Search Results (1,445)

Bisantrene (9,10-anthracenedicarboxaldehyde bis[(4,5-dihydro-1H-imidazol-2-yl)hydrazone]) and its monosubstituted analogue anthracen-9-imidazoline hydrazone (9-AIH) are bioactive anthracene derivatives whose antitumor activity stems from DNA intercalation and topoisomerase II inhibition. Bisantrene lacks the quinone–hydroquinone redox system responsible for anthracycline cardiotoxicity and was recently identified as a potent inhibitor of the RNA demethylase FTO, adding an epitranscriptomic dimension that has renewed interest in the scaffold. Here, we report the stepwise synthesis of 9-AIH (65%; m.p. 282 °C) and bisantrene (60%; m.p. 244 °C) by condensation of the corresponding anthracene carboxaldehydes with 2-hydrazino-2-imidazoline hydrobromide, followed by complexation with Cu(II), Fe(III), Zn(II), Mn(II), and Cr(III) chloride salts to afford ten reaction products. Product identity was confirmed by melting point, elemental analysis (C, H, N by combustion; metal content by classical volumetric titration), and qualitative ionic testing before and after acid digestion. Nine of the ten products gave elemental analyses consistent with discrete mononuclear [9-AIH·M] or binuclear [Bis·M₂] coordination compounds. Eight of these nine match calculated values; the ninth, Bis·Cu, deviates by up to 3.3 percentage points (Cu content), a deviation quantitatively accounted for by a co-precipitated Cu₂O impurity phase identified by XRD rather than by failure of complexation. The tenth product, from the bisantrene/FeCl₃ reaction (Bis·Fe), did not match any discrete coordination formula. Room-temperature ⁵⁷Fe Mössbauer spectroscopy of this material resolved two quadrupole doublets with isomer shifts and quadrupole splittings closely matching literature values for akaganeite (β-FeOOH), independently confirming, at the level of local iron coordination environment, that the isolated solid is dominated by a hydrolyzed iron oxyhydroxide phase rather than a discrete bisantrene–Fe(III) complex. FTIR and X-ray powder diffraction of the zinc(II) complexes revealed a diagnostic C=N (azomethine/hydrazone) shift upon coordination and closely related diffraction patterns, consistent with a common N,N-donor environment across both ligands. These results establish the feasibility of metal-directed functionalization of bisantrene-type ligands across a broad range of first-row transition metals and identify iron(III) as an outlier under the present conditions, opening a route to metallodrugs that combine bisantrene’s established and newly discovered pharmacophores with the enhanced bioactivity conferred by metal coordination. Full article

Drug-induced ocular toxicity is difficult to predict and evaluate, particularly for prostaglandin F2α (PGF2α) analogs used in the management of glaucoma. Traditional global predictive models, which are built with large and various datasets (n = 6187), provide systematic false-negative results for groups of structurally uniform compounds. To address this limitation, we developed special local classification models for PGF2α analogs. A structurally consistent local training dataset (n = 350) was assembled using Murcko scaffold filtering and Tanimoto similarity selection (≥0.5). Binary classification models were built using three different molecular fingerprints in combination with machine learning and two deep learning methods. Although two-dimensional molecular representations do not encode stereochemistry, computational predictions still apply to the shared two-dimensional scaffold of these compounds. These improved models were used to predict the ocular toxicity of latanoprost and its related impurities. The local models (n = 350) provided accurate toxicity predictions for latanoprost, latanoprost acid, 15(S)-latanoprost, and the trans-5,6-latanoprost isomer, whereas all 16 global computational models provided false-negative results. The experimental assessment performed with primary rabbit corneal epithelial cells (pRCECs) and a human corneal epithelial cell line (HCE-T) confirmed the cytotoxic effects, which were in agreement with the predictions made by the models. Among the tested compounds, 15(S)-latanoprost exhibited the highest cytotoxicity (IC50 = 86.22 μM, 95% CI: 82.90–89.56 μM), followed by trans-5,6-latanoprost (IC50 = 106.70 μM, 95% CI: 103.4–110.0 μM) and latanoprost (IC50 = 112.60 μM, 95% CI: 106.7–118.6 μM). At the standard therapeutic dosage (0.005%), no significant toxic response was observed. Virtual molecular docking was employed to explore the mechanism, and all analogs docked favorably into the quinone-binding channel of mitochondrial complex I and the catalytic cleft of SIRT3. These results show how a localized modeling approach is better able to capture structure–toxicity correlations among chemically similar compounds and highlight the critical need for rigorous impurity management in latanoprost products, particularly regarding 15(S)-latanoprost. Full article

