, the left ventricle was isolated and used to measure the levels of proteins in the RAS pathway, including AngII (Angiotensin2), AT1R (Angiotensin2type1receptor), AT2R (Angiotensin2type2 receptor), and downstream pathway proteins pERK1/2 (Phosphorylated Extracellular Signal-Regulated Kinase1/2), NHE1 (Na+/H+ Exchanger1), NCX (Na+/Ca²+Exchanger), and NLRP3 (NOD-like-receptor-protein3) by Western blot, as well as ROS (reactive oxygen species) levels by ELISA. Results: EMPA treatment in MS significantly decreased FBS, TG, and LDL, increased HDL, and improved cardiac function. It was also associated with increased AT2R expression and attenuation of AngII, AT1R, pERK1/2–NHE1–NCX signaling, oxidative stress, and inflammatory markers (ROS and NLRP3) in rats with MS. Conclusion: Our findings suggest that EMPA treatment is associated with improvement in selected local cardiac RAS components and modulation of the pERK1/2–NHE1–NCX signaling pathway, along with reduced oxidative stress, decreased inflammation, and improved cardiac function in MS. Full article

Capsaicin, the main pungent capsaicinoid of Capsicum species, is often described as either an antioxidant or a pro-oxidant compound. This binary view is useful but does not fully explain its effects on cellular redox homeostasis. The response to capsaicin depends on dose, exposure time, cell type, metabolic state, mitochondrial function, antioxidant capacity, and TRPV1 expression. Capsaicin can modulate reactive oxygen species (ROS) production through TRPV1-dependent calcium signaling, but also through TRPV1-independent effects on plasma and mitochondrial membranes. These mechanisms influence mitochondrial bioenergetics, membrane potential, lipid peroxidation, and redox-sensitive signaling. Moderate ROS formation may support adaptive responses, including Nrf2 activation, mitochondrial quality control, and cellular stress tolerance. In contrast, persistent or excessive ROS accumulation may promote mitochondrial dysfunction, apoptosis, and oxidative cell death. Evidence for capsaicin-associated ferroptosis is emerging, particularly through changes in lipid peroxidation, glutathione availability, GPX4 activity, and SLC7A11 expression or activity, but remains incomplete in many models. This review summarizes current evidence on capsaicin-mediated ROS regulation, mitochondrial stress, TRPV1-dependent and TRPV1-independent mechanisms, ferroptosis-related pathways, and methodological challenges in oxidative stress assessment. Full article

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two main neurodegenerative diseases and cause disability and death in patients worldwide. Neurodegeneration is characterized by a progressive loss of neuronal function and structure, causing enormous impairment in cognitive–motor function. Magnolol and honokiol are isomeric biphenyl neolignans and have exhibited neuroprotective activity in previous studies. Hence, we assessed and compared honokiol, magnolol, and mixtures of honokiol and magnolol in honokiol/magnolol molar ratios of 1:3, 1:1, and 3:1 in terms of their neurotoxicity, using the cell counting kit-8 (CCK-8) assay, and of their neuroprotective effect on intracellular reactive oxygen species (iROS) against amyloid-beta (Aβ)- and 1-methyl-4-phenylpyridinium ion (MPP⁺)-induced neurotoxicity in SH-SY5Y cells, using the 2′,7′-dichlorodihydrofluorescein diacetate (H₂DCF-DA) assay. The results showed that honokiol (H) and magnolol (M) at 0.1 μM and the mixtures of honokiol and magnolol in H/M ratios of 1:3, 1:1, and 3:1 at 0.0001 μM exhibited a significant neuroprotective effect of reducing iROS in SH-SY5Y cells where neurotoxicity was induced by Aβ- and MPP⁺ (p-value with respect to Aβ-treated cells < 0.005 and p-value with respect to MPP⁺-treated cells < 0.0001). Moreover, magnolol and honokiol possess antioxidant properties according to computational molecular analysis with Highest Occupied Molecular Orbital (HOMO)- Lowest Unoccupied Molecular Orbital (LUMO) prediction, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and Ferric Reducing Antioxidant Power (FRAP) assays. The mixtures of honokiol and magnolol exerted synergistic neuroprotective ability at all ratios while showing better antioxidation ability than that of pure magnolol alone but comparable to that of pure honokiol alone. Drug-likeness, Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) prediction, and toxicity profiles showed that both compounds are promising neuroprotective agents and that one of the possible targeting mechanisms is the ROS-mediated oxidative stress pathway. Additional neuronal cell lines and in vivo models are required to determine similar effects or other protective mechanisms involving the neuroprotective ability of honokiol and magnolol. Full article

