Search Results (5,626)

Natural deep eutectic solvents (NADES) offer a potentially food-compatible alternative for extracting plant polyphenols, although their direct application in yoghurt remains limited. This study evaluated the antioxidant and physicochemical properties of yoghurt fortified with SunGold kiwifruit extracts obtained using a selected choline chloride and glycerol NADES, with water extraction used for comparison. The phenolic profile of the NADES extract was characterised using LC-MS/MS. Both extracts were incorporated before (PRE) or after (POS) fermentation at concentrations of 10%, 20%, and 30% (v/v). The extracts and fortified yoghurts were analysed for total phenolic content (TPC), total flavonoid content (TFC), DPPH radical scavenging activity, FRAP, CUPRAC, and physicochemical properties. LC-MS/MS tentatively annotated several phenolic compounds in the NADES extract, with catechin showing the largest peak area among the annotated compounds. The water extract showed higher TPC and DPPH activity, whereas the NADES extract showed higher TFC, FRAP, and CUPRAC values. Increasing extract concentration generally increased the measured bioactive properties of the yoghurts, although the magnitude of change varied among assays and treatments. Water extract-fortified yoghurts generally showed higher TPC and DPPH values, while NADES extract-fortified yoghurts showed higher TFC, FRAP, and CUPRAC values. Extract type, fortification stage, and concentration also influenced pH, °Brix, viscosity, colour, and syneresis. Higher fortification concentrations reduced viscosity and increased syneresis, while low-concentration NADES extract-fortified yoghurts retained physicochemical properties closer to those of the control. Overall, the NADES extract showed potential as an ingredient for yoghurt fortification. Further studies are required to evaluate sensory acceptability, storage stability, starter culture viability, and gastrointestinal bioaccessibility. Full article

Glioblastoma (GBM) frequently recurs after temozolomide (TMZ) therapy and exhibits substantial redox plasticity. Our previous work showed that the effects of hydrogen peroxide (H₂O₂) vary with its level and between parental and TMZ-resistant GBM cells. Succinate dehydrogenase subunit D (SDHD), a membrane-anchoring component of mitochondrial complex II, is positioned at the interface of electron transport and redox homeostasis, but its regulation in GBM remains unclear. We therefore examined whether SDHD expression changes across distinct H₂O₂-responsive contexts involving aquaporins (AQPs) and AKT. TCGA transcriptomic analysis showed higher SDHD mRNA expression in WHO grade IV than in grade II/III gliomas, whereas paired primary/recurrent high-grade glioma samples showed heterogeneous SDHD changes at recurrence. TMZ reduced SDHD, and SDHD knockdown decreased intracellular reactive oxygen species. Combined redox perturbation reduced SDHD, whereas AKT inhibition restored SDHD expression. Under receptor-associated signaling conditions, EGFRvIII expression or CXCL12 stimulation increased measured H₂O₂ together with AQP3, AKT Ser473 phosphorylation, and SDHD. In TMZ-resistant cells, pharmacological perturbation of aquaporin-associated signaling decreased AQP9 together with AKT Ser473 phosphorylation and SDHD. An AQP3-targeting compound further reduced cell density when combined with TMZ. Together, these findings suggest that changes in SDHD expression are consistent with a compensatory redox response in GBM cells and that its regulation varies with the nature of H₂O₂-associated signaling during TMZ-related stress. Full article

Amniotic oxidative stress in women with vaginal infection but no documented intra-amniotic infection has received little attention. In this prospective cohort study of 90 women undergoing elective cesarean delivery, 45 had symptomatic, culture- or Nugent-confirmed vaginal infection and 45 were asymptomatic controls. Amniotic fluid advanced oxidation protein products (AOPP) and malondialdehyde (MDA) were measured by commercial ELISA. Both were higher in the infection group (median 7.96 versus 5.77 ng/mL and 12.49 versus 7.73 nmol/mL, both p < 0.001), with lower cord blood pH (p = 0.003) and more frequent neonatal intensive care unit (NICU) admission (26.7% versus 4.4%, p = 0.007). AOPP was associated with NICU admission (area under the curve 0.917, 95% CI 0.777 to 0.999), although this rests on 14 events with thresholds derived and evaluated in the same sample. Elevations were largest in the bacterial vaginosis and aerobic bacterial subgroups, but the etiologies did not differ. Both kits were designed for serum and are not validated for amniotic fluid, and 16.7% of MDA measurements fell outside the calibration range, so the MDA results are semi-quantitative. Vaginal infection at cesarean delivery is associated with higher amniotic oxidative stress markers; these findings are exploratory and require external validation. Full article

