Reactive Oxygen Species Research Articles

ABSTRACT Glioma has long been a threat to human health and new treatments are required to address this health problem. We here explored the potential use of benzbromarone as a supplement to existing chemotherapy strategies. The effects of benzbromarone on the proliferation and migration of C6 glioma cells were evaluated by MTT and wound healing assays. The effects of benzbromarone on cell cycle arrest and apoptosis in C6 glioma cells were determined by flow cytometry. The effect of benzbromarone on reactive oxygen species (ROS) production was determined through fluorescence microscopy and flow cytometry. Finally, the effect of benzbromarone on the NF-κB pathway was determined by western blotting and immunofluorescence. Benzbromarone inhibited the growth and migration of C6 glioma cells in a concentration-dependent manner. Benzbromarone also induced cell cycle arrest and apoptosis in C6 glioma cells, in addition to increasing ROS generation. Western blot analysis revealed that benzbromarone activated the NF-κB signaling pathway. Our results suggest that benzbromarone induces cytotoxicity through ROS production. These findings indicate the potential of benzbromarone as a treatment of glioma.

Abstract Background Pancreatic cancer, a highly aggressive malignancy of the digestive tract, is characterized by an insidious onset, nonspecific early symptoms, early metastatic propensity, and resistance to conventional radiotherapy and chemotherapy. These features contribute to its poor clinical outcomes and dismal prognosis. Aims This study aimed to elucidate the molecular mechanisms underlying pancreatic cancer progression, identify clinically actionable diagnostic and therapeutic targets, and ultimately improve patient survival rates and treatment efficacy. Methods Using Enhancer Linking by Methylation/Expression Relationships (ELMER), a computational approach, we identified MAFF as a pivotal transcription factor driving pancreatic cancer progression. The oncogenic role of MAFF was validated through in vitro cellular assays and in vivo xenograft models in nude mice. Transcriptome sequencing and functional experiments further delineated the molecular mechanisms by which MAFF promotes tumorigenesis. Results MAFF knockdown significantly suppressed cell proliferation, colony formation, migration, and invasion in AsPC-1 and SUIT-2 cell lines. Bioinformatics analysis and dual-luciferase reporter assays identified AKR1C1 as a downstream effector of MAFF. Mechanistically, MAFF-AKR1C1 axis led to malondialdehyde (MDA) accumulation, elevated lipid reactive oxygen species (ROS), and ferroptosis inhibition, thereby fostering pancreatic cancer progression. Conclusions Our findings demonstrate that MAFF promotes tumorigenesis by suppressing ferroptosis and nominates MAFF as a promising therapeutic target for pancreatic cancer.

Terazosin (TZ), a well-known antagonist of the α1-adrenergic receptor (α1-AR), has demonstrated protective effects on vascular endothelial cells (ECs) and reduced vascular stiffness in clinical studies. Endothelial dysfunction and oxidative stress are central drivers of cardiometabolic diseases such as diabetes, where sustained ROS burden accelerates EC senescence and barrier failure. These findings suggest its potential role in combating vascular aging and atherosclerosis; however, the underlying mechanisms remain partially understood. In this study, we investigated whether TZ can prevent atherosclerosis in ApoE-/- mice fed a high-cholesterol diet and aimed to elucidate the mechanisms involved. Our results showed that TZ significantly reduced plaque size, EC senescence, vascular permeability, and reactive oxygen species (ROS) levels, effectively inhibiting atherosclerosis independently of α1-AR signaling. In cultured primary human umbilical vein ECs (HUVECs), TZ inhibited EC senescence via the Pgk1/Hsp90 pathway. It enhanced the interaction between Hsp90 and the antioxidant enzyme peroxiredoxin 1 (Prdx1), leading to lower ROS levels-a key driver of cellular senescence. These findings were confirmed in atherosclerotic ApoE-/- mice. Furthermore, senescent ECs exhibited increased levels of vascular endothelial growth factor A (VEGFA) and decreased levels of angiostatin, contributing to higher vascular permeability and exacerbating atherosclerosis. TZ effectively reversed these changes. Overall, our study demonstrates that TZ primarily alleviates EC senescence and atherosclerosis through the Pgk1/Hsp90/Prdx1 pathway, highlighting Pgk1 activation as a strategy that may also mitigate endothelial dysfunction and oxidative stress in broader cardiometabolic contexts (e.g., diabetes), suggesting that TZ is a promising senomorphic agent for treating vascular aging and atherosclerosis in clinical settings and that Pgk1-targeted interventions could have implications beyond atherosclerosis.

