Search Results (691)

To address the limitations of the tumor microenvironment (TME) and the inadequate efficacy of standalone chemodynamic therapy (CDT), this study developed a tannic acid-copper coordination gel-coated mesoporous Cu₂O nanodelivery system (Cu₂O@TA@5-FU) for synergistic enhanced CDT and chemotherapy. The system exhibits a high specific surface area (98 m²·g⁻¹) and mesoporosity, achieving a 5-fluorouracil (5-FU) loading efficiency of 46.2%. Under simulated TME conditions, the nanodelivery system displayed markedly accelerated drug release and enhanced catalytic activity, indicative of pronounced TME responsiveness. In vitro, the Cu₂O@TA support efficiently catalyzed a Fenton-like reaction with H₂O₂ to generate cytotoxic hydroxyl radicals (·OH) while depleting overexpressed intracellular GSH, thereby disrupting antioxidant defenses and amplifying oxidative stress. Combined with the antiproliferative action of released 5-FU, the synergistic treatment reduced 4T1 cell viability to approximately 23%, accompanied by sharp declines in intracellular ATP and GSH levels. This work overcomes the systemic toxicity of free 5-FU and the instability of Cu₂O by employing a protective and stimuli-responsive TA-Cu coordination gel shell, offering a reliable strategy for TME-responsive synergistic nanotherapeutics that disrupt tumor metabolic and redox homeostasis. Full article

Background and Objectives: Dental pulp stem cells (DPSCs) possess significant regenerative potential; however, oxidative stress impairs their viability and osteogenic differentiation. Gingerol, the principal bioactive component of ginger, exhibits antioxidant and cytoprotective properties. This study evaluated the protective effects of gingerol on DPSCs exposed to H₂O₂-induced oxidative stress. Materials and Methods: DPSCs isolated from extracted human teeth following Institutional Review Board approval and informed consent were exposed to H₂O₂-induced oxidative stress and treated with varying concentrations of gingerol. Cell viability, migration, osteogenic activity, mineralization, intracellular ROS accumulation, and Wnt/β-catenin signaling-related gene expression were evaluated using MTT, scratch wound healing assay, Alizarin Red S staining, ROS staining, ELISA, and real-time PCR. Results: Gingerol improved DPSC viability, migration, and mineralization under oxidative stress conditions. Increased ALP and BSP expression indicated enhanced osteogenic activity, while reduced ROS accumulation suggested attenuation of oxidative injury. Gingerol also modulated MMP-2 and MMP-9 expression and normalized oxidative stress-associated alterations in inflammatory and Wnt/β-catenin signaling-related gene expression. Conclusions: Gingerol demonstrated protective effects against oxidative stress-induced dysfunction in DPSCs and supported osteogenic differentiation. These findings suggest that gingerol may serve as a supportive bioactive candidate for regenerative dental applications; however, further mechanistic and in vivo studies are required to confirm its therapeutic potential. Full article

Sulfane sulfur species are increasingly recognized as integral cellular components involved in signaling pathways and cytoprotection against oxidative stress in mammals. While their production in bacteria has been extensively studied, their functional role in bacterial oxidative stress defense remains poorly understood. Here, we demonstrate that sulfane sulfur generated by sulfide: quinone oxidoreductase decreases H₂O₂ sensitivity in Pseudomonas aeruginosa PAO1. Notably, this protective mechanism does not depend on sulfane sulfur acting as a direct H₂O₂ scavenger via nucleophilic reactions. Through persulfidation proteomic profiling, we reveal that persulfidation is a prominent post-translational modification in P. aeruginosa, reflecting the prevalence of deprotonated sulfane sulfur species. These species modify cysteine residues in proteins, including the well-known oxidative stress regulator OxyR. Specifically, sulfane sulfur modifies OxyR at Cys199 to form persulfidated OxyR C199-SSH, contributing to a single-Cys activated state that modulates promoter activity and DNA-binding affinity. Furthermore, sulfane sulfur-mediated persulfidation protects the critical cysteine residue of LpdG, a ROS-vulnerable dihydrolipoamide dehydrogenase, from irreversible overoxidation. Although LpdG is not part of the canonical H₂O₂-scavenging system, its preservation is essential for cell viability under oxidative stress. These findings establish endogenous sulfane sulfur species as key mediators of antioxidant defense in P. aeruginosa. Full article

