Search Results (2,196)

Oxidative stress caused by excessive reactive oxygen species (ROS) contributes to numerous chronic diseases. Marine green algae of the Caulerpa genus are rich in bioactive compounds with potential antioxidant activity. Objective: This study aimed to evaluate the intracellular antioxidant effects of caulerpin (CAU) and its derivative caulerpinic acid (CA) using Saccharomyces cerevisiae as a eukaryotic model. Methods: Yeast cells were pretreated with 1 μM of CAU or CA, or with 1 μM of resveratrol (RESV) as a positive control, then exposed to 2 mM of H₂O₂. Growth, ROS levels, oxidative damage markers, and antioxidant defenses were assessed. Results: Both CAU and CA significantly improved cell survival under oxidative stress, restoring growth rates (CAU: 0.129 h⁻¹, CA: 0.137 h⁻¹) and doubling times (CAU: 5.38 h, CA: 5.07 h) close to control values. Intracellular ROS accumulation, protein carbonylation, and lipid peroxidation were reduced to near-baseline levels. While catalase (Cat) and superoxide dismutase (Sod) activity remained unchanged, CAU and CA elevated intracellular glutathione (GSH) levels (1.6–1.8 fold) and preserved glutathione peroxidase (GPx) activity, compared to stressed cells without antioxidant pretreatment. Conclusions: CAU and CA act as effective intracellular antioxidants, primarily via ROS scavenging and GSH-dependent pathways. These findings support their potential as natural candidates for developing antioxidant-based therapies against ROS-related disorders. Full article

Repeated UV exposure, air pollution, and toxins promote skin oxidative stress. ROS destroy macromolecules, changing cellular mechanisms and signaling cascades. Inflammation and injury to skin cells degrade function and accelerate aging, causing wrinkles, firmness loss, and dermatological disorders. Gymnema inodorum (GI) contains phytochemical antioxidants such polyphenols and triterpenoids that lower ROS and strengthen skin. GI extracts (GIEs) have never been examined for their effects on dermal skin fibroblasts’ oxidative stress and intracellular cytoprotective mechanisms. In this study, GIEs were prepared as a water extract (GIE0) and ethanol extracts with concentrations ranging from 20% to 95% v/v (GIE20, GIE40, GIE60, GIE80, and GIE95). These extracts were assessed for phytochemical content, antioxidant capacity, and free radical scavenging efficacy. The results were compared to a commercially available native Gymnema extract (NGE) obtained from Gymnema sylvestre. During principal component analysis (PCA), the most effective extracts were identified and subsequently evaluated for their ability to mitigate oxidative stress in fibroblasts. Cytoprotective effects of GIE and NGE against H₂O₂-induced human dermal fibroblast injury were investigated by cell viability, intracellular ROS production, and signaling pathways. GIE0, GIE80, GIE95, and NGE were the best antioxidants. By preserving ROS balance and redox homeostasis, GIE and NGE reduce fibroblast inflammation and oxidative stress-induced damage. Decreased ROS levels reduce MAPK/AP-1/NF-κB and PI3K/AKT/NF-κB signaling pathways, diminishing inflammatory cytokines. In conclusion, GIE and NGE have antioxidant and anti-inflammatory capabilities that can reduce H₂O₂-induced fibroblast oxidative stress and damage, thereby preventing skin aging and targeting cancer-associated fibroblasts. Full article

