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Hashimoto's thyroiditis (HT) is a chronic autoimmune disorder primarily driven by T cell. The apoptosis of the follicular thyroid cells plays an important role in HT apart from the lymphocyte-mediated cytotoxicity. Advanced oxidation protein products (AOPPs), resulting from oxidative stress, are known to be involved in various inflammatory diseases. However, their role in HT development has not been explored. Here, we discovered that AOPP levels were significantly elevated in thyroid tissues of both HT patients (Ctrl 4.12 ± 0.56, HT 30.00 ± 2.78; p < 0.0001) and experimental autoimmune thyroiditis (EAT) mice (Ctrl 8.37 ± 1.43, HT 55.82 ± 2.87; p < 0.0001), accompanied by extensive thyroid follicular epithelial cell apoptosis in HT patients (Ctrl 32.16 ± 1.79, HT 147.10 ± 13.32; p < 0.0001) and EAT mice (Ctrl 66.78 ± 6.72, HT 249.10 ± 9.77; p < 0.0001). In vitro study showed that AOPPs induced reactive oxygen species (ROS) production via nicotinamide adenine dinucleotide phosphate oxidase (NOX), leading to apoptosis in human thyroid follicular epithelial cell (Nthy-ori 3-1). Treatment with apocynin, a NOX inhibitor, reduced AOPP-induced ROS production and apoptosis in Nthy-ori 3-1 cells, and in turn alleviated thyroid follicular epithelial cell apoptosis and autoimmune thyroiditis symptoms in mice. Mechanistically, AOPP treatment activated JNK pathway, leading to the downregulation of Bcl-2, upregulation of Bax, the mitochondrial membrane potential depolarization and consequently triggered the activation of mitochondria-dependent intrinsic apoptosis pathway. Collectively, our findings highlight the promotive roles of AOPP in HT and provide an attractive therapeutic target for HT therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Down syndrome (DS), caused by trisomy 21, is characterized by intellectual disability and accelerated aging, with chronic oxidative stress contributing to neurological deficits. REST (Repressor Element-1 Silencing Transcription factor), a crucial regulator of neuronal gene expression implicated in DS neuropathology. This study investigates the neuroprotective potential of lithium, a mood stabilizer with known cognitive-enhancing effects, in restoring levels of REST. Using three pairs of human disomic and trisomic DS induced pluripotent stem cell (iPSC) isogenic lines, we differentiated neurons and treated them with lithium. Nuclear REST expression and reactive oxygen species (ROS) levels were quantified. Results showed the significantly lower nuclear REST expression in DS neurons was restored after 24 h of 10 mM lithium carbonate treatment. Notably, lithium treatment selectively reduced ROS levels in DS neurons to near-baseline levels. When challenged with hydrogen peroxide, DS neurons exhibited increased vulnerability to oxidative stress. The lithium treatment also significantly reduced ROS levels in the stressed control neurons. These findings reveal a positive association between lithium treatment, REST restoration, and oxidative stress reduction, suggesting that repurposing lithium could contribute to developing therapeutic strategies for DS neuropathologies. This study provides novel insights into DS molecular mechanisms and highlights the potential of lithium as a targeted intervention for improving neuronal function in DS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

Charcot Marie Tooth (CMT) or hereditary motor and sensory neuropathy is a heterogeneous neurological disorder leading to nerve damage and muscle weakness. Although multiple mutations associated with CMT were identified, the cellular and molecular mechanisms of this pathology are still unclear, although most of the subtype of this disease involve mitochondrial dysfunction and oxidative stress in the mechanism of pathology. Using patients' fibroblasts of autosomal recessive, predominantly demyelinating form of CMT-CMT4B3 subtype, we studied the effect of these mutations on mitochondrial metabolism and redox balance. We have found that CMT4B3-associated mutations decrease mitochondrial membrane potential and mitochondrial NADH redox index suggesting an increase rate of mitochondrial respiration in these cells. However, mitochondrial dysfunction had no profound effect on the overall levels of ATP and on the energy capacity of these cells. Although the rate of reactive oxygen species production in mitochondria and cytosol in fibroblasts with CMT4B3 pathology was not significantly higher than in control, the level of GSH was significantly lower. Lower level of glutathione was most likely induced by the lower level of NADPH production, which was used for a GSH cycling, however, expression levels and activity of the major NADPH producing enzyme Glucose-6-Phosphate Dehydrogenase (G6PDH) was not altered. Low level of GSH renders the fibroblast with CMT4B3 pathology more sensitive to oxidative stress and further treatment of cells with hydroperoxide increases CMT patients' fibroblast death rates compared to control. Thus, CMT4B3 pathology makes cells vulnerable to oxidative stress due to the lack of major endogenous antioxidant GSH., Competing Interests: Declarations. Conflict of interests: The authors declare no conflict of interest., (© 2025. The Author(s).)

The oxidative species generated by cold atmospheric plasma (CAP) treatment can impact the plant stress response system. We hypothesized that this response is not limited to the site of CAP application and it is transmitted through the plant. The resulting stress response can influence the plant microbiome on the intact plant. These hypotheses were tested by the application of CAP to live sweet basil (Ocimum basilicum var. Kiera). A single upper leaf of the plant underwent a 60 s CAP treatment at three different wattage intensity levels. Reactive oxygen species (ROS) generation in directly treated leaves and leaves in the vicinity of the treatment site (i.e., one, two, or three nodes away) was measured using the fluorescein degradation assay (ex/em: 485/525). Leaves directly exposed to CAP showed a marked increase in ROS production. Interestingly, basil leaves not directly treated by CAP also showed a significant (p < 0.05) increase in ROS generation compared to untreated control, extending to the two nearest nodes from the treatment site in all plants tested. The leaf microbiomes were evaluated using 16S rRNA gene sequencing. CAP appeared to drive restructuring of the leaf microbiota profiles, despite maintaining a similar α-diversity. CAP treatment intensity led to significant differences (p < 0.05) in the relative abundances of a variety of dominant bacterial families (e.g., Psuedomonadaceae and Streptomycetaceae) and phyla, and the effects on certain taxa were dependent on leaf distance from the treatment site. CAP's ability to restructure plant microbiota may have applications to improve produce microbial safety and shelf-life. PRACTICAL APPLICATION: Cold atmospheric plasma induces a stress response in a living plant beyond the site of application. This response includes an increase in the production of reactive oxygen species that can trigger pathways to enhance the production of phytochemicals. CAP treatment also alters the microbial community profile, possibly through plant stress response. Results from this study can be useful in developing CAP treatment of intact plant for improved growth, production of health-benefiting phytochemicals, and managing its microbiota., (© 2025 The Author(s). Journal of Food Science published by Wiley Periodicals LLC on behalf of Institute of Food Technologists.)

Cerebrovascular disease and dementia risk increases with age, and lifetime risk is greater in women. Cerebrovascular dysfunction likely precedes cerebrovascular disease and dementia but the mechanisms are incompletely understood. We hypothesized that oxidative stress mediates cerebrovascular dysfunction with human aging. Internal carotid artery dilation (ICA CO2 dilation) and middle cerebral artery cerebrovascular reactivity (MCA CVR CO2 ) in response to hypercapnia (5% CO 2 ) were measured in 20 young [10 F/10 M; age 23 ± 3 yr (means ± SD)] and 21 older (11 F/10 M; age 69 ± 9 yr) adults during intravenous infusions of saline (control) and vitamin C (acutely reduced oxidative stress condition). ICA CO2 dilation increased in response to vitamin C infusion in older adults (saline = 4.3 ± 2.4%; vitamin C = 6.7 ± 3.3%) but was unchanged in young adults (saline = 6.1 ± 2.7%; vitamin C = 5.5 ± 1.9%) (group × condition: P = 0.004). MCA CVR CO2 was not different in response to vitamin C in either group (group × condition: P = 0.341). However, when separated by sex, older female participants exhibited increased MCA CVR CO2 with vitamin C (saline = 0.85 ± 0.79 cm/s/mmHg; vitamin C = 1.33 ± 1.01 cm/s/mmHg) compared with older male participants (saline = 1.21 ± 0.57 cm/s/mmHg; vitamin C = 0.99 ± 0.47 cm/s/mmHg) (sex × condition: P = 0.011). Oxidative stress selectively impairs cerebrovascular function in older adults in an artery- and sex-specific manner. NEW & NOTEWORTHY This study is the first to report oxidative stress-mediated suppression of cerebrovascular reactivity to hypercapnia in the internal carotid artery in older compared with young adults. Overall, these in vivo findings identify oxidative stress as an important pathophysiological contributor to cerebrovascular aging in humans, highlighting the need to identify novel interventions that can reduce oxidative stress in the aging population.

