Search Results (494)

Food safety hazards induce diverse cellular damages including DNA damage, oxidative stress, proteotoxic stress, and membrane disruption, ultimately contributing to various human diseases. Conventional toxicity assays, while effective, are often resource-intensive and lack the capacity to distinguish among these different damage types, thereby limiting insight into toxic responses and the development of effective strategies for targeted risk mitigation. Here, we constructed a panel of Escherichia coli whole-cell biosensors capable of distinguishing distinct categories of cellular damage. Specifically, an optimized RecA-LexA-based DNA damage biosensor that precisely controls the exogenous expression of the transcriptional repressor LexA achieved a 35.5% reduction in baseline signal and a 36.6-fold induction of fluorescence. In parallel, systematic promoter screening identified P_fpr, P_katG, P_grpE, and P_fabA as effective modules for constructing oxidative, proteotoxic, and membrane stress biosensors. These biosensors exhibited high specificity and sensitivity, generating dose-dependent responses to model toxicants and enabling discrimination of cellular damage induced by typical hazards such as norfloxacin and ciprofloxacin. Notably, the DNA damage biosensor detected norfloxacin with a limit of detection (LOD) of 1.3 ng/mL in standard solution and 3.0 ng/mL in milk, comparable to that of high-performance liquid chromatography (HPLC). Together, our work not only provides a versatile, cost-effective, and sensitive tool for assessing diverse cellular damages induced by food safety hazards, but also demonstrates potential utility for practical food safety monitoring. Full article

Human DNA is continuously exposed to endogenous and exogenous agents that generate over 100,000 lesions per cell each day. In addition to damage to nucleobases, deoxyribose, and phosphate groups, a particularly harmful class of lesions involves non-canonical DNA termini—structures deviating from the canonical 3′-hydroxyl and 5′-phosphate ends. These aberrant DNA ends can obstruct essential DNA transactions and, if left unrepaired, contribute to cytotoxicity and mutagenesis. Their biological significance is further highlighted by the severe pathologies linked to deficiencies in DNA end-processing enzymes, including inflammation, cancer predisposition syndromes, neurodegeneration, and aging. This review highlights recent advances in our understanding of the formation, prevalence, and repair mechanisms of several key non-canonical DNA end structures, including 3′-phosphate, 3′-phosphoglycolate, 3′-α,β-unsaturated aldehyde and its glutathione derivative, 5′-deoxyribose-5-phosphate, 2′-deoxyribonucleoside-5′-aldehyde, and 5′-adenosine monophosphate. These non-canonical DNA terminal structures arise from various sources, such as radical-induced oxidation of the 2-deoxyribose moiety and DNA repair pathways. While this review does not cover the full spectrum of non-canonical termini, the selected structures are emphasized based on quantitative data supporting their biological relevance. The review also discusses their broader implications in mitochondrial DNA maintenance and inflammatory signaling and highlights key knowledge gaps that warrant further investigation. Full article

The persistent residual tumor cells that survive after chemotherapy are a major cause of treatment failure, but their survival mechanisms remain largely elusive. These cancer cells are typically characterized by a quiescent state with suppressed activity of MYC and MTOR. We observed that the MYC-suppressed persistent triple-negative breast cancer (TNBC) cells are metabolically flexible and can upregulate mitochondrial oxidative phosphorylation (OXPHOS) genes and respiratory function (“OXPHOS-high” cell state) in response to DNA-damaging anthracyclines such as doxorubicin, but not to taxanes. The elevated biomass and respiratory function of mitochondria in OXPHOS-high persistent cancer cells were associated with mitochondrial elongation and remodeling, suggestive of increased mitochondrial fusion. A genome-wide CRISPR editing screen in doxorubicin-persistent OXPHOS-high TNBC cells revealed the BCL-XL gene as the top survival dependency in these quiescent tumor cells, but not in their untreated proliferating counterparts. Quiescent OXPHOS-high TNBC cells were highly sensitive to BCL-XL inhibitors, but not to inhibitors of BCL2 and MCL1. Interestingly, inhibition of BCL-XL in doxorubicin-persistent OXPHOS-high TNBC cells rapidly abrogated mitochondrial elongation and respiratory function, followed by caspase 3/7 activation and cell death. The platelet-sparing proteolysis-targeted chimera (PROTAC) BCL-XL degrader DT2216 enhanced the efficacy of doxorubicin against TNBC xenografts in vivo without induction of thrombocytopenia that is often observed with the first-generation BCL-XL inhibitors, supporting the development of this combinatorial treatment strategy for eliminating dormant tumor cells that persist after treatment with anthracycline-based chemotherapy. Full article