We resolved that SlMYC2 positively regulated tomato leaf senescence by inhibiting ROS scavenging capacity and exacerbating oxidative damage and PSII functional decline using a darkness-induced senescence model. Tomato leaf senescence seriously affects its yield and quality. Jasmonic acid (JA) signaling can promote tomato leaf senescence, but the mechanism is unclear. SlMYC2, as a core transcription factor in JA signaling, may play a role in regulating leaf senescence. Therefore, this study used SlMYC2 overexpression and silencing lines to systematically analyze the mechanism of SlMYC2 regulation of leaf senescence through a darkness-induced senescence model. The results showed SlMYC2 accelerated the leaf senescence process in tomato by increased chlorophyll degradation and malondialdehyde accumulation in SlMYC2-OE lines after dark treatment, and the expressions of senescence-related genes SlSGR1, SlSAG12, and SlSAG15 were significantly upregulated. At the photosynthetic physiological level, SlMYC2-OE caused damage to photosystem II (PSII) function, with a significant decrease in maximum photochemical efficiency (Fv/Fm) and performance index (PIABS), and exacerbated damage to the donor side (Wk). Further studies found SlMYC2 accelerated programmed cell death (PCD) by promoting the accumulation of reactive oxygen species (ROS). The contents of superoxide anion (O₂⁻·) and hydrogen peroxide (H₂O₂) significantly increased in the SlMYC2-OE lines, while the contents of ascorbic acid (AsA) and glutathione (GSH), as well as the activities and gene expressions of key antioxidant enzymes such as SOD, POD, CAT, APX, and GR were all inhibited. In summary, SlMYC2 has been shown to inhibit the removal of reactive oxygen species (ROS), exacerbate oxidative damage and photosystem II (PSII) function decline, and positively regulate the process of leaf senescence in tomato. This study will provide a theoretical foundation for targeting the JA signaling pathway to regulate tomato senescence.

Renal ischemia-reperfusion injury (IRI) remains a critical obstacle to optimal renal transplant outcomes, driving acute graft dysfunction and long-term allograft failure. While ferroptosis-an iron-dependent form of cell death-has been linked to IRI pathogenesis, the role of lipocalin-2 (LCN2), a regulator of iron homeostasis and inflammation, in transplant-related renal IRI remains uncharacterized. Six murine IRI transcriptomic datasets (83 samples) were integrated using weighted gene co-expression network analysis (WGCNA) and differential expression profiling to screen for IRI-associated hub genes. Findings were validated in two human transplant cohorts (212 samples) via 113 machine learning algorithms, including logistic regression, random forest, and ensemble models. Single-cell RNA sequencing (GSE237429) was used to map gene expression to specific renal cell populations, while a murine warm IRI model evaluated the effects of LCN2 inhibition (ZINC00640089) on tubular injury, ferroptosis markers (MDA, GSH, Fe²⁺), and inflammatory cytokines (IL-6, TNF-α) across mild (50-minute) and severe (80-minute) ischemia subgroups. WGCNA identified 36 hub genes, with LCN2 emerging as a key node in ferroptosis and immune regulation pathways. A six-gene machine learning model, including LCN2, CLU, and SOX9, demonstrated robust predictive accuracy for IRI (AUC = 0.93). Single-cell analysis revealed elevated LCN2 expression in neutrophils and macrophages in IRI kidneys, correlated with increased immune cell infiltration. In vivo, LCN2 inhibition significantly reduced severe ischemia-induced tubular injury, suppressed lipid peroxidation (MDA), restored glutathione levels (GSH), and alleviated iron overload (Fe2+) and reactive oxygen species (ROS). Systemic inflammation was mitigated, with IL-6 and TNF-α levels significantly reduced. This study establishes LCN2 as a pivotal mediator of ferroptosis and immune dysregulation in transplant IRI. A machine learning-driven multi-omics approach provides a novel diagnostic framework, while the inhibition of LCN2 is shown to alleviate IRI-induced tissue damage in these models. These findings highlight the utility of integrative analytics in uncovering biological targets and offer new therapeutic avenues for improving kidney transplant outcomes.