High-grade osteosarcoma presents a significant clinical challenge due to unpredictable therapeutic responses and aggressive progression. This study aimed to identify the critical molecular pathways driving chemotherapy resistance and aggressive phenotypes in osteosarcoma patients. Through transcriptomic and bioinformatic analyses, we identified cholesterol biosynthesis as a key upregulated metabolic pathway in poor chemotherapy responders, where squalene epoxidase (SQLE) emerged as an exploratory candidate hub gene whose elevated expression significantly correlates with shortened survival in the TCGA cohort. We validated these findings by administering terbinafine, a known SQLE inhibitor. In highly chemoresistant SaOS-2 cells exhibiting the highest baseline SQLE expression, terbinafine synergistically sensitized cells to doxorubicin by driving cell death partly through apoptosis, as confirmed by caspase inhibition. The combination also promoted ferroptosis, indicated by elevated ROS and MDA along with decreased FSP1 and GPX4 expression. Furthermore, the co-treatment effectively suppressed clonogenic potential, induced G2/M phase cell cycle arrest, and inhibited metastatic progression. These effects were mediated by the modulation of cell proliferation, metastasis, and survival genes through the coordinated regulation of the PI3K/AKT/mTOR, ERK, and JNK signaling cascades. Together, these results highlight the therapeutic potential of targeting the SQLE pathway to overcome doxorubicin resistance and suppress aggressive progression in high-grade osteosarcoma. Full article

Keloids are characterized by fibrosis and chronic inflammation, but links between mitochondrial dysfunction and keloid pathogenesis remain unclear. This study examined whether impaired PINK1/Parkin-dependent mitophagy is associated with mitochondrial DNA (mtDNA)-mediated innate immune activation and fibrosis in keloids, and evaluated mitochondrial transplantation as a potential therapeutic strategy. Primary keloid fibroblasts (KFs), normal skin fibroblasts (NFs), adipose-derived stem cells (ADSCs), human keloid tissues, and human keloid xenografts in immunodeficient BALB/c nude mice were analyzed using ultrastructural, molecular, and functional approaches. Freshly isolated NF-derived mitochondria (nMito) and ADSC-derived mitochondria (aMito) were compared at protein-equivalent doses. KFs exhibited mitochondrial abnormalities, impaired oxidative phosphorylation, increased reactive oxygen species, mtDNA leakage, and cGAS/STING pathway activation. Elevated PINK1 expression, reduced Parkin expression and p62 accumulation were consistent with impaired downstream mitophagic clearance. Both nMito and aMito were associated with improved mitochondrial function, changes in mitophagy-related markers, reduced cytosolic mtDNA and cGAS/STING signaling, and attenuated fibroblast activation, with greater aMito-associated changes in selected endpoints. In xenografts, intralesional administration of either mitochondria improved collagen organization and reduced fibrotic and inflammatory signaling. Together, these findings link altered PINK1/Parkin-dependent mitophagy to mtDNA-driven inflammation and fibrosis and support mitochondrial transplantation as a potential organelle-based therapeutic approach. Full article

