Heavy metal contamination from industrial activities in coastal regions can lead to pollution in mangrove ecosystems. Mangroves produce antioxidant compounds to mitigate the impact of free radicals. This study aimed to analyze the correlation between the concentration of heavy metals Pb and Cu and antioxidant activity in Avicennia alba and Excoecaria agallocha mangroves from areas affected by industrial activities and conservation areas, Banyuasin, South Sumatra, Indonesia. This study was conducted in September 2023 with sampling locations in the Payung Island area and the Barong River conservation area, Berbak Sembilang National Park. The samples taken included sediment and mangrove leaves. The concentration of heavy metals Pb and Cu was measured by atomic absorption spectrometry. Antioxidant activity test using the DPPH test, total phenol using the Folin-Ciocalteu method, and phytochemical profile screening using GCMS. Statistical analysis of the correlation between antioxidant activity and heavy metal concentration using the Pearson correlation. The results showed that the highest concentration of heavy metals in sediment and mangrove leaves was found in the area affected by industrial activity, with a range of Pb values of 0.67 ± 0.16-18.70 ± 0.48 mg/kg and Cu values of 3.39 ± 0.20-6.07 ± 0.37 mg / kg. The results of sediment pollution assessment for heavy metals Pb and Cu at Igeo < 0 indicates uncontaminated, 1 < Cf < 3 indicates low contamination, and PLI 0-2 indicates not polluted. While the results of heavy metal bioaccumulation in leaves were BCF < 1, indicates low bioaccumulation. E. agallocha leaves from the Pulau Payung area showed very strong antioxidant activity of 21.63 μg/ml, and the highest total phenol content reached 398.80 mg GAE/g. Analysis of compounds with the highest antioxidant activity identified the presence of esters, aldehydes, alcohols, fatty acids, glycosides, flavonoids, terpenoids, and steroids. Correlation analysis shows that higher heavy metal concentrations correspond to increased antioxidant activity and total phenol content (r ≠ 0). These findings are expected to contribute to scientific knowledge that enhances environmental sustainability, supporting effective management of coastal natural resources.

Dyslipidemia exacerbates pancreatic β-cell apoptosis, heightening the risk of type 2 diabetes (T2DM). Kansuinine A (KA), a diterpene from Euphorbia roots, exhibits antiapoptotic properties, suggestive of its therapeutic potential against T2DM. In this study, we evaluated the protective effects of KA against apolipoprotein C3 (ApoC3)-rich low-density lipoprotein (LDL) (AC3RL)-induced β-cell apoptosis and its underlying mechanism of action. ApoE-/- mice fed a high-fat diet and treated with KA demonstrated improved glucose and insulin tolerance, enhanced antioxidant capacity, and reduced pancreatic β-cell apoptosis. In rat pancreatic β-cells (RIN-m5F) exposed to AC3RL, KA significantly improved cell viability, suppressed oxidative stress, and mitigated apoptosis by downregulating lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression and inhibiting the IκB kinase β (IKKβ)/Inhibitor of κB alpha (IκB⍺)/Nuclear Factor kappa B(NF-κB) signaling pathway. Molecular docking and pathway analyses revealed the interactions of KA with key targets involved in oxidative stress and apoptosis. These findings highlight the ability of KA to counteract AC3RL-induced β-cell dysfunction, offering promise as a potential intervention for dyslipidemia-driven diabetes.

Prussian blue (PB) has garnered considerable scholarly interest in the field of biomedical research owing to its notably high biocompatibility, formidable multi-enzyme mimetic capabilities, and established clinical safety profile. These properties in combination with its reactive oxygen species (ROS) scavenging activity have facilitated significant progress in disease diagnosis and therapy for various ROS-mediated pathologies, where overproduced ROS exacerbates disease symptoms. Additionally, the underlying ROS-associated mechanisms are disease-specific. Hence, we systematically examined the role of ROS and its basic underlying mechanisms in representative disease categories and comprehensively reviewed the effect of PB-based materials in effectively alleviating pathological states. Furthermore, we present a thorough synthesis of disease-specific design methodologies and prospective directions for PB as a potent ROS-scavenging biotherapeutic material with emphasis on its applications in neurological, cardiovascular, inflammatory, and other pathological states. Through this review, we aim to accelerate the progress of research on disease treatment using PB-based integrated therapeutic system.

Polynuclear transition metal complexes (PTMCs) represent a promising class of compounds with significant potential for advancing microbial diagnostics and treatment due to their multifunctional properties. This perspective highlights recent progress in the design of PTMCs for detecting and combating microbial infections. Complexes with multiple metal centers, such as silver(I), rhenium(I), iron(II), cobalt(II), nickel(II), copper(II), zinc(II), cadmium(II), ruthenium(II), iridium(III), gold(I), and gold(III), exhibit a wide range of structural motifs and are effective against a broad spectrum of multidrug-resistant bacterial infections. PTMCs show their antimicrobial effects through several mechanisms that include the generation of reactive oxygen species, which cause oxidative stress and damage bacterial cells, disrupt bacterial membranes, bind selectively to bacterial biomolecules, and interfere with critical cellular functions. Additionally, luminescent PTMCs are ideal for real-time imaging and tracking of bacterial cells during infection. In this perspective, we discuss their various applications, safety concerns, and emerging trends in the clinical use of PTMCs due to their enormous possibilities for future medical applications.

Context: Coenzyme Q10 (CoQ10) is a vital compound found in nearly all cells, and in mitochondria, it facilitates ATP production, and its reduced form acts as a powerful antioxidant, neutralizing reactive oxygen species (ROS) and preventing oxidative damage. Notably, during intense or endurance exercise, the body's increased energy demands and ROS production can lead to oxidative stress, muscle fatigue, inflammation, and exercise-induced muscle damage (EIMD).

Objectives: This review will explore the mechanisms of CoQ10, its impact on exercise performance to be addressed.

Results: CoQ10 has been shown to counteract these effects by supporting mitochondrial function, cell membranes, and reducing ROS. Research has demonstrated that CoQ10 supplementation lowers lipid peroxidation, reduces muscle damage indicators like creatine kinase (CK), lactate dehydrogenase (LDH-5 or LDH M), and myoglobin (Mb), and accelerates recovery from EIMD. Nevertheless, the impact of CoQ10 on performance has varied depending on factors such as dosage, duration, exercise type, and individual characteristics.

Preeclampsia is a pregnancy-specific syndrome, linked to oxidative stress, affecting 5-8% of pregnancies, with no effective treatment available. Here, diaryl-hydrazones have been designed, synthesized, and investigated as mitochondria-targeting antioxidants to reduce placental oxidative stress and mitigate preeclampsia symptoms. The design, based on density functional theory studies, revealed that conjugated electron structure with the NH-motif appeared to explain their effect. Thirty compounds were synthesized and tested in three assays, where they exhibited excellent radical scavenging activity, significantly greater than that of the standard, Trolox. Based on the data, eight compounds were selected for cell-based assays. Oxidative stress was induced in human trophoblast cells and assessed whether the compounds reduced downstream antiangiogenic responses using ascorbic acid and MitoTEMPO as standards. The pretreatment with the hydrazones reduced mitochondrial superoxide and sFLT-1 production in H2O2-exposed trophoblast cells, indicating that mitochondrial oxidative stress and the anti-angiogenic response can be alleviated by these compounds.