Extracellular acidosis stemming from altered tumor metabolism promotes cancer progression by enabling tumor cell adaptation to the hostile microenvironment. In osteosarcoma, we have previously shown that acidosis increases tumor cell survival alongside substantial lipid droplet accumulation. In this study, we explored the role of lipid droplet formation in mitigating cellular stress induced by extracellular acidosis in osteosarcoma cells, thereby enhancing tumor survival during progression. Specifically, we examined how lipid droplets shield against reactive oxygen species induced by extracellular acidosis. We demonstrated that lipid droplet biogenesis is critical for acid-exposed tumor cell survival, as it starts shortly after acid exposure (24 h) and inversely correlates with ROS levels (DCFH-DA assay), lipid peroxidation (Bodipy assay), and the antioxidant response, as also revealed by NRF2 transcript. Additionally, extracellular metabolites, such as lactate, and interaction with mesenchymal stromal cells within the tumor microenvironment intensify lipid droplet build-up in osteosarcoma cells. Critically, upon targeting two key proteins implicated in LD formation - PLIN2 and DGAT1 - cell viability significantly declined while ROS production escalated. In summary, our findings underscore the vital reliance of acid-exposed tumor cells on lipid droplet formation to scavenge oxidative stress. We conclude that the rewiring of lipid metabolism driven by microenvironmental cues is of paramount importance for the survival of metabolically altered osteosarcoma cells in acidic condition. Overall, we suggest that targeting key members of lipid droplet biogenesis may eradicate more aggressive and resistant tumor cells, uncovering potential new treatment strategies for osteosarcoma., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nicola Baldini reports financial support was provided by Italian Association for Cancer Research. Nicola Baldini reports financial support was provided by National Recovery and Resilience Plan, PNRRM4C2. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Neuropathic pain is associated with diverse etiologies, including sciatica, diabetes, and the use of chemotherapeutic agents. Despite the varied origins, mitochondrial dysfunction, oxidative stress, and inflammatory cytokines are recognized as key contributing factors in both the initiation and maintenance of neuropathic pain. The effects of the mitochondrial-derived peptide humanin on neuropathic pain, however, remain unclear, despite its demonstrated influence on these mechanisms in numerous disease models. This study aimed to evaluate the effects of humanin on pain behavior in murine models of metabolic (streptozotocin/STZ), toxic (oxaliplatin/OXA), traumatic (sciatic nerve cuffing/cuff), and neuropathic pain. A secondary objective was to assess whether humanin modulates oxidative damage and inflammatory cytokine levels in these neuropathic pain models. Humanin (4 mg/kg) was administered intraperitoneally (i.p.) to BALB/c male mice with induced neuropathic pain over a period of 15 days, with pain thresholds assessed using hot plate, cold plate, and Von Frey tests. Serum levels of antioxidant enzymes, oxidative stress markers, and inflammatory/anti-inflammatory cytokines were measured via enzyme-linked immunosorbent assay (ELISA). In neuropathic pain-induced mice, humanin administration resulted in a statistically significant increase in pain threshold values in the STZ + Humanin, OXA + Humanin, and cuff + Humanin groups compared to their respective control groups (P < 0.05) over 15 days. Furthermore, humanin treatment significantly elevated antioxidant enzyme levels and anti-inflammatory cytokine concentrations, while reducing oxidative stress markers and pro-inflammatory cytokine levels compared to control groups (P < 0.01). These findings suggest that humanin exhibits therapeutic potential in the treatment of neuropathic pain induced by STZ, OXA, and cuff models. The ability of humanin to mitigate neuropathic pain through the suppression of oxidative stress and inflammatory cytokines indicates its promise as a novel therapeutic strategy., Competing Interests: Declaration of competing interest All authors declare that the manuscript contain original data, not published before in any language, it is not under reciprocal consideration for publication in any journal. We also declare that we approve the final version of the paper, no third party interest is present, and we transfer the copyright if accepted for publication in your Neuropharmacology. We all confirm that we have met the criteria for authorship as established by the International Committee of Medical Journal Editors, believe that the paper represents honest work., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Curcumin (CUR) is a natural compound recognized for stimulating the expression of antioxidant genes. This characteristic has been used to promote animal health and production in aquaculture settings. We hypothesized that supplementing embryos of Crassostrea gigas oysters with CUR would improve their antioxidant capacity, development, and resilience to stress. Embryos were exposed to CUR ranging from 0.03 to 30 µM for 24 h. Their development was assessed, along with measurements of glutathione levels, glutathione S-transferase activity, antioxidant capacity, production of reactive oxygen species (ROS), metabolic activity, and resistance to organic hydroperoxide and the antifouling compound dichlorooctylisothiazolinone (DCOIT). Low curcumin concentrations (up to 1 μM) activated the d-larvae antioxidant system, with a significant threefold increase in glutathione levels and a 50 % decrease in ROS production. This enhancement in antioxidant defense improved the ability of larvae to detoxify organic hydroperoxide. It also resulted in larger larval size and increased survival rates, whether under normal conditions or exposure to peroxide or DCOIT. CUR shows great promise in supporting larval development, but high concentrations were toxic (EC 50 = 2.90 μM), probably due to excessive antioxidant activation. Our results indicate that the antioxidant system may play a role in controlling bivalve early development. Understanding how antioxidants influence redox balance and gene expression during early life can enhance our knowledge of stress response mechanisms in marine organisms, offering insights into how they cope with pollutants and environmental challenges. Integrating CUR and antioxidant defense pathway approaches into aquaculture practices could boost productivity and sustainability in oyster aquaculture., Competing Interests: Declaration of competing interest Heloisa Barbara Gabe reports financial support was provided by National Council for Scientific and Technological Development. Rafael Trevisan reports financial support was provided by European Institute for Marine Studies. Heloisa Barbara Gabe reports financial support was provided by Coordination of Higher Education Personnel Improvement. Karine Amabile Taruhn reports financial support was provided by National Council for Scientific and Technological Development. Rafael Trevisan reports financial support was provided by Horizon Europe. Fernando Ramos Queiroga reports financial support was provided by Horizon Europe. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The aim of this study was to explore the effect and mechanism of formononetin (FMNT) in thermal-injured fibroblast proliferation, apoptosis, and oxidative stress. After thermal injury, human skin fibroblast (HSF) cells showed inhibited proliferation, migration, extracellular matrix (ECM) synthesis; and increased apoptosis, reactive oxygen species (ROS) production, and inflammation. Specifically, after thermal injury, cell viability, migration distance, and protein levels of collagen I, collagen III, α-SMA, MMP1, and MMP3 were reduced; cell apoptosis rate and TUNEL-positive cell numbers were increased; the levels of Bax and cleaved caspase-3 were elevated, while Bcl-2 level was reduced. Moreover, the thermally injured HSF cells showed increased levels of ROS, MDA, LDH, TNF-α, and IL-1β, and decreased GSH, SOD, GSH-Px, and CAT. FMNT levels can partially eliminate the effects of thermal injury on HSF cells, as shown by promoting thermally injured HSF cell proliferation and migration, and inhibiting cell apoptosis, ROS production, and inflammation. FMNT exerted no significant effect on normal HSF cells. Additionally, the levels of the P13K/AKT/mTOR signaling-related proteins (p-P13K, p-AKT, and p-mTOR) were reduced in thermally injured HSF cells, whereas FMNT could promote p-P13K, p-AKT, and p-mTOR levels. FMNT can partially alleviate the thermal injury-induced inhibition of fibroblast proliferation and migration; FMNT also inhibited the apoptosis, ROS level, and inflammation in thermal-injured cells. The effects of FMNT may be mediated by regulating the P13K/AKT/mTOR pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Oxidative stress (OS) inhibits the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). Equol (Eq), a phytoestrogen, exhibits notable antioxidant properties and potential for preventing osteoporosis. However, the research on the regulatory effects of Eq on stem cell osteogenesis remains limited. This investigation aimed to identify whether Eq could protect the osteogenic potential of hPDLSCs under H 2 O 2 -induced oxidative microenvironment. We employed a series of assays, including CCK-8, DCFH-DA, ALP staining, ARS, RT-qPCR, and Western Blotting, to assess the changes in cell viability, antioxidant capacity, and osteogenic potential following H 2 O 2 and Eq treatments. Our findings indicated that low concentrations of Eq had no cytotoxic effects on hPDLSCs and promoted their proliferation. Eq pre-treatment (0.5 μmol/L) partially counteracted the inhibitory effect of H 2 O 2 , reduced the generation of reactive oxygen species, and increased glutathione levels, thereby inhibiting oxidative damage. Eq suppressed the H 2 O 2 -induced inhibition of osteogenic differentiation, presenting as restoring the alkaline phosphatase levels and calcium nodule formation, as well as by upregulating the expression of BMP2 and RUNX2. Furthermore, bioinformatics analysis in this study suggested that the IL1B/NF-κB/CXCL1 signaling pathway might be a key pathway for Eq's enhancement of osteogenic differentiation potential of hPDLSCs under OS conditions. The activation of this axis by H 2 O 2 , which Eq can alleviate, was confirmed by validation experiments. This study provides new insights into the potential therapeutic application of Eq in alveolar bone resorption and bone regeneration research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Reactive oxygen species (ROS) play a critical role in modulating a range of proinflammatory functions in neutrophils, as well as regulating neutrophil apoptosis and facilitating the resolution of an inflammatory response. Selenoproteins with the 21st amino acid, selenocysteine (Sec), regulate immune mechanisms through the modulation of redox homeostasis aiding in the efficient resolution of inflammation, while their role in neutrophil functions during diseases remains unclear. To study the role of selenoproteins in neutrophils during infection, we challenged the granulocyte-specific tRNA Sec (Trsp) knockout mice (Trsp N ) with Citrobacter rodentium (C. rodentium), a murine pathogenic bacterium. Reduced bacterial shedding during the disease-clearing phase and increased tissue damage and neutrophil accumulation in the colon of the Trsp N mice were observed following infection. Trsp N neutrophils showed increased intracellular ROS accumulation during ex vivo C. rodentium stimulation and upregulated fMLP or Cx3cl1-induced chemotaxis. We also observed delayed neutrophil apoptosis, reduced efferocytosis of Trsp N neutrophils, and increased abundance of apoptotic cells in the colon of Trsp N mice. Together, these studies indicate that selenoprotein depletion results in increased neutrophil migration to the gut accompanied by ROS accumulation, while downregulating neutrophil apoptosis and subsequent efferocytosis by macrophages. Such an increase in inflammation followed by impaired resolution culminates in decreased bacterial load but with exacerbated host tissue damage., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: K. Sandeep Prabhu reports financial support was provided by National Institutes of Health. K. Sandeep Prabhu reports financial support was provided by National Institute of Food and Agriculture. Other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Emerging evidence suggests that lipid-laden macrophages (LLM) participate in lung damage in various clinical conditions. However, the mechanisms involved in LLM formation are not fully understood. In this study, we aimed to investigate the link between reactive oxygen species (ROS) and LLM formation. We found that ROS triggered by cigarette smoke extract (CSE) or H 2 O 2 significantly promoted LLM formation. Given the key role of ROS in LLM formation, we further demonstrated that LLM formation is induced by various ROS-producing stimuli, including bacteria, oxidized low-density lipoprotein (OxLDL), hyperoxia, and E-cigarette vapor extract (EVE). Meanwhile, cytochrome P450 family-1 subfamily B member 1 (CYP1B1) was highly upregulated in lung macrophages from chronic obstructive pulmonary disease (COPD) patients and CSE-treated macrophages. Functionally, CYP1B1 contributes to the CSE-induced lipid accumulation and LLM formation. CYP1B1 expression and LLM formation were effectively suppressed by antioxidant N-acetylcysteine (NAC) and carvedilol. The formation of LLM was also associated with classically activated M1 but not the M2 state. CSE-induced LLM showed time-dependent alterations in inflammatory response and phagocytic ability. In summary, our study highlights the role of oxidative stress in LLM formation. CYP1B1 contributes to ROS-induced LLM formation and may serve as a therapeutic target for reducing LLM-induced lung damage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. CAO is currently employed in Early Clinical Development, Respiratory and Immunology at AstraZeneca Biopharmaceuticals R&D but has no conflicts relevant to this manuscript., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Hemolytic anemia (HA) is characterized by massive destruction of red blood cells (RBCs) and insufficient oxygen supply, which can lead to shock, organ failure, even death. Recent studies have preliminarily demonstrated the therapeutic effectiveness of whole blood exchange (WBE) in the management of acute hemolytic anemia and exhibited potential for reducing the duration of corticosteroid treatment, while the underlying mechanism of WBE therapy was not investigated in preclinical study. Hence, we investigate the therapeutic mechanisms of WBE in HA through established continued WBE therapy in rats creatively. This study aims to examine the mechanism of WBE on phenylhydrazine hydrochloride-induced hemolytic anemia in SD rats to aid the development of therapeutics for drug-induced hemolytic anemia (DIHA). Research results demonstrated the efficacy of WBE therapy in reducing mortality and ameliorating anemia in DIHA, as evidenced by significant improvements in representative hematological parameters such as RBCs, hemoglobin, and lactate dehydrogenase levels. Additionally, WBE indicated the ability to suppress oxidative stress and inflammation, and it mitigated organ damage and biochemical function by stabilizing hepatic ferroportin levels and decreasing organ iron content. These results highlighted the effectiveness of WBE as an innovative treatment for HA, furnishing evidence to prioritize it over traditional blood transfusion for severe anemias., (© 2025 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Metabolic and insulin-resistant diseases, such as type 2 diabetes mellitus (T2DM), have become major health issues worldwide. The prevalence of insulin resistance in the general population ranges from 15.5% to 44.6%. Shockingly, the global T2DM population is anticipated to double by 2050 compared with 2021. Prior studies indicate that oxidative stress and inflammation are instrumental in causing insulin resistance and instigating metabolic diseases. Numerous methods and drugs have been designed to combat insulin resistance, including metformin, thiazolidinediones (TZDs), sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP1RA), and dipeptidyl peptidase 4 inhibitors (DPP4i). Bilirubin is an antioxidant with fat-burning actions by binding to the PPARα nuclear receptor transcription factor, improving insulin sensitivity, reducing inflammation, and reversing metabolic dysfunction. Potential treatment with antioxidants like bilirubin and increasing the enzyme that produces it, heme oxygenase (HMOX), has also gained attention. This review discusses the relationships between bilirubin, HMOX, and insulin sensitivity, how T2DM medications affect HMOX levels and activity, and potentially using bilirubin nanoparticles to treat insulin resistance. We explore the sex differences between these treatments in the HMOX system and how bilirubin levels are affected. We discuss the emerging concept that bilirubin bioconversion to urobilin may have a role in metabolic diseases. This comprehensive review summarizes our understanding of bilirubin functioning as a hormone, discusses the HMOX isoforms and their beneficial mechanisms, analyzes the sex differences that might cause a dichotomy in responses, and examines the potential use of HMOX and bilirubin nanoparticle therapies in treating metabolic diseases., (© 2025 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.)