Triple-negative breast cancer (TNBC) urgently requires new therapeutic strategies due to the limited efficacy of conventional treatments. Recently, PANoptosis, an integrated form of apoptosis, necroptosis, and pyroptosis, has emerged as a promising target in cancer therapy, though effective agents remain scarce. Paclitaxel, a Taxus-derived natural product, is often combined with other drugs to enhance efficacy, yet optimal combinations are limited. This study investigates the synergistic antitumor effects of paclitaxel and cephalomannine in TNBC, focusing on oxygen-regulated cell death pathways. Network pharmacology and molecular docking revealed that the combination targets multiple cell death- and inflammation-related proteins, including BCL2L1, MAPK14, SYK, TNF, and ADAM17, suggesting multi-target synergy. In vitro, the combination significantly inhibited MDA-MB-231 cell viability, proliferation, and migration, while inducing apoptosis and necrosis. Mechanistically, co-treatment markedly increased intracellular ROS levels and γ-H2AX expression, indicating oxidative stress and DNA damage, both of which were reversible by ROS inhibition. Further analysis demonstrated that the treatment activated the p38 and p53 pathways, regulated the Bax/Bcl-2 ratio, and initiated mitochondrial apoptosis. It also promoted RIPK1/RIPK3/MLKL phosphorylation and MLKL membrane translocation, triggering necroptosis, as well as upregulated NLRP3, cleaved Caspase-1, and GSDMD, inducing pyroptosis. The use of specific inhibitors partially reversed these effects, confirming the involvement of ROS-mediated PANoptosis. Similar antitumor effects were also observed in BT-549 cells, indicating the broad applicability of this combination in TNBC. MCF-10A cells exhibited mild but acceptable cytotoxicity, reflecting manageable side effects typical of chemotherapeutic agents. In vivo experiments further validated the combination’s antitumor efficacy and safety. In summary, paclitaxel and cephalomannine synergistically induce PANoptosis in TNBC through oxygen-regulated cell death pathways, offering a novel therapeutic strategy based on oxidative stress modulation by natural compounds. Full article

Combating antibiotic resistance is critically significant for global public health. The development of new antibacterial nanomaterial is a promising way to do this. In this study, a bottom-up approach was employed to fabricate antibacterial carbon dots (ACDs). During the synthesis, quaternary ammonium function groups with long alkyl chains were successfully grafted on ACDs’ surfaces. The obtained ACDs exhibited potent inhibitory against methicillin-resistant Staphylococcus aureus (MRSA) bacteria with minimum inhibitory concentrations of 2.5 µg/mL. Crucially, 2.5 µg/mL of ACDs could inhibit the growth of MRSA for as long as 72 h, which highlighted their long-term activity. Mechanistic investigations revealed that ACDs exerted bactericidal effects for MRSA bacteria primarily through disrupting the cell wall/membrane, destroying cell membrane potential, inducing the generation of excessive ROS, and triggering the leakage of nucleic acids and intracellular components. In sum, this work provided a kind of ACD with high efficiency and long-term antibacterial activity, offering promising potential for combating drug-resistant bacterial infections. Full article

Background: Gold nanoparticles (AuNPs) have several beneficial properties that make them effective as intracellular drug carriers, and their potential for various diagnostic and therapeutic applications is gaining recognition. Depending on their size and shape, AuNPs can cross the central nervous system (CNS) through the blood–brain barrier (BBB). In the CNS, they can exert a variety of influences on neuronal and glial cells, which can be both supportive—promoting cell health and function—and cytotoxic, potentially leading to cellular damage. The hypothalamus (HT) is the first region where nanoparticles (NPs) interact, as this neuroendocrine center is particularly sensitive to factors in the systemic circulation due to its function and location. This area is affected by systemic factors, including pro-opiomelanocortin (POMC) neurons, which regulate metabolic function and maintain homeostasis. The activity of mitochondria within these cells influences their response to both external factors and the presence of AuNPs, thereby facilitating a complex interplay between nanoparticle interactions and cellular metabolism in this vital brain region. Aims: This study investigates how AuNPs, at different concentrations and exposure times under in vitro conditions, affect the mitochondrial activity of POMC neurons, aiming to provide a comprehensive understanding of the mechanisms in the HT. Methods: The study investigates the effect of varying gold nanoparticle concentrations on the mitochondrial activity of POMC neurons over treatment periods of 1, 15, 24, and 48 h. Mitochondrial activity was measured using a Seahorse XFp Analyzer to provide high-resolution insights. Additionally, mitochondrial functionality was assessed through the detection of reactive oxygen species (ROS) and cell viability. Results: The findings indicated that the effects of gold nanoparticles on mitochondrial activity depend significantly on their concentration and exposure time. Specifically, exposure leads to an increase in early response systems, the citric acid cycle, and proton efflux, ultimately resulting in the inhibition of mitochondrial function and ATP production in POMC cells. This disruption may affect hypothalamic regulation and energy metabolism. Full article

