Search Results (9,447)

The therapeutic potential of functional nutrients has garnered considerable attention for enhancing resilience signaling and counteracting the damage to human health caused by microplastic pollutants. The intricate interactions between microplastics (MPs) and nanoplastics (NPs) and functional nutrients, including polyphenols, flavonoids, phenylpropanoids, phenolic acids, diterpenoids, and triterpenoids, have been shown to improve blood–brain barrier (BBB) homeostasis and brain function by inhibiting oxidative stress, ferroptosis, and inflammation linked to the pathogenesis of metabolic and brain disorders. Interestingly, nutrients exhibit biphasic dose–response effects by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and stress-resilience proteins at minimum doses, thereby preventing or blocking MP and NP-induced damage. Notably, chronic exposure to environmental pollutants causes aberrant regulation of NFE2L2 gene and related antioxidant signaling, which can exacerbate selective susceptibility to brain insulin resistance under inflammatory conditions. This, in turn, impairs glucose metabolism and facilitates β-amyloid (Aβ) plaque synthesis leading to the onset and progression of Alzheimer’s disease (AD), also known as “Type 3 diabetes”. This pathological process triggered by oxidative stress, inflammation, and ferroptosis creates a vicious cycle that ultimately contributes to neuronal damage and loss. The review aims to investigate the therapeutic potential of functional nutrients targeting the Nrf2 pathway and stress resilience proteins to regulate epigenetic alterations, and to explore the underlying molecular mechanisms using innovative in vitro platforms for the development of promising preventive strategies and personalized nutritional interventions to attenuate oxidative stress, ferroptosis, and inflammation, with the goal of ultimately improving clinical outcomes. Full article

Plastic pollution, particularly the widespread presence of microplastics, has emerged as a global environmental threat. Conventional plastics are highly resistant to degradation and can persist in ecosystems for decades, posing a serious long-term risk to wildlife, habitats, and human health. Increasing evidence suggests that insects and their gut microbiota may play a significant role in the degradation of these plastics. This review examines the mechanisms by which insects and their associated microorganisms contribute to microplastic biodegradation. Plastivorous insect larvae such as Spodoptera frugiperda, Galleria mellonella, Tenebrio molitor and Zophobas atratus have demonstrated the ability to ingest and partially degrade diverse polymers. The initial mechanical breakdown caused by insect mandibles increases the surface area, which allows gut microbes to colonize the material. Once these microbes are established, they form biofilms that help with adhesion, create localized redox environments, and concentrate degradative enzymes at the polymer interface. The enzymatic machinery of insect-associated microbes plays a crucial role in breaking down polymers. Oxidative enzymes, including DyP-type peroxidases, multicopper oxidases, alkane monooxygenases, and laccases, initiate the oxidation of polymers, while hydrolases and esterases further break down the resulting fragments. Co-metabolic processes and microbial consortia improve degradation efficiency by primary degraders by producing oxidized intermediates, which are then consumed and mineralized by secondary fermenters. Despite significant progress, the complete biochemical pathways of microplastic mineralization remain unclear. Degradation rates are slow, and scalability challenges hinder practical applications, with incomplete mineralization in insect biodegradation potentially causing secondary microplastics. Understanding these mechanisms will lay the groundwork for developing insect-microbe systems as potential biotechnological solutions to mitigate plastic pollution in terrestrial environments. Full article

Background: Oxidative stress is a key contributor to many chronic diseases. Natural biocompounds with antioxidant activity are of growing therapeutic interest. Brassica macrocarpa, a plant from the Brassicaceae family, has shown in vitro safety and antioxidant potential due to its rich content of glucosinolates and phenolics. However, in vivo, its effects remain poorly characterized. This study aimed to evaluate the in vivo safety and biological effects of Brassica macrocarpa leaf extract in zebrafish embryos and to assess its potential to counteract copper sulphate (CuSO₄)-induced oxidative stress. Methods: Zebrafish embryos were exposed to Brassica macrocarpa extract at concentrations from 125 to 2000 µg/mL. Embryonic mortality and malformations were monitored daily to determine sub-lethal concentrations (125–500 µg/mL) for further behavioural and biochemical analysis. Antioxidant properties were tested in a CuSO₄-induced oxidative stress model. Results: No teratogenic effects were observed over 96 h. Larvae showed normal swimming and no behavioural changes. Pre-treatment with the extract significantly reduced CuSO₄-induced ROS and NO production, modulated antioxidant enzyme (SOD, CAT) activity, and lowered lipid peroxidation and protein oxidation, slightly affecting DNA damage. Conclusions: Brassica macrocarpa extract in vivo appears safe at sub-lethal doses and shows promising antioxidant effects, suggesting its potential role in managing oxidative stress-related conditions. Full article