Mung bean seed coat (MBSC) is a byproduct of commercial vermicelli production that possesses essential activities capable of delaying diabetic wound progression. This study aimed to evaluate the potential of MBSC extracts to promote diabetic wound healing, an effect that has not yet been reported. The hypoglycemic effect was assessed by glucose uptake stimulation in L6 myotubes and by an α-glucosidase inhibition assay. Antiglycation was determined by BSA-glucose and BSA-methylglyoxal assays. Intracellular reactive oxygen species (ROS) reduction and wound healing were assessed in human keratinocytes (HaCaT) exposed to high glucose (HG), and gene expression in HG-wounded cells was analyzed by qPCR. The results demonstrated that the ethanolic extract (EE) from MBSC exhibited glucose-lowering effects and suppressed glycation reactions at the early and intermediate stages, with IC₅₀ values of 75 and 140 µg/mL, respectively. EE reduced ROS by 70%, stimulated cell proliferation by 57% in the high-glucose (HG)-exposed HaCaT cells, and accelerated cell migration to close the HG-exposed wound. EE increased the gene expression of Nrf2, NQO-1, SOD2, and CAT. It also downregulated TNF-α, upregulated TGF-β1, and downregulated MMP-9. In conclusion, EE has the potential to delay the progression of diabetic wounds by lowering blood glucose levels, inhibiting AGE and ROS formation, and enhancing cell proliferation and migration in HG-exposed HaCaT cells. The gene regulatory effects of EE were demonstrated as an Nrf2 activator that reduced oxidative stress, exerted anti-inflammatory effects, and regulated ECM balance. The preparation of oral and topical products could be further developed. Full article

Skin aging is a complex process influenced by oxidative stress, protein glycation, chronic inflammation, and increased extracellular matrix remodeling. Intensive research is underway on new anti-aging substances with multi-target mechanisms of action while maintaining safety and efficacy. Ergothioneine, selenoneine, and ovothiol A are natural histidine derivatives of marine origin, in which the oxygen atom of the hydroxyl group has been replaced with sulphur or selenium. In recent years, a broad spectrum of their biological activity has been demonstrated. Despite the well-documented antioxidant potential of these compounds, their anti-aging effects, particularly in terms of antiglycation and anti-inflammatory activity, remain insufficiently understood. This study presents the current state of knowledge regarding the biological activity of ergothioneine, selenoneine, and ovothiol A, and discusses available cosmetic preparations and dietary supplements containing these compounds. Meanwhile, significant research gaps have been identified regarding their potential use in the prevention and treatment of skin aging. Full article

Chronic kidney disease (CKD) represents a major global health challenge, affecting more than 10% of the population and contributing substantially to morbidity and premature mortality. Growing evidence identifies oxidative stress and mitochondrial dysfunction as central drivers of renal injury and disease progression across diverse etiologies. The kidney is one of the most mitochondria-rich organs in the body, reflecting the high bioenergetic demands required for tubular reabsorption and metabolic homeostasis. Disruption of mitochondrial oxidative phosphorylation, excessive production of reactive oxygen species (ROS), and impaired mitochondrial quality control mechanisms promote tubular injury, inflammation, and fibrosis. In particular, dysfunction of the electron transport chain, activation of NADPH oxidase isoforms—especially NOX4—and alterations in mitochondrial dynamics create a vicious cycle of oxidative damage and bioenergetic failure. Emerging evidence highlights the importance of mitochondrial quality control pathways, including fusion–fission balance, PINK1/Parkin-mediated mitophagy, and mitochondrial biogenesis regulated by PGC-1α and TFAM. Additional mechanisms include ferroptosis, epigenetic regulation, mitochondrial DNA-mediated innate immune activation, and Na⁺/K⁺-ATPase-linked redox signaling. At the translational level, redox and mitochondrial biomarkers and targeted therapies are biologically compelling, but the evidence is uneven: most candidate biomarkers remain insufficiently standardized, and direct mitochondria-targeted interventions are supported predominantly by preclinical studies or small human proof-of-concept trials. This review therefore emphasizes not only mechanistic advances but also conflicting findings, model limitations, and the barriers that currently separate experimental efficacy from clinically meaningful CKD outcomes. Full article