We explored the possibility of antioxidant and antifibrotic effects of panthenol (PL) associated with modulation of coenzyme A (CoA) biosynthesis in the liver in a rat model of chronic obstructive cholestasis induced by bile duct ligation (BDL). We found that PL increased alcohol dehydrogenase (ADH) activity in the liver of BDL rats. PL and its analog pantethine increased pantothenate kinase (PANK) activity, restored hepatic CoA levels reduced by BDL, lowered protein-bound CoA, and normalized impaired mitochondrial functions associated with induced oxidative stress after BDL. These effects were accompanied by decreased collagen deposition and improved morphological features of hepatocytes. In contrast, PANK inhibitor, hopantenic acid (HPA), reduced hepatic CoA levels, aggravated hepatocellular damage, and promoted fibrosis. In the human hepatic stellate cell line LX-2, PL exhibited no cytotoxicity over a wide concentration range, increased intracellular CoA levels, decreased reactive oxygen species (ROS) production, and attenuated collagen accumulation associated with oxidative stress in vitro. Importantly, inhibition of ADH by 4-methylpyrazole completely abolished the protective effects of panthenol, indicating that its activity depends on metabolic pathways involving CoA. Notably, PL did not directly reduce H₂O₂ or superoxide anion radical production in cell-free systems but significantly suppressed lipid peroxidation in liposomes and red blood cells in vitro. Ultimately, these findings indicate that the antioxidant and antifibrotic effects of PL are associated with modulation of CoA metabolism and enhanced resistance of biological membranes to oxidative damage. Full article

15,16-Dihydrotanshinone I (DHT) is a prominent lipophilic diterpenoid from Salvia miltiorrhiza with significant pharmacological potential, though its therapeutic application is limited by poor aqueous solubility. In this study, a microbial biotransformation strategy using Ganoderma lingzhi, known for its wide variety of enzyme, was employed to diversify the chemical structure of DHT and improve its bioactivity profile. Through systematic screening and optimization of fermentation conditions, seven transformation products were isolated and characterized. Among these, five are reported as novel compounds: 17-hydroxy-salvianone (A), 18,19-dihydroxy-danshinspiroketallactone (B-2), epi-18,19-hydroxy-danshinspiroketallactone (B-3), 20-hydroxy-salvianone (C), and 19-hydroxy-danshinspiroketallactone (D). Biological evaluations demonstrated that these derivatives possess multi-target therapeutic potential, including moderate cytotoxic effects against 4T1 and A549 cancer cell lines, alongside anti-inflammatory and neuroprotective activities. However, no significant antibacterial activity was observed for any of the derivatives against six common pathogens. Specifically, compound A significantly inhibited nitric oxide (NO) production in LPS-stimulated RAW 264.7 cells, while B-3 protected SH-SY5Y cells against ${\mathrm{H}}_2{\mathrm{O}}_2$-induced oxidative stress. Transcriptomic profiling of the biotransformation process identified 2221 differentially expressed genes (DEGs), showing significant enrichment in cytochrome P450-mediated metabolism and oxidative stress response pathways, which were further validated by qPCR. These results establish G. lingzhi as an efficient biocatalyst for the structural modification of tanshinones and provide a library of novel DHT derivatives for drug discovery. Full article

Oxidative stress causes brain damage contributing to neurodegenerative and vascular diseases. In Alzheimer’s disease (AD), elevated oxidative stress and mitochondrial damage are closely linked to misfolded protein accumulation. ROS also plays a major role in ischemic brain injury, particularly during reperfusion, impairing the blood–brain barrier and highlighting the association between vascular pathology and AD. To investigate perturbations in brain cells occurring in mixed dementia (AD combined with vascular dementia components), we used a triple culture system comprising neurons, astrocytes, and microglia and induced neuronal injury by combining LPS and H₂O₂ exposures. Cell viability assays revealed that neuronal death occurred mainly through apoptosis and DNA damage. In neurons and astrocytes exposed to LPS+H₂O₂, the expression of NADPH oxidase isoform 2, a major source of ROS, increased, along with FOXO3 and SOD2, a key mitochondrial ROS scavenger. Indeed, these changes were accompanied by altered mitochondrial morphology and integrity, as well as reduced neurite extension and thickness. The treatment with extracellular vesicles (EVs) derived from amniotic fluid stem cells was tested due to their rich content of antioxidant molecules. Interestingly, EVs reversed the negative effects of LPS+H₂O₂, suggesting the protective role against neuronal injury in vitro may be mediated by the EV-cargo. Full article