There is a surplus of byproducts from food processing in the food industry, which has potential nutritional value. The process of transforming these leftover materials into products of higher value or utility is currently referred to as upcycling. The objective of this systematic review was to answer the following question: "Can byproducts from the food industry promote health-related benefits in vivo?". To answer this question, three scientific databases were considered for the literature search: PubMed, Scopus, and Web of Science. The inclusion criteria were outlined by the PICOS, and data analysis was conducted following the PRISMA guidelines. Thirteen studies that used animal models to evaluate the potential benefits of food byproducts were included in this review. These food byproducts demonstrated potential positive effects on overall health. The main results identified are related to the reduction of reactive oxygen species, reduction of enzymes related to liver damage, improvement of cytokines such as IL-6, IL-2, and TNF-α, and improvement of glucose and lipid plasma levels. However, more studies are necessary to better elucidate the activities, mechanisms of action, and potential toxicity of these compounds. PROSPERO (CRD42024576869).

Soil contamination with arsenic (As) is becoming a serious concern for living organisms. Arsenic is a nonessential metalloid for plants, humans, and other living organisms. Biochar (BC) is a very effective amendment to remediate polluted soils and it received great attention owing to its appreciable results. Arsenic toxicity negatively affects plant morph-physiological and biochemical functioning and upsurges the generation of reactive oxygen species (ROS), which negatively affect cellular structures. Arsenic toxicity also reduces seed germination and impedes plant growth by decreasing nutrient uptake, causing oxidative damage and disrupting the photosynthetic efficiency. Plants use different strategies like antioxidant defense and increased osmolyte synthesis to counteract As toxicity; nevertheless, this is not enough to counter the toxic impacts of As. Thus, applying BC has shown tremendous potential to counteract the As toxicity. Biochar application to As-polluted soils improves water uptake, maintains membrane stability and nutrient homeostasis, and increases osmolyte synthesis, gene expression, and antioxidant activities, leading to better plant performance. Additionally, BC modulates soil pH, increases nutrient availability, causes As immobilization, decreases its uptake and accumulation in plant tissues, and ensures safer production. The present review describes the sources, toxic impacts of As, and ways to lower As in the environment to decrease its toxic impacts on humans, the ecosystem, and the food chain. It concentrates on different mechanisms mediated by BC to alleviate As toxicity and remediate As-polluted soils and different research gaps that must be fulfilled in the future. Therefore, the current review will help to develop innovative strategies to minimize As uptake and accumulation and remediate As-polluted soils to reduce their impacts on humans and the environment.

This study evaluates the health of a captive colony of Hamadryas baboons at Ravenna Zoo Safari (Italy), focusing on oxidative stress markers and biometric data. Forty-eight individuals were assessed during routine veterinary procedures: males underwent vasectomy, and females were checked for pregnancy. Biometric data collected included body weight, body length, and genital measurements in males, while females were evaluated for reproductive status. Oxidative stress was measured using two tests that assess both harmful pro-oxidant levels and the body's antioxidant defenses. Results showed no significant differences in oxidative stress levels between sexes, although males and females differed in body weight. Pregnant and postpartum females exhibited higher oxidative stress, likely due to the metabolic and hormonal demands of reproduction. This supports the idea that reproductive activity increases the production of reactive oxygen species, requiring stronger antioxidant responses. In males, correlations between body weight and genital measurements suggest these could help estimate age in the absence of birth records. No link was found between oxidative stress and body weight, indicating limited age-related effects on these markers. Overall, the study highlights the importance of monitoring oxidative stress in captive primates to better understand the effects of reproduction and aging, and to improve welfare and management practices.

Male-factor infertility accounts for nearly half of all infertility cases, and mounting evidence points to oxidative stress as a pivotal driver of sperm dysfunction, genetic instability, and epigenetic dysregulation. In particular, the oxidative DNA lesion 8-hydroxy-2'-deoxyguanosine (8-OHdG) has emerged as a central mediator at the interface of DNA damage and epigenetic regulation. We discuss how this lesion can disrupt key epigenetic mechanisms such as DNA methylation, histone modifications, and small non-coding RNAs, thereby influencing fertilization outcomes, embryo development, and offspring health. We propose that the interplay between oxidative DNA damage and epigenetic reprogramming is further exacerbated by aging in both the paternal and maternal germlines, creating a "perfect storm" that increases the risk of heritable (epi)mutations. The consequences of unresolved oxidative lesions can thus persist beyond fertilization, contributing to transgenerational health risks. Finally, we explore the promise and potential pitfalls of antioxidant therapy as a strategy to mitigate sperm oxidative damage. While antioxidant supplementation may hold significant therapeutic value for men with subfertility experiencing elevated oxidative stress, a careful, personalized approach is essential to avoid reductive stress and unintended epigenetic disruptions. Recognizing the dual role of oxidative stress in shaping both the genome and the epigenome underscores the need for integrating redox biology into reproductive medicine, with the aim of improving fertility treatments and safeguarding the health of future generations.

Malignant neoplasms constitute a substantial health concern for the human population, currently ranking as the second leading cause of mortality worldwide. In 2022, approximately 10 million deaths were attributable to cancer, and projections estimate that this number will rise to 35 million in 2050. Consequently, the development of effective cancer treatments and prevention strategies remains a primary focus of medical research. In this context, the impacts on the redox balance are being considered. The objective of this study was to present the current knowledge on oxidation and reduction processes in cancer. This review discloses the intricate and multifaceted interplay of oxidoreductive systems during carcinogenesis, which engenders discordant findings in the domain of tumor prevention and treatment. This study also examines the controversies surrounding the use of antioxidants, including their impact on other therapeutic interventions. The review offers a comprehensive overview of the existing knowledge on the subject, concluding that personalized and precise anticancer therapies targeting the redox processes can serve as both effective diagnostic and therapeutic tools.

Pediatric nephrotic syndrome remains a complex clinical entity, with incompletely elucidated pathogenetic mechanisms, in which oxidative stress appears to have a substantial etiopathogenic role. Recent evidence supports the involvement of redox imbalance in podocyte damage, impaired glomerular function, and systemic decline. All this suggests that antioxidant interventions can favorably modulate the course of the disease. This narrative review aims to synthesize the most relevant data from the current literature on the interaction between oxidative stress and nephrotic syndrome in children, with a focus on the therapeutic potential of antioxidants. The analysis focuses on the molecular mechanisms by which oxidative stress contributes to the progression of renal dysfunction, the role of oxidative biomarkers in disease monitoring, and the ability of antioxidants to reduce the need for immunosuppressants and corticosteroids, thus contributing to the decrease in associated morbidity. The translational perspectives of antioxidant therapy are also discussed, in the context of the urgent need for effective adjuvant strategies with a safety profile superior to conventional therapies. By integrating these data, the paper supports the valorization of antioxidant interventions as an emerging direction in the management of pediatric nephrotic syndrome and substantiates the need for controlled clinical trials, with rigorous design, in this field.