A novel bacterial strain, CR191^T, was isolated from maize (Zea mays) rhizosphere soil. The strain is Gram-stain-negative, oxidase-positive, rod-shaped, non-motile, and aerobic. Phylogenetic analysis based on 16S rRNA gene sequences placed CR191^T within the genus Dyella, with highest similarity to Dyella flava DHOC52^T (98.23%) and Dyella dinghuensis DHOA06^T (98.16%). The genomic DNA G+C content was 66.19%. Average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain CR191^T and the type strains of the other 36 validly published Dyella species ranged from 79.0 to 86.6% and 20.2–28.7%, respectively, both below the recognized thresholds for species delineation. Genome mining identified several putative biosynthetic gene clusters showing similarity to known clusters associated with diverse secondary metabolites, including saframycin, cosmomycin, and malleobactin biosynthesis. The major cellular fatty acids were iso-C_17:0, iso-C_15:0, and summed feature 9 (comprising iso-C_17:1 ω9c and/or C_16:0 10-methyl). The polar lipid profile comprised phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine and two unidentified polar lipids; the sole respiratory quinone was ubiquinone Q-8. Based on a combination of phenotypic, chemotaxonomic, genomic, and phylogenetic characteristics, strain CR191^T is considered to represent a novel species of the genus Dyella, for which the name Dyella cornirhiza sp. nov. is proposed. The type strain is CR191^T (=CCAM 2032^T = JCM 36807^T). Full article

In deep-sea hydrothermal ecosystems, inorganic sulfur compounds serve as key energy sources for microbes through oxidation, reduction, or disproportionation reactions. However, to date, the bacteria that disproportionate sulfur remain poorly understood. Here, we characterized the physiological and metabolic characteristics of Sulfurovum sp. MH2-6, which was isolated from hydrothermal sediments of the South Mid-Atlantic Ridge. Based on the results of 16S rRNA gene sequence, average nucleotide identity, and DNA–DNA hybridization value, strain MH2-6 belonged to the same species as Sulfurovum mangrovi ST1-3^T. The isolate was able to grow chemolithoautotrophically using thiosulfate, sulfite, or sulfide as the sole energy source, and molecular oxygen as the sole electron acceptor. When using hydrogen as the sole energy source, this bacterium could utilize a wide range of electron acceptors, including oxygen, elemental sulfur, thiosulfate, nitrate, and sulfate. Various organic compounds also supported growth as carbon sources during hydrogen oxidation, suggesting a potential for chemolithomixotrophy. Notably, the isolate could grow via the disproportionation of thiosulfate and elemental sulfur in the presence of ferrihydrite. Further, genome analyses revealed that this bacterium contains a complete reductive citric acid cycle (rTCA) for carbon fixation, multiple hydrogenases, sulfur oxidation, reduction, and transfer enzymes, nitrogenase, and oxygen reductases. Transcriptomic comparisons between sulfur reduction and disproportionation conditions revealed that thiosulfate reductase, type IV sulfide: quinone oxidoreductase, and sulfite dehydrogenase were highly abundant in thiosulfate-disproportionating cultures, while rhodanese-like sulfurtransferases and sulfide dehydrogenase showed increased abundances when grown via elemental sulfur disproportionation. Together, these flexible energy- and carbon-utilizing strategies may enhance the persistence of MH2-6 in hydrothermal vent environments. Full article