Epidermal lipid homeostasis is crucial for skin barrier integrity. This study investigated the effects of an aqueous extract from Beta vulgaris subsp. vulgaris Beetroot Group (BvE) on stress responses and lipid metabolism in HaCaT keratinocytes. BvE, obtained from leaves grown in SETIS^® bioreactors as a standardized biomass source, was chemically characterized by ¹H NMR and ¹³C NMR. HaCaT cells were treated with BvE (1 µg/mL), H₂O₂, or palmitic/oleic acids (PA/OA) to evaluate its protective effects against oxidative damage and lipotoxic stress. Under these conditions, BvE exhibited a distinctive dual action as a reactive oxygen species (ROS) scavenger and triacylglycerol (TAG)-lowering agent. On the one hand, BvE was associated with decreased intracellular ROS levels and changes in NRF2 protein expression, suggesting involvement of redox-regulatory pathways. On the other hand, it was associated with attenuation of lipotoxicity, as evidenced by reduced lipid droplet (LD) formation and decreased expression of DGAT1 and PLIN2. Furthermore, these effects were accompanied by a reduction in Unfolded Protein Response (UPR) markers, modulation of AMPK-associated signaling, attenuation of mitochondrial disfunction, and decreased p53 phosphorylation, findings collectively consistent with a coordinated cytoprotective response. In conclusion, BvE shows potential to protect keratinocytes against lipotoxicity and oxidative stress through mechanisms that may involve both chemical and biological antioxidant activity and metabolic reprogramming, supporting its further investigation for dermatological applications. Full article

Stress-induced premature senescence (SIPS) of endothelial cells can cause endothelial dysfunction. As a first-line antidiabetic agent, the specific role of metformin in SIPS has not yet been clarified. In this study, an in vitro SIPS model was induced by exposing human umbilical vein endothelial cells (HUVECs) to hydrogen peroxide (H₂O₂), and the effects of metformin on cell senescence, proliferation, migration, tube formation, and mitochondrial function were evaluated. Gene expressions altered by metformin were profiled via transcriptome sequencing. Specifically, the potential involvement of migrasome-mediated mitocytosis in metformin-driven effects was examined using confocal microscopy and siRNA-mediated silencing. The results showed that metformin significantly reduced SA-β-gal activity and restored the migration and tube-forming capacities of H₂O₂-induced senescent HUVECs. Moreover, metformin regulated mitochondrial dynamics, restored mitochondrial membrane potential, and attenuated intracellular oxidative stress. Notably, transcriptomic and functional analyses suggested that metformin enhanced migrasome formation and migrasome-mediated mitocytosis. Inhibition of migrasome formation by siTSPAN4 abolished the protective effect of metformin against SIPS. Collectively, these findings demonstrate that metformin alleviates early SIPS-associated changes in HUVECs and suggest that migrasome-mediated mitocytosis contributes to this protection by ameliorating mitochondrial dysfunction. This provides novel mechanistic insight into the vascular protective effects of metformin. Full article

Vitexin is a potent C-glycosyl flavone from mung bean coats with significant antioxidant properties, constrained by poor solubility and bioavailability. In this study, Nanovitexin (NV) was encapsulated within a biocompatible Alginate/Carboxymethyl Cellulose (Alg/CMC) matrix via a modified solvent evaporation technique assisted by chemical cross-linking. The optimized NV exhibited a mean dry particle size of 50–70 nm, high concentration (0.05–0.25 mg/mL), and stability (Zeta potential >30 mV). FT-IR analysis confirmed the successful entrapment via intermolecular interactions. Notably, NV exhibited enhanced activities compared to free vitexin (FV), showing superior DPPH scavenging (IC₅₀ of 115.38 μg/mL) versus FV (IC₅₀ of 226.06 μg/mL). Furthermore, NV demonstrated significantly enhanced in vitro antidiabetic potential, displayed no cytotoxicity towards HepG2 cells, and effectively protected against H₂O₂-induced oxidative stress. The Alg/CMC nanomatrix effectively improves vitexin bioactivity, suggesting promising potential for pharmaceutical and nutraceutical applications. Full article