Reactive oxygen species (ROS), a class of highly reactive molecules, are closely linked to the pathogenesis of various cancers. While ROS primarily originate from normal cellular processes, external stimuli can also contribute to their production. Cancer cells typically exhibit elevated ROS levels due to disrupted redox homeostasis, characterized by an imbalance between antioxidant and oxidant species. ROS play a dual role in cancer biology: at moderate levels, they facilitate tumor progression by regulating oncogenes and tumor suppressor genes, inducing mutations, promoting proliferation, extracellular matrix remodeling, invasion, immune modulation, and angiogenesis. However, excessive ROS levels can cause cellular damage and initiate apoptosis, necroptosis, or ferroptosis.

This review explores molecular targets involved in redox homeostasis dysregulation and examines the impact of ROS on the tumor microenvironment (TME). Literature from recent in vitro and in vivo studies was analyzed to assess how ROS modulation contributes to cancer development and therapy.

Findings indicate that ROS influence cancer progression through various pathways and cellular mechanisms. Targeting ROS synthesis or enhancing ROS accumulation in tumor cells has shown promising anticancer effects. These therapeutic strategies exhibit significant potential to impair tumor growth while also interacting with elements of the TME.

The ROS serve as both promoters and suppressors of cancer depending on their intracellular concentration. Their complex role offers valuable opportunities for targeted cancer therapies. While challenges remain in precisely modulating ROS for therapeutic benefit, they hold promise as synergistic agents alongside conventional treatments, opening new avenues in cancer management.

Pentachlorophenol (PCP) was extensively utilized as an organochlorine pesticide and wood preservative in the United States from the 1930s until the Environmental Protection Agency (EPA) imposed restrictions due to concerns about its toxicity and potential carcinogenic properties. Although it is no longer widely used, PCP remains a concern due to its environmental persistence and potential for long-term health effects. Significant occupational and environmental exposures have likely occurred, with the health and economic costs of PCP exposure potentially being substantial given its known toxicity. Notably, PCP exhibits rapid absorption through both the skin and respiratory system and has been shown to cause hepatotoxicity, developmental toxicity, immunotoxicity, irritation, and carcinogenicity in laboratory animal studies. PCP exposure induces oxidative stress, a key mechanism underlying its inflammatory and toxic effects, which can activate cellular stress responses including upregulation of heat shock protein 70 (Hsp70). Previous studies in lung and liver epithelial cells have shown that Hsp70 and oxidative stress play pivotal roles in triggering autophagy. This study establishes the critical role of the Hsp70-reactive oxygen species (ROS)-autophagy axis in regulating cellular responses to PCP exposure in human alveolar (A549) and liver carcinoma (HepG2) epithelial cells. Our research elucidated the molecular mechanisms underlying PCP's cellular effects, demonstrating that its exposure resulted in increased expression of autophagy-related proteins (Beclin-1, LC3B, ATG12, and ATG16), subunits of NADPH oxidase (NCF-1, NCF-2, NOX2, and Rac), and antioxidant proteins (SOD and GPx) in both lung and liver cell types. Notably, PCP augmented the interaction between Hsp70 and the autophagy regulator Beclin-1. Pretreatment with the ROS inhibitor N-acetylcysteine or Hsp70 knockdown markedly reversed PCP-induced responses. Our in-silico protein-protein docking analysis and molecular dynamics simulation studies revealed enhanced interactions and/or stable confirmations maintained throughout the simulations for TLR4-Hsp70 and Hsp70-Beclin-1 complexes in the presence of PCP. These findings provide a strong foundation for future studies, employing in vivo experimental models and human populations to identify promising targets for PCP-induced toxicity and cellular injury. Furthermore, these findings may have far-reaching implications for public health and environmental policy, ultimately leading to the identification of biomarkers and the development of more effective interventions for environmentally induced toxicity and diseases.

This study aimed to evaluate to what extent lifestyle habits, contribute to associations between EA and various conditions, and test the variability in risk reduction for specific health conditions linked to a healthy lifestyle across different EA levels.

Data were analyzed from 341,632 UK Biobank participants without baseline cardiovascular disease or cancer (2006-2010). A healthy lifestyle score (0-5) was created by assigning one point for each of five habits: a healthy diet, sufficient physical activity, non-current smoking, moderate alcohol consumption, and low-risk sleep duration. Baseline data on self-reported and genotype-predicted EA were collected, with 45 health outcomes assessed until January 2021. Logistic regression models were used to assess the relationship between EA and lifestyle habits, and associations between the healthy lifestyle score and health/mortality outcomes were examined using Cox proportional hazards model. Moderation analysis tested whether EA modified the associations between a healthy lifestyle and health outcomes, while mediation analysis estimated the proportion of the association between EA and health outcomes explained by lifestyle habits.

Both self-reported and genotype-predicted EA were associated with a healthy diet, non-current smoking, low-risk sleep duration, and moderate alcohol consumption, but not low-risk physical activity. A healthy lifestyle is inversely linked to risks for 38 of 45 outcomes, including CVD, type 2 diabetes, lung and colon cancer, depression, and chronic kidney disease, as well as overall, CVD, and cancer mortality. Higher EA reduced risk for 25 conditions, such as CVD, certain cancers, chronic liver disease, and fractures; stronger inverse lifestyle-risk associations were observed among less educated individuals. Lifestyle habits explained 47.2% (95% CI: 35.3-59.4%) of the association between genotype-predicted EA and all-cause mortality, mediating a large proportion of associations with CVDs, cancers, dementia, respiratory diseases, and chronic kidney disease.

Higher EA might encourage the adoption of more healthy lifestyle habits, thus promoting healthy aging. Placing greater emphasis on lifestyle modification is essential for individuals with lower EA to effectively address health inequalities associated with EA.

Enzymatic hydrolysis of proteins to obtain bioactive peptides is increasingly attractive, but the poor stability and low reusability of enzymes remain unsolved. Here, the magnetically recyclable immobilized Alcalase (Alcalase@SGO-PEGA) was constructed by immobilizing the free protease of Alcalase to the superparamagnetic graphene oxide (SGO) whose surface was modified with polyethylene glycol diamine (PEGA). The results indicate that Alcalase@SGO-PEGA significantly improved the thermostability and pH tolerance of Alcalase, withstanding temperatures up to 70 °C and pH levels up to 12. Additionally, Alcalase@SGO-PEGA with a saturation magnetizations (Ms) of 20.64 emu/g allowed for efficient recovery using external magnetic fields, and its catalytic stability was demonstrated by retaining 50 % of its initial activity after seven cycles of reuse. Using Alcalase@SGO-PEGA for the enzymatic hydrolysis of soy protein isolate, casein, bovine, serum protein, β-lactoglobulin, sesame protein and flaxseed, bioactive peptides with different molecular weights were obtained by adjusting the hydrolysis temperature and time. Additionally, the antioxidative capacity of the bioactive peptides was confirmed by their ABTS+ free radicals scavenging rate and Fe2+ chelating activity. This paper presents a novel, sustainable strategy for obtaining antioxidant peptides with adjustable molecular weights using magnetically recyclable immobilized Alcalase, advancing its application and promoting cleaner protein processing.