Parkinson's disease (PD) is a progressive age-related neurodegenerative disease whose annual incidence is increasing as populations continue to age. Although its pathogenesis has not been fully elucidated, oxidative stress has been shown to play an important role in promoting the occurrence and development of the disease. Long noncoding RNAs (lncRNAs), which are more than 200 nucleotides in length, are also involved in the pathogenesis of PD at the transcriptional level via epigenetic regulation, or at the post-transcriptional level by participating in physiological processes, including aggregation of the α-synuclein, mitochondrial dysfunction, oxidative stress, calcium stabilization, and neuroinflammation. LncRNAs and oxidative stress are correlated during neurodegenerative processes: oxidative stress affects the expression of multiple lncRNAs, while lncRNAs regulate many genes involved in oxidative stress responses. Oxidative stress and lncRNAs also affect other processes associated with neurodegeneration, including mitochondrial dysfunction and increased neuroinflammation that lead to neuronal death. Therefore, modulating the levels of specific lncRNAs may alleviate pathological oxidative damage and have neuroprotective effects. This review discusses the general mechanisms of oxidative stress, pathological mechanism underlying the role of oxidative stress in the pathogenesis of PD, and teases out the mechanisms through which lncRNAs regulate oxidative stress during PD pathogenesis, as well as identifies the possible neuroprotective mechanisms of lncRNAs. Reviewing published studies will help us further understand the mechanisms underlying the role of lncRNAs in the oxidative stress process in PD and to identify potential therapeutic strategies for PD., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Photoimmunotherapy, which combines phototherapy with immunotherapy, exhibits significantly improved therapeutic effects compared with mono-treatment regimens. However, its use is associated with drawbacks, such as insufficient reactive oxygen species (ROS) production and uneven photosensitizer distribution. To address these issues, we developed a controllable, targeted nanosystem that enhances oxidative stress through multiple pathways, achieving synergistic photothermal, photodynamic, and immunotherapy effects for tumor treatment. These nanoparticles (D/I@HST NPs) accurately target overexpressed transferrin receptors (TfRs) on the surface of tumor cells through surface-modified transferrin (Tf). After endocytosis, D/I@HST NPs generate ROS under 808-nm laser irradiation, breaking the ROS-responsive crosslinking agent and increasing drug release and utilization. Tf also carries Fe 3+ , which is reduced to Fe 2+ by iron reductase in the acidic tumor microenvironment (TME). Consequently, the endoperoxide bridge structure in dihydroartemisinin is cleaved, causing additional ROS generation. Furthermore, the released IR-780 exerts both photodynamic and photothermal effects, enhancing tumor cell death. This multi-pathway oxidative stress amplification and photothermal effect can trigger immunogenic cell death in tumors, promoting the release of relevant antigens and damage-associated molecular patterns, thereby increasing dendritic cell maturation and sensitivity of tumor cells to immunotherapy. Mature dendritic cells transmit signals to T cells, increasing T cells infiltration and activation, facilitating tumor growth inhibition and the suppression of lung metastasis. Furthermore, the myeloid-derived suppressor cells in the tumor decreases significantly after treatment. In summary, this multi-pathway oxidative stress-amplified targeted nanosystem effectively inhibits tumors, reverses the immunosuppressive tumor microenvironment, and provides new insights into tumor immunotherapy combined with phototherapy., Competing Interests: Declarations. Ethical approval: All animal experiments were carried out in accordance with the guidelines of the Animal Care and Use Committee of the Binzhou Medical University and under the ethical approval for research involving animals of Binzhou Medical University (2020-33). Consent for publication: All authors approved the final manuscript and the submission to this journal. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Oxidative stress (OS) refers to the disruption in the balance between free radical generation and antioxidant defenses, leading to potential tissue damage. Reactive oxygen species (ROS) can interact with biological components, triggering processes like protein oxidation, lipid peroxidation, or DNA damage, resulting in the generation of several volatile organic compounds (VOCs). Recently, VOCs provided new insight into cellular metabolism and can serve as potential biomarkers. The objective is to investigate the impact of OS on cell metabolism by analyzing the release or alterations of VOCs in the headspace of differentiated 3T3-L1 adipocytes. An OS model in differentiated 3T3-L1 cell lines was constructed using hydrogen peroxide (H 2 O 2 ) treatment. The effect of OS on cell metabolism was analyzed by detecting VOCs in the headspace of the cells using solid phase micro extraction (SPME) and gas chromatography-mass spectrometry (GCMS). Our findings indicate that H 2 O 2 concentrations exceeding 300 µM induce significant OS, leading to adipocyte apoptosis, as evidenced by various assays. Of the twenty VOCs identified, ten were upregulated in the cells. VOCs such as diphenyl ether, 1,3,5-trioxane, 5-methyl tridecane, 2-ethyl-1-hexanol, and 2,4-di-tert-butyl phenol emerged as potential biomarkers for OS. This study demonstrates that elevated OS alters VOC profiles in differentiated 3T3-L1 adipocytes, providing insights into the effects of OS on adipose tissue and identifying potential OS biomarkers., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Oxidative stress (OS), generated by the overrun of reactive species of oxygen and nitrogen (RONS), is the key cause of several human diseases. With inflammation, OS is responsible for the onset and development of clinical signs and the pathological hallmarks of Alzheimer's disease (AD). AD is a multifactorial chronic neurodegenerative syndrome indicated by a form of progressive dementia associated with aging. While one-target drugs only soften its symptoms while generating drug resistance, multi-target polyphenols from fruits and vegetables, such as ellagitannins (ETs), ellagic acid (EA), and urolithins (UROs), having potent antioxidant and radical scavenging effects capable of counteracting OS, could be new green options to treat human degenerative diseases, thus representing hopeful alternatives and/or adjuvants to one-target drugs to ameliorate AD. Unfortunately, in vivo ETs are not absorbed, while providing mainly ellagic acid (EA), which, due to its trivial water-solubility and first-pass effect, metabolizes in the intestine to yield UROs, or irreversible binding to cellular DNA and proteins, which have very low bioavailability, thus failing as a therapeutic in vivo. Currently, only UROs have confirmed the beneficial effect demonstrated in vitro by reaching tissues to the extent necessary for therapeutic outcomes. Unfortunately, upon the administration of food rich in ETs or ETs and EA, URO formation is affected by extreme interindividual variability that renders them unreliable as novel clinically usable drugs. Significant attention has therefore been paid specifically to multitarget EA, which is incessantly investigated as such or nanotechnologically manipulated to be a potential "lead compound" with protective action toward AD. An overview of the multi-factorial and multi-target aspects that characterize AD and polyphenol activity, respectively, as well as the traditional and/or innovative clinical treatments available to treat AD, constitutes the opening of this work. Upon focus on the pathophysiology of OS and on EA's chemical features and mechanisms leading to its antioxidant activity, an all-around updated analysis of the current EA-rich foods and EA involvement in the field of AD is provided. The possible clinical usage of EA to treat AD is discussed, reporting results of its applications in vitro, in vivo, and during clinical trials. A critical view of the need for more extensive use of the most rapid diagnostic methods to detect AD from its early symptoms is also included in this work.