Successful embryo implantation requires intimate crosstalk between the blastocyst and the uterine epithelium within a defined window of receptivity. However, the metabolic signals that mediate this process in mammals remain poorly understood. In this study, pregnant mice, primary uterine cell culture and uterine epithelial organoids were used to examine the regulation and function of heme oxygenase-1 (HO-1) during mouse embryo implantation and decidualization. We demonstrate that embryo-derived lactic acid drives heme catabolism and regulates epithelial receptivity in mice through a hypoxia-inducible factor 1α (HIF1α) -heme oxygenase-1 (HO-1) signaling axis. Specifically, lactic acid stabilizes HIF1α to induce HO-1 expression in uterine epithelial cells by promoting von Hippel-Lindau (VHL) nucleolar sequestration and downregulating PHD2/3. Additionally, lactic acid suppresses the transcriptional repressor BACH1, further facilitating HO-1 induction. At physiological heme levels, HO-1-derived bilirubin promotes epithelial receptivity by increasing phosphorylated STAT3 (p-STAT3) and downregulating MUC1. A low dose of hemin promotes epithelial receptivity and decidualization, whereas a high dose of hemin suppresses these processes. Pharmacological inhibition of HO-1 in mice markedly reduces implantation sites, establishing the functional necessity of this pathway. However, when heme levels exceed the regulatory capacity of HO-1, epithelial dysfunction ensues, characterized by reduced p-STAT3 and elevated MUC1, which ultimately disrupts implantation. Consistent with this, chronic heme exposure by oral gavage in mice increases uterine heme levels and upregulates BACH1, thereby suppressing HO-1 and trapping the uterus in a non-receptive state, causing implantation failure. Our findings define a lactic acid-HIF1α-HO-1-heme metabolic checkpoint that couples glycolytic signaling to heme regulation and endometrial receptivity. Dysregulation of this checkpoint may contribute to implantation disorders associated with heme stress, providing mechanistic insights into heme stress-related uterine receptivity failure. Full article

Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy (prevalence ~1:4000) and a leading Mendelian cause of working-age blindness. Despite marked genetic heterogeneity, its progression converges on a common secondary cascade of outer-retinal hyperoxia, increased reactive oxygen species (ROS), and mitochondrial dysfunction that drives cone degeneration and central vision loss. Because this oxidative cascade is largely genotype-independent and pharmacologically tractable, oxidative stress is a cross-cutting therapeutic target. Within it, mitochondrial DNA (mtDNA) is a key element: once released from damaged photoreceptors—free or within exosomes—it may act as a damage-associated molecular pattern (DAMP), engaging TLR9, cGAS–STING, and the NLRP3 inflammasome and sustaining chronic neuroinflammation. Extracellular mtDNA is therefore a potential integrative marker, simultaneously reflecting oxidative stress, mitochondrial dysfunction, cell death, and innate-immune activation. A central knowledge gap, however, remains: the mechanistic steps linking mtDNA to inflammation and to photoreceptor death have not been demonstrated in RP itself, and extracellular mtDNA has never been quantified in the ocular fluids of RP patients. In this review we appraise oxidative biomarkers in RP, propose extracellular mtDNA as a candidate biomarker of disease activity, and examine antioxidant and redox-modulating therapies—from N-acetylcysteine and elamipretide trials to DAMP-sensor inhibition—across experimental and clinical models. Finally, we propose extracellular mtDNA as a candidate pharmacodynamic endpoint and outline a path toward its validation. Full article

