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At least 19 recordsLinked to original sources
PubMed2026

CaCl2 Priming Boosts Salinity-Alkalinity Tolerance in Germinating Soybean by Reducing DNA Oxidative Damage and Enhancing Ca2+ -ROS Signaling Crosstalk.

Soybean (Glycine max) seed germination is highly sensitive to saline-alkaline stress. Seed priming represents an effective strategy to mitigate its detrimental effects. However, the optimal priming conditions (agent, concentration, duration) and the underlying molecular mechanisms remain poorly understood. This study investigated the effects of priming with distilled water (Control), calcium chloride (CaCl2), melatonin (MT), and proline (Pro) under saline-alkaline stress on soybean seed germination and the molecular basis of enhanced tolerance. Evaluation of ten germination-related parameters revealed that priming with 100 mM CaCl2 for 12 h significantly enhanced the germination rate. Physiological analyses demonstrated that CaCl2 priming effectively reduced reactive oxygen species (ROS) accumulation by increasing the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), while decreasing malondialdehyde (MDA) content. Furthermore, CaCl2 priming activated the Ca2+ signaling pathway by increasing radicle Ca2+ content and upregulating the expression levels of Ca2+ signaling-related genes (e.g., GmCAM7, GmCNGC2, GmCNGC19, GmMPK2, and GmMKK2). Additionally, CaCl2 priming significantly enhanced DNA damage repair capacity of soybean cultivars with differing saline-alkaline tolerance. This was manifested by reduced DNA oxidative damage and decreased random amplified polymorphic DNA (RAPD) polymorphism, thereby enhancing genomic stability and alleviating cell cycle arrest. These findings deepen our understanding of the complex regulatory role of calcium signaling in plant abiotic stress responses and provide important novel theoretical insights for improving crop resilience.

Glycine max↗
PubMed2026

Enoxaparin induces apoptosis and autophagy, modulates inflammatory signaling, and reduces oxidative DNA damage in breast and liver cancer cells.

Cancer progression involves intricate interactions between inflammatory signaling, programmed cell death mechanisms, and oxidative stress. Although enoxaparin is widely used for managing cancer-associated thrombosis, its direct cellular effects on tumor biology remain insufficiently characterized. This study aimed to evaluate the impact of enoxaparin on apoptosis, autophagy, inflammatory mediators, and oxidative DNA damage in breast (MDA-MB-231) and liver (HepG2) cancer cell lines. MDA-MB-231, HepG2, and non-cancerous HEK-293 cells were treated with varying concentrations (5, 10, 20, 40, and 80 mg/mL) of enoxaparin for 24 and 48 h. Cell viability was assessed using the MTT assay, while apoptosis was quantified by TUNEL analysis. Immunofluorescence staining was employed to evaluate the expression of NF-κB, IL-6, TNF-α, LC3, and p62. Oxidative DNA damage was determined by measuring extracellular 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels using a competitive ELISA. Statistical analyses were conducted to compare the treated and control groups. Enoxaparin significantly reduced cell viability in MDA-MB-231 and HepG2 cells without inducing cytotoxicity in HEK-293 cells. Apoptosis was markedly increased in both cancer cell lines following treatment. Enoxaparin differentially modulated inflammatory signaling; NF-κB expression was significantly increased in MDA-MB-231 cells, accompanied by suppression of IL-6 and TNF-α, whereas no significant inflammatory changes were observed in HepG2 cells. Enoxaparin treatment was observed to increase LC3 and p62 expression in both MDA-MB-231 and HepG2 cells, triggering autophagy-related pathways. Moreover, enoxaparin significantly reduced extracellular 8-OHdG levels, suggesting a reduction in oxidative DNA damage. Enoxaparin exhibits multifaceted anticancer effects by promoting apoptosis and autophagy, selectively modulating inflammatory pathways, and reducing oxidative DNA damage in breast and liver cancer cells.

Humans↗
PubMed2026

Navigating the base excision repair pathway in chromatin-focus on oxidative DNA damage.