Autism spectrum disorder (ASD) risk reflects genetic susceptibility and modifiable environmental exposures acting during fetal and early postnatal critical periods. Building on our prior two-path model, in which folate receptor autoantibody-driven cerebral folate deficiency and oxidative stress/neuroinflammation converge on disrupted neurodevelopment, this review provides the first full mechanistic treatment of environmental pollutants within that framework. We synthesize evidence across seven exposure categories: micro/nanoplastics, plastic-associated endocrine-disrupting chemicals, ambient/indoor air pollution, tire wear particles and 6PPD-quinone, heavy metals and pesticides, industrial chemicals and persistent organic pollutants, and ultra-processed food intake as a parallel, non-pollutant contributor to the same inflammatory pathway. Human biomonitoring of micro/nanoplastics has progressed beyond detection in the placenta, brain and breast milk to direct evidence of placental genotoxicity and fetal endocrine disruption, complementing rodent data linking early-life exposure to impaired corticogenesis, disrupted microglial synaptic pruning, and ASD-relevant behavioral deficits. Across categories, oxidative stress, barrier disruption, neuroinflammation, endocrine disruption, and epigenetic modification recur as convergent mechanisms acting on trimester- and age-specific windows of vulnerability. Genetic variation in folate pathway and mitochondrial genes, as well as folate/vitamin B sufficiency, are proposed as candidate effect modifiers rather than established protective factors to modify susceptibility to this pollutant burden. Most evidence is associational or mechanistic rather than trial-based; we grade evidence strength and translate findings into biomarker-guided clinical and population-level policy guidance. Full article

N-(1,3-dimethylbutyl)-N′phenyl-p-phenylenediamine, more commonly known as 6PPD, is a tire antiozonant used to prevent rubber oxidation and degradation. When 6PPD reacts with ozone, it becomes 6PPD-Quinone (6PPD-Q). Stormwater road runoff facilitates the transport of phenylenediamines (PPDs) into the environment. In recent years, 6PPD-Q has been identified as an acute environmental toxicant causing major disruptions to aquatic life. To aid in the growing body of knowledge on the mechanism of action of PPD and potentially support environmental regulations, this study aims to elucidate the toxic effects of 6PPD and 6PPD-Q in Saccharomyces cerevisiae. To accomplish this, a growth assay, RNA sequencing, mitochondrial staining, and RT-qPCR were performed. The results suggest that 6PPD and 6PPD-Q impact growth and gene regulation by dysregulating Complex III, IV, and V of the oxidative phosphorylation pathway. Additionally, 6PPD and 6PPD-Q are, seemingly, agglomerated at different pHs and in various media. The agglomeration of 6PPD-Q may inhibit cellular uptake, leading to fewer discernible toxic effects. Taken together, we can posit that 6PPD and 6PPD-Q both induce oxidative stress upon exposure to budding yeast, but 6PPD seems to be more toxic than 6PPD-Q. Full article

In vitro maturation (IVM) of oocytes is a critical initial step in mammalian in vitro production (IVP), and its quality directly influences the developmental competence of subsequent embryos. Oxidative stress is a major constraint on oocyte quality, which can be mitigated by exogenous antioxidants. In this study, porcine oocytes were matured in IVM medium supplemented with the antioxidant N-acetyl-L-cysteine (NAC; 0, 0.5, 1.5, and 4 mM) to evaluate its effects on maturation rate, antioxidant capacity, mitochondrial function, vitrification–warming survival rate, post-warming ROS levels, and early embryonic developmental rate. To elucidate the molecular mechanisms underlying the effects of NAC on porcine oocyte maturation, we conducted single-cell transcriptome sequencing. The results showed that, versus the control, 1.5 mM NAC substantially enhanced the IVM rate (p < 0.05), reduced ROS levels (p < 0.05), and increased mitochondrial activity, as assessed by MitoTracker, mitochondrial membrane potential (MMP), and ATP content (p < 0.05). These results suggest that 1.5 mM NAC relieves oxidative stress in oocytes and improves mitochondrial function. However, NAC addition showed no significant differences in vitrification–warming survival rate and post-warming ROS levels relative to the control group (p > 0.05). In addition, 1.5 mM NAC markedly improved the cleavage rate and blastocyst rate of porcine oocytes after in vitro fertilization (IVF, p < 0.05), and also enhanced the cleavage rate after parthenogenetic activation (PA, p < 0.05). Single-cell transcriptome sequencing revealed that, versus the control, differentially expressed genes (DEGs) identified after 1.5 mM NAC supplementation were mainly enriched in pathways related to oxidative phosphorylation (OXPHOS), spliceosome, and ubiquinone/terpenoid-quinone biosynthesis. Among these, the OXPHOS pathway showed the most significant enrichment, with upregulated expression of pathway-related genes such as COX6C, CYCS, and SDHD. The accuracy of the transcriptomic results was further validated by qPCR. In conclusion, supplementing with 1.5 mM NAC relieved oxidative stress, improved mitochondrial function, and thereby promoted oocyte maturation and improved oocyte quality, ultimately facilitating subsequent IVF early embryonic development. Full article

Fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are chronic multisystem disorders characterized by persistent fatigue, pain, cognitive dysfunction, sleep disturbances, and reduced quality of life. Increasing evidence implicates mitochondrial dysfunction, oxidative and nitrosative stress, immune dysregulation, and altered redox and nicotinamide adenine dinucleotide (NAD⁺) metabolism as interconnected mechanisms contributing to fatigue, although the strength of evidence varies across these pathways. Micronutrients are essential components of mitochondrial bioenergetics, antioxidant defense, and immune–metabolic regulation. This narrative review critically examines the mechanistic and clinical evidence supporting mitochondrial-oriented micronutritional interventions in fibromyalgia and ME/CFS, including NAD⁺ precursors, B-complex vitamins, magnesium, coenzyme Q10, alpha-lipoic acid, GlyNAC, L-carnitine, pyrroloquinoline quinone, taurine, and creatine. Mechanistic plausibility is distinguished from clinical efficacy, as disease-specific randomized controlled evidence remains limited for several interventions. We further discuss biomarkers, metabolic phenotyping, and precision nutrition within a systems-based micronutrition framework. Finally, we present the rationale for a future randomized, double-blind, placebo-controlled trial in fibromyalgia patients with clinically significant fatigue, which is planned for 2027, subject to ethics approval and prospective registration, as a strategy for future clinical validation. Full article

Background: Mitochondrial dysfunction is increasingly recognized as a central contributor to intrinsic skin aging, photoaging, cellular senescence, impaired extracellular-matrix homeostasis, dysregulated pigmentation, and delayed recovery after energy-based or minimally invasive procedures. Pyrroloquinoline quinone (PQQ) is a redox-active ortho-quinone that has attracted interest because it can participate in repeated redox cycling, protect mitochondrial function, and activate signaling associated with mitochondrial biogenesis. Objective: This narrative review evaluates the mechanistic basis, available dermatologic evidence, translational opportunities, and major uncertainties surrounding PQQ as a mitochondrial rejuvenation strategy in aesthetic dermatology. Methods: PubMed/MEDLINE and Europe PMC were searched from database inception through 10 August 2026 using PQQ-, mitochondrial-, skin-, delivery-, and safety-related terms; reference lists were also screened. Mechanistic, preclinical, skin-focused, human, and regulatory evidence was synthesized narratively. Results: Experimental studies support PQQ-mediated activation of mitochondrial biogenesis pathways and protection against oxidative injury in several cell and animal systems. Skin-specific evidence includes attenuation of oxidative stress, DNA damage, senescence markers, and matrix metalloproteinases in accelerated-aging mouse models; protection of UVA-exposed human dermal fibroblasts; suppression of UVB-induced caspase-1 release in keratinocytes; a small oral dry-skin study; and a multi-ingredient topical study containing an allyl PQQ derivative. These studies do not establish PQQ-specific clinical aesthetic efficacy. Conclusion: PQQ is a biologically plausible mitochondrial-support compound, but it should currently be regarded as an investigational ingredient rather than an established aesthetic treatment. Carefully designed formulation, toxicology, dose-finding, biomarker, and randomized clinical studies are required before claims regarding wrinkle reduction, pigment improvement, enhanced collagen production, or accelerated post-procedure recovery can be justified. Full article

The electrochemical sensing of similar catecholamines remains challenging due to their overlapping redox behavior and similar reactivity, which often results in poorly selective reaction pathways. Herein, we report a bioinspired tyrosinase electro-catalytic system that enables the modulation of the catecholamine reactivity through the integration of enzymatic oxidation with electrochemical transformation. The biocatalytic platform consisted of electroactive lignin nanoparticles (LNPs) supporting tyrosinase drop cast on the graphene-based screen-printed electrode. The overall reaction included the oxidation of catecholamines to ortho-quinones, followed by nucleophile addition of cysteine under control of the redox environment. Overall, coupling enzymatic catalysis with electrochemical regulation enabled selectivity in the oxidative functionalization of catecholamines, providing a sustainable strategy for tuning reactivity in advanced bioinspired catalytic systems. Full article