Current study evaluates the beneficial role of bio-functionalized zinc ferrite nanoparticles fabricated from an aqueous extract of Decalepis hamiltonii leaves (DHLE.ZnFe2O4 NPs) on sodium nitrite (NaNO2) and Diclofenac (DFC) induced oxidative stress in RBCs and Sprague Dawley male rat models. DHLE.ZnFe2O4 NPs were characterized using PXRD, FTIR, SEM-EDAX, HR-TEM and VSM. The data suggests that, DHLE.ZnFe2O4 NPs were crystalline, ellipsoidal in shape with an average size of 10.95 nm and super paramagnetic in nature. DHLE.ZnFe2O4 NPs exhibited anti-oxidant properties by scavenging DPPH, H2O2 and reducing ferric to ferrous ions. Furthermore, DHLE.ZnFe2O4 NPs normalized key parameters of oxidative stress such as LPO, PCC, TT and anti-oxidant enzymes (SOD & CAT). Similar to the previous in-vitro results, DHLE.ZnFe2O4 NPs restored all the said stress parameters in homogenates of the liver, kidney, pancreas and heart. In addition, DHLE.ZnFe2O4 NPs repaired Diclofenac induced tissue damage in the liver, kidney, pancreas and heart by regulating all biochemical parameters. Most importantly, DHLE.ZnFe2O4 NPs exhibited anti-inflammatory, anti-diabetic, anti-thrombotic activities and were non-toxic to RBCs. In conclusion, DHLE.ZnFe2O4 NPs through its anti-oxidant potential ameliorate oxidative stress induced pathogenesis such as, inflammation, tissue damage, diabetes and thrombosis.

This study compares the therapeutic efficiency of bovine serum albumin-stabilized selenium nanoparticles in reducing oxidative stress and improving cellular health. The nanoparticles were synthesized using mussel-extracted selenium with two reducing agents: d-glucose and orange. Inductively coupled plasma-optical emission spectroscopy and X-ray diffraction analyses confirmed the presence of selenium. The reducing agent and duration influenced the nanoparticle size. Reduction with d-glucose for 1 hour revealed that the particles exhibited an average size of 10 nm. Copper sulfate-induced malformations such as yolk sac and pericardial edema were observed with 25 μg ml-1 of orange-reduced nanoparticles, while d-glucose-reduced nanoparticles mitigated these malformations at 25 μg ml-1. Treatment with stabilized Se-NPs reduced with d-glucose for 30 minutes showed 33% dose-dependent radical scavenging activities, upregulated approximately 2-fold of superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase encoding genes and restored homeostasis by decreasing lipid peroxidation (27.32 nmol mg-1 ml-1) and nitric oxide levels (6.71 μM). They also had the potential to restore cognitive properties such as larval movement (93.40 m) without altering larval behaviour. Live cell imaging indicated a significant decrease in cellular reactive oxygen species and lipid peroxidation levels in the gut and liver. These findings suggest that Se-NPs reduced for 30 minutes with d-glucose are promising candidates for oxidative stress-induced neurodegeneration.

Sickle cell disease (SCD) is a monogenic blood disorder characterized by abnormal hemoglobin S production, which polymerizes under hypoxia conditions to produce chronic red blood cell hemolysis, widespread organ damage, and vasculopathy. As a result of vaso-occlusion and ischemia-reperfusion injury, individuals with SCD have recurrent pain episodes, infection, pulmonary disease, and fall victim to early death. Oxidative stress due to chronic hemolysis and the release of hemoglobin and free heme is a key driver of the clinical manifestations of SCD. The net result is the generation of reactive oxygen species that consume nitric oxide and overwhelm the antioxidant system due to a reduction in enzymes such as superoxide dismutase and glutathione peroxidase. The primary mechanism for handling cellular oxidative stress is the activation of antioxidant proteins by the transcription factor NRF2, a promising target for treatment development, given the significant role of oxidative stress in the clinical severity of SCD. In this review, we discuss the role of oxidative stress in health and the clinical complications of SCD, and the potential of NRF2 as a treatment target, offering hope for developing effective therapies for SCD. This task requires our collective dedication and focus.

Following unfavorable environmental cues, cells reprogram pathways that govern transcription, translation, and protein degradation systems. This reprogramming is essential to restore homeostasis or commit to cell death. This review focuses on the secondary roles of two nuclear transcriptional regulators, cyclin C and Med13, which play key roles in this decision process. Both proteins are members of the Mediator kinase module (MKM) of the Mediator complex, which, under normal physiological conditions, positively and negatively regulates a subset of stress response genes. However, cyclin C and Med13 translocate to the cytoplasm following cell death or cell survival cues, interacting with a host of cell death and cell survival proteins, respectively. In the cytoplasm, cyclin C is required for stress-induced mitochondrial hyperfission and promotes regulated cell death pathways. Cytoplasmic Med13 stimulates the stress-induced assembly of processing bodies (P-bodies) and is required for the autophagic degradation of a subset of P-body assembly factors by cargo hitchhiking autophagy. This review focuses on these secondary, a.k.a. "night jobs" of cyclin C and Med13, outlining the importance of these secondary functions in maintaining cellular homeostasis following stress.

Cancer treatments often exploit oxidative stress to selectively kill tumour cells by disrupting their lipid peroxidation membranes and inhibiting antioxidant enzymes. However, lipid peroxidation plays a dual role in cancer progression, acting as both a tumour promoter and a suppressor. Balancing oxidative stress through antioxidant therapy remains a challenge, as excessive antioxidant activity may compromise the efficacy of chemotherapy and radiotherapy.

This review explores the role of antioxidants in mitigating lipid peroxidation in cancer therapy while maintaining treatment efficacy. It highlights recent advancements in nanotechnology-based targeted antioxidant delivery to optimize therapeutic outcomes.

A comprehensive literature review was conducted using reputable databases, including PubMed, Scopus, Web of Science, and ScienceDirect. The search focused on publications from the past five years (2020-2025), supplemented by relevant studies from earlier years. Keywords such as "antioxidants," "lipid peroxidation," "nanotechnology in cancer therapy," and "oxidative stress" were utilized. Relevant articles were critically analysed, and graphical illustrations were created.

Emerging evidence suggests that nanoparticles, including liposomes, polymeric nanoparticles, metal-organic frameworks, and others, can effectively encapsulate and control the release of antioxidants in tumour cells while minimizing systemic toxicity. Stimuli-responsive carriers with tumour-specific targeting mechanisms further enhance antioxidant delivery. Studies indicate that these strategies help preserve normal cells, mitigate oxidative stress-related damage, and improve treatment efficacy. However, challenges such as bioavailability, stability, and potential interactions with standard therapies remain.

Integrating nanotechnology with antioxidant-based interventions presents a promising approach for optimizing cancer therapy. Future research should focus on refining lipid peroxidation modulation strategies, assessing oxidative stress profiles during treatment, and employing biomarkers to determine optimal antioxidant dosing. A balanced approach to antioxidant use may enhance therapeutic efficacy while minimizing adverse effects.

Precision health symptom science applies person-centered approaches to elucidate interindividual differences in patients' symptom experiences and incorporates omics methods with social, societal, and environmental determinants of health to develop symptom management strategies. By filling scientific gaps related to patients' symptom experiences and their underlying mechanisms, interventions can be developed to improve quality of life and outcomes. The purposes of this article are to describe symptom phenotype development; review analytical approaches to identify a symptom phenotype; and discuss common and emerging methods for biomarker discovery and their implications in precision health symptom science.