Green-synthesized nanozymes represent a transformative approach to microbial control, integrating sustainability with advanced nano-catalytic function. These nanozymes exhibit remarkable enzyme-like activity, including oxidase, peroxidase, and catalase mimetic properties, enabling effective antimicrobial action via reactive oxygen species (ROS) generation, metal ion release, and biofilm disruption. Their synthesis through plant, microbial, algal, and waste-derived methods reduces toxicity and environmental impact while enhancing biocompatibility and cost-effectiveness. Applications in clinical therapies, food and water decontamination, and environmental remediation demonstrate their vast potential. Despite these promising attributes, green nanozymes still face challenges such as inconsistent catalytic efficiency, scalability, and limited substrate specificity. Future innovations must prioritize mechanistic understanding, atomic-level design, and AI-assisted synthesis to improve selectivity and reproducibility. Regulatory clarity and eco-toxicological evaluations will be critical for their clinical and commercial translation. Overall, green-synthesized nanozymes hold the promise to redefine antimicrobial strategies, offering multifunctional, low-carbon solutions aligned with the global sustainability agenda.

Photodynamic therapy (PDT) harnesses the combination of light, oxygen, and photosensitizers to induce cell death via reactive oxygen species (ROS) formation. Given its intrinsic properties, PDT represents an alluring way of stymieing the increasing surge of antimicrobial resistance (AMR). Despite favorable assets, various hurdles need to be circumvented before PDT can efficiently be used to combat AMR. Here, we have evaluated the possibility of generating aptamers equipped with ruthenium polypyridyl complexes against entire Gram-positive Streptococcus pneumoniae bacteria. This combination is hypothesized to improve the poor specificity of photosensitizers, increase PDT efficiency, and potentially penetrate biofilms. Toward these aims, we first prepared nucleotides equipped with various ruthenium complexes and investigated their capacity at serving as substrates for polymerases for enzymatic DNA synthesis. Depending on the nature of the polypyridyl ligands, strong intercalation into dsDNA was observed even when connected to negatively charged nucleotide backbones. We then carried out SELEX and identified two unmodified aptamers that bound to the fixed bacterial target with Kd values of 118 nM and 541 nM. The SELEX experiment with the ruthenium-modified nucleotide led to the identification of one aptamer. The enzymatic synthesis of the modified aptamer was complicated by the formation of a very stable secondary structure confirmed by UV melting experiments (Tm of 84 °C). The modified aptamer displayed a high affinity (Kd value of 125 nM) for fixed Streptococcus pneumoniae bacteria. Collectively, these results highlight the possibility of using nucleotides equipped with large modifications such as ruthenium polypyridyl complexes in SELEX to raise potent aptamers against entire bacterial targets. These findings open directions to convert aptamers into potent devices to combat AMR via PDT-based approaches.

Liver cancer is the third most common cause of cancer-related death after lung and colorectal cancers. Hepatocellular carcinoma (LIHC) is the predominant subtype. Doxorubicin (DOX), an anthracycline chemotherapy drug, is extensively employed in the clinical treatment of early-stage and mid-stage liver cancer. Unfortunately, resistance that develops with long-term treatment severely undermines its therapeutic efficacy. Dihydroartemisinin (DHA), an antimalarial drug, has shown great potential in modulating the tumor microenvironment and inhibiting tumor growth, yet our understanding of its mechanisms remains limited. Network pharmacology identified CCT3 as a potential DHA target. Autodock predicted the binding of CCT3 and DHA. CCT3 expression in tumor and normal samples was analyzed using the TCGA-LIHC dataset. GSEA mapped out the pathways enriched by CCT3. qPCR and WB were used to measure CCT3 expression. Drug affinity responsive target stability assay verified the binding of CCT3 and DHA. The effects of DOX and DHA on cancer cell viability were probed using CCK-8, TUNEL, and flow cytometry. Cellular oxidative stress (OS) levels were assessed with intracellular reactive oxygen species (ROS) detection and JC-1 staining. DHA and DOX both proved effective in suppressing cancer cell viability and boosting apoptosis. Their combined use further amplified these effects. CCT3 was identified as a crucial target protein for DHA in LIHC treatment, with a strong binding capacity. This protein was particularly enriched in pathways associated with OS. In DOX-resistant cells, overexpressing CCT3 remarkably heightened resistance and reduced apoptosis, which possibly stemmed from the role of CCT3 in maintaining cellular ROS and mitochondrial membrane potential homeostasis, thereby reducing OS. Notably, these effects of CCT3 could be effectively inhibited by targeting DHA. DHA can target and inhibit CCT3 to induce OS, thereby enhancing the therapeutic efficacy of DOX.