Autism spectrum disorder (ASD) is a complex group of severe neurodevelopmental disorders characterized by varying degrees of dysfunctional communication and social abilities as well as repetitive and compulsive stereotypic behaviors. We aim to evaluate the genetic predisposition to oxidative response and its relationship with altered oxidative stress markers in ASD patients. Genomic DNA was isolated from peripheral blood lymphocytes of 106 (83 M, 23 F; 7.9 ± 3.2 years) ASD patients and 90 healthy subjects (63 M, 27 F; 21.2 ± 1.8 years). Genotyping was performed by real-time PCR-based allelic discrimination, PCR and electrophoresis of GST deletion variants. Reactive oxygen metabolites (dROMs), the Biological Antioxidant Potential (BAP), and the advanced oxidation protein products (AOPP) were also measured. Furthermore, we assessed oxidative DNA damage by Single Cell Gel Electrophoresis. The evaluation of oxidative stress markers indicated a mild oxidative stress status and a higher level of DNA damage in nuclei of ASD patients’ lymphocytes. We found significant associations between ASD and several polymorphisms of genes involved in the detoxification and the response to oxidative stress. Genetic and environmental factors contribute to the onset of autism spectrum disorder, and ASD patients’ treatment requires a multimodal approach, including behavioral, educational, and pharmacological approaches. Full article

Chronic kidney disease (CKD) affects nearly 10% of the global population, ranks among the top ten causes of death, and often progresses silently to end-stage disease without timely intervention. Increasing evidence indicates that many adult-onset cases originate in early life through adverse influences on kidney development, a process termed kidney programming within the Developmental Origins of Health and Disease (DOHaD) framework. Environmental pollutants are now recognized as key drivers of kidney injury across the life course. Heavy metals, air pollutants, plastic contaminants such as bisphenol A, phthalates, and micro/nanoplastics—as well as biocontaminants like mycotoxins and aristolochic acid—and chronic light pollution can accumulate in kidney tissue or act systemically to impair function. These exposures promote oxidative stress, inflammation, and endothelial and circadian disruption, culminating in tubular injury, glomerular damage, and fibrosis. Notably, early-life exposures can induce epigenetic modifications that program lifelong susceptibility to CKD and related complications. Oxidative stress is central to these effects, mediating DNA, lipid, and protein damage while influencing developmental reprogramming during gestation. Preclinical studies demonstrate that antioxidant-based interventions may mitigate these processes, providing both renoprotective and reprogramming benefits. This review explores the mechanistic links between environmental pollutants, oxidative stress, and kidney disease and highlights antioxidant strategies as promising avenues for prevention and intervention in vulnerable populations. Full article

Oxidative stress, resulting from an imbalance between reactive oxygen species (ROS) production and the antioxidant defense system, plays a central role in the pathophysiology of numerous diseases, including cardiovascular, neurodegenerative, and inflammatory disorders. This review explores the biochemical mechanisms of ROS-induced damage to lipids, proteins, cholesterol, and DNA, and analyzes both endogenous (enzymatic and non-enzymatic) and exogenous (nutritional) antioxidant systems that counteract oxidative damage. Key enzymes such as superoxide dismutase, catalase, and glutathione peroxidase, alongside dietary antioxidants like vitamins C and E, polyphenols, and carotenoids, are highlighted for their protective roles. The dual antioxidant/pro-oxidant behavior of these compounds under varying physiological conditions is discussed. Furthermore, this paper reviews the cellular repair systems activated in response to oxidative injury and the biomarkers used to assess oxidative stress in clinical settings. Special attention is given to the implications of oxidative stress in cardiovascular and autoimmune diseases and the potential of antioxidant strategies in disease prevention and therapy. The findings underscore the importance of maintaining redox homeostasis and support further research into antioxidant-based interventions. Full article