Peer-reviewed research studies, review articles, and scientific expertise were synthesized to provide a broad overview of several methods of biomarker discovery and their implications for precision health symptom science.

Approaches to symptom phenotype development and analytical methods for phenotype identification were reviewed. Common (ie, genomic, epigenomic, transcriptomic, proteomic, metabolomic, microbiome) and emerging (ie, polygenic risk scores, microRNA, epigenetic clocks, allostatic load, wearables) methods for biomarker discovery were described. Each method provides unique information to improve our understanding of the complex biological processes that underlie symptoms and may be used for risk prediction, screening, surveillance, and treatment response.

While the exemplar approaches to conducting precision health symptom science were shared through an oncology lens, they are generalizable across acute and chronic conditions.

Symptom biomarker identification is inherently complex and the methods for biomarker collection, processing, measurement, and analysis are continually evolving. Therefore, symptom scientists need to form transdisciplinary teams with experts in omics methodologies and bioinformatics. Despite the challenges, symptom scientists are well suited to lead the way in precision health symptom science to reduce symptom burden and improve quality of life among patients with various chronic conditions.

The development of new strategies to raise the survival and viability of transplanted mesenchymal stem cells (MSCs) is very important for the therapeutic potential of stem cells. The natural flavonoid myricetin has anticancer, antioxidant, anti-inflammatory and antiapoptotic effects. The effects of myricetin on human umbilical cord-derived MSCs (HUC-MSCs) induced oxidative stress with hydrogen peroxide (H2O2) were evaluated by transmission electron microscopy (TEM) and immunocytochemistry (ICC) staining. Myricetin showed an increase in the number of live cells, a decrease in caspase-3 and tumor necrosis factor-α (TNF-α) ICC staining intensity, an increase in the translocase of the mitochondrial inner membrane 17 (TIM17) ICC staining intensity, and a decrease in degeneration of cell ultrastructure in TEM against oxidative stress damage in HUC-MSCs. The results suggest that myricetin prevents oxidative stress-induced apoptosis and inflammation in the HUC-MSCs. Myricetin can be combined with HUC-MSCs in cell culture and considered as a supportive alternative treatment option.

Insects represent a traditional food in different parts of the world, where eating insects is not only related to nutrition, but also results from a variety of sociocultural customs. Insects' nutritional profiles typically vary by species. Nevertheless, in terms of nutrition, edible insects can be a rich source of protein, dietary fiber, healthy fatty acids, and micronutrients, including minerals and vitamins. Insects have a low carbon footprint and require fewer resources in terms of land, water, and food with respect to animal livestock. Interestingly, insects are a source of bioactive compounds with different pharmacological activities, including antioxidant, antimicrobial, antidiabetic, antiobesity, antihypertensive, and antilipidemic. Among the bioactive compounds, polyphenols, chitosan, and protein hydrolysates are the most important ones, with direct activity on ROS quenching and enzymatic inhibition. Glucosidase, DPP-IV, ACE, and lipases are directly inhibited by insects' bioactive peptides. Lipids and tocopherols reduce inflammation and lipid peroxidation by acting on LOX and COX-2 enzymes and on ROS quenching. The insects' nutrient composition, coupled with their easy and economical breeding, is the cause of the growing interest in edible insects. During the last 20 years, the study and development of novel insect-based products increased, with relevant effects on the market. This review focuses on the edible insects currently approved in Europe, namely, Acheta domesticus, Alphitobus diaperinus, Locusta migratoria, and Tenebrio molitor. The nutrient profile and the functional compounds are examined, with an eye on market trends and on the patent applications filed in the last decades.

This study investigated the suppressor effects of carrots depending on cultivation method on AOM/DSS-induced colon cancer in mice by examining cell apoptosis, inflammation response, and metabolites. Carrots grown using different fertilizers significantly suppressed tumor development by modulating cell apoptosis and inflammatory responses in our experimental settings.

Naturaldream Fertilizer Carrot (NFC) cultivated with deep sea water minerals (DSWM) showed effectively increased the expression of apoptosis-related genes and proteins including p53, p21, Bim, Bad, Bax, Bak, Caspase 9, and Caspase 3 in colon tissue, while inhibiting the production of inflammatory factors and related genes and proteins such as TNF-a, IL-1b, IL-6, IFN-g, NF-kB, and iNOS in serum, spleen cells, and liver tissues. Intestinal microbiota analysis revealed a distinct composition in mice receiving carrots compared to the control group, with accumulation of intestinal microorganisms such as Lachnospiraceae, and Mucispirillum schaedleri closely associated with anti-tumor effects.

Overall, our results indicate that carrots, especially carrots grown with DSWM fertilizers, play a crucial role in inhibiting AOM/DSS-induced colon cancer in mice by regulating cell apoptosis and inflammation responses. The present findings provide valuable insights for further exploration of carrots depending on the cultivation method, as a potential dietary source against colon cancer.

The COVID-19 pandemic has exacerbated health disparities, with long COVID emerging as a major global public health challenge. Although clinical risk factors for long COVID are well-documented, the cumulative burden of adverse social determinants of health (SDoH) remains underexplored. This study aims to investigate the association between cumulative social disadvantage and long COVID.

Using data from the 2022 and 2023 National Health Interview Survey cycles (n = 16,446 U.S.adults), cumulative social disadvantage was quantified through 18 SDoH indicators and categorized into quartiles. The highest quartile represents the most disadvantaged individuals. Long COVID was defined as self-reported symptoms persisting for three months or longer. Weighted logistic regression models were used to examine the association, adjusting for demographic and clinical variables.

Adults in the highest quartile of cumulative social disadvantage exhibited an increased odds of experiencing long COVID compared to those in the lowest quartile (AOR = 2.52, 95% Cl: 2.13, 2.98). This association persisted across demographic subgroups, with particularly pronounced effects among women and non-Hispanic Blacks. Hispanics and non-Hispanic Whites showed weaker, but still statistically significant. Key contributors included mental health difficulties, economic instability, and healthcare access barriers. Furthermore, cumulative social disadvantage was linked to fair or poor general health status among individuals with long COVID.

This study highlights the positive association between cumulative social disadvantage and long COVID. Addressing systemic inequities through integrated public health strategies is essential to mitigate the burden of long COVID and reduce social disparities in health.

Tamarillo (Solanum betaceum Cav.) is rich in polyphenols, anthocyanins, and carotenoids, making it a promising candidate for functional food development. This study investigated phytochemical profiles and bioactivities in different tamarillo parts. Various parts of tamarillo were extracted using water and ethanol (0-95%), with 95% ethanol yielding the highest content of bioactive compounds in the peel, pulp, mucilage, and whole fruit, while 75% ethanol was more effective for the seeds. Among tamarillo components, the peel exhibited the highest concentrations of hydroxycinnamoyl derivatives, anthocyanins, and carotenoids, along with superior antioxidant capacity, including strong scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals (EC50, 45.26 µg extract/mL) and high reducing power (EC50, 113.3 µg extract/mL). The peel extract exhibited the strongest inhibitory effects on α-glucosidase (IC50, 1.623 mg/mL) and angiotensin-converting enzymes (IC50, 1.435 mg/mL). In contrast, the pulp extract demonstrated the highest inhibitory activity against pancreatic lipase (IC50, 0.882 mg/mL) and α-amylase (IC50, 2.369 mg/mL). These findings suggest that tamarillo extracts possess potent antioxidant activity and enzyme-inhibitory properties related to metabolic syndrome (MetS). However, gastrointestinal digestion simulation influenced the bioactive compound content and bioactivities. Overall, tamarillo has promising potential as a functional ingredient for MetS prevention, but processing strategies are needed to retain its bioactive properties.