Chromatin environment influences all nuclear processes, including DNA repair. Conversely, DNA damage itself triggers chromatin modifications and remodeling, which are essential for efficient DNA repair and its coordination with transcription, replication, and epigenetic regulation to preserve genome function. While chromatin dynamics associated with double-strand break repair and nucleotide excision repair are well understood, those accompanying base excision repair (BER) remain comparatively poorly characterized. Yet, BER is responsible for eliminating a wide spectrum of chemically diverse and non-helix-distorting base modifications, arising from both endogenous and exogenous sources, and is implicated in numerous pathologies. This review examines how BER operates in the context of chromatin, with a focus on its interplay with other repair factors, chromatin modifications, and remodeling. It also explores the diversity of BER substrates, the blurred distinction between base lesions and programmed modifications, and the intricate link between BER, transcriptional regulation, and epigenetic reprogramming. Together, these insights highlight BER's pivotal role in maintaining genome stability, shaping transcriptional programs, and preventing disease.

Excision Repair↗
PubMed2026

A novel DNA-protective function of Escherichia coli thioredoxin 2 mediated by its N-terminal zinc-binding domain.

Thioredoxins are ubiquitous thiol-disulfide oxidoreductases that maintain intracellular redox homeostasis. In addition to its conserved catalytic domain, Escherichia coli thioredoxin 2 (EcTrx2) possesses a unique N-terminal zinc-binding domain whose physiological function remains largely unknown. Here, we identify a previously unrecognized DNA-binding activity of EcTrx2 and demonstrate its role in protecting DNA during oxidative stress. Electrophoretic mobility shift assays showed that EcTrx2 bound plasmid DNA in a concentration-dependent and GST-tag-independent manner, whereas EcTrx1 exhibited no detectable DNA-binding activity. DNA binding was abolished by deletion of the N-terminal zinc-binding domain and was blocked by zinc occupancy, indicating that this unique domain is essential for DNA interaction. Consistent with these findings, EcTrx2 significantly protected plasmid DNA from DNase I digestion and hydroxyl radical-mediated oxidative damage in vitro. Furthermore, EcTrx2 enhanced bacterial tolerance to the DNA-damaging agents zeocin and diamide, supporting the physiological relevance of its DNA-binding activity. Our results reveal a DNA-binding role for EcTrx2 and identify its N-terminal zinc-binding domain as a key determinant of DNA binding and protection against oxidative DNA damage.

DNA binding↗
PubMed2025

A bacterial PrimPol-reverse transcriptase hybrid protein has a proofreading exonuclease activity that can be transferred to other reverse transcriptases.

Gene disruption analysis revealed that an E. coli PPRT protein, which has an N-terminal Primase-Polymerase (PrimPol) domain fused to a group II intron-like reverse transcriptase (RT) domain followed by a long C-terminal domain (CTD), contributes to a cellular oxidative DNA damage response in addition to its previously described function in phage defense. Biochemical analysis showed that the PrimPol domain has an error-prone DNA polymerase activity that enables read through of oxidation-induced DNA damage. Surprisingly, we found that the RT-like domain, in addition to synthesizing protein-primed DNAs for phage defense, has a 3' to 5' DNA exonuclease activity that functions in proofreading DNAs synthesized by the PrimPol domain. Extending these findings, we identified structural features that contribute to this proofreading activity, enabling us to associate it with both a group II intron-encoded and retroviral RT and suggesting general methods for incorporating proofreading activity into RTs.

DNA sequencing↗
PubMed2025

Combination of cycling hyperthermia and echinacoside creates a synergistic curing effect on pancreatic cancer PANC-1 cells.