Plant pathogenic fungi pose a major threat to global crop production and food security, necessitating the development of sustainable control agents. This study investigated the antifungal potential of Pseudophaeolus soloniensis, a wood-decaying fungus. A wild strain was isolated from Hebei, China, and identified via morphology and ITS sequencing. A bioactive crude extract (P1) was obtained through optimized solid-state fermentation on A3M medium. Its antimicrobial spectrum was evaluated against major phytopathogenic fungi (e.g., Fusarium graminearum, Aspergillus flavus) and model bacteria (Staphylococcus aureus, Escherichia coli) using mycelial growth inhibition, Minimum Inhibitory Concentration (MIC), and agar diffusion assays. P1 exhibited strong, selective activity, showing significantly greater inhibition against S. aureus than E. coli and pronounced effects against F. graminearum (43.79% inhibition at 20 µg/mL) and A. flavus (73.5% at 0.2 mg/mL). A hormetic-like response was observed for F. oxysporum. Liquid Chromatography-Mass Spectrometry (LC-MS) analysis revealed a diverse secondary metabolome, including flavonoids, alkaloids, quinones, and saponins. These results establish P. soloniensis as a promising source of bioactive metabolites for developing eco-friendly fungicides. Full article

Glaucoma is the leading cause of irreversible blindness worldwide and a paradigmatic age-related neurodegenerative disease in which retinal ganglion cells (RGCs) are selectively lost through mechanisms that extend beyond intraocular pressure. Age-dependent NAD⁺ depletion in RGCs, compounded by the progressive impairment of NAD⁺ biosynthesis and by the hyperactivation of NAD⁺-consuming enzymes under oxidative stress, defines a metabolic vulnerability that current pressure-lowering therapy does not address. Pyrroloquinoline quinone (PQQ) is a tricyclic ortho-quinone present in plant-derived foods that acts on the NAD⁺ pool through a mechanism distinct from that of conventional precursors. Rather than expanding the pool by net synthesis, PQQ binds lactate dehydrogenase and oxidizes NADH to NAD⁺ through catalytic redox cycling, raising NAD⁺ availability without altering the total dinucleotide content and independently of the two biosynthetic enzymes selectively impaired in glaucomatous RGCs. The resulting increase in NAD⁺ availability activates sirtuin-dependent programs that drive mitochondrial biogenesis. PQQ additionally engages an NRF2-dependent antioxidant response, addressing molecular deficits directly implicated in glaucomatous RGC degeneration. In retinal cell models, PQQ preserves ATP content and viability under mitochondrial stress. In vivo, it protects RGC density in optic nerve degeneration models and elevates NAD⁺ along the visual pathway. A randomized clinical trial demonstrated functional improvement in glaucoma patients receiving a PQQ-containing combination. The redox biochemistry of PQQ places it at a mechanistic intersection with the NAD⁺ deficit that characterizes glaucomatous neurodegeneration. Its complementarity with conventional NAD⁺ precursors and neuroprotective compounds acting on distinct molecular targets supports the design of combination regimens addressing multiple dimensions of RGC vulnerability. Critical questions regarding bioavailability, molecular target characterization, and clinical validation in dedicated trials remain open. Full article

Oxidative stress plays an important role in systemic lupus erythematosus (SLE). To elucidate whether it is already present in early phases, we investigate oxidative stress-related genes in incomplete SLE (iSLE) and quiescent SLE (qSLE, inactive disease), as well as the effect of nuclear factor erythroid-derived 2-like 2 (NRF2) activators on NRF2-related genes in peripheral blood mononuclear cells (PBMCs) and HaCaT keratinocytes. In total, 28 qSLE patients, 29 iSLE patients and 21 age- and sex-matched healthy controls (HCs) were included. Serum free thiols, reactive oxygen species (ROS) levels and NRF2-related antioxidant gene expression were measured. Furthermore, PBMCs and HaCaT keratinocytes were treated with the NRF2 activators sulforaphane (SFN) and dimethyl fumarate (DMF) in vitro to assess expression of antioxidant genes. Finally, NRF2 and Heme oxygenase-1 (HMOX1) proteins in non-sun-exposed skin sections were assessed. Thiols were significantly lower in qSLE patients compared to HCs. In whole blood, Kelch-like ECH-associating protein 1 (KEAP1) and catalase (CAT) mRNA levels were significantly reduced in iSLE and qSLE. Treatment with SFN or DMF in PBMCs upregulated HMOX1 and NAD(P)H quinone dehydrogenase-1 (NQO1) mRNA expression and downregulated CAT expression. In HaCaT cells, mRNA expression of HMOX1, NQO1 and thioredoxin was upregulated. There were no differences in protein expression of NRF2 and HMOX1 in skin tissues. In conclusion, in qSLE patients, oxidative stress is elevated, while antioxidant capacity is decreased. A similar trend, although not significant, is seen in iSLE patients, which indicates that redox imbalances are already present in early phases, but not as obvious as in established SLE. NRF2 activators upregulate antioxidant gene expression in PBMCs and HaCaT cells, highlighting their potential role to modulate oxidative stress pathways in SLE. Full article