Background: The oxidative handicap hypothesis posits that testosterone-dependent traits, such as muscle mass and strength, may be costly to develop due to testosterone's pro-oxidative properties, leading to increased oxidative stress. This hypothesis suggests that only individuals with superior biological conditions can afford these costs. This study examines the oxidative handicap hypothesis, exploring the relationship between muscle mass or handgrip strength and oxidative stress markers in men., Methods: Handgrip strength and muscle mass were measured in 179 men, with muscle mass assessed using bioelectrical impedance analysis (BIA) and handgrip strength measured using a hydraulic dynamometer. Serum testosterone levels and antioxidant capacity were measured. 8-OH-dG, 8-epi-PGF2α, and protein carbonyls were measured to evaluate oxidative stress level. Pearson's correlation and multivariate regression analyses were performed to examine the relationships between handgrip strength, muscle mass, and oxidative stress markers, controlling for age, serum testosterone levels, and antioxidant capacity., Results: No significant correlations were found between handgrip strength and oxidative stress markers, even when controlling for muscle mass, antioxidant capacity, testosterone levels, and age., Conclusions: The study's findings do not support the oxidative handicap hypothesis in the context of muscle parameters in men. The results suggest that testosterone-driven traits like handgrip strength or muscle mass may not necessarily incur oxidative stress costs in healthy young men, possibly due to effective compensatory antioxidant mechanisms. Factors like lifestyle, diet, and genetic predisposition, which were not controlled in this study, could also influence the observed outcomes and should be included in future research., Competing Interests: Declarations. Ethics approval and consent to participate: The recruitment and data collection procedure was approved by the Bioethics Commission at the Wrocław Medical University (number 222/2019). Each participant signed an informed consent to participate in the study and to use the obtained data for scientific purposes. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Male reproductive health is governed by an intricate interplay of genetic, epigenetic, and environmental factors. Epigenetic mechanisms-encompassing DNA methylation, histone modifications, and non-coding RNA activity-are crucial both for spermatogenesis and sperm maturation. However, oxidative stress, driven by excessive reactive oxygen species, disrupts these processes, leading to impaired sperm function and male infertility. This disruption extends to epigenetic modifications, resulting in abnormal gene expression and chromatin remodeling that compromise genomic integrity and fertilization potential. Importantly, oxidative-stress-induced epigenetic alterations can be inherited, affecting the health and fertility of offspring and future generations. This review investigates how oxidative stress influences epigenetic regulation in male reproduction by modifying DNA methylation, histone modifications, and non-coding RNAs, ultimately compromising spermatogenesis. Additionally, it discusses the transgenerational implications of these epigenetic disruptions and their potential role in hereditary infertility and disease predisposition. Understanding these mechanisms is vital for developing therapeutic strategies that mitigate oxidative damage and restore epigenetic homeostasis in the male germline. By integrating insights from molecular, clinical, and transgenerational research, this work emphasizes the need for targeted interventions to enhance male reproductive health and prevent adverse outcomes in progeny. Furthermore, elucidating the dose-response relationships between oxidative stress and epigenetic changes remains a critical research priority, informing personalized diagnostics and therapeutic interventions. In this context, future studies should adopt standardized markers of oxidative damage, robust clinical trials, and multi-omic approaches to capture the complexity of epigenetic regulation in spermatogenesis. Such rigorous investigations will ultimately reduce the risk of transgenerational disorders and optimize reproductive health outcomes.

Oxidative stress (OS) is established as a key factor in the etiology of both male and female infertility, arising from an imbalance between reactive oxygen species (ROS) production and the endogenous antioxidant (AOX) defenses. In men, OS adversely affects sperm function by inducing DNA damage, reducing motility, significantly impairing sperm vitality through plasma membrane peroxidation and loss of membrane integrity, and ultimately compromising overall sperm quality. In women, OS is implicated in various reproductive disorders, including polycystic ovary syndrome, endometriosis, and premature ovarian failure, leading to diminished oocyte quality, disrupted folliculogenesis, and poorer reproductive outcomes. Antioxidant therapy represents a promising intervention to mitigate the harmful effects of ROS on reproductive health in additions to its easy accessibility, safety, and low cost. Despite several findings suggesting improvements in fertility potential with AOX therapy, the data remains inconclusive regarding optimal dosage and combination, duration of treatment, and the specific patient populations most likely to benefit. In this review, we discuss the role of AOXs in the management of infertile couples, focusing on their biological mechanisms, potential adverse effects, therapeutic efficacy, and clinical applications in improving reproductive outcomes in both natural conception and medically assisted reproduction. Additionally, we highlight the current practice patterns and recommendations for AOX supplementation during the course of infertility treatment. Further, we provide an overview on the limitations of the current research on the topic and insights for future studies to establish standardized AOX regimens and to assess their long-term impact on key outcomes such as live birth rates and miscarriage rates., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2025 Saleh, Sallam, Elsuity, Dutta, Sengupta and Nasr.)

Maize (Zea mays L.) faces significant challenges to its growth and productivity from heavy metal stress, particularly Chromium (Cr) stress, which induces reactive oxygen species (ROS) generation and damages photosynthetic tissues. This study aimed to investigate the effects of fulvic acid (FA) application, via foliar spray or root irrigation, on mitigating chromium stress in maize by evaluating its impact on antioxidant activity and growth parameters. Two maize varieties, P3939 and 30Y87, were subjected to chromium stress (CrCl 3 ·6H 2 O) at concentrations of 300 µM and 100 µM for a duration of 5 weeks. The experiment was conducted in a wire house under natural environmental conditions at the Seed Centre, Institute of Botany, University of the Punjab, Lahore, Pakistan. Physiological assessments included electrolyte leakage, chlorophyll pigment content, malondialdehyde (MDA) levels, and activities of antioxidant enzymes such as catalase (CAT), ascorbate peroxidase (APX), and guaiacol peroxidase (GPX) in maize leaves. Growth parameters were also monitored. The results revealed that chromium stress significantly reduced chlorophyll content and increased oxidative stress, as evidenced by elevated MDA levels and electrolyte leakage. However, FA application notably mitigated these effects: chlorophyll content improved by 15%, and MDA levels decreased significantly. Irrigation with FA was particularly effective, reducing MDA levels by 40% compared to the 300 µM chromium treatment. Furthermore, while chromium stress enhanced antioxidant enzyme activities, FA application further boosted total soluble protein levels and antioxidant enzyme activities under stress conditions. In conclusion, FA application demonstrates potential in improving maize tolerance to heavy metal stress by enhancing the antioxidant defense system and preserving photosynthetic pigments. These findings highlight FA's promise as a practical strategy for mitigating the negative impacts of chromium stress on maize, promoting sustainable agricultural practices in contaminated environments., Competing Interests: Declarations. Ethics approval and consent to participate: All methods were performed in accordance with the relevant guidelines and regulations. We have obtained permission to collect plant material and seedlings. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Traumatic brain injury (TBI) is an inflammatory disease causing neurodegeneration. One of the consequences of inflammation is an elevated blood level of fibrinogen (Fg). Earlier we found that extravasated Fg induced an increased expression of neuronal nuclear factor kappa B (NF-κB) p65. In the present study, we aimed to evaluate the effect of caffeic acid phenethyl ester (CAPE), an inhibitor of NF-κB, on Fg-induced neurodegeneration in vitro and in mice with mild-to-moderate TBI. Primary mouse brain cortical neurons were treated with Fg (0.5 or 1 mg/mL) in the presence or absence of CAPE. A cortical contusion injury -induced model of TBI in C57BL/6 mice was used. Mice were treated with CAPE for two weeks. The generation of reactive oxygen species (ROS) and neuronal viability were assessed. Mice memory was assessed using novel object recognition and contextual fear conditioning tests. The generation of ROS and viability of neurons in vitro and in the brain samples were assessed. Data showed that CAPE attenuated the Fg-induced generation of ROS and neuronal death. CAPE improved the cognitive function of the mice with TBI. The results suggest that Fg-induced generation of ROS could be a mechanism involved in cognitive impairment and that CAPE can offer protection against oxidative damage and neurodegeneration.