Therapy targeting the suppression of human MutT homolog 1 (MTH1) has been gaining ground in recent years, thanks to its resulting significant increase of 8-hydroxy-2'-deoxyguanosine triphosphate (8-oxo-dGTP) accumulation in genomic DNA, causing DNA damage and apoptotic cell death. Echinacoside (Ech), a natural phenylethanoid glycoside first extracted from Echinacea angustifolia or desert plant Cistanches, is one of a few natural products that are capable of inhibiting the MTH1 function. It, however, is difficult to apply it in clinical trials, due to high cost for effective dosage in need. In this study, we show that the integration of Ech with thermal cycling-hyperthermia (TC-HT), a novel physical treatment, significantly augments its anticancer efficacy while simultaneously decreasing the necessary dosage. Specifically, 20 μM Ech with TC-HT reduced human pancreatic carcinoma cell line PANC-1 viability to 29.6% of the control, comparable to 28.7% of the control by 100 μM Ech alone. The combined treatment reduced MTH1 expression to 0.42-fold, initiating oxidative damage and apoptosis. Notably, 8-oxo-dGTP increased to 3.67-fold of the control, indicating enhanced oxidative DNA damage and 31.8% apoptosis. This oxidative stress further influenced critical signaling pathways, as p-ERK and p-JNK shifted to 0.59- and 5.55-fold, respectively, indicating a switch from survival to apoptotic signaling. Concurrently, mitochondrial apoptotic markers Bax/Bcl-2 and cleaved poly (ADP-ribose) polymerase increased to 4.22- and 7.12-fold, respectively. These results indicate that its effect is expected to be comparable to the treatment strategy containing MTH1, Bcl-2, and extracellular signal-regulated kinase inhibitors, posing as new promising approach in cancer treatment.

DNA damage↗
PubMed2026

UVB-aged polystyrene microplastics induce enhanced stress responses in human proximal tubular cells.

Microplastics (MPs) are increasingly detected in human biological matrices, raising concerns about their potential systemic effects, including on the kidney. However, the cellular responses of renal tubular epithelium to MPs and the role of environmental aging processes in modulating their biological activity remain poorly defined. Under environmental conditions, MPs undergo photo-oxidative transformations that alter their surface chemistry and may influence their interactions with biological systems. In this study, we investigated the effects of 1 µm polystyrene MPs in virgin (MPsV) and UVB-oxidised (MPsOx) forms in a human renal proximal tubular cell line (HK-2). Cells were exposed to MPs (25 and 50 µg/mL), and multiple endpoints related to cellular stress and genomic stability were evaluated, including lysosome-associated responses, oxidative damage, DNA integrity, micronucleus formation, DNA-content distribution profiles as an indirect proxy of proliferative status, and cytoskeletal organisation. Exposure to MPs induced measurable stress responses in tubular cells, with oxidised particles generally eliciting stronger effects than MPsV. These responses were consistent with increased oxidative stress, lysosome-associated cellular responses, genomic instability-associated alterations, activation of stress-responsive molecular pathways, and cytoskeletal perturbation. Collectively, these findings indicate that environmentally aged polystyrene MPs elicit more evident cellular stress responses than their virgin counterparts in HK-2 cells. Our results highlight the importance of incorporating environmentally transformed MPs into toxicological testing frameworks to improve the biological relevance of hazard assessment.

Genotoxicity↗
PubMed2026

CRISPR/Cas9-mediated editing of ERCC6 in iPSCs: A disease model for Cockayne Syndrome type B.

Cockayne Syndrome type B (CSB) is caused by mutations in the ERCC6 gene, which encodes a key protein involved in transcription-coupled nucleotide excision repair (TC-NER) and chromatin remodeling. Deficiency in CSB leads to defective transcriptional recovery after DNA damage, oxidative stress accumulation, and progressive neurodegeneration. In this work, we generated a CRISPR/Cas9-engineered human induced pluripotent stem cell (iPSC) line, IUFi004-A-12, carrying a homozygous mutation in ERCC6 causing a premature stop codon in its 10th exon. The modified iPSCs displayed normal morphology, expressed pluripotency markers, and differentiated into all three germ layers. This model enables mechanistic studies of CSB dysfunction and facilitates therapeutic development for Cockayne Syndrome.

Humans↗
PubMed2026

Vitamin D Supplementation Modulates Base Excision Repair (BER) Machinery in Systemic Sclerosis: A Prospective Longitudinal Study.