Oxidative stress is a key contributor to retinal degeneration, as the retina is highly metabolically active and exposed to constant light stimulation. This review explores the crucial roles of cysteine and selenocysteine in redox homeostasis and retinal protection. Cysteine, primarily synthesized via the transsulfuration pathway, is the rate-limiting precursor for glutathione (GSH), the most abundant intracellular antioxidant. Selenocysteine enables the enzymatic activity of selenoproteins, particularly glutathione peroxidases (GPXs), which counteract reactive oxygen species (ROS). Experimental evidence from retinal models confirms that depletion of cysteine or selenocysteine results in impaired antioxidant defense and photoreceptor death. Furthermore, dysregulation of these amino acids contributes to the pathogenesis of age-related macular degeneration (AMD), retinitis pigmentosa (RP), and diabetic retinopathy (DR). Therapeutic approaches including N-acetylcysteine, selenium compounds, and gene therapy targeting thioredoxin systems have demonstrated protective effects in preclinical studies. Targeting cysteine and selenocysteine-dependent systems, as well as modulating the KEAP1–NRF2 pathway, may offer promising strategies for managing retinal neurodegeneration. Advancing our understanding of redox mechanisms and their role in retinal cell viability could unlock new precision treatment strategies for retinal diseases. Full article

Chronic inflammation is closely associated with various diseases, underscoring the need for natural, biocompatible anti-inflammatory candidates. For this purpose, mussel foot protein could be an excellent candidate due to its diverse biological activities. Hence, this study systematically evaluates the anti-inflammatory effects of a highly soluble mussel foot protein (HMFP) and HMFP-PEG using LPS-stimulated RAW264.7 cells as an in vitro inflammation model. The results reveal that both HMFP and HMFP-PEG markedly reduced intracellular reactive oxygen species (ROS) levels and suppressed the secretion of pro-inflammatory mediators, including IL-1β, TNF-α, and NO, while promoting the production of anti-inflammatory cytokines such as IL-10 and TGF-β. Mechanistically, both agents markedly inhibited the LPS-induced phosphorylation of PI3K, Akt, NF-κB, and IκB, indicating that their anti-inflammatory effects are mediated via suppression of the PI3K/Akt and NF-κB signaling pathways. Furthermore, HMFP and HMFP-PEG downregulated the expression of the inflammatory marker iNOS and markedly upregulated the M2 macrophage marker CD206, suggesting a role in promoting macrophage polarization toward an anti-inflammatory M2 phenotype. Notably, NF-κB signaling was identified as a key mediator in the anti-inflammatory mechanisms of both HMFP and its PEG-modified form. Collectively, these findings demonstrate that HMFP and HMFP-PEG exert significant anti-inflammatory effects through dual inhibition of NF-κB and PI3K/Akt signaling and by promoting M2 macrophage polarization, indicating their potential as promising candidates for the treatment of inflammation-related diseases. Full article