Oxidative stress is caused by an imbalance between accumulation and production of oxygen reactive species (ROS) in tissues and cells and play a key role in many diseases. This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to analyze the effects of walnut consumption on biomarkers of oxidative stress. Databases including PubMed, Scopus, Embase and Web of science were searched until November 30th, 2024. Data were subjected to meta-analysis using a random effects model to examine the effect sizes of the pooled results. Four studies were identified eligible to be included in current meta-analysis. Walnut consumption resulted in a significant increase in catalase activity (CAT) (WMD: 42.20; 95% CI: 34.28, 50.11). Walnut consumption did not affect other biomarkers of oxidative stress such as lipid peroxidation (LPO), reduced glutathione (GSH), oxidized glutathione (GSSG) and oxygen radical absorbance capacity (ORAC). Overall, this meta-analysis demonstrated walnut consumption increase CAT, but did not affect other biomarkers of oxidative stress. This suggests that walnut may have played an indirect and mild role in health. However, due to the limited number of studies, further investigations is suggested in this regard.

Oxidative stress plays an important role in the development of hypertension (HTN). A population-based cross-sectional study was conducted in Fujian province of China. The construction of FoodL-OBS relied on diet and lifestyle components, which included four food and six lifestyle factors. Multivariable-adjusted logistic regression was performed to investigate the association between FoodL-OBS and the risk of HTN. A subgroup analysis was also conducted. Restricted cubic spline (RCS) regression was used to elucidate the dose-response relationship between FoodL-OBS and the risk of HTN. A total of 9578 participants were included, 3271 of whom suffered from HTN. The results of multivariable logistic regression analysis showed that the HTN risk decreased by 14% for each FoodL-OBS unit added [OR: 0.86 (0.84, 0.88), p < 0.01]. Compared with participants with the lowest levels of Food-L-OBS, those with the highest quartile were less likely to have HTN [0.43 (0.37, 0.50)]. Further stratified analysis showed that Food-L-OBS was negatively associated with the risk of HTN, which was statistically significant in participants in subgroups of ≤60 years, female, and no-dyslipidemia. The results of RCS showed a linear negative correlation between Food-L-OBS and HTN in men, but not in women. In conclusion, FoodL-OBS was negatively associated with HTN, and a healthy lifestyle and antioxidant-rich diet may be useful for preventing HTN.

Clerodendrum glandulosum is utilized as a soup or vegetable in Northeast India and has been reported to exhibit a range of medicinal and pharmacological properties. Its use in traditional cuisine and medicine highlights its potential importance in both dietary and therapeutic applications. This study focuses on the bioactive potential of the ethyl acetate fraction (EAF) derived from the hydro-alcoholic extract of C. glandulosum leaves against palmitate-induced oxidative stress and mitochondrial dysfunction. The EAF exhibited significant radical scavenging activities, with IC50 values of 29.56 µg/mL (ABTS inhibition) and 36.61 µg/mL (DPPH inhibition). Additionally, EAF demonstrated strong anti-glycation properties, effectively reducing fructosamine levels and protein carbonylation while increasing total thiol content. Phytochemical analysis revealed the presence of several bioactive compounds--namely verbascoside, isoverbascoside, and ferulic acid--associated with potential biological activities. Chromatographic analysis showed that verbascoside is the primary compound, with a concentration of 240.41 ± 8.62 µg/mg. Furthermore, EAF pretreatment significantly lowered the levels of reactive oxygen species, DNA damage, and lactate dehydrogenase release in palmitate-induced cells. During extracellular flux analysis for mitochondrial and glycolysis stress tests, EAF treatment demonstrated effective recovery of mitochondrial respiration and ATP production in palmitate-induced cells. EAF also upregulated essential mitochondrial markers, including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial transcription factor A (TFAM), which enhanced mitochondrial biogenesis and function. Overall, our study underscores the potential of the EAF from Clerodendrum glandulosum as a therapeutic agent to mitigate oxidative stress and mitochondrial dysfunction. This study suggests the efficacy of the active compounds for further development of phytopharmaceutical interventions for metabolic syndrome and related disorders.

The manufacturing process of regulatory T (Treg) cells for clinical application begins with the positive selection of CD25+ cells using superparamagnetic iron oxide nanoparticle (SPION)-conjugated anti-CD25 antibodies (spCD25) and immunomagnetic cell separation technology. Our findings revealed that the interaction of spCD25 with its cell target induced the internalization of the complex spCD25-interleukin-2 receptor. Accumulation of intracellular spCD25 triggered oxidative stress, causing delayed Treg expansion and temporary reduction in suppressor activity. This activation delay hindered the efficient generation of clinically competent cells. During this early phase, Treg cells exhibited elevated mitochondrial superoxide and lipid peroxidation levels, with a concomitant decrease in mitochondrial respiration rates. The results uncovered the increased mitochondrial unfolded protein response. This protective, redox-sensitive activity is inherent in Tregs when contrasted with homologous, spCD25-treated, conventional T cells. Although the temporary effects of spCD25 on clinically competent cells did not impede their use in a safety/feasibility pilot study with kidney transplant recipients, it is reasonable to anticipate a potential reduction in their therapeutic efficacy. The mechanistic understanding of the adverse effects triggered by spCD25 is crucial for improving the manufacturing process of clinically competent Treg cells, a pivotal step in the successful implementation of immune cell therapy in transplantation.

Antarctic organisms are known for producing unique secondary metabolites, and this study specifically focuses on the less-explored metabolites of the moss Warnstorfia fontinaliopsis. To evaluate their potential bioactivity, we extracted secondary metabolites using four different solvents and identified significant lipase inhibitory activity in the methanol extract. Non-targeted metabolomic analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) on this extract predicted the presence of 12 compounds, including several not previously reported in mosses. To gain insights into their enzyme inhibitory activity, the binding affinities of these candidate compounds to lipase were evaluated through in silico molecular docking. Further validation by molecular dynamics (MD) simulations revealed that hyocholic acid and pheophorbide A form stable complexes with human pancreatic lipase (HPL). Based on these results, targeted fractionation experiments were performed, yielding eight fractions. Among these, Fractions 4 and 6, which are assumed to contain those compounds, exhibited higher lipase inhibitory activity compared to the crude extract. Additionally, pharmacokinetic properties of those compounds were analyzed using SwissADME and Molinspiration calculations, suggesting their potential as drug candidates. This study establishes a promising methodology for identifying rare bioactive compounds of low abundance in underexplored natural resources by combining LC-MS/MS analysis with molecular docking. These findings also provide new insights into the chemical ecology of Antarctic mosses and their potential applications in pharmaceutical development.

The study aimed to examine the individual and joint effects of hypertension and diabetes on cardiovascular diseases and all-cause mortality among the middle-aged and older Chinese population.