Isocitrate dehydrogenase 1 (IDH1) mutations are key drivers of glioma biology, influencing tumor aggressiveness and treatment response. To elucidate their molecular impact, we performed proteome analysis on patient-derived (PD) and U87MG glioma cell models with either mutant or wild-type IDH1. We quantified over 6000 protein groups per model, identifying 1594 differentially expressed proteins in PD-AS (IDH1_MUT) vs. PD-GB (IDH1_WT) and 904 in U87_MUT vs. U87_WT. Both IDH1_MUT models exhibited enhanced MHC antigen presentation and interferon signaling, indicative of an altered immune microenvironment. However, metabolic alterations were model-dependent: PD-AS cells shifted toward glycolysis and purine salvage, while U87_MUT cells retained oxidative phosphorylation, potentially due to D2-hydroxyglutarate (2OHG)-mediated HIF1A stabilization. We also observed a predominance of downregulated DNA repair proteins in IDH1_MUT models, particularly those involved in homologous recombination. In contrast, RB1 and ASMTL were strongly upregulated in both IDH1_MUT models, implicating them in DNA repair and cellular stress responses. We also found distinct expression patterns of proteins regulating histone methylation in IDH1_MUT cells, favoring increased methylation of H3K4, H3K9, and H3K36. A key driver of this may be the upregulation of SETD2 in PD-AS, an H3K4 and H3K36 trimethyltransferase linked to the recruitment of HIF1A as well as DNA mismatch repair proteins. This study uncovers candidate biomarkers and pathways relevant to glioma progression and therapeutic targeting, but also underscores the complexity of predicting glioma pathogenesis and treatment responses based on IDH1 mutation status. While proteome profiling provides valuable insights, a comprehensive understanding of IDH1_MUT gliomas will likely require integrative multi-omics approaches, including DNA/RNA methylation profiling, histone and protein post-translational modification analyses, and targeted DNA damage and repair assays. Full article

Vascular health relies on the proper function of endothelial cells, which regulate vascular tone, blood fluidity, and barrier integrity. Endothelial dysfunction, often aggravated by inadequate vitamin absorption, contributes to a spectrum of clinical disorders, including cardiovascular disease, cerebrovascular disease, peripheral artery disease, age-related macular degeneration, lymphedema, and chronic venous insufficiency. B-group vitamins (especially folate, or vitamin B9), along with vitamins B12, B6, C, D, and E, are essential in maintaining endothelial function, supporting DNA synthesis, regulating methylation, enhancing cellular repair, mitigating oxidative stress and inflammatory signaling, and curtailing vascular damage. Folate is noted for its central function in one-carbon metabolism and in converting homocysteine to methionine, thereby reducing vascular toxicity. We cover natural dietary sources of folate, synthetic folic acid, and the biologically active forms 5-methyl-(6S)-tetrahydrofolate (L-5-MTHF, L-methylfolate) and 5-formyl-(6S)-tetrahydrofolate (levoleucovorin). Therapeutic strategies to address vascular health and prevent hyperhomocysteinemia in order to preclude follow-on disorders include targeted vitamin supplementation, dietary improvements to ensure a sufficient intake of bioavailable nutrient forms, and, in certain clinical contexts, the use of active L-methylfolate or levoleucovorin (a drug product) to bypass metabolic conversion issues. These evidence-based interventions aim to restore endothelial homeostasis, slow disease progression, and improve patient outcomes across a variety of disorders linked to poor vascular health. Full article