Cardiovascular and metabolic disorders significantly reduce healthspan and lifespan, with oxidative stress being a major contributing factor. Oxidative stress, marked by elevated reactive oxygen species (ROS), disrupts cellular and systemic functions. One proposed mechanism involves TRPM2 (Transient Receptor Potential Melastatin2)-dependent Ca²⁺ dysregulation. These channels, activated by ROS (via ADP-ribose), not only respond to ROS but also amplify it, creating a self-sustaining cycle. Recent studies suggest that TRPM2 activation triggers a cascade of signals from intracellular organelles, enhancing ROS production and affecting cell physiology and viability. This review examines the role of TRPM2 channels in oxidative stress-associated cardiovascular and metabolic diseases. Oxidative stress induces TRPM2-mediated Ca²⁺ influx, leading to lysosomal damage and the release of Zn²⁺ from lysosomal stores to the mitochondria. In mitochondria, Zn²⁺ facilitates electron leakage from respiratory complexes, reducing membrane potential, increasing ROS production, and accelerating mitochondrial degradation. Excess ROS activates PARP1 in the nucleus, releasing ADP-ribose, a TRPM2 agonist, thus perpetuating the cycle. Lysosomes act as Ca²⁺-sensitive signalling platforms, delivering toxic Zn²⁺ signals to mitochondria. This represents a paradigm shift, proposing that the toxic effects of Ca²⁺ on mitochondria are not direct, but are instead mediated by lysosomes and subsequent Zn²⁺ release. This cycle exhibits a ‘domino’ effect, causing sequential and progressive decline in the function of lysosomes, mitochondria, and the nucleus—hallmarks of ageing and oxidative stress-related cardiovascular and metabolic diseases. These insights could lead to new therapeutic strategies for addressing the widespread issue of cardiovascular and metabolic diseases. Full article

Grape pomace is a major by-product of winemaking and a rich source of phenolic compounds with antioxidant potential. The Carménère variety, emblematic of Chilean viticulture, remains underutilized despite its high anthocyanin and flavanol content. This study aimed to develop a cost-effective method to recover and stabilize bioactive compounds from Carménère grape pomace. Five extracts were obtained using ethanol–water mixtures (0–100%) and characterized by HPLC-DAD and antioxidant assays (DPPH, FRAP, ORAC-FL). The 80% ethanol extract (EET-80) showed the highest antioxidant capacity (FRAP: 2909.3 ± 37.6; ORAC-FL: 1864.3 ± 157.8 µmol TE/g dw) and was selected for microencapsulation via spray drying using maltodextrin. This scalable technique protects thermosensitive compounds and enhances their applicability. The optimized 1:50 extract-to-carrier ratio achieved high encapsulation efficiency (85.7 ± 0.7%). In Caco-2 cells, the microencapsulated extract (5–250 µg/mL) showed no alteration in metabolic activity and significantly reduced intracellular ROS levels (65% inhibition at 250 µg/mL). Solvent polarity selectively influenced polyphenol recovery—50% ethanol favored catechin (581.1 µg/g) and epicatechin (1788.3 µg/g), while 80% ethanol enhanced malvidin-3-O-glucoside (118.0 µg/g). These findings support the valorization of Carménère grape pomace as a sustainable source of antioxidants and highlight the role of microencapsulation in improving extract stability and functionality. Full article

The colonization of Fusobacterium nucleatum (F. nucleatum) in the microenvironment of gastric cancer (GC) is closely associated with tumor progression, but its impact on host metabolic remodeling remains unclear. This study aims to elucidate the mechanistic link between F. nucleatum infection and metabolic changes in GC tissue. By integrating 16S rRNA microbiome sequencing and LC-MS/MS metabolomics, the differences in microbial composition and metabolic profiles between Fusobacterium sp.-positive and -negative GC tissues were systematically compared, and the correlation of differential microbes and differential metabolites was analyzed. The impact of F. nucleatum on the glutathione (GSH) metabolic pathway was validated through in vitro tissue testing and the use of the infection model of GC cell lines (such as AGS and HGC27). Integrative omics analysis showed a strong negative correlation between Fusobacterium sp. infection and antioxidant metabolite GSH levels in GCs (p < 0.001). Metabolic reprogramming features: Eleven differentially expressed metabolites were identified using LC-MS/MS metabolomics screening (p < 0.05). GSH was significantly depleted in the Fusobacterium sp.-positive group. Experimental validation: At the histological level, the abundance of F. nucleatum in GC tissues was higher than that in the paired adjacent non-cancerous (NC) tissues; at the cellular level, after F. nucleatum infection of GC cells, the intracellular GSH level decreased (p < 0.01), accompanied by a decrease in glutathione synthetase (GSS) mRNA expression and reactive oxygen species (ROS). This study is the first to demonstrate that F. nucleatum suppresses the GSH synthesis pathway, leading to the breakdown of antioxidant capacity and the formation of an oxidative stress microenvironment in GC cells. These findings provide new insights into the metabolic mechanism of F. nucleatum in promoting GC progression and suggest that targeting the F. nucleatum-GSH axis could offer a novel strategy for GC therapeutic intervention. Full article