Complex IV of the mitochondrial respiratory chain, or cytochrome c oxidase (CcO), contributes to the proton motive force necessary for ATP synthesis. CcO can slow the formation of reactive oxygen species and is key to physiology and drug development. The exact molecular mechanisms underlying its proton-pumping function remain elusive. The redox state of CcO's metallic cofactors is intimately connected to structural changes and proton pumping via proton-coupled electron transfer. Time-resolved UV/Vis and IR spectroscopy are used to investigate the effects of the electronic backreaction triggered by photolyzing the CO-inhibited 2-electron reduced state, R2CO, in the aa3 oxidase from Cereibacter sphaeroides. An intermediate is identified, in which the binuclear center matches the redox state of the catalytic intermediate E (one-electron reduced state), with a rise time of ≈2 μs. The electron transfer induces structural changes that lead to E286 deprotonation, with a time constant of 13 μs. Thus, it is inferred that transient reduction of heme a alone drives E286 deprotonation. E286 is reprotonated with a time constant of 72 ms when CO rebinds. The results support the view that transient heme a reduction in the physiological E state modulates the electrostatic environment, triggering proton transfer toward the proton-loading site.

Psoriasis vulgaris (PV) is a chronic inflammatory skin disorder in which oxidative stress, redox imbalance, and genetic susceptibility play crucial roles. Glutathione peroxidase-3 (GPx-3), a selenium-dependent antioxidant enzyme, regulates redox homeostasis by detoxifying reactive oxygen species. Variants in the GPx-3 gene may alter antioxidant defense and trace element metabolism, thereby contributing to PV pathogenesis. This case-control study investigated the association between the GPx-3 +1494A/G polymorphism and serum trace element levels in PV. A total of 71 patients with PV and 71 age- and sex-matched healthy controls were genotyped using allele-specific polymerase chain reaction (AS-PCR) followed by agarose gel electrophoresis. Serum zinc (Zn), copper (Cu), and iron (Fe) concentrations were measured by atomic absorption spectrometry. Statistical analyses were performed using chi-square (χ²) and Mann-Whitney U tests. The AG genotype was significantly more prevalent in PV patients than in controls (88.7% vs. 50.6%, p = 0.002). Among AG carriers, PV patients exhibited higher Zn levels (p < 0.001), lower Fe concentrations (p = 0.037), and a reduced Cu/Zn ratio (p = 0.025). Additionally, the AG genotype was associated with increased body mass index (p = 0.049). This study demonstrates a significant association between the GPx-3 +1494A/G polymorphism and serum trace element levels in PV. The AG genotype was more prevalent among patients and accompanied by elevated Zn, reduced Fe and a lower Cu/Zn ratio, suggesting genotype-related alterations in trace element balance. These findings indicate that the +1494A/G variant may contribute to psoriasis susceptibility by modulating oxidative stress and redox homeostasis.

This study investigated the role of ferroptosis in acute depleted uranium (DU)-induced nephrotoxicity. Using Sprague-Dawley rats and HK-2 cells to establish models of acute DU exposure (rats: 10mg/kg; cells: 500μM for 24h), we found that DU exposure caused mitochondrial dysfunction, lipid peroxidation, and iron accumulation, all hallmarks of ferroptosis, which were inhibited by ferrostatin-1 (Fer-1). We identified mitochondrial ethylmalonic encephalopathy 1 (ETHE1) as a key DU target. ETHE1 downregulation exacerbated DU-induced reactive oxygen species (ROS), ferrous ions (Fe2+) overload and ferroptosis, while exogenous ETHE1 protein alleviated them. Furthermore, DU-triggered ROS activated the p38 mitogen-activated protein kinase (P38-MAPK) pathway, an effect enhanced by ETHE1 knockdown. Inhibiting P38-MAPK with adezmapimod (SB203580) suppressed ferroptosis and autophagy, and reduced the expression of nuclear receptor coactivator 4 (NCOA4), a mediator of ferritinophagy. Knockdown of NCOA4 also attenuated ferroptosis. In conclusion, acute DU exposure downregulates ETHE1, promoting mitochondrial ROS that activates P38-MAPK signaling. This pathway induces NCOA4-mediated ferritinophagy, ultimately leading to renal cell ferroptosis. These findings elucidate a novel mechanism for DU-induced kidney injury.