Oxidative stress is a key contributor to aging and chronic diseases, highlighting the need for safe and effective natural antioxidants. Monascus yellow pigments (MYPs) and ginsenoside Rg3 exhibit antioxidant activity, but their applications are restricted by low solubility and limited natural abundance. In this research, a bidirectional liquid fermentation system of Monascus ruber using ginseng decoction was established for the simultaneous production of water-soluble MYPs (WSMYPs) and ginsenoside Rg3. Process conditions were optimized to enhance the yields and the antioxidant activity of the system. Antioxidant assays and H₂O₂-induced RAW264.7 cell models confirmed that WSMYPs were strongly correlated with antioxidant capacity, with ABTS and DPPH scavenging activities showing 2.28-fold and 3.33-fold increases, respectively, compared to the control. Their combination with Rg3 exerted synergistic protective effects by enhancing the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT). Network pharmacology and molecular docking further revealed that Monapurone C, a representative WSMYP, and Rg3 act through a multi-target, multi-pathway antioxidant network involving signaling pathways such as PI3K-Akt. This study demonstrates a cost-effective strategy for co-producing WSMYPs and Rg3, providing new insights into the value-added utilization of edible and medicinal resources. Full article

The resurrection plant Haberlea rhodopensis is a rare species endemic to Greece and Bulgaria, renowned for its exceptional desiccation tolerance and rich phytochemical composition. This study investigated the antioxidant, cytoprotective, and wound-healing-associated effects of H. rhodopensis ethanolic extract (HEE) in human keratinocytes (HaCaT cells) under oxidative and cytotoxic stress conditions. Antioxidant capacity was initially evaluated using a plasmid DNA protection assay, in which HEE attenuated oxidative DNA damage induced by a Fenton reaction system and preserved the native supercoiled structure of pUC19 plasmid DNA. Cytotoxicity screening using the sulforhodamine B (SRB) assay and real-time proliferation monitoring (HoloMonitor^® M4) identified 20 μg/mL as a non-toxic pre-treatment concentration (EC₁₀). Under hydrogen peroxide (H₂O₂)-induced oxidative stress, HEE pre-treatment maintained cell viability and significantly reduced intracellular reactive oxygen species (ROS) levels, indicating a protective effect. In vitro wound-healing assays demonstrated enhanced scratch closure in keratinocyte monolayers. RT-qPCR analysis revealed modulation of antioxidant-related genes (CAT, SOD1, HMOX1, NQO1, GPX, GSR), while mRNA sequencing suggested selective stress-adaptive responses, involving extracellular matrix (ECM)-, metabolic-, and tissue-repair/aging-associated pathways. Overall, HEE exhibits antioxidant and cytoprotective effects in keratinocytes and is associated with transcriptional changes linked to cellular stress responses and wound closure. These findings support its potential relevance for dermatological, pharmaceutical, and cosmeceutical applications, while further studies are required to establish the underlying molecular mechanisms. Full article

Endometriosis is associated with oxidative stress and debilitating symptoms, yet its pathophysiology remains incompletely understood, and current treatments are still limited. In this study, oxidative stress responses were compared in 2D and 3D cultures of 12Z and Ishikawa cells using hydrogen peroxide (H₂O₂) as a pro-oxidant and N-acetylcysteine (NAC) as an antioxidant. We evaluated H₂O₂ sensitivity, Reactive Oxygen Species (ROS) production, glutathione redox homeostasis, and biomolecular damage. The results showed that 12Z cells display greater vulnerability to oxidative stress than Ishikawa cells, with higher basal ROS levels (p < 0.01) and increased sensitivity to H₂O₂. In 3D culture, 12Z cells exhibited a 72% depletion of total glutathione under oxidative stress, a response not observed in 2D cultures, which instead showed a compensatory pattern. This vulnerability was further supported by increased lipid peroxidation and protein carbonylation. Although NAC restored cell viability and protected lipids and proteins, it did not prevent DNA damage. Together, these findings demonstrate marked differences in antioxidant responses between the two cell models and reinforce the value of 3D systems for investigating oxidative stress-related mechanisms. These results provide mechanistic insights relevant to endometriosis-associated redox imbalance and support further investigation of glutathione dysregulation and ROS-mediated damage in disease-related contexts. Full article