Background: H₂ gas inhalation has been proposed as a selective modulator of reactive oxygen species (ROS), potentially mitigating treatment-related oxidative damage. This study investigated the effects of adjunctive H₂ gas inhalation on serum metabolomic profiles and clinical toxicities in patients with LAHNC undergoing CCRT. Methods: Twenty patients were prospectively randomized to receive either standard CCRT alone (Group A) or CCRT combined with adjunctive H₂ gas inhalation (Group B). Serum samples collected before and after treatment were analyzed using untargeted ultra-high-performance liquid chromatography coupled with ion mobility quadrupole time-of-flight high-resolution mass spectrometry (UHPLC-IM-QTOF-HRMS)-based metabolomics. Results: One patient in Group B discontinued participation, leaving 19 patients for the final analysis. Patients receiving adjunctive H₂ gas inhalation tended to exhibit numerically lower frequencies of moderate treatment-related toxicities, fewer chemotherapy delays, and a shorter overall treatment duration than those receiving CCRT alone. Metabolomic profiling in the CCRT-alone group revealed exploratory alterations in metabolites associated with arginine metabolism, glutathione metabolism, and purine metabolism following treatment. Ornithine, uric acid, and tetrahydrodeoxycorticosterone were among the candidate discriminative metabolites with exploratory discriminatory performance after CCRT. In contrast, patients receiving adjunctive H₂ gas inhalation showed a more limited pattern of pathway mapping, with exploratory evidence from an illustrative single-hit pathway assignment suggesting possible involvement of purine metabolism. Altered uric acid levels together with changes in several lipid-related metabolites may collectively reflect metabolic responses associated with treatment-related oxidative stress during CCRT. Consistent with these findings, direct between-group comparison of within-subject changes (Δ = post − pre) indicated a numerically smaller reduction in serum uric acid levels in the adjunctive H₂ gas inhalation group; however, this difference did not reach statistical significance. Conclusions: Adjunctive H₂ gas inhalation during CCRT may be associated with reduced moderate treatment-related toxicities and exploratory changes in systemic metabolic profiles in patients with LAHNC. However, the study was not designed to evaluate oncological outcomes, and the metabolomic findings, particularly the pathway-level interpretations, should be considered exploratory because several pathway assignments were based on only one or a few mapped metabolites, together with the limited sample size, patient heterogeneity, and lack of independent external validation. Further validation in larger, independent cohorts using comprehensive between-group metabolomic analyses is warranted. Full article

Neutrophils are essential for antimicrobial defense through reactive oxygen species (ROS) production, tumor necrosis factor-alpha (TNF-α) release, and neutrophil extracellular trap formation. Lipoic acid, a redox-active antioxidant, modulates activation in human neutrophils. Neutrophils isolated from healthy donors were pretreated with lipoic acid and then exposed to lipopolysaccharide (LPS) or whole Escherichia coli, according to the specific assay. ROS production, NET formation, TNF-α release, bacterial killing, metabolic activity, and cell death were assessed using fluorometric assays, enzyme-linked immunosorbent assay, colony-forming unit assays, MTT reduction, and Annexin V-FITC/propidium iodide flow cytometry. Lipoic acid significantly reduced ROS production and NET formation induced by LPS and Escherichia coli. at 0.5 mM, lipoic acid also reduced E. coli-induced NET formation by approximately 50% and attenuated TNF-α release at early stimulation times. In colony-forming unit assays, lipoic acid did not significantly reduce neutrophil-mediated killing of Escherichia coli or Staphylococcus aureus. Although only neutrophil preparations with high baseline viability were used, Escherichia coli challenge markedly reduced cell viability during the assay; under this condition, lipoic acid pretreatment limited bacteria-induced necrosis and preserved a higher proportion of viable neutrophils. These findings indicate that lipoic acid dampens excessive oxidative and inflammatory neutrophil responses while maintaining measurable bactericidal capacity in vitro. Full article