Liver transplantation is commonly used for end-stage liver disease, but the demand for organs exceeds the supply, leading to the use of expanded criteria donors (ECDs). Organs from ECDs, especially from donors after circulatory death (DCD), encounter challenges like increased ischemia damage. Biomarkers, especially oxidative stress markers, may provide valuable insights for understanding and monitoring post-transplant events. Here, we highlight the unique value of organ preservation solution (OPS) as a non-invasive and early source of redox biomarkers, directly reflecting graft status during critical cold storage. This study investigated oxidative stress in 74 donated livers using OPS samples collected after cold storage, and also liver biopsies obtained before and after storage. We measured lipid peroxidation, protein carbonylation, DNA oxidation, and total antioxidant capacity from OPS, and performed gene expression analysis of liver biopsies. Oxidative stress markers differed based on donation type, with higher lipid peroxidation in DCD samples compared with donation after brain death (18.51 ± 2.77 vs. 11.03 ± 1.31 nmoles malondialdehyde (MDA)/mg protein; p = 0.049). Likewise, oxidative damage markers were associated with clinical outcomes: lipid peroxidation was increased in patients who developed biliary complications (21.86 ± 5.91 vs. 11.97 ± 1.12 nmol MDA/mg protein; p = 0.05), and protein carbonylation was elevated in those experiencing acute rejection (199.6 ± 22.02 vs. 141.6 ± 15.94 nmol carbonyl/mg protein; p = 0.005). Moreover, higher protein carbonylation levels showed a trend toward reduced survival (p = 0.091). Transcriptomic analysis revealed overexpression of genes associated with reactive oxygen species production in DCD livers. A predictive model for acute rejection integrating OPS biomarkers with clinical variables achieved 83% accuracy. Hence, this study underscores the importance of assessing oxidative stress status in preservation fluid as a biomarker for evaluating liver transplant outcomes and highlights the need for validation in larger, independent cohorts. Full article

Computed tomography (CT) is fundamental to modern medicine, yet ionizing radiation (IR) exposure causes DNA damage. Although often underestimated, at current doses, CT may account for ~5% of new cancer diagnoses. Complementary radioprotective approaches beyond dose reduction are needed. We conducted a prospective observational study to characterize IR-induced oxidative stress (OS)-mediated DNA damage in modern CT to explore potential antioxidant-based radioprotective strategies. In volunteers not exposed to IR (A_NONE) and in patients with two-phase abdominal–pelvis CT (B_EXPOSURE), blood samples were collected at T_BASE-min 0 and T_POST-min 60 to measure biomarkers of OS (oxidative damage and antioxidant capacity) and DNA damage. Thirty-five subjects (n = 17 A_NONE/18 B_EXPOSURE) were studied. Body mass index and DNA damage in T_BASE were comparable between groups. In A_NONE, biomarkers of OS and DNA damage did not change between T_BASE and T_POST (p > 0.05 for all). In B_EXPOSURE, DNA damage was significantly increased [15% (−15–60); p < 0.001], which was associated with consistent increased antioxidant enzyme activity [p < 0.05 for all antioxidant enzymes]. In modern CT with relatively low effective dose (ED) levels, a significant increase in DNA damage was observed along with increased antioxidant enzyme activity as defensive response and marker of OS-mediated damage-mediating mechanisms. These findings warrant interventional studies to evaluate antioxidant-based radioprotective strategies. Full article

Nanoparticles have emerged as innovative tools for combating bacterial infections, offering a potential solution to antibiotic resistance and the limitations of conventional antimicrobials. Nanoparticles exhibit antibacterial activity through multiple mechanisms, including oxidative stress induction, metal ion release, direct membrane damage, disruption of DNA and proteins, and indirect immune system enhancement. Rickettsia helvetica, R. monacensis, R. slovaca, and R. conorii subsp. raoultii are tick-borne pathogens transmitted by Ixodes ricinus, Dermacentor reticulatus, and D. marginatus ticks across Europe causing spotted fever rickettsiosis. While rickettsioses are successfully treated with antibiotics, resistance of rickettsiae to antimicrobial therapy has been reported. Here, we evaluated the anti-rickettsial activity of silver (AgNPs), selenium (SeNPs), and chitosan (CSNPs) nanoparticles against R. conorii subsp. caspia, a tick-borne bacterial pathogen, in African green monkey kidney cell line (Vero). At their highest non-cytotoxic concentrations, CSNPs exhibited the strongest inhibitory effect (87%). SeNPs also significantly reduced bacterial load (76%), although their efficacy was constrained by cytotoxicity at higher doses. In contrast, AgNPs did not show significant activity under the tested conditions. The differences observed among nanoparticles reflect both the antimicrobial properties and host cell tolerance limits. These findings highlight CSNPs and SeNPs as promising candidates for further development of nanoparticle-based strategies to combat intracellular, tick-borne pathogens. Full article