Systemic sclerosis (SSc) is a chronic, autoimmune, fibrotic disorder involving immune dysregulation, vascular abnormalities and progressive fibrosis. Although oxidative stress and defective DNA repair have been implicated in its pathogenesis, the impact of vitamin D on DNA repair pathways remains unclear. This study aimed to investigate the expression of DNA repair enzymes in SSc, explore their relationship with vitamin D status and assess the effects of vitamin D supplementation on the transcriptional expression of these enzymes. Peripheral blood samples were collected from 52 female patients with SSc and 31 age-matched healthy controls (HCs). Gene expression levels of base excision repair (BER) enzymes (APE1 and OGG1) and nucleotide excision repair (NER) enzymes (XPA and XPC) were analyzed. Serum vitamin D levels were measured and correlated with disease activity scores. In a prospective arm of the study, patients received six months of vitamin D supplementation and their DNA repair capacity was evaluated pre- and post-intervention. Baseline expression of APE1 and OGG1 was significantly lower in SSc patients than in HCs, whereas expression of the NER genes remained unchanged, indicating selective impairment of the BER pathway. Vitamin D deficiency was prevalent in SSc and inversely correlated with disease severity. Supplementation significantly increased serum vitamin D levels and up-regulated APE1 and OGG1 expression; while NER genes remained unaffected. These findings are consistent with evidence of elevated oxidative DNA lesions in SSc and support a mechanistic link between BER activity and the repair of oxidative DNA damage. SSc patients exhibit reduced transcription of BER-specific enzymes associated with vitamin D deficiency andrestoration of vitamin D levels partially rescues BER enzyme expression. These findingshighlight a potentially modifiable axis linking micronutrient status, genomic stability and disease activity and provide a rationale for investigating vitamin D optimization as an adjunctive strategy to enhance DNA repair and potentially attenuate inflammatory and fibrotic processes in SSc.

Humans↗
PubMed2024

The Ercc1-/Δ mouse model of XFE progeroid syndrome undergoes accelerated retinal degeneration.

Age-related macular degeneration (AMD) is a major cause of vision loss in older adults. AMD is caused by degeneration in the macula of the retina. The retina is the highest oxygen consuming tissue in our body and is prone to oxidative damage. DNA damage is one hallmark of aging implicated in loss of organ function. Genome instability has been associated with several disorders that result in premature vision loss. We hypothesized that endogenous DNA damage plays a causal role in age-related retinal changes. To address this, we used a genetic model of systemic depletion of expression of the DNA repair enzyme ERCC1-XPF. The neural retina and retinal pigment epithelium (RPE) from Ercc1-/Δ mice, which models a human progeroid syndrome, were compared to age-matched wild-type (WT) and old WT mice. By 3-months-of age, Ercc1-/Δ mice presented abnormal optokinetic and electroretinogram responses consistent with photoreceptor dysfunction and visual impairment. Ercc1-/Δ mice shared many ocular characteristics with old WT mice including morphological changes, elevated DNA damage markers (γ-H2AX and 53BP1), and increased cellular senescence in the neural retinal and RPE, as well as pathological angiogenesis. The RPE is essential for the metabolic health of photoreceptors. The RPE from Ercc1-/Δ mice displayed mitochondrial dysfunction causing a compensatory glycolytic shift, a characteristic feature of aging RPE. Hence, our study suggests spontaneous endogenous DNA damage promotes the hallmarks of age-related retinal degeneration.

Animals↗
PubMed2026

Interpreting cancer genetics through a two-step "evolutionary cascade hypothesis": bridging neutral and selective perspectives.

BACKGROUND: DNA mutations are the fundamental engines of cancer, driving its initiation and progression. The forces that fuel malignancy are also the architects of evolution, shaping life through genetic variations. Mutations, in fact, can emerge naturally from endogenous processes, such as oxidative DNA damage or errors in replication, as well as induced by external factors, including cosmic radiation and chemical carcinogens. MAIN BODY: A key question in cancer research is whether tumor evolution is primarily governed by selective bottlenecks, neutral evolution, or dynamic genetic plasticity. In this work, we examine cancer as a disease driven by evolutionary processes rooted in fundamental biological requirements, including sustained proliferation and nutrient utilization. We hypothesize that the accumulation of mutations activates an evolutionary switch, enabling tumor cells to acquire an enhanced capacity for survival, adaptation, and growth at rates far exceeding typical evolutionary timescales. We propose the "evolutionary cascade hypothesis," a unifying framework that integrates these models into a coherent sequence. At its core lies the failure of DNA repair mechanisms, representing a critical transition in cancer progression. This shift marks the transition from an initial non-Darwinian, neutral phase to a Darwinian, more deterministic phase. CONCLUSIONS: As predictive models of tumor evolution advance through genomic big data and artificial intelligence-driven analysis, the future of cancer treatment may extend beyond targeting individual mutations to disrupting the underlying evolutionary mechanisms that sustain malignancy. This paradigm shift could redefine therapeutic strategies and ultimately improve patient outcomes.