Red blood cells (RBCs) are uniquely vulnerable to oxidative stress due to their role in O₂ transport and their high content of heme iron and polyunsaturated fatty acids (PUFAs). Despite lacking nuclei and organelles, RBC homeostasis relies on a finely tuned redox system to preserve membrane integrity, cytoskeletal organization, and metabolic function. Impairment of this delicate balance results in a series of oxidative events that ultimately leads to the premature clearance of RBCs from the bloodstream. This review outlines the main oxidative mechanisms that affect RBC at different levels, such as membrane, cytoskeleton, and intracellular environment, with a focus on the molecular targets of reactive species. The role of major antioxidant systems in preventing or reversing redox damage will also be examined, revealing their multiple mechanisms of action ranging from direct ROS scavenging to the enhancement of endogenous antioxidant defense pathways. Redox regulatory mechanisms in RBCs are required to maintain membrane integrity, cytoskeletal organization, and metabolic function. Disruption of these processes causes several oxidative processes that trigger premature RBC removal. Cumulative evidence places oxidative stress at the core of RBC dysfunction in both physiological aging and pathological conditions, including diabetes, inflammatory conditions, and hemolytic disorders. Antioxidant-based strategies, rather than providing generalized protection, should aim to selectively target the specific molecular pathways affected in distinct clinical settings. Full article

The accelerating threat of antimicrobial resistance (AMR) demands transformative strategies that go beyond conventional antibiotic therapies. Nanoparticles (NPs) have emerged as versatile antimicrobial agents, offering a combination of physical, chemical, and immunological mechanisms to combat multidrug-resistant (MDR) pathogens. Their small size, surface tunability, and ability to disrupt microbial membranes, generate reactive oxygen species (ROS), and deliver antibiotics directly to infection sites position them as powerful tools for infection control. This narrative review explores the major classes, mechanisms of action, and biomedical applications of antimicrobial NPs—including their roles in wound healing, implant coatings, targeted drug delivery, inhalation-based therapies, and the treatment of intracellular infections. We also highlight the current landscape of clinical trials and evolving regulatory frameworks that govern the translation of these technologies into clinical practice. A distinctive feature of this review is its focus on the interplay between NPs and the human microbiota—an emerging frontier with significant implications for therapeutic efficacy and safety. Addressing this bidirectional interaction is essential for developing microbiota-informed, safe-by-design nanomedicines. Despite promising advances, challenges such as scalability, regulatory standardization, and long-term biosafety remain. With interdisciplinary collaboration and continued innovation, antimicrobial NPs could reshape the future of infectious disease treatment and help curb the growing tide of AMR. Full article