Oxidative stress and neuroinflammation are recognized as key factors in the development of neurodegenerative diseases, yet effective interventions and biomarkers to address oxidative stress and neuroinflammation in these conditions are limited. Uric acid (UA), traditionally associated with gout, is now gaining prominence as a potential target in neurodegenerative diseases. Soluble UA stands out as one of the most vital antioxidant compounds produced by the human body, accounting for up to 55% of the extracellular capacity to neutralize free radicals. While there is increasing evidence supporting the neuroprotective properties of UA in Parkinson's disease and Alzheimer's disease, gaps in knowledge still exist regarding the underlying mechanisms and how to effectively translate these benefits into clinical practice. Moreover, the current UA elevation therapy exhibits unstable antioxidant properties, individual variability, and even adverse effects, limiting its potential clinical applications. This review consolidates recent advancements in understanding how UA exerts neuroprotective effects on neurodegenerative diseases and emphasizes the dual roles of UA in managing oxidative stress and neuroinflammation. Additionally, the review elucidates the mechanisms through which UA confers neuroprotection. Based on this, the review underscores the significance of UA as a potential biomarker and aims to provide a comprehensive understanding of its potential as a therapeutic target, while also addressing possible challenges to clinical implementation., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

This study aims to investigate the potential role of antioxidants in oxidative stress and its consequent impact on the mechanical properties of neuronal cells, particularly the stress induced by amyloid-beta (1-42) (Aβ 42 ) aggregates. A key aspect of our research involved using scanning ion-conductance microscopy (SICM) to assess the mechanical properties (Young's modulus) of neuronal cells under oxidative stress. Reactive oxygen species (ROS) level was measured in single-cell using the electrochemical method by low-invasive Pt nanoelectrode. We investigated the effects of the low molecular weight antioxidant N-acetylcysteine (NAC) and the antioxidant enzyme superoxide dismutase 1 (SOD1) on the physiological and mechanical properties of neuronal cells using SICM. Using electrochemical method and SICM, NAC effectively reduces oxidative stress and restores Young's Modulus in SH-SY5Y cells exposed to hydrogen peroxide and Aβ 42 oligomers. Our study first examined the influence of SOD1 on intracellular ROS levels in the presence of Aβ oligomers. The investigation into the effects of SOD1 and its nanoparticle form SOD1 on SH-SY5Y cells reveals impacts on mechanical properties and oxidative stress. The combined use of SICM and electrochemical measurements provided a comprehensive understanding of how oxidative stress, including that triggered by the Aβ oligomers affects the mechanical properties of cells., (© 2024 Wiley-VCH GmbH.)

Objective: The objective of this review is to qualitatively appraise the available literature to evaluate the efficacy of circulatory systemic oxidative stress markers (OSMx) in determining the diagnosis and outcome of TBI., Methods: A systematic review was conducted of PubMed/Medline, Embase and Google Scholar databases per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) for studies which employed serum or plasma OSMx analysis for diagnostic or prognostic purposes in patients with TBI., Results: Eight studies were included. There were 654 patients across the eight studies, of which 518 (79.2%) patients had sustained a TBI. The heterogeneity between studies in terms of OSMxs analyzed ultimately made collective analysis inappropriate. Nevertheless, several studies highlighted the potential role of circulatory OSMx levels in determining the diagnosis (presence and severity) and prognosis (functional outcome and mortality) of TBI., Conclusion: The care for patients with TBI remains a complex clinical challenge with a high morbidity and mortality profile. Evidenced by this review, circulatory OSMxs appear to have the potential to supplement current diagnostic measures, in addition to identifying new treatment strategies and monitoring recovery. Despite early promise, the evidence for such markers remains in its infancy and robust prospective studies are needed.

This study investigated the protective effects of ursodeoxycholic acid (UDCA) against PA-induced apoptosis in the MAC-T bovine mammary epithelial cell (bMEC) line by assessing the level of cell viability, oxidative stress indicators, and expression of endoplasmic reticulum (ER) stress markers. MAC-T cells were pretreated with UDCA at 25, 50, and 100 μM before exposure to PA at 300 μM. UDCA was noncytotoxic at these concentrations and significantly improved cell viability, which was reduced by PA. UDCA pretreatment notably decreased PA-induced expression of GRP78, XBP1s, ATF4, and CHOP mRNA, indicating reduced ER stress. Moreover, UDCA substantially lowered PA-induced reactive oxygen species production and dichlorofluorescein fluorescence intensities. Although PA treatment elevated GSSG levels and disrupted redox balance by decreasing both the total GSH/GSSG and reduced GSH/GSSG ratios, UDCA effectively counteracted these effects. Specifically, UDCA reduced PA-induced GSSG levels and restored redox balance by increasing both total and reduced GSH/GSSG ratios. These findings suggest that UDCA mitigates PA-induced apoptosis in MAC-T cells by enhancing redox homeostasis. Therefore, incorporating UDCA into dairy cow feed could help reduce PA-induced cellular stress and improve milk production during periods of negative energy balance., (© 2025 The Author(s). Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.)