Humans↗
PubMed2026

Revealing the Association of LIG1 Genetic Variants With Pterygium Susceptibility and Demographic Characteristics in a Taiwanese Population.

BACKGROUND/AIM: Pterygium is a common ocular surface disorder associated with long-term ultraviolet exposure and/or oxidative DNA damage. Accumulated evidence suggests that defects in DNA repair pathways may contribute to pterygium risk. DNA ligase I (LIG1), a key enzyme involved in DNA replication and base excision repair, has been involved in the etiology of several human diseases, including cancers. However, its role in pterygium has never been examined before. This study aimed at exploring the association between the LIG1 genotypes and pterygium risk in a Taiwanese population. PATIENTS AND METHODS: The hospital-based case-control study was conducted including 165 patients with pterygium and 320 age- and sex-matched non-pterygium controls. LIG1 rs20579 genotypes were accessed utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Stratified analysis and the calculation of odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used for evaluating the associations between genotypes and pterygium risk. RESULTS: Individuals carrying the homozygous variant AA genotype exhibited a significantly elevated risk of pterygium compared with those carrying the GG genotype (OR=2.74, 95% CI=1.17-6.43, p=0.0305). Under the recessive model, the AA genotype conferred a 2.65-fold elevated risk (95% CI=1.14-6.18, p=0.0350). The variant A allele was also associated with increased susceptibility (OR=1.46, 95% CI=1.03-2.07, p=0.0413). Stratified analyses revealed significant associations specifically among individuals aged ≥60 years (OR=5.64, 95% CI=1.67-19.04, p=0.0039) and males (OR=5.23, 95% CI=1.74-15.73, p=0.0034), but not those of younger ages or females. CONCLUSION: The LIG1 rs20579 genotype is significantly associated with pterygium susceptibility in Taiwanese individuals, particularly among elderly and male subjects. These findings support the involvement of impaired DNA repair machinery in pterygium pathogenesis and suggest that LIG1 rs20579 may serve as a novel genetic biomarker for risk assessment and early detection of pterygium.

Humans↗
PubMed2025

Transposition element MERVL regulates DNA demethylation through TET3 in oxidative-damaged mouse preimplantation embryos.

Transposable elements (TEs) comprise approximately half of eukaryotic genomes and significantly contribute to genome plasticity. In this study, we focused on a specific TE, MERVL, which exhibits particular expression during the 2-cell stage and commonly serves as an indicator of embryonic totipotency. However, its precise role in embryo development remains mysterious. We utilized DRUG-seq to investigate the effects of oxidative damage on genes and TEs expression. Our findings revealed that exposure to hydrogen peroxide (H2O2) could induce DNA damage, apoptosis, and incomplete DNA demethylation in embryos, which were potentially associated with MERVL expression. To further explore its function, antisense nucleotides (ASO) targeting MERVL were constructed to knockdown the expression in early embryos. Notably, this knockdown led to the occurrence of DNA damage and apoptosis as early as the 2-cell stage, consequently reducing the number of embryos that could progress to the blastocyst stage. Moreover, we discovered that MERVL exerted an influence on the reprogramming of embryonic DNA methylation. In MERVL-deficient embryos, the activity of the DNA demethylase ten-eleven translocation 3 (TET3) was suppressed, resulting in impaired demethylation when compared to normal development. This impairment might underpin the mechanism that impacts embryonic development. Collectively, our study not only verified the crucial role of MERVL in embryonic development but also probed its regulatory function in DNA methylation reprogramming, thereby laying a solid foundation for further investigations into MERVL's role.

Animals↗
PubMed1977

A test for mutation theory of cancer: carcinogenesis by misrepair of DNA damaged by 4-nitroquinoline 1-oxide.