Background: Chronic autoimmune thyroiditis (CAT) is characterized by persistent autoimmune activity and increased oxidative stress, which may contribute to thyroid follicular injury and disease progression. Photobiomodulation (PBM) has shown potential beneficial effects on thyroid function and autoimmunity; however, its independent effect on systemic antioxidant status, particularly serum glutathione (GSH), has not been established. This study aimed to evaluate the effect of thyroid-directed PBM on serum GSH concentrations and thyroid-related outcomes in treatment-naïve euthyroid women with CAT. Methods: This prospective, non-randomized, open-label, parallel-group comparative interventional study included 50 treatment-naïve euthyroid women with CAT. Participants were allocated to receive either thyroid-directed transdermal PBM (n = 25) or selenium plus vitamin D supplementation (n = 25). The primary outcome was the change in serum GSH concentration. Secondary outcomes included changes in thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), anti-thyroid peroxidase antibodies (anti-TPO), anti-thyroglobulin antibodies (anti-Tg), thyroid volume, and anthropometric parameters. Assessments were performed at baseline (T0), after the intervention period (T1), and three months after intervention completion (T2). Results: A significant time × group interaction was observed for serum GSH concentrations (F = 19.101, p < 0.0001). Significant interactions were also observed for anti-TPO (F = 7.513, p = 0.001), anti-Tg (F = 7.389, p = 0.002), and thyroid volume (F = 13.081, p < 0.0001). In the PBM group, GSH increased from baseline to T1 and remained higher at T2, while TSH, anti-TPO, anti-Tg, and thyroid volume decreased, and FT3 and FT4 increased. No significant longitudinal changes in GSH or thyroid autoantibodies were observed in the supplementation group. No participant in the PBM group required levothyroxine (LT4) initiation during follow-up, whereas 24% of participants in the supplementation group initiated LT4 therapy at T1, with some requiring dose escalation by T2. Conclusions: Thyroid-directed PBM was associated with improved systemic GSH status and favorable changes in thyroid autoimmunity, thyroid function parameters, and thyroid volume compared with selenium plus vitamin D supplementation in treatment-naïve euthyroid women with CAT. These findings suggest that modulation of oxidative stress may represent one potential biological pathway underlying the observed effects of PBM. Larger randomized controlled studies with longer follow-up are required to confirm these findings and define the clinical role of PBM in autoimmune thyroid disease. Full article

Cardiovascular diseases remain the leading cause of global mortality, and environmental toxic metals and metalloids (TMMs) exposure has emerged as an important and potentially modifiable cardiovascular (CV) risk factor. Due to their persistence, bioaccumulation, and widespread distribution, represent a significant public health concern and have been associated with adverse CV outcomes. Mechanistically, TMM-induced cardiotoxicity is primarily mediated through oxidative stress (OS) and inflammatory pathways. Accordingly, related biomarkers, may be considered markers of biological effect and potential pathophysiological mediators associated with TMM exposure. This narrative review summarizes epidemiological evidence linking environmental TMMs exposure with OS and inflammatory biomarkers to CV outcomes. A structured literature search identified 1915 records in PubMed, of which 42 epidemiological studies met the inclusion criteria. The reviewed evidence consistently indicates that environmental and occupational TMMs exposure is associated with significant alterations in biomarkers of lipid peroxidation, antioxidant defense, systemic inflammation, and endothelial dysfunction, all of which reflect early biological CV effects associated with exposure. However, substantial heterogeneity across studies and the predominance of cross-sectional designs limit causal inference and the evaluation of their predictive capacity for future CV events. Future prospective studies integrating mixture-based exposure assessment, standardized biomarker measurements, and multi-omics approaches are needed to clarify whether these biomarkers can serve as markers of biological effect or subclinical CV toxicity and as potential mediators of CV risk, while also assessing their potential contribution to cardiovascular risk stratification in exposed populations. Full article