Understanding oxidative stress in high-mountain lake fish offers crucial insights into their health, resilience, and adaptation to extreme environmental changes. This study investigates the oxidative stress response of Cottus gobio in a high-mountain lake (Dimon Lake) located in the northeast Italy during the ice-free season, focusing on the relationship between oxidative stress biomarkers and physicochemical water parameters, as well as persistent and emerging contaminants. Significant seasonal variations were observed in water parameters, with lower oxygen, pH, conductivity, and phosphate levels in summer compared to autumn, while temperature, ammonium, and nitrate were higher in summer. Metal concentrations in C. gobio muscle were higher in autumn, with Zn showing the most significant increase. PAHs, NDL-PCBs, and pesticides were all below the limit of quantification in the fish muscle samples. No microplastics items were found in the gastrointestinal tracts of fish. Oxidative stress biomarkers revealed organ-specific and seasonal variations. The liver exhibited the highest activities of catalase (CAT), glutathione peroxidase (GPx), glutathione S-tranferase (GST), and glutathione reductase (GR), highlighting its central role in detoxification and metabolic processes. Superoxide dismutase (SOD) activity was notably higher in muscle tissue during summer, suggesting increased metabolic activity. A strong correlation was found between pH and the activities of SOD, CAT, GPx, GR, and metallothioneins (MTs), emphasizing the importance of water chemistry in influencing oxidative stress responses. This approach not only aids in understanding the local adaptations of these fish but also highlights the impacts of environmental stressors on high-mountain ecosystems. Continuous monitoring of water chemistry, particularly pH, is crucial for understanding and managing oxidative stress in aquatic organisms, especially in the context of global environmental changes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The macula, a small but highly important area in the retina, is crucial for healthy vision. Age-related macular degeneration is responsible for approximately 8.7 % of blindness worldwide, and affected individuals are burgeoning. The age-related macular degeneration is often triggered by oxidative stress and excessive inflammation that damage the retinal pigment epithelial cells in the macula. Curcumin, a potent antioxidant and anti-inflammatory carotenoid, is hampered by low compatibility and stability issues in food science. Innovatively, this study harnessed milk-derived exosomes as a novel delivery method yielding a curcumin-infused system (curcumin@exosome) to increase its biocompatibility and stability. This fusion not only curbed excessive reactive oxygen species but also neutralized H 2 O 2 -induced mitochondrial disruption in cellular models. It revitalized retinal pigment epithelial cells, reverting their function near to baseline in vitro. The curcumin@exosome outshined in subduing pro-inflammatory cytokines tumor necrosis factor-α and interleukin-1β induced by sodium iodate. This study illuminates that the curcumin@exosome is promise as a therapeutic intervention for retinal ailments marked by oxidative and inflammatory distress., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Entomopathogenic nematodes (EPNs) of the genera Heterorhabditis and Steinernema represent an alternative for the biological control of insects. The limited half-life of EPNs is still one of the most concerning issues in their commercialization. Lipid peroxidation (LPO) caused by reactive oxygen species (ROS) may be one of the most important causes of loss of infectivity and survival of EPNs when exposed to various physicochemical stress conditions (temperature, pH, hypoxia and osmotic pressure). Because LPO generates free radicals (FRs), it can trigger membrane peroxidation and lipid energy reserves of EPNs. However, in EPNs there is no data on the role of LPO on their physiology, making strategies for the conservation of derived biopreparations difficult. In this sense, the influence of LPO on the species of EPNs S. feltiae and H. indica under various conditions of physicochemical stress was studied. In both EPNs, the proposed stress conditions altered infectivity and survival over time, generating ROS associated with LPO with a variable tolerance depending on the species, type and time of exposure to stress. A relationship was observed between the LPO induced by stress conditions and infectivity-survival., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Ischemic stroke is a major cause of disability and mortality worldwide, with oxidative stress and blood-brain barrier (BBB) injury playing crucial roles in its pathogenesis. Our RNA sequencing results revealed that S100 calcium-binding protein A4 (S100A4) is highly expressed in the middle cerebral artery occlusion (MCAO) mouse model. We analyzed S100A4 expression in ischemic stroke patients and in mice subjected to the MCAO model. Moreover, using adeno-associated virus (AAV)-mediated knockdown of S100A4 in mice, we evaluated its effects on neurological deficits, BBB integrity, and oxidative stress in MCAO mice. Bioinformatic analyses explored the potential downstream pathways of S100A4.S100A4 expression was significantly elevated in the serum of ischemic stroke patients and brain tissues of MCAO mice. AAV-mediated knockdown of S100A4 exacerbated neurological deficits, BBB disruption, and oxidative stress in MCAO mice. The upregulation of S100A4 mitigated these outcomes, which were facilitated through the stimulation of the PI3K/Akt/Nrf2 signaling cascade.Our results illustrate that S100A4 plays a protective role in preventing neuronal damage during ischemic stroke by reducing oxidative stress and preserving BBB integrity through the PI3K/Akt/Nrf2 pathway. This highlights its promise as a potential therapeutic approach for ischemic stroke., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Yangtze finless porpoise (YFP) is a critically endangered species in China. It has been found that YFP is constantly exposed to perfluorooctane sulfonate (PFOS) in aquatic environments, leading to significant bioaccumulation. However, the impacts of PFOS on YFP health and survival are still unknown. To circumvent the limitations in YFP research, this study used YFP umbilical cord fibroblast cell line and exposed the cells to PFOS for 48 h, with objectives to uncover the cytotoxicity and mechanisms of PFOS in YFP. A high-throughput proteomics assay showed that PFOS exposure at 50 μM for 48 h perturbed the proteome structure in YFP umbilical cord fibroblast cells. Functional annotation found the high relevance of oxidative stress, mitochondrial oxidative phosphorylation, and DNA damage to PFOS cytotoxic mechanisms. Concordantly, PFOS exposure significantly increased the deposition of reactive oxygen species (ROS) in YFP cells. The potential of mitochondria to produce ATP was also compromised by PFOS, which was accompanied by the higher permeability of mitochondrial membrane. In addition, exposure of YFP umbilical cord fibroblast cells to 50 μM PFOS damaged the DNA assembly as evidenced by the increase in the percentage of DNA fragmentation. Gene transcription and enzymatic activity of caspases were up-regulated by PFOS, subsequently favoring the occurrence of early and late apoptosis. It was notable that ROS scavenger could successfully mitigate the cytotoxicity of PFOS on oxidative stress and apoptosis, thus pinpointing ROS as the molecular initiating event in apoptosis endpoints. To our knowledge, this is the first study that investigates the detrimental effects of PFOS using YFP umbilical cord fibroblast cells. The data will support an accurate assessment of ecological risks imposed by environmental pollutants on the health and sustainability of YFP, which is especially important under the context of sharp decline in YFP population and national initiative in YFP conservation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Elevated free fatty acids and oxidative stress may function as pathogenic factors in endothelial dysfunction that is associated with various cardiovascular complications. In recent work, Feng and colleagues report that activation of a lysosomal Ca 2+ channel may be a viable option to alleviate oxidative damage by boosting lysosome biogenesis and mitophagy., Competing Interests: Declaration of competing interest The authors declare no competing interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Aim: Hepatic ischemia-reperfusion (I/R) injury is the primary cause of liver dysfunction and liver failure, commonly occurring in liver transplantation, hepatectomy, and hemorrhagic shock. Polo-like kinase 2 (PLK2), a pivotal regulator of centriole duplication, plays a crucial role in cell proliferation and injury repair. However, the function of PLK2 in hepatic I/R remains unclear., Methods: The effect of PLK2 was investigated in the mouse hepatic I/R model and the hepatocyte hypoxia-reoxygenation (H/R) model. Liver injury was assessed by serum transaminase and hematoxylin and eosin staining. Cell apoptosis was analyzed using TUNEL analysis and immunoblotting. Inflammatory factors were evaluated by reverse transcription-quantitative polymerase chain reaction. Mice or cultured cells during the I/R or H/R were treated by overexpressing PLK2. ROS fluorescence staining was used to assess oxidative stress injury., Results: PLK2 was upregulated after hepatic I/R injury. Overexpressed PLK2 significantly improved liver enzyme levels and alleviated liver histological injury. Moreover, PLK2 decreased hepatocyte apoptosis and inhibited the expression of inflammatory factors in liver. Mechanistically, PLK2 increased the phosphorylation of GSK3β and enhanced expression of the antioxidant enzyme HO-1, leading to less ROS production. Inhibition of the HO-1 aggravated ROS generation and abolished the protective effect of PLK2., Conclusion: Overall, these findings revealed that PLK2 enhanced HO-1 expression and reduced oxidative stress damage in hepatic I/R injury, and this protective effect related to GSK3β activity., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Osteoarthritis (OA) is a chronic inflammation that gradually leads to cartilage degradation. Prolonged chondrocyte oxidative stress contributes to the development of diseases, including chondrocyte apoptosis, cartilage matrix degradation, and aggravation of articular cartilage damage. Bilirubin (BR) possesses strong antioxidant properties by scavenging reactive oxygen species (ROS) and potent protection effects against inflammation. However, its insolubility and short half-life limit its clinical use. Therefore, we developed a supramolecular system of ε-polylysine (EPL) conjugated by β-cyclodextrin (β-CD) on the side chain, and bilirubin was loaded via host-guest interactions, which resulted in the self-assemble of this system into bilirubin-loaded polylysine-β-cyclodextrin nanoparticle (PB) with improving solubility while reducing toxicity and prolonging medication action time. To explore PB's potential pharmacological mechanisms on OA, we established in vitro and in vivo OA models. PB exerted ROS-scavenging proficiency and anti-apoptotic effects on rat chondrocytes by activating the Nrf2-HO-1/GPX4 signaling pathway. Additionally, PB reprogrammed the cartilage microenvironment by regulating the NF-κB signaling pathway to maintain chondrocyte function. Animal experiments further confirmed that PB had excellent scavenging ability for ROS and inflammatory factors related to charge adsorption with cartilage as well as long retention ability. Together, this work suggests that PB has superior protective abilities with beneficial effects on OA, indicating its great potential for intervention therapy targeting chondrocytes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A significant number of deaths and disabilities worldwide are brought on by inflammatory lung diseases. Many inflammatory lung disorders, including chronic respiratory emphysema, resistant asthma, resistance to steroids, and coronavirus-infected lung infections, have severe variants for which there are no viable treatments; as a result, new treatment alternatives are needed. Here, we emphasize how oxidative imbalance contributes to the emergence of provocative lung problems that are challenging to treat. Endogenic antioxidant systems are not enough to avert free radical-mediated damage due to the induced overproduction of ROS. Pro-inflammatory mediators are then produced due to intracellular signaling events, which can harm the tissue and worsen the inflammatory response. Overproduction of ROS causes oxidative stress, which causes lung damage and various disease conditions. Invasive microorganisms or hazardous substances that are inhaled repeatedly can cause an excessive amount of ROS to be produced. By starting signal transduction pathways, increased ROS generation during inflammation may cause recurrent DNA damage and apoptosis and activate proto-oncogenes. This review provides information about new targets for conducting research in related domains or target factors to prevent, control, or treat such inflammatory oxidative stress-induced inflammatory lung disorders., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Triple negative breast cancer (TNBC) seriously endangers women's life and health due to its high invasion and mortality. Reactive oxygen species (ROS) mediated tumor cells apoptosis is considered an effective anticancer approach. Herein, we designed a natural active triple helix β-Glucan (BFP) wrapped single walled carbon nanotubes (SWNTs)-loaded doxorubicin (DOX) self-assembly (BSD) via generating excess ROS to induce oxidative stress damage for TNBC therapy. BSD could directly consume glutathione (GSH) to promote ROS. In vitro results demonstrated that BSD exhibited obvious antitumor effects to breast cancer cells by promoting apoptosis. Un-targeted metabolomics under molecular level identified the specific metabolic targets and unveiled that BSD markedly disturbed multiple metabolic pathways, including purine metabolism, pentose phosphate pathway, glutathione metabolism pathways, amino sugar and nucleotide sugar metabolism and energy metabolism, led to the inhibition of DNA and RNA synthesis, the generation of ROS, the exacerbation of DNA damage, the disruption of cell membrane integrity and the decrease of ATP. In vitro and in vivo oxidative stress assays further verified that BSD significantly promoted intracellular oxidative stress and resulted in cell damage. This study provides theoretical basis for the development and screening of new drugs based on ROS therapy for TNBC., Competing Interests: Declaration of competing interest All listed authors have approved the enclosed version of this manuscript. The manuscript has not been published or accepted for publication nor is it under consideration elsewhere., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, we aimed to understand the effects of changes in temperature on biochemical and molecular responses associated with the antioxidant defense system in the bay scallop, Argopecten irradians. We measured the contents of H 2 O 2 and malondialdehyde (MDA), as well as the activities of antioxidant enzymes (e.g., glutathione S-transferase [GST], superoxide dismutase [SOD], and catalase [CAT]), and the regulation of stress-related genes (e.g., GST, SOD, CAT, and heat shock protein 70 [HSP70]). In addition, total antioxidant capacity (TAC) was examined in scallops exposed to different temperatures. A. irradians showed high levels of H 2 O 2 and MDA in response to acute thermal stress (48 and 72 h of exposure). Temperature changes also led to a significant increase in antioxidant enzyme activity and mRNA expression levels in A. irradians. Interestingly, the TAC increased in response to acute thermal stress (28 °C) for up to 12 h and decreased thereafter. The oxidative stress induced by high temperatures could not be alleviated by an increase in levels of antioxidant enzymes, such as GST, SOD, and CAT, resulting in high levels of H 2 O 2 and MDA and low levels of TAC. In addition, significant changes (P < 0.05) in HSP70 levels were observed in response to changes in temperature, suggesting that HSP70 played an important role in the heat tolerance of A. irradians. In conclusion, A. irradians exhibits a greater degree of oxidative stress responses in high-temperature environments than that in low-temperature environments. Overall, these findings indicate that temperature changes lead to oxidative stress, resulting in cellular damage and activation of the antioxidant defense system in bay scallops. Further experiments are required to elucidate other antioxidants and fully understand the redox system in A. irradians., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Type 2 diabetes mellitus (T2DM) is marked by chronic hyperglycemia, gradually worsening β-cell failure, and insulin resistance. Glucotoxicity and oxidative stress cause β-cell failure by increasing reactive oxygen species (ROS) production, impairing insulin secretion, and disrupting transcription factors such as pancreatic and duodenal homeobox 1 (PDX-1) and musculoaponeurotic fibrosarcoma oncogene family A (MafA). Cluster determinant 36 (CD36), an essential glycoprotein responsible for fatty acid uptake, exacerbates oxidative stress and induces the apoptosis of β-cells under hyperglycemic conditions through pathways involving ceramide, thioredoxin-interacting protein (TXNIP), and Rac1-nicotinamide adenine dinucleotide phosphate oxidase (NOX)-mediated redoxosome formation. Targeting CD36 pathways has emerged as a promising therapeutic strategy. Oral hypoglycemic agents, such as metformin, teneligliptin, and pioglitazone, have shown protective effects on β-cells by enhancing antioxidant defenses. These agents reduce glucotoxicity via mechanisms such as suppressing CD36 expression and stabilizing mitochondrial function. Additionally, novel insights into the glutathione antioxidant system and its role in β-cell survival underscore its therapeutic potential. This review focuses on the key contribution of oxidative stress and CD36 to β-cell impairment, the therapeutic promise of antioxidants, and the need for further research to apply these findings in clinical practice. Promising strategies targeting these mechanisms may help preserve β-cell function and slow T2DM progression.