Evidence for a mutation theory of cancer is presented by reviewing the experimental work on 4-nitroquinoline 1-oxide (4NQO) carcinogenesis. 4NQO almost completely mimics u.v. light and produces 4NQO-purine adducts on DNA. When 4NQO-treated cells are held in liquid medium under appropriate conditions, the 4NQO adducts disappear from DNA, in parallel to decrease of premutational damage in Escherichia coli, or pretransformational damage in cultured mouse cells. Post-treatment with caffeine greatly diminishes the yields by 4NQO of mutants in E. coli, malignant transformants in cultured mouse cells and tumour nodules in the lung of mice. Potentially tumourigenized stem cells in the lung remain sensitive to selective killing by caffeine for at least 5 days after 4NQO treatment, in spite of their DNA being apparently replicated, an indication that carcinogen-damaged DNA in the stem cell can be transmitted to its successive daughter stem cells for many generations. This peculiar characteristic is discussed as a possible lead to the crux of the mutation theory of cancer in vivo, and a model for carcinogenesis is proposed.

4-Nitroquinoline-1-oxide↗
PubMed2026

UVB photoprotection by thiourea and (thio)semicarbazone derivatives: cellular and molecular evidence.

BACKGROUND: Ultraviolet B (UVB) radiation is a major environmental stressor that contributes to oxidative stress, inflammation, DNA damage, and ultimately an increased risk of skin carcinogenesis. The development of safer, multifaceted UV filters with improved photostability and bioprotective properties remains an important research priority. Here, alkyl chain-conjugated thiourea (I-XIX) and aryl-linked (thio)semicarbazone (XX-XXV) derivatives have been systematically assessed for their photoprotective potential against UVB-induced cellular damage. METHODS: The UV absorption properties, molar absorptivity, and photostability of the test compounds were assessed through spectroscopic studies. Cytotoxicity, effective concentrations, and bioprotective effects of the compounds were evaluated using in vitro cellular methods. RESULTS: Several compounds exhibited robust UVB absorption with high molar absorptivity, particularly semicarbazone derivatives, while displaying minimal cytotoxicity to normal human dermal fibroblasts. Among the evaluated compounds, ten compounds were found to be more photostable than benzophenone (reference compound). Selected compounds significantly reduced UVB-induced intracellular reactive oxygen species and nitric oxide production, signifying effective attenuation of oxidative and nitrosative stress. In addition, compounds IV, XXI, and XXIII alleviated UVB-induced inflammatory cascades by diminishing Interleukin-1 beta (IL-1β) and Tumor Necrosis Factor alpha (TNF-α) levels. Therefore, these compounds also protected fibroblast morphology. Moreover, the same compounds protected from DNA damage by preventing UVB-induced genomic DNA fragmentation and formation of cyclobutane pyrimidine dimers. In particular, compound XXIII displayed selective UVB absorption, better photostability, low cytotoxicity, and moderate biological photoprotection (SPF 16). CONCLUSION: Together, the results suggest that thiourea and (thio)semicarbazone derivatives, notably compound XXIII, represent promising photoprotective scaffolds requiring further formulation, in vivo, permeability, phototoxicity, and safety studies to validate their potential as UV-filtering agents.

Humans↗
PubMed2025

Serum uric acid and its metabolism-a vital factor in the inflammatory transformation of cancer.

BACKGROUND: Uric acid (UA) is the terminal product of purine metabolism. Elevated serum uric acid (SUA) levels, resulting from excessive synthesis or impaired excretion, are link to chronic inflammatory stress and increased risks of colorectal, breast, and prostate cancers. Hyperuricemia triggers a cascade of proinflammatory and oxidative responses, establishing a microenvironment conducive to tumorigenesis. AIM OF REVIEW: This review synthesizes evidence on how hyperuricemia drive inflammation and cancer transformation from global foundational research and clinical practice, elucidate UA metabolism as potential therapeutic strategy for inflammation-associated malignancies. KEY SCIENTIFIC CONCEPTS OF REVIEW: Hyperuricemia-induced oxidative stress, DNA damage and genomic instability, while simultaneously activating proinflammatory signaling pathways. These interconnected pathways establish a persistent, proinflammatory microenvironment that fosters the transition from inflammation to cancer. Therapeutic strategies targeting UA metabolism (including pharmacologic interventions and dietary modifications) may mitigate chronic low-grade inflammation and reduce the cancer risk associated with hyperuricemia. Dysregulated UA metabolism emerges as a critical modulator linking chronic inflammation with oncogenesis.