In this century, cancer is one of the most important causes of death worldwide, and the need for the development of new treatment options is imperative. The use of metal-based compounds in cancer treatment has increased significantly due to certain properties of these elements, and vanadium has been one of the most studied transition metals in recent decades. Vanadium compounds are being explored as an option for cancer treatment because of their wide range of action mechanisms such as the induction of oxidative stress, DNA damage, cell cycle arrest, induction of apoptosis and regulation of the autophagy process, among the most important mechanisms. Their compounds have been demonstrated to be effective against the cancer types with the highest incidence and mortality rates worldwide, such as lung and breast cancer, with promising results. This review discusses a variety of new vanadium compounds, indicating their mechanisms of action and the neoplasms in which they have shown effectiveness. Full article

Spinal cord injury (SCI) is a debilitating neurological condition marked by primary mechanical damage followed by a complex secondary injury cascade, in which oxidative stress plays a central role. Mitochondrial dysfunction, ionic imbalance, and inflammatory responses drive excessive generation of reactive oxygen and nitrogen species, leading to lipid peroxidation, protein and DNA damage, apoptosis, and progressive neurological impairment. Antioxidant-based therapies have emerged as promising neuroprotective strategies, with compounds such as A91 peptide, curcumin, edaravone, ginsenosides, and glutathione demonstrating preclinical efficacy in reducing oxidative damage, restoring redox balance, modulating signaling pathways (e.g., Nrf2, NF-κB, MAPK, PI3K/Akt), and enhancing neuronal survival. While therapeutic outcomes depend on injury severity, timing, and combinatorial approaches, translating these findings into clinical practice and integrating antioxidants with cell-based therapies, biomaterials, and rehabilitation offers a critical avenue for improving functional recovery in SCI. Full article

Oxidative stress, defined as the imbalance between reactive oxygen species (ROS) and antioxidant defenses, plays a pivotal role in the pathogenesis of several pregnancy complications, notably preeclampsia (PE), gestational diabetes mellitus (GDM), fetal growth restriction (FGR), and recurrent pregnancy loss (RPL). During normal pregnancy, low to moderate ROS levels support essential placental functions such as angiogenesis and trophoblast differentiation. However, excessive ROS production overwhelms antioxidant systems, leading to lipid peroxidation, protein and DNA damage, and impaired placental function. This review synthesizes current evidence linking oxidative stress to adverse pregnancy outcomes, highlighting key biomarkers such as malondialdehyde (MDA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and 8-iso-prostaglandin F2α (8-iso-PGF2α). While antioxidant therapies—particularly vitamins C and E, selenium, and folic acid—have shown promise in reducing oxidative markers, their impact on clinical outcomes remains inconsistent. The variability in results underscores the need for standardized biomarker protocols and personalized treatment strategies based on genetic predispositions and baseline oxidative status. Future research may better harness antioxidant interventions to improve maternal–fetal health by addressing these gaps. Full article

Equine semen preservation is fundamental to modern equine reproduction, supporting breeding programs, genetic conservation, and industry sustainability. However, significant challenges persist, including temperature sensitivity, oxidative stress, bacterial contamination, individual variability, and lack of standardized preservation protocols. These factors contribute to reduced sperm viability and fertility following cryopreservation. This review examines critical obstacles in equine semen preservation, focusing on cryopreservation sensitivity, molecular damage mechanisms, economic constraints, and seasonal quality variations. We analyze the molecular and structural alterations (e.g., oxidative stress, membrane damage, and DNA fragmentation) and their impact on cryopreservation success. The review evaluates evidence-based enhancement strategies, including nutritional supplementation and genetic approaches, for improving semen quality. Nutritional interventions that utilize antioxidants, polyunsaturated fatty acids (PUFAs), and nutraceuticals have demonstrated promising results in enhancing sperm motility, preserving membrane integrity, and improving overall semen quality. Additionally, we discuss key candidate genes associated with equine semen-quality traits, including sperm motility, viability, and cryotolerance. The integration of nutritional supplementation and genetic selection strategies presents viable pathways for optimizing equine semen preservation techniques. These combined approaches offer potential solutions for overcoming current limitations, ultimately supporting sustainable breeding programs and advancing genetic conservation efforts in the equine industry. Full article