Ovum pick-up (OPU) enables high-frequency oocyte retrieval from selected dairy cow donors, facilitating favorable genetic progression. However, oocytes obtained via OPU and subjected to in vitro maturation frequently suffer from severe oxidative stress, mitochondrial dysfunction, and DNA damage, resulting in lower pregnancy rates compared to those of in vivo-derived embryos. Melatonin (MT), as a potent antioxidant, may exert beneficial effects on these OPU-retrieved oocytes. In the current study, by combining in vitro and in vivo experiments, the protective effects and potential molecular mechanisms of MT on disrupted oocyte quality and development caused by OPU were systemically investigated. By integrating oocyte quality assessment, follicular fluid metabolomics, and blastocyst transcriptomics, the results showed that subcutaneous administration of MT to cows prior to OPU significantly increased the number of high-quality Grade A oocytes and reduced the number of low-quality Grade D oocytes compared to the control. These improvements were accompanied by reduced local and systemic oxidative stress, enhanced glutathione metabolism, and lower serum progesterone concentrations at the measured time points, coinciding with a more favorable endocrine environment for follicular development. The results from untargeted metabolomics of the follicular fluid revealed that MT supplementation was associated with an altered follicular fluid microenvironment characterized by the upregulation of estrogen derivatives and glutathione-related pathways. Transcriptomic analysis of blastocysts showed significant upregulation of the rate-limiting genes steroidogenic acute regulatory protein (STAR) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), suggesting a potential role in promoting the synthesis of reproductive hormones and maintaining the progress of embryo development. The in vitro study showed that MT supplementation at a concentration of 10⁻⁷ mol/L in oocyte maturation media significantly improved cleavage rates, blastocyst rates, and total blastocyst cell numbers compared to the control. In vitro evaluations demonstrated that MT scavenged intracellular reactive oxygen species (ROS), while transcriptomic analysis indicated a reprogramming of the embryonic transcriptome. These transcriptomic changes were associated with the AMPK, FoxO, and autophagy pathways, as well as the modulation of endoplasmic reticulum stress and cellular senescence. The results from both the in vivo and in vitro studies suggested that MT supplementation was associated with a follicular microenvironment favorable for oocyte growth and protected embryos from oxidative damage. Therefore, MT supplementation effectively reduced the disrupted oocyte development caused by OPU and improved oocyte recovery and quality in general. These findings provide promising experimental evidence for the potential application of MT in dairy breeding and offer insights into the associated molecular pathways. However, further functional validation is required to fully elucidate the underlying mechanisms and establish its large-scale applicability. Full article

This integrative review examines the potential of dates, omega-3 (ω-3) and omega-6 (ω-6) polyunsaturated fatty acids (PUFAs), dietary fibers (DFs), and probiotic bacteria to support gut health through complementary nutritional pathways. The literature was searched in PubMed, Web of Science, Scopus, and Google Scholar for English-language studies published through June 2026. Dates contain fermentable substrates, including DFs and non-digestible oligosaccharides, that can serve as growth substrates for beneficial gut microbes. However, the whole fruit has not been formally established as a prebiotic under current consensus definitions. ω-3 and ω-6 fatty acids contribute to membrane integrity, eicosanoid synthesis, immune regulation, and inflammatory signaling, with effects influenced by dietary balance. DFs support gastrointestinal function, glycemic regulation, lipid metabolism, and colonic fermentation, including short-chain fatty acid (SCFA) production, whereas probiotics may exert strain-specific effects on microbial balance, barrier function, immune responses, and host metabolism. Together, these components may influence gut microbiota, oxidative stress, inflammation, and metabolic homeostasis. However, the evidence is heterogeneous, combined interventions are scarce, and several proposed effects rely mainly on preclinical studies or surrogate human outcomes. Thus, potential collaborative effects and disease-prevention implications remain unconfirmed. Well-designed human trials using standardized preparations, realistic intake levels, and clinically relevant outcomes are needed to clarify their combined effects. Full article

Diabetic retinopathy (DR) is a major cause of preventable visual impairment and develops through intertwined metabolic, oxidative, inflammatory, and neurovascular disturbances. This review examines how chronic hyperglycaemia disrupts retinal glucose handling and redox homeostasis, with particular emphasis on glycogen metabolism as an underappreciated contributor to disease progression. Pathological glycogen accumulation in retinal amacrine cells and the retinal pigment epithelium may arise through altered glycogen synthase localisation and glucose-6-phosphate-dependent activation, potentially disturbing intracellular trafficking and cellular energy balance. These metabolic changes converge with mitochondrial electron transport chain dysfunction, NADPH oxidase activation, polyol pathway flux, and light-driven lipid peroxidation to increase reactive oxygen species generation. At the same time, transient suppression of Nrf2-dependent antioxidant defences, TXNIP-NLRP3 inflammasome signalling, ferroptotic injury, and VEGF-associated oxidative feedback promote blood–retinal barrier breakdown and persistent neuroinflammation. We propose that dysregulated glycogen metabolism and impaired antioxidant capacity form an integrated metabolic–redox network that helps explain cell-specific vulnerability and metabolic memory in DR. Targeting multiple nodes within this network may support earlier, disease-modifying strategies beyond treatment of advanced vascular complications. Full article