Radiation-induced skin injury (RISI) is among the most common complications of cancer radiotherapy, affecting up to 95% of patients. These injuries include acute and chronic reactions that impair quality of life, necessitate treatment modifications, and contribute to long-term morbidity. This review synthesizes current understanding of the pathophysiology, clinical manifestations, histopathologic features, and management strategies for RISI, with emphasis on approaches most relevant to dermatologists and oncology clinicians. Acute radiation dermatitis (ARD) develops in 85%-95% of patients receiving radiotherapy, driven by DNA damage, reactive oxygen species, and pro-inflammatory cytokines. Clinical severity ranges from faint erythema to moist desquamation and ulceration, with severe reactions in up to 20%. Chronic radiation dermatitis (CRD) affects 5%-15% of survivors and results from sustained fibroblast activation and microvascular injury, leading to fibrosis, pigmentary changes, atrophy, and a two- to threefold increased risk of secondary skin cancer. Histopathology varies from basal keratinocyte apoptosis and epidermal thinning in ARD to dermal sclerosis, adnexal loss, and vascular ectasia in CRD. Preventive measures such as gentle cleansing, moisturization, and prophylactic corticosteroids reduce ARD severity by 15%-30%. For established disease, antimicrobial dressings shorten ulcer healing by 20%-40%, while long-term therapies including pentoxifylline-tocopherol, vascular lasers, and autologous fat grafting improve tissue pliability, pigmentation, and function. Dermatologists are uniquely positioned to lead prevention, diagnosis, and management of RISI. A proactive, multidisciplinary approach anchored by dermatologic expertise and evidence-based strategies is essential to reducing morbidity, enhancing healing, and improving quality of life. Given the worldwide use of radiotherapy, these approaches are intended to be adaptable across diverse healthcare systems, supporting dermatologists globally in patient care.

Drought is the major abiotic stress threatening global crop yields, thus identifying potential candidates with promising breeding value has become a central goal of current breeding programmes. Here, we found that miR164b functions as a negative regulator in plant drought tolerance, whose expression is dramatically inhibited under drought stress. Overexpressing MIR164b reduced the drought tolerance, while STTM164 transgenic seedlings showed enhanced drought tolerance in foxtail millet. We further identified that NAC (NAM-ATAF1/2-CUC2) transcription factor SiNAC015 was a target of miR164b. The sinac015 mutants showed attenuated drought tolerance, whereas overexpressing mSiNAC015 (miR164b-resistant version) improved drought tolerance in foxtail millet. Genetic evidence indicated that SiNAC015 could function in the same pathway as miR164b to mediate drought response by directly repressing the expression levels of SitPRX genes, which encoded peroxidase (POD) involved in reactive oxygen species (ROS) scavenging. Additionally, the superior SiNAC015Hap1 possessing higher SiNAC015 expression was found to be associated with enhanced drought tolerance in foxtail millet. Collectively, our study reveals that the miR164b-SiNAC015 module mediates drought stress response and provides a valuable genetic resource for drought-resistant breeding in foxtail millet.

Hemorrhagic transformation (HT) is a severe complication occurring in ischemic stroke patients undergoing tPA thrombolytic therapy, which significantly limits its clinical applicability. The mechanism and intervention of HT is still not fully understood. In our study, we found that an increased mobilization of circulating formyl peptide receptor 1 (FPR1) expressing leucocytes into the ischemic brain after tPA treatment in mice. In Fpr1-/- mice, neutrophil mobilization and HT occurrence after tPA thrombolysis decreased. Notably, pharmacological inhibition of FPR1 using a novel antagonist T0080 effectively mitigated tPA-associated HT, concurrently reducing neutrophil infiltration into the brain and preserving blood-brain barrier (BBB) integrity. We further revealed that brain infiltration neutrophils facilitate BBB leakage and neuron death by producing cytotoxic molecules such as reactive oxygen species (ROS), matrix metalloproteinase-9 (MMP9), and tumor necrosis factor-alpha (TNF-α). Neutrophil depletion and adoptive transfer experiments in vivo with FPR1+ neutrophils demonstrate that the essential role of FPR1+ neutrophils in mediating HT post-tPA administration in mice. Collectively, these findings identify neutrophils FPR1 activation as a key mechanistic driver exacerbating HT following tPA thrombolysis in ischemic stroke.