Free radicals have been implicated in the pathogenesis of cancer along with cardiovascular, neurodegenerative, pulmonary and inflammatory disorders. Further, the relationship between oxidative stress and disease is distinctively established. Clinical trials using anti-oxidants for the prevention of disease progression have indicated some beneficial effects. However, these trials failed to establish anti-oxidants as therapeutic agents due to lack of efficacy. This is attributed to the fact that living systems are under dynamic redox control wherein their redox behavior is compartmentalized and simple aggregation of redox couples, distributed throughout the system, is of miniscule importance while determining their overall redox state. Further, free radical metabolism is intriguingly complex as they play plural roles segregated in a spatio-temporal manner. Depending on quality, quantity and site of generation, free radicals exhibit beneficial or harmful effects. Use of nonspecific, non-targeted, general ROS scavengers lead to systemic elimination of all types of ROS and interferes in cellular signaling. Failure of anti-oxidants to act as therapeutic agents lies in this oversimplification of extremely dynamic cellular redox environment as a static and non-compartmentalized redox state. Rather than generalizing the term "oxidative stress" if we can identify the "type of oxidative stress" in different types of diseases, a targeted and more specific anti-oxidant therapy may be developed. In this review, we discuss the concept of redox dynamics, role and type of oxidative stress in disease conditions, and current status of anti-oxidants as therapeutic agents. Further, we probe the possibility of developing novel, targeted and efficacious anti-oxidants with drug-like properties.

Problem: COVID-19 during pregnancy is linked to increased maternal morbidity and a higher incidence of preterm births (PTBs), yet the underlying mechanisms remain unclear. Cellular senescence, characterized by the irreversible cessation of cell division, is a critical process in placental function, and its dysregulation has been implicated in pregnancy complications like PTB. Senescence can be induced by various stressors, including oxidative stress, DNA damage, and viral infections., Method of Study: In this study, we determined whether COVID-19 had an impact on placental senescence. We examined placentas from women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n = 10 term, 4 preterm) compared to uninfected controls (n = 10 term, 3 preterm). The placentas were analyzed for SARS-CoV-2 infection (spike and nucleocapsid viral proteins), markers of DNA damage (γH2AX) and oxidative stress (ROS), and senescence (telomere length, cell cycle regulators, and senescence-associated secretory phenotype [SASP])., Results: Although no overall differences in cellular senescence markers were observed between the COVID-19 positive and negative groups, we found increased secreted SASP markers. Confocal microscopy of placentas from COVID-19 positive cases revealed localized areas of oxidative stress and DNA damage colocalized with SARS-CoV-2 spike protein., Conclusions: These findings indicate that SARS-CoV-2 infection induces localized focal placental damage, warranting further investigation into its impact on maternal and perinatal outcomes., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Melanin-like nanoparticles (MNPs) have recently emerged as valuable agents in antioxidant therapy due to their excellent biocompatibility and potent capacity to scavenge various reactive oxygen species (ROS). However, previous studies have mainly focused on acute ROS-related diseases, leaving a knowledge gap regarding their potential in chronic conditions. Furthermore, apart from their well-established antioxidant effects, it remains unclear whether MNPs target other intracellular molecular pathways. In this study, we synthesized ultra-small polyethylene glycol-incorporated Mn 2+ -chelated MNP (MMPP). We found that MMPP traversed the glomerular filtration barrier and specifically accumulated in renal tubules. Autosomal dominant polycystic kidney disease (ADPKD) is a chronic genetic disorder closely associated with increased oxidative stress and featured by the progressive enlargement of cysts originating from various segments of the renal tubules. Treatment with MMPP markedly attenuated oxidative stress levels, inhibited cyst growth, thereby improving renal function. Interestingly, we found that MMPP effectively inhibits a cyst-promoting gene program downstream of the cAMP-CREB pathway, a crucial signaling pathway implicated in ADPKD progression. Mechanistically, we observed that MMPP directly binds to the bZIP DNA-binding domain of CREB, leading to competitive inhibition of CREB's DNA binding ability and subsequent reduction in CREB target gene expression. In summary, our findings identify an intracellular target of MMPP and demonstrate its potential for treating ADPKD by simultaneously targeting oxidative stress and CREB transcriptional activity., Competing Interests: Disclosure and competing interests statement. The authors declare no competing interests., (© 2024. The Author(s).)