Substituted p-phenylenediamine-derived quinones (PPD-Qs) have become ubiquitous contaminants in various environmental matrices. However, the understanding of the potential health risks posed by human exposure to these emerging compounds remains limited. In this case–control study, we investigated the association between urinary concentrations of six PPD-Q congeners and colorectal cancer (CRC) risk. Detection frequencies of all target PPD-Qs in human urine ranged from 73.7% to 88.2% in the control group and from 70.2% to 89.6% in the case group. 6PPD-Q (2-((4-methylpentan-2-yl)amino)-5-(phenylamino)cyclohexa-2,5-diene-1,4-dione; mean 1.37 μg/g creatinine), 77PD-Q (2,5-bis((5-methylhexan-2-yl)amino)cyclohexa-2,5-diene-1,4-dione; 0.68 μg/g creatinine), and IPPD-Q (2-(isopropylamino)-5-(phenylamino)cyclohexa-2,5-diene-1,4-dione; 0.70 μg/g creatinine) were the predominant PPD-Qs in urine from healthy controls. In CRC cases, 6PPD-Q had the highest mean urinary level (mean 1.75 μg/g creatinine), followed by DPPD-Q (2,5-bis(phenylamino)cyclohexa-2,5-diene-1,4-dione; 0.83 μg/g creatinine) and IPPD-Q (0.73 μg/g creatinine). After multivariable adjustment, higher urinary levels of 6PPD-Q (OR for Q4 vs. Q1 = 1.79, 95% CI: 1.26–2.32), CPPD-Q (2-(cyclohexylamino)-5-(phenylamino)cyclohexa-2,5-diene-1,4-dione; OR = 1.60, 95% CI: 1.26–1.94), and DPPD-Q (OR = 1.47, 95% CI: 1.25–1.68) were significantly associated with increased CRC odds, with nonlinear exposure–response patterns observed. Mixture analysis suggested a positive joint association between urinary PPD-Q concentrations and the odds of CRC, with 6PPD-Q and DPPD-Q contributing most strongly to the estimated statistical association. These findings highlight the need for further prospective studies and potential regulatory considerations to mitigate public health impacts from these contaminants. Full article

Substituted p-phenylenediamine-quinones (PPD-Qs) are commonly employed as antioxidants in varying rubbers with potential biotoxicological implications in humans. Associations between human PPD-Q exposure and oxidative stress and immune system modulation remain insufficiently characterized. This study investigated the human exposure profile of six PPD-Q homologues and their associations with malondialdehyde (MDA) and immune function biomarkers in a general adult population from Quzhou, China. The six target PPD-Qs were detected in most human serum samples (n = 205), with 2-((4-methylpentan-2-yl)amino)-5-(phenylamino)cyclohexa-2,5-diene-1,4-dione (6PPD-Q) emerging as the dominant compound (mean 1.67 ng/mL; range < LOD–5.46 ng/mL). Serum MDA levels showed significant positive correlations with several PPD-Qs, such as 6PPD-Q, 2,5-bis(o-tolylamino)cyclohexa-2,5-diene-1,4-dione (DTPD-Q), and 2,5-bis(phenylamino)cyclohexa-2,5-diene-1,4-dione (DPPD-Q), suggesting enhanced oxidative stress in humans. Moreover, the serum C-reactive protein level was positively associated with DTPD-Q, 77PD-Q (2,5-bis((5-methylhexan-2-yl)amino)cyclohexa-2,5-diene-1,4-dione), and DPPD-Q; IgA was negatively associated with CPPD-Q (2-(cyclohexylamino)-5-(phenylamino)cyclohexa-2,5-diene-1,4-dione) and 6PPD-Q; IgM was negatively associated with DPPD-Q and 6PPD-Q. These findings provide the first human correlational evidence suggesting associations between PPD-Q exposure and oxidative stress- and immune-related biomarkers, highlighting the need for further research and regulatory attention regarding these tire-derived pollutants. Full article