Acute lung injury is a common and fatal inflammatory condition in critically ill patients. Tetrahedral framework nucleic acids (TFNAs) have good potential for treating inflammatory diseases. The aim of this study was to use TFNAs in the treatment of acute lung injury (ALI) in mice to investigate the effect and possible mechanism. The characteristics of the TFNAs, including particle size and cellular uptake, were detected. TFNAs were subsequently used to treat an ALI mouse lung epithelial cells (MLE12) model with or without an autophagy inhibitor. Flow cytometry and Western blotting (WB) were performed to detect apoptosis and autophagy. The oxidative stress level was assessed by measuring the malondialdehyde (MDA) content, superoxide dismutase (SOD) activity and reactive oxygen species (ROS) content. A survival curve of the ALI model mice treated with TFNAs was constructed, and the lung injury score was assessed through pathological staining. The lung wet/dry weight ratio and inflammatory cytokine content in bronchoalveolar lavage fluid were measured and recorded. Transcription sequencing was performed to elucidate the biological processes associated with TFNA treatment. Finally, the regulatory effect of the cGAS-STING signalling pathway on TFNA-induced autophagy was explored. The synthesized TFNAs are typical nanomaterials. TFNAs significantly reduced the apoptosis rate according to flow cytometry and decreased the BAX/BCL2 ratio in MLE12 cells. Meanwhile, the autophagy level increased, as indicated by the increased expression of the ATG5, ATG7 and LC3II proteins when the cells were incubated with TFNAs. TFNAs could also inhibit the accumulation of ROS, increasing SOD activity and reducing the MDA content. Autophagy inhibitors can significantly inhibit the autophagy and antiapoptotic effects of TFNAs. In the ALI mouse model, TFNAs effectively reduced mortality, BALF inflammatory factor levels, pulmonary oedema, lung injury scores and neutrophil infiltration. The protective effect was significantly reduced with the use of autophagy inhibitors. In addition to autophagy, antigen processing and presentation, antiviral biological processes, and cytoplasmic membrane signal receptor complex functions were significantly upregulated, indicating that TFNAs might activate the cGAS-STING signalling pathway. Inhibition of the cGAS-STING signalling pathway effectively suppressed TFNA-induced autophagy. This study is the first to demonstrate that TFNAs protect MLE-12 cells against LPS-induced oxidative stress injury via autophagy activated by the nonclassical cGAS-STING signalling pathway. Therefore, TFNAs can attenuate ALI and improve patient prognosis in mice. These findings indicate that the cGAS-STING signalling pathway may be a basic mechanism contributing to various therapeutic immunologic effects. This study demonstrated the value of TFNAs in the treatment of ALI, with potential clinical translational value.

Esophageal squamous cell carcinoma (ESCC) is associated with poor prognosis because it is typically diagnosed at a moderate or advanced stage. Investigating the precise molecular mechanism of ESCC pathogenesis is essential for developing new therapeutic strategies. In this study, we demonstrated that ceramide synthase 6 (CERS6) was overexpressed and correlated with a worse prognosis in ESCC. Moreover, CERS6 promoted ESCC cell proliferation in vitro and in vivo. Mechanistically, CERS6 sustained the stability of ribophorin 1 (RPN1) by inhibiting its ubiquitination. Subsequently, CERS6 reduced endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) by activating the RPN1-inositol-requiring enzyme 1 (IRE1)-X-box binding protein 1 (XBP1) signaling pathway. Interestingly, the antisense oligonucleotides (ASOs) targeting CERS6 inhibited the growth of ESCC through the RPN1-IRE1-XBP1 signaling pathway. Collectively, our study reveals an unprecedented function and mechanism of CERS6, which is distinct from ceramide synthases, in the development of ESCC, highlighting its potential as a promising therapeutic target.