Background: Cryopreservation induces the production of excessive reactive oxygen species (ROS), which decreases sperm physiological functions. Phytochemicals with antioxidant properties, such as fisetin, have shown promising results in reducing oxidative stress (OS). Aim: We aimed to evaluate whether fisetin can counteract the OS exerted on sperm. Methodology: Fisetin (15 and 30 µM) was tested on normozoospermic semen samples that were either frozen in liquid nitrogen or treated with H₂O₂ to induce OS. Sperm motility, sperm viability, mitochondrial membrane potential, metabolic activity, ROS content, lipid peroxidation, reduced glutathione, ATP contents, and apoptosis were tested and compared to controls. Results: The protective effect of fisetin on human sperm was observed against OS-induced stress. Fisetin significantly improved sperm motility, viability, mitochondrial and metabolic activity, and ATP content by reducing OS and lipid peroxidation. Fisetin reduced necrotic cell death and improved sperm survival under H₂O₂-OS. Conclusions: Fisetin protects human sperm from OS, with 30 µM showing greater effectiveness, supporting its potential use in sperm preservation and OS conditions. Further studies are needed to optimize its concentration, elucidate its mechanism of action, and confirm its putative use as an additive in sperm cryoprotective media. Full article

This study optimized the extraction, purification, and structural chemical characterization of polysaccharides from fruitless wolfberry bud tea (FWP), and evaluated their antioxidant activities against H₂O₂-induced oxidative damage in SH-SY5Y cells. Crude FWP was obtained by ultrasonic-assisted water extraction followed by ethanol precipitation. An orthogonal experiment was conducted to optimize decolorization using D301G macroporous resin, achieving a decolorization rate of 74%, a polysaccharide retention rate of 85%, and a protein removal rate of 61%. Two main purified polysaccharide fractions, FWP-1 (52.3 kDa) and FWP-2 (9.95 kDa), were isolated by DEAE-52 and Sephadex G-150 chromatography. Structural analysis revealed that FWP-1 was a neutral heteropolysaccharide rich in glucose and galactose, while FWP-2 was an acidic polysaccharide with a high content of galacturonic acid. In H₂O₂-induced SH-SY5Y cells, both polysaccharides significantly enhanced cell viability, increased superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels, reduced lactate dehydrogenase (LDH) leakage and malondialdehyde (MDA) content, scavenged excessive reactive oxygen species (ROS), and maintained mitochondrial membrane potential. FWP-2 exhibited stronger ROS-scavenging capacity than FWP-1. This study established reliable methods for the purification and characterization of FWP, and verified their potential as natural antioxidants against neuronal oxidative injury. Full article

Oxidative stress is one of the major environmental stresses that the fungal pathogen Candida albicans frequently encounters. In view of the negative regulatory effect of Ume6 on autophagy in Saccharomyces cerevisiae and the close link between autophagy and oxidative stress in mammals, we explored the regulatory effect of Ume6 on autophagy and oxidative stress in C. albicans in this study. Here, we identify the transcriptional regulator Ume6 as a key positive regulator of autophagy under oxidative stress conditions. Deletion of UME6 resulted in reduced autophagy levels under H₂O₂ treatment, correlating with reduced transcriptional expression of core autophagy-related genes. Although UME6 deletion alone did not alter H₂O₂ sensitivity, it significantly exacerbated the sensitivity of a catalase mutant, revealing a functional role for Ume6 in oxidative stress tolerance. Intriguingly, we discovered that 3-methyladenine (3-MA), a canonical autophagy inhibitor in other systems, acts as an autophagy activator in C. albicans, promoting Atg8 transport to the vacuole and enhancing autophagy levels. This 3-MA-induced autophagy alleviated oxidative stress damage, as evidenced by improved growth and protection of vacuolar membrane integrity in H₂O₂-treated cells. Furthermore, deletion of UME6 or nitrogen starvation reduced apoptosis under oxidative stress, including decreased Annexin-V binding, metacaspase activation, mitochondrial membrane depolarization, and mitochondrial cytochrome c release. This study uncovers the critical role of Ume6 in governing oxidative stress, autophagy, and apoptosis. Full article