A total of 9681 individuals without preexisting CVD from the China Health and Retirement Longitudinal Study (CHARLS) were included. Participants were classified into four different groups: hypertension alone, diabetes alone, both conditions, neither condition. Multivariate Cox proportional hazards models were performed to estimate the risks of all-cause mortality and CVD.

During the 7-year follow-up, 967 deaths and 1535 CVD events were documented. Compared to individuals without hypertension and diabetes, hypertension alone [adjusted hazard ratio (aHR) 1.571, 95% confidence interval (CI) 1.316-1.875, P  < 0.001], diabetes alone (aHR 1.618, 95% CI 1.187-2.205, P  < 0.01) and comorbid hypertension and diabetes (aHR 2.041, 95% CI 1.557-2.677, P  < 0.001) increased risks of all-cause mortality. The aHRs for CVD events in individuals with both conditions, hypertension alone and diabetes only were 2.011 (95% CI 1.651-2.449, P  < 0.001), 1.408 (95% CI 1.233-1.608, P  < 0.001) and 1.036 (95% CI 0.808-1.327, P  > 0.05), respectively. The risk of CVD among those with comorbid hypertension and diabetes exceeded the sum of the risks due to hypertension and diabetes alone (relative excess risk ratio = 0.567, 95% CI 0.136-0.999).

Individuals with comorbid hypertension and diabetes had greater risks of CVD and all-cause mortality, beyond those associated with either condition alone. The synergistic interaction between hypertension and diabetes aggravated the risk of CVD.

Micro- and nanoplastics (MPs and NPs) are pervasive environmental pollutants detected in aquatic ecosystems, with emerging evidence suggesting their presence in airborne particles generated by water body motion. Inhalation exposure to airborne MPs and NPs remains understudied despite documented links between occupational exposure to these particles and adverse respiratory outcomes, including airway inflammation, oxidative stress, and chronic respiratory diseases. This study explored the effects of acute NP exposure on a fully differentiated 3D human airway epithelial model derived from 14 healthy donors. Airway epithelium was exposed to aerosolized 50 nm polystyrene NPs at concentrations ranging from 2.5 to 2500 µg/mL for three minutes per day over three days. Functional assays revealed no significant alterations in tissue integrity, cell survival, mucociliary clearance, or cilia beat frequency, suggesting intact epithelial function post-exposure. However, cytokine and chemokine profiling identified a significant five-fold increase in CCL3 (MIP-1α), a neutrophilic chemoattractant, in NP-exposed samples compared to controls. This was corroborated by increased neutrophil chemotaxis in response to conditioned media from NP-exposed tissues, indicating a pro-inflammatory neutrophilic response. Conversely, levels of interleukins (IL-21, IL-2, IL-15), CXCL10, and TGF-β were significantly reduced, suggesting immunomodulatory effects that may impair adaptive immune responses and tissue repair mechanisms. These findings demonstrate that short-term exposure to NP-containing aerosols induces a distinct pro-inflammatory response in airway epithelium, characterized by enhanced neutrophil recruitment and reduced secretion of key immune modulators. These findings underscore the potential for aerosolized NPs to induce oxidative and inflammatory stress, raising concerns about their long-term impact on respiratory health and redox regulation.

This study reports the first successful establishment of Perovskia atriplicifolia hairy root cultures using Rhizobium rhizogenes and evaluates their potential for bioactive phenolic acid production, particularly rosmarinic acid (RA). Hairy roots were induced using two R. rhizogenes strains, A4 and ATCC 15834; transformation was confirmed by PCR analysis targeting the rol and aux genes. The A4 strain exhibited higher transformation efficiency (41.3%) than ATCC 15834 (30.2%). Eight transgenic root clones (C1-C8) were established and confirmed as transformed. The clones exhibited significant variation in biomass accumulation and phenolic acid production. RA production was most strongly correlated with PAL, RAS, and CYP98A14 expression. Hierarchical clustering clustered the clones into three groups based on growth, metabolite content, and gene expression. Lines C1 and C2 exhibiting the highest RA, total polyphenol content, and the highest productivity were selected for further experiments. McCown Woody Plant (WP) and Schenk and Hildebrandt (SH) media demonstrated the greatest biomass accumulation, with growth indexes exceeding 13. Conversely, Gamborg (B5) medium enhanced RA content, achieving 38.3 and 40.8 mg/g dry weight (DW) for clones C1 and C2, respectively, representing a fourfold increase compared to the least favorable Murashige and Skoog (MS) medium. These findings establish P. atriplicifolia hairy roots as efficient systems for RA biosynthesis and can provide a basis for metabolic engineering and scale-up production of phenolic acids in medicinal plants.

Currently, there is a particular interest in the study and identification of bioactive metabolites that can be used as phytomarkers in the standardization of fruit products consumed as natural alternatives for the prevention of chronic degenerative diseases. In this investigation, the chemometric analyses of data obtained from the metabolic (1H-NMR) and chromatographic (UPLC-MS) profiles, together with the results from antioxidant activity evaluations, allowed the identification of gallic acid and a quinic acid derivative as phytomarkers responsible for the antioxidant activity detected in crude extract of the fruits of Byrsonima bucidifolia. While the antioxidant activity of the fruit extract of B. bucidifolia is comparable to that of the positive control, its high content of gallic acid could be of interest to the pharmaceutical, cosmetic, and food industries.

Gastrointestinal disorders (GIDs) in the elderly often lead to impaired gastric motility and nutrient absorption, exacerbating malnutrition. Probiotics, particularly Lactobacillus rhamnosus GG (LGG), may enhance gastric motility and nutrient absorption. This study evaluates the impact of LGG supplementation on gastric motility and nutrient absorption in elderly patients with GIDs.

A retrospective analysis was conducted on 231 elderly patients with GIDs, divided into a probiotic supplementation (PS) group (n = 110) and a NPS group (n = 121). The PS group received LGG (1 × 1010 CFU, twice daily) for at least 7 days. Baseline and post-treatment measurements included gastric motility via ultrasonography, gastrointestinal hormone levels using radioimmunoassay, and nutrient absorption markers through ELISA and calorimetry.

Post-treatment, the PS group exhibited significantly improved gastric motility, with increased antral contraction amplitude (58.65 mm vs. 56.53 mm; P = 0.004), frequency (4.06 vs. 3.81 times/min; P = 0.009), and reduced gastric half-emptying time (28.15 min vs. 29.77 min; P = 0.007). Hormone analyses showed elevated motilin and neuropeptide Y levels and decreased vasoactive intestinal peptide levels in the PS group (P < 0.05). Nutrient absorption markers indicated decreased stool fat, protein, and carbohydrate content, enhanced intestinal permeability, increased weight and digestibility of energy, fat, and protein in the PS group (P < 0.05).

PS with LGG significantly enhances gastric motility and nutrient absorption in elderly patients with GIDs, indicating potential therapeutic benefits for addressing digestive dysfunction and malnutrition in this demographic.