Melatonin ameliorates oxybenzone-induced meiotic defects in mouse oocytes via regulation of mitochondrial dynamics and calcium signaling.

This study proposes a novel multimodal framework for assessing the time-dependent toxicity of iron oxide nanoparticles (SPIONs), aiming to improve in vitro to in vivo extrapolation (IVIVE). The framework integrates experimental data from Caco-2 cells and C. elegans with sequential mathematical modeling and neural network analysis. By accounting for complex, time-dependent processes such as cellular uptake, intracellular transport, and SPION degradation, this approach addresses the unique toxicological profile of nanoparticles. In vitro experiments evaluated cytotoxicity, reactive oxygen species (ROS) production, and antioxidant enzyme expression over 96 hours, revealing strong correlations between nanoparticle uptake, iron levels, oxidative stress, and cell viability. Mathematical models, validated against experimental data, enable the calculation of IC50 values and facilitate interspecies extrapolation. This integrated methodology, achieving an R2 > 0.85 for predictive correlations, holds significant promise for reducing reliance on animal testing in future nanotoxicity evaluations.

Oral lichen planus (OLP) is a chronic inflammatory condition that has been clinically linked with the risk of developing oral cancer. The present study aimed to determine the oxidative stress in oral lichen planus (OLP) by assessing the immunohistochemical (IHC) expression of 8-hydroxydeoxyguanosine (8-OHdG) in OLP tissue samples and comparing it with that of normal oral mucosa. The study group consisted of 30 formalin-fixed, paraffin-embedded (FFPE) tissue blocks from oral lichen planus (OLP) cases, while 10 normal oral mucosa samples served as the control group. Tissue sections of 5-micron thickness were prepared and immunostained with the 8-hydroxydeoxyguanosine (8-OHdG) antibody. The stained slides were examined under a light microscope, and statistical analysis was conducted using Fisher's exact test. A significant increase in oxidative DNA damage marker 8-OHdG expression (p < 0.05) was observed within the basal and suprabasal epithelial layers of lichen planus tissue samples. In contrast, no immunoreactivity was detected in the normal oral mucosa. Excessive production of reactive oxygen species (ROS) during chronic inflammation is believed to play a crucial role in inducing DNA damage. The mutagenic marker 8-hydroxydeoxyguanosine (8-OHdG) in oral lichen planus tissue highlights its potential as a biomarker for assessing the risk of inflammation-driven carcinogenesis. Further research, incorporating various oxidative stress markers and clinicopathological correlations, is essential to enhance early prediction of malignant transformation in oral lichen planus.

The development and pathogenesis of rheumatoid arthritis (RA) are associated with ferroptosis. This study aims to investigate the regulatory role of ribonucleotide reductase subunit M2 (RRM2) in ferroptosis and the pathogenic phenotype of fibroblast-like synoviocytes (FLSs) in RA. Transcriptomic datasets associated with rheumatoid arthritis were analyzed to identify differentially expressed genes (DEGs), which were then intersected with known ferroptosis-related genes using a Venn diagram to determine overlapping candidates. The receiver operating characteristic (ROC) curve was utilized to evaluate the diagnostic value of key genes. The expression of RRM2 was silenced using short hairpin RNA transfection. Cell viability, motility, and invasive capacity were evaluated through the CCK-8 assay, scratch assay, Transwell, and ELISA assay, respectively. Inflammatory cytokines and ferroptosis-associated indicators were quantified using ELISA and specific biochemical detection kits. Additionally, the transcriptional and protein levels of genes linked to FLS function were analyzed. RRM2 was upregulated in tumor necrosis factor-alpha (TNF-α)-induced MH7A cells. Knockdown of RRM2 significantly inhibited TNF-α-induced cell proliferation, migration, invasiveness, and the release of pro-inflammatory cytokines in MH7A cells. Additionally, RRM2 knockdown induced ferroptosis, as evidenced by increased reactive oxygen species (ROS), ferrous iron (Fe2+), and malondialdehyde (MDA), alongside decreased expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11). Further mechanistic analysis revealed that RRM2 led to nuclear factor-kappa B (NF-κB) signaling activation. RRM2 inhibits ferroptosis and enhances the pathogenic behavior of RA FLSs through activation of the NF-κB pathway, highlighting its pivotal contribution to RA development.