Humans↗
PubMed2026

Integrative Multidimensional Profiling of Individuals Recovered from Mild COVID-19 Reveals Immune-Metabolic-Oxidative Network Interactions.

The COVID-19 pandemic underscored the need to better characterize immune and molecular responses following SARS-CoV-2 infection and vaccination. Beyond antibody and cellular immunity, COVID-19 involves oxidative stress and DNA damage, affecting repair mechanisms and metabolic adaptation linked to immune resilience. Here, we present a multidimensional analysis of 20 individuals who recovered from mild COVID-19, integrating clinical features with humoral and cellular immune responses, T cell and myeloid phenotypes, oxidative stress, DNA damage, and metabolomic and lipidomic profiles. Although most individual parameters fell within physiological ranges, network modeling revealed structured associations spanning multiple biological domains. A central finding was a coherent cluster organized around vaccine dose number, linking anti-Spike antibody titers, oxidative stress, bioenergetic signatures, and granulocyte activation. Higher vaccination was associated with stronger humoral responses, lower oxidative stress, and a more balanced myeloid-metabolic profile, suggesting a potential protective role extending beyond antibody induction. Additional associations linked symptom patterns to T cell differentiation states, anti-nucleocapsid responses to systemic inflammation, and anaerobic signatures to DNA damage markers, revealing interconnections between immunometabolism, clinical expression, and genomic stress. Despite the small sample size, these findings offer a preliminary systems-level perspective on mild COVID-19 recovery and illustrate the value of integrative exploratory frameworks in infectious disease research, laying the groundwork for validation in larger longitudinal cohorts.

Humans↗
PubMed2026

Telomere Length Dynamics as a Biomarker of Individual Radiation Sensitivity and Pneumonitis in Lung Cancer Patients Receiving Thoracic Radiation Therapy.

PURPOSE: Telomere shortening is a biomarker for genome instability and aging, and the vulnerability of telomeric DNA to oxidative damage suggests its potential role in mediating radiation therapy (RT) side effects. This study evaluates telomere length (TL) as a biomarker for clinical radiosensitivity and adverse outcomes in thoracic RT-treated patients. METHODS AND MATERIALS: Patients with cancer receiving thoracic RT (2019-2022) were prospectively enrolled at Brigham and Women's Hospital, Boston, Massachusetts. Peripheral blood mononuclear cells (PBMCs) were collected pre-RT and ≤12 months post-RT. TL was measured using quantitative PCR, and multipathway DNA repair capacity (DRC) was simultaneously assessed by fluorescence multiplex host cell reactivation assays. RT outcomes included patient-reported quality of life and radiation pneumonitis. Linear mixed-effects models were used to analyze TL dynamics; risk prediction models for RT outcomes were evaluated using area under the curve. RESULTS: Pre-RT TL decreased with age (0.44% lower per year; 95% CI, 0.12%-0.77%) and advanced cancer stage (6.87% lower per step increase of stage; 95% CI, 3.45%-10.16%). Radical RT was associated with telomere shortening (3.7% lower; 95% CI, 0.27%-7.07%) in PBMCs, detectable ≤6 months post-RT. Pre-RT TL strongly predicted post-RT changes, and TL dynamics outperformed static measures in predicting symptom burden and radiation pneumonitis. Positive associations were observed between TL and DRC against oxidative lesions, with A:8-oxoG repair capacity mediating 12.8% of RT-induced TL shortening. CONCLUSIONS: Lymphocyte TL can reflect individual radiosensitivity and interact with oxidative damage repair. Longitudinal assessment of TL dynamics provides additional predictive value for adverse RT outcomes compared with static measures. Further studies are needed to fully determine the clinical utility of TL.

Humans↗