Epilepsy, affecting approximately 50 million individuals worldwide, is a neurological disorder characterized by recurrent seizures. Mitochondrial dysfunction and oxidative stress are critical factors in its pathophysiology, leading to neuronal hyperexcitability and cell death. Because of the multiple mitochondrial pathways that can be involved in epilepsy and mitochondrial dysfunction, it is optimal to treat epilepsy with multiple antioxidants in combination. Recent advancements highlight the potential of antioxidant therapy as a novel treatment strategy. This approach involves tailoring antioxidant interventions-such as melatonin, idebenone, and plant-derived compounds-based on individual mitochondrial health, including mitochondrial DNA mutations and haplogroups that influence oxidative stress susceptibility and treatment response. By combining antioxidants that target multiple pathways, reducing oxidative stress, modulating neurotransmitter systems, and attenuating neuroinflammation, synergistic effects can be achieved, enhancing therapeutic efficacy beyond that of a single antioxidant on its own. Future directions include conducting clinical trials to evaluate these combination therapies, and to translate preclinical successes into effective clinical interventions. Targeting oxidative stress and mitochondrial dysfunction through combination antioxidant therapy represents a promising adjunctive strategy to modify disease progression and improve outcomes for individuals living with epilepsy.

Erectile dysfunction (ED) is a medical condition characterized by the inability to achieve or maintain a satisfactory erection, primarily treated with oral phosphodiesterase type 5 inhibitors. Treatment effectiveness is diminished in severe vasculogenic ED, particularly in patients with diabetes mellitus, highlighting the need for exploring alternative/complementary interventions. Among them, dietary phenolic compounds are known for their antioxidant and anti-inflammatory properties. This systematic review focuses on catechin (EGCG), quercetin, resveratrol, and curcumin and their influence on the pathophysiology of ED. Following PRISMA 2020 guidelines (PROSPERO registration number CRD42023402016) searches across PubMed, Scopus, and Web of Science until October 2024 were conducted using relevant keywords. Inclusion criteria required original articles in English, while in silico studies, review articles, editorials, and original studies lacking essential polyphenol administration information were excluded. After an initial search that located 409, 445, and 285 publications in each database respectively, rigorous screening resulted in 26 publications comprising animal, ex vivo, and in vitro studies. Their quality was assessed using GRADE and SYRCLE ROB tools, revealing an overall "medium-high" or "high quality." These polyphenols consistently demonstrated improvements in erectile function, encompassing behavioral, functional, molecular, and hormonal aspects. However, limitations were identified, such as the predominant reliance on animal models and in vitro trials, which may not precisely reflect human physiological responses. Further clinical investigations are needed to ascertain data translational potential, standardize dosages, and establish safe and effective prescription recommendations. Prioritizing clinical trials is essential for validating the widespread applicability and efficacy of polyphenols in managing ED.

High oxidative balance score (OBS) may mitigate inflammation levels and thereby alleviate the adverse health effects induced by toxic metals. We assessed the independent, joint effects as well as their interactions of toxic metals and OBS on mortality among individuals with non-alcoholic fatty liver diseases (NAFLD).

Participants with NAFLD from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included. Mortality and underlying causes of death were certain by National Death Index records through 31 December 2019. Cox regression models were used to estimate hazard ratios (HRs) for all-cause and disease-specific mortality. Additionally, we assessed multiplicative and additive interactions of OBS and toxic metals on mortality.

Among 5263 patients with NAFLD, 1097 deaths occurred during a mean follow-up of 10.27 years. Compared with those in the OBS tertile 1, participants in tertile 3 had lower risk of all-cause mortality (HR=0.79, 95 %CI: 0.64, 0.96). Compared with individuals in the lowest lead concentration in blood, those in the highest had an increased risk of mortality, with the HRs (95 %CIs) being 1.23 (1.01, 1.51), 1.53(1.06, 2.20) and 1.94(1.25, 3.01) for all-cause, CVD and cancer mortality, respectively. Similar results were also found for blood cadmium level. Joint associations analyses found that individuals with low lead and high-OBS levels had the lowest risk of all-cause, CVD and cancer mortality, with the HRs(95 %CIs) being 0.58(0.40, 0.85), 0.45(0.21, 0.93) and 0.35(0.15, 0.81), respectively. Multiplicative interactions between OBS and blood cadmium on all-cause death (HR=0.87, 95 %CI: 0.78, 0.97) and CVD death (HR=0.81, 95 %CI: 0.67, 0.99) were found.

High OBS and low exposure to toxic metals were associated with lower risk of mortality among participants with NAFLD. Adopting anti-oxidative lifestyle could alleviate the harmful effects of toxic metals in NAFLD patients. Comprehensive strategies are essential to decrease the risk of mortality and potentially mitigate the overall burden of NAFLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a multifactorial chronic disease that can progress to metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis, ultimately leading to liver cirrhosis and hepatocellular carcinoma. Oxidative stress is believed to play an important role in the development of MASH. Small aminothiol compounds such as cysteamine and its oxidized precursor, cystamine, are known pleiotropic compounds that exhibit relatively potent antioxidant and other effects. Herein, we evaluate the efficacy of cystamine, as well as two deuterated derivatives, in a choline-deficient, L-amino acid-defined, high-fat-diet (CDAA-HFD) mouse model of rapidly progressing liver fibrosis. Compared to control mice, daily oral administration of isotopically reinforced cystamine derivatives (200 mg/kg) led to a significant reduction of liver fibrosis and inflammation as well as oxidative stress. Moreover, the efficacy of treatment appeared to increase with the deuteration state of cystamine, with the tetradeuterated derivative, d 4 -cystamine, being the most effective. These results indicate that deuterated cystamine derivatives hold promise as potential candidates for the treatment of MASH.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), Gulf War Syndrome (GWS), and Fibromyalgia (FM) are complex, chronic illnesses with overlapping clinical features. Symptoms that are reported across these conditions include post-exertional malaise (PEM), fatigue, and pain, yet the etiology of these illnesses remains largely unknown. Diagnosis is challenging in patients with these conditions as definitive biomarkers are lacking; patients are required to meet clinical criteria and often undergo lengthy testing to exclude other conditions, a process that is often prolonged, costly, and burdensome for patients. The identification of reliable validated biomarkers could facilitate earlier and more accurate diagnosis and drive the development of targeted pharmacological therapies that might address the underlying pathophysiology of these diseases. Major driving forces for biomarker identification are the advancing fields of metabolomics and proteomics that allow for comprehensive characterization of metabolites and proteins in biological specimens. Recent technological developments in these areas enable high-throughput analysis of thousands of metabolites and proteins from a variety of biological samples and model systems, that provides a powerful approach to unraveling the metabolic phenotypes associated with these complex diseases. Emerging evidence suggests that ME/CFS, GWS, and FM are all characterized by disturbances in metabolic pathways, particularly those related to energy production, lipid metabolism, and oxidative stress. Altered levels of key metabolites in these pathways have been reported in studies highlighting potential common biochemical abnormalities. The precise mechanisms driving altered metabolic pathways in ME/CFS, GWS, and FM remain to be elucidated; however, the elevated oxidative stress observed across these illnesses may contribute to symptoms and offer a potential target for therapeutic intervention. Investigating the mechanisms, and their role in the disease process, could provide insights into disease pathogenesis and reveal novel treatment targets. As such, comprehensive metabolomic and proteomic analyses are crucial for advancing the understanding of these conditions in-order to identify both common, and unique, metabolic alterations that could serve as diagnostic markers or therapeutic targets.