Background: Oxidative injury occurs in septic people, but the role of oxidative stress and antioxidants has rarely been evaluated in foals., Objectives/hypothesis: To measure reactive oxygen species (ROS), biomarkers of oxidative injury, and antioxidants in neonatal foals. We hypothesized that ill foals would have higher blood concentrations of ROS and biomarkers of oxidative injury and lower concentrations of antioxidants compared to healthy foals., Animals: Seventy-two hospitalized and 21 healthy neonatal foals., Methods: Prospective cohort study. Reactive oxygen species (hydrogen peroxide [H 2 O 2 ]), biomarkers of oxidative injury (malondialdehyde [MDA], protein carbonyl), and antioxidants (superoxide dismutase [SOD], catalase [CAT], glutathione, and glutathione reductase [GR] and peroxidase [GPx]) were measured from foals at admission. Measured variables were compared between healthy and ill foals using a 1-way ANOVA by Tukey's multiple comparisons test., Results: Ill foals (n = 51) had significantly higher mean concentrations of H 2 O 2 (healthy 2.6 ± 1.4 nmol/mL, ill 6.8 ± 4.6 L nmol/mL; 95% CI), MDA (healthy 31.2 ± 14.4 nmol/mL, ill 114.3 ± 94.0 nmol/mL; 95% CI), and protein carbonyl (healthy 0.07 ± 0.01 nmol/mg protein, ill 0.12 ± 0.02 nmol/mg protein, 95% CI). Significant lower CAT (healthy 0.4 ± 0.3 mU/mg protein, ill 0.02 ± 0.02 mU/mg protein, 95% CI), glutathione (healthy 238.5 ± 101.9 μg/mL, ill 110.7 ± 37.8 μg/mL, 95% CI; P < .0001), GR (healthy 1.6 ± 1.8 mU/mg protein, ill 0.4 ± 0.5 mU/mg protein, 95% CI), and GPx (healthy 0.01 ± 0.003 mU/mg protein, ill 0.007 ± 0.002 mU/mg protein, 95% CI) were also noted., Conclusions and Clinical Importance: Oxidative stress and lower antioxidant concentrations occur in ill and bacteremic neonatal foals. These variables should be considered during the treatment of ill foals., (© 2025 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Oxidative stress (OS) is a key biological challenge and selective pressure for organisms with aerobic metabolism. The result of the imbalance between reactive oxygen species production and antioxidant defense, OS can damage proteins, lipids, and nucleic acids and plays an important role in driving variation in biological aging and health. Among humans, OS research has focused overwhelmingly on adults, with demonstrated connections between OS, inflammation, and metabolic and neurodegenerative conditions. Relatively little attention has been given to OS during childhood and adolescence. This lack of early life OS research exists despite clear implications for informing human life history evolution, subadult development, and lifelong health. Here, we review current knowledge on OS during human subadulthood. Our objectives are threefold: (1) To highlight common methods for measuring OS among children and adolescents and to establish typical measurement values; (2) To summarize the evidence linking demographic and ecological factors to variation in subadult OS; (3) To identify avenues for future OS research in human biology. Our review underscores an expanding methodological toolkit for assessing OS among children and adolescents. Subadult OS is considerably elevated compared to OS among adults, a pattern eliciting unknown consequences and likely related to increased early life metabolic demands (e.g., unique human brain development). Factors such as diet, physical activity, infectious disease, and structural neglect also appear to drive subadult OS. Current limitations for research on subadult OS are evident. Future work should emphasize evolutionary, biocultural, and energetic life course perspectives to advance this promising area of human biology., (© 2025 The Author(s). American Journal of Human Biology published by Wiley Periodicals LLC.)

In Hepatitis B patients, the virus targets liver cells, leading to inflammation and liver damage, which can result in severe complications such as liver failure, cirrhosis, and liver cancer. Therapeutic options for liver disease are currently limited. Curcumin, a polyphenol with potential protective effects against chronic diseases like cancer, suffers from poor water solubility, restricting its pharmacological applications. This study explores the encapsulation of curcumin in glucan nanoparticles (NPs) and its impact on oxidative stress in liver cancer cells. Two sizes of curcumin-loaded glucan NPs, GC111 (111 nm) and GC398 (398 nm), were produced with nearly 100 % encapsulation efficiency. Cytotoxicity studies revealed that particle size influences the extent of observed effects, with GC111 NPs causing a greater reduction in cell viability. Additionally, the smaller GC111 NPs demonstrated a higher capacity to induce oxidative stress in cancer cells by stimulating the production of ROS, NO, and the chemokine RANTES in a concentration-dependent manner. These findings suggest that the smaller GC111 NPs are promising candidates for future studies aimed at evaluating oxidative stress-induced tumor cell death mechanisms., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This study aimed to investigate the protective effect of a novel capsaicinoid glucoside (CG) against H 2 O 2 -induced oxidative stress in HepG2 cells and elucidate its underlying molecular mechanism. CG treatment significantly reduced H 2 O 2 -induced cell mortality and attenuated the production of lactate dehydrogenase and malondialdehyde in a dose-dependent manner. Moreover, CG drastically reduced the ROS levels 18.7, 37.4, and 43.8% at concentrations of 25, 50, and 100 µg/mL, respectively. while increased glutathione content and catalase activity. Most importantly, in silico analysis revealed that CG effectively interacted with each of TRPV1 and Nrf2 by H-bonds, π-π interactions, and hydrophobic forces without simulation fluctuations over 50 ns. TRP, LYS, THR, LEU, GLN, VAL, ILE, and TYR residues of the tested proteins were all involved in the interaction with CG. These findings suggested that CG could reduce H 2 O 2 -induced oxidative stress in HepG2 cells via TRPV1/Nrf2 pathway which could be validated in functional foods/supplements formulations., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Oxidative stress (OS) is the imbalance between oxidant and antioxidant molecules, in favour of oxidants, that has been associated with an increased risk of morbidity and mortality in ART-treated people living with HIV (PLWH). We aimed to assess factors associated with OS in virologically suppressed PLWH on long-term modern ART., Method: In this cross-sectional study we evaluated OS by measuring both the levels of derivatives-reactive oxygen metabolites (d-ROMs) and the biological antioxidant potential (BAP). We also calculated the BAP/d-ROMs ratio, (OS index, OSi); a cut-off value < 7.3 indicated OS. Factors associated with OS markers were explored by linear regression model., Results: We enrolled 299 experienced PLWH with virological suppression (HIV-RNA < 50cps/mL). The mean of the d-ROMs levels was 409 UCARR (95%CI 394-422), whereas the mean of the BAP levels was 1.809 µmol/L (95%CI 1706-1851). The OSi mean value was 4.84, and 91.6% of the participants were below the cut-off value. By regression analysis, higher production of oxidants was associated with female sex (p < 0.001), current exposition to PIs (p = 0.030) and HCV co-infection (p = 0.006). Higher antioxidant capacity was correlated with higher HDL levels (p = 0.001). A lower OSi was associated with female sex (p = 0.003) and the current use of triple vs. dual regimen (p = 0.036). The OSi correlated negatively with cholesterol levels (p = 0.002) and positively with HDL (p < 0.001)., Conclusions: Virologically suppressed PLWH on long-term ART showed a marked OS. Female sex, the exposure to PIs, and HCV co-infection were associated with higher oxidants, while higher HDL levels were linked to better antioxidant capacity. Interestingly, dual therapy, especially INSTI-based regimens, was associated with lower oxidative stress compared to triple therapy., Competing Interests: Ethics declarations. Ethics approval and consent to participate: The study was conducted in accordance with the Good Clinical Practice and ethical principles of the Declaration of Helsinki. The protocol was reviewed and approved by our local Ethics Committees (ID4477 14/10/2021). Written informed consent was obtained from all participants. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Type 2 diabetes development has been associated with islet amyloid polypeptide (IAPP) fibrillation. IAPP fibrils have various deleterious effects, such as oxidative stress and disruption of cellular membrane integrity, resulting in pancreatic β-cell toxicity. Rutin, a plant polyphenol, possesses promising cytoprotective effects as a fibrillation inhibitor. Similarly, bioactive peptides have been identified as potential inhibitors to IAPP fibrillation. In this study, the effect of peptide/polyphenol mixtures consisting of rutin and each peptide, TNGQ, MANT, and YMSV, on anti-fibrillation activity and cellular response was elucidated. Results indicated a 54.7-75.1 % decrease in thioflavin T fluorescence, confirming anti-fibrillation activity. The combination decreased the average particle diameters of IAPP more than the single inhibitors, suggesting a combined effect of peptide/rutin mixtures in enhancing anti-fibrillation activity. IAPP fibrillation-induced rat insulinoma RIN-m cell death was minimized in the presence of the peptide/rutin mixture, but the activity was lower relative to rutin alone, suggesting a non-additive effect of the mixtures. Transmission electron microscopy showed a near-complete inhibition of IAPP fibrillation by TNGQ/rutin mixtures, which translated to a decreased production of membrane-bound IAPP oligomers in RIN-m cells based on immunofluorescence staining. Additionally, TNGQ/rutin mixtures significantly decreased reactive oxygen species production by 30 %, higher than the effects of single inhibitors, but no effect was observed on glucose-stimulated insulin secretion. The results demonstrate the potential of multifunctional compounds as dual inhibitor systems in controlling IAPP fibrillation and provide insight into the implications of peptide/polyphenol mixtures towards the rational development of novel anti-diabetic nutraceutical combinations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This review discusses sources of reactive oxygen species, enzymatic antioxidant systems, and low molecular weight antioxidants. We present the pathology of varicose veins (VVs), including factors such as hypoxia, inflammation, dysfunctional endothelial cells, risk factors in varicose veins, the role of RBCs in venous thrombus formation, the influence of reactive oxygen species (ROS) and RBCs on VV pathology, and the role of hemoglobin in the damage of particles and macromolecules in VVs. This review discusses the production of ROS, enzymatic and nonenzymatic antioxidants, the pathogenesis of varicose veins as a pathology based on hypoxia, inflammation, and oxidative stress, as well as the participation of red blood cells in the pathology of varicose veins.

An excess of reactive oxygen species (ROS), leading to oxidative stress, is a major factor in aging. Antioxidant therapies are considered crucial for delaying aging. Nanoceria, a nanozyme with antioxidant activity, holds significant potential in protecting cells from oxidative stress-induced damage. This research examines the neuroprotective role of nanoceria on HT22 cells subjected to oxidative stress induced by hydrogen peroxide (H 2 O 2 ) and explores the associated molecular mechanisms. Our findings indicate that nanoceria enhances bcl-2 expression and significantly reduces Bax expression, resulting in an increased bcl-2/Bax ratio, which confirms its anti-apoptotic effect. Nanoceria boosts catalase expression and suppresses the p38 MAPK signaling pathway, indicating its role in shielding HT22 cells from oxidative stress damage induced by H 2 O 2 through various protective mechanisms. These findings provide crucial experimental evidence for the potential applications of nanoceria in skin anti-aging and the prevention and treatment of other oxidative stress-related diseases.