Cerium oxide nanoparticles (CeO₂NPs) can boost crops’ salt tolerance, yet their regulatory mechanisms in rice cultivars with contrasting salt tolerance remain unclear. This study investigated the regulatory differences in poly (acrylic acid)-coated nanoceria (PNC)-primed in salt-sensitive (Huanghuazhan, H) and salt-tolerant (Xiangliangyou900, X) rice. The results showed that PNC priming improved salt tolerance in two cultivars, but the underlying mechanisms differed. In the H cultivar, the enhanced tolerance was primarily attributed to enhanced photosynthesis (net photosynthesis and transpiration rates were 53.27% and 20.52% higher than the X cultivar); increased abscisic acid (ABA) content (up by 18.80% compared to the X cultivar), and activated stress-responsive signaling. Metabolomics further revealed that the differential metabolites were enriched in galactose metabolism, ascorbate, and aldarate metabolism, synergistically maintaining intracellular redox balance. In the X cultivar, PNC boosted reactive oxygen species’ (ROS) scavenging capacity (catalase (CAT) increased 36.07%, H₂O₂ and malondialdehyde (MDA) decreased 27.31% and 48.61% compared to H); elevated endogenous indole-3-acetic acid (IAA) and gibberellic acid3 (GA3) levels by 9.55% and 9.08%; and specifically activated cellular defense response and glutathione metabolism. Transcriptome analysis further revealed that the expression of IAA/GA3 signal-responsive genes (OsARGOS/OsGASR2) and antioxidant genes (OsCatA, OsAPX1) were significantly higher in the X cultivar than the H cultivar (p < 0.05), whereas the H cultivar showed higher expression of GST and ABA-related genes. This study provides a new perspective for the mechanism of PNC-enhanced salt tolerance in rice. Full article

This study used NMR-based metabolomics to investigate the mode of action (MoA) of 6-hydroxydopamine (6-OHDA) toxicity in the SH-SY5Y neuroblastoma cell model. 6-OHDA, a structural analogue of dopamine, has been used to create a Parkinson’s disease model since 1968. Its selective uptake via catecholaminergic transporters leads to intracellular oxidative stress and mitochondrial dysfunction. SH-SY5Y cells were treated with 6-OHDA at its IC₅₀ concentration of 60 μM, and samples of treated and untreated groups were collected after 24 h. The endo metabolome was extracted using a methanol–water mixture, while the exo metabolome was represented by the culture media. Further, endo- and exo metabolomes of treated and untreated cells were analysed for metabolic changes. Our results demonstrated significantly high levels of glutathione, acetate, propionate, and NAD⁺, which are oxidative stress markers, enhanced due to ROS production in the system. In addition, alteration of myoinositol, taurine, and o-phosphocholine could be due to oxidative stress-induced membrane potential disturbance. Mitochondrial complex I inhibition causes electron transport chain (ETC) dysfunction. Changes in key metabolites of glycolysis and energy metabolism, such as glucose, pyruvate, lactate, creatine, creatine phosphate, glycine, and methionine, respectively, demonstrated ETC dysfunction. We also identified changes in amino acids such as glutamine, glutamate, and proline, followed by nucleotide metabolism such as uridine and uridine monophosphate levels, which were decreased in the treated group. Full article

Citrinin (CTN), a mycotoxin commonly found in contaminated food and animal feed, impairs intestinal barrier integrity through oxidative stress and cytotoxicity. However, its link to ferroptosis, an iron-dependent form of regulated cell death, remains unclear. This study investigated whether CTN induces ferroptosis in intestinal epithelial cells and evaluated the protective role of Euphorbia hypericifolia (EH) against CTN-induced oxidative damage and tight junction (TJ) disruption. Using IPEC-J2 cells exposed to CTN, intracellular ferrous ion (Fe²⁺) levels, reactive oxygen species (ROS) accumulation, and TJ integrity were assessed using FerroOrange and DCFH-DA staining, RT-qPCR, immunofluorescence, and WST-1 assays. Additionally, a high-throughput screen of 459 natural products identified EH extract as a top candidate in mitigating CTN toxicity. The CTN treatment significantly elevated intracellular Fe²⁺ and ROS levels, downregulated antioxidant genes (notably CAT), and disrupted ZO-1 expression and TJ morphology in IPEC-J2 cells, all hallmarks of ferroptosis-like cell death. Co-treatment with EH extract effectively reversed these effects, restoring antioxidant gene expression, reducing Fe²⁺ and ROS accumulation, and preserving TJ structure. Phytochemical profiling of EH extract revealed several bioactive compounds potentially responsible for its protective effects. These findings suggest that CTN induces ferroptosis-related cytotoxicity in IPEC-J2 cells, but EH alleviates this toxicity by modulating oxidative stress and iron homeostasis, supporting its potential use as a natural feed additive for intestinal protection Full article