Microbial degradation of pectin is a fundamental process for the carbon cycle and a strategic approach for treating industrial residues. This study characterizes a novel marine bacterium, Paenarthrobacter sp. FR1, isolated from East China Sea intertidal sediment, which exhibits the ability to utilize pectin. Its draft genome (4.83 Mb, 62.92% GC content) is predicted to encode 4498 protein-coding genes. Genomic analysis revealed a rich repertoire of Carbohydrate-Active Enzymes (CAZymes) crucial for this process, including 108 glycoside hydrolases (GHs), 7 polysaccharide lyases (PLs), 35 carbohydrate esterases (CEs), and 11 auxiliary activities (AAs). Genomic analysis provides supportive evidence that FR1 may target both homogalacturonan (HG) and rhamnogalacturonan (RG) pectin domains, potentially through complementary hydrolytic and oxidative pathways. Phylogenomic analysis based on Average Nucleotide Identity (ANI, 83.56%) and digital DNA-DNA Hybridization (dDDH, 27.8%) confirmed its status as a potential novel species. Notably, FR1 is a rare Paenarthrobacter isolate with innate pectinolytic capability, a characteristic not previously documented in this genus. This strain’s unique enzymatic machinery highlights its importance in marine carbon cycling and provides a valuable biotechnological resource for degrading pectin-rich wastes. Full article

Hydrogenases are key enzymes in microbial energy metabolism, catalyzing the reversible conversion between molecular hydrogen and protons. Among them, [NiFe]-hydrogenases are particularly attractive for biocatalytic applications due to the oxygen tolerance of several members of this class and their ability to couple hydrogen oxidation with redox cofactor regeneration. In this study, a recombinant soluble [NiFe]-hydrogenase from Cupriavidus necator H16 was successfully expressed in Escherichia coli BL21 (DE3), purified, and characterised with a focus on its applicability for NAD⁺ regeneration. Unlike previous studies that primarily used native C. necator extracts or complex maturation systems, this work provides the first quantitative demonstration that an aerobically purified recombinant soluble [NiFe]-hydrogenase expressed in E. coli can function effectively as an NAD⁺ regeneration catalyst and operate within multi-enzymatic cascade reactions under application-relevant conditions. The crude recombinant enzyme displayed a volumetric activity of 0.273 ± 0.024 U/mL and a specific activity of 0.018 ± 0.002 U/mg_cells in the hydrogen oxidation assay, while purification yielded a specific activity of 0.114 ± 0.001 U/mg with an overall recovery of 79.2%. The enzyme exhibited an optimal temperature of 35 °C and a pH optimum of 7.00. Thermal stability analysis revealed rapid deactivation at 40 °C (k_d = 0.4186 ± 0.0788 h⁻¹, t_1/2 ≈ 1.7 h) and substantially slower deactivation at 4 °C (k_d = 0.1141 ± 0.0139 h⁻¹, t_1/2 ≈ 6.1 h). Batch NADH oxidation experiments confirmed efficient cofactor turnover and high specificity towards NADH over NADPH. Finally, integration of the hydrogenase into a one-pot two-enzyme glucose oxidation system demonstrated its capacity for in situ NAD⁺ regeneration, although the reaction stopped after approximately 5 min due to acidification from gluconic acid formation, highlighting pH control as a key requirement for future process optimization. Full article

Breast cancer remains a leading cause of cancer-related morbidity and mortality globally, highlighting the urgent need for novel therapeutic strategies. This study investigates the molecular mechanisms underlying the anti-proliferative potential of Cannabis sativa dichloromethane extract (C. sativa DCM) on oxidative stress, apoptosis, and invasion in human breast cancer cells. Key biomarkers, such as antioxidant enzymes (Superoxide Dismutase (SOD) and Glutathione (GSH)), the transcription factor Nrf2, apoptotic proteins (p53, caspase-8 and 9), metalloproteinase (MMP-1 and MMP-9), and Transforming Growth Factor Beta (TGF-β) were examined. Cytotoxicity was assessed using an MTT assay in the MDA-MB-231 and MCF-7 breast cancer cell lines, with comparisons to normal skin fibroblasts (HS27). Oxidative stress biomarkers were quantified using enzymatic assays and ELISA kits, while apoptotic and anti-metastatic factors were determined by Western blotting. Results demonstrated that C. sativa DCM extract induced significant cell death in a concentration-dependent manner, with IC50 values of 75.46 ± 0.132 μg/mL for MDA-MB-231 and 78.68 ± 0.50 μg/mL for MCF-7 cells. The extract decreased SOD and GSH levels while increasing p53 and caspase activity, confirming apoptosis activation. Additionally, C. sativa DCM inhibited migration and invasion by downregulating MMP-1, MMP-9, and TGF-β. The anti-proliferative potential of C. sativa DCM in breast cancer cells is mediated through a continuous biological pathway involving oxidative stress modulation, apoptotic signaling, and anti-invasive effects. Phytochemical analysis revealed terpenoids and steroids, including compounds like cannabidiol and tetrahydrocannabinol acid. These findings suggest that C. sativa DCM extract holds potential as an anti-breast cancer therapeutic and warrants further preclinical and clinical investigations. Full article

Background: The senescence of testicular Leydig cells (LCs) is a key cause of age-related testosterone deficiency, in which oxidative stress (OS) and mitochondrial dysfunction are critical driving mechanisms. We explore whether the bioactive peptide C248 of PRDX4, an intracellular antioxidant, exerts mitochondrial protection to ameliorate LCs’ function. Methods: Based on the antioxidant domains of the PRDX4 protein, small molecular peptides were designed, and bioactive peptide C248 stood out from the crowd. An OS-induced senescence model of LCs was constructed by treating the MLTC-1 cell line with hydrogen peroxide (H₂O₂). C248 peptide or nicotinamide mononucleotide (NMN), as the positive control, was administered in the culture medium. The cellular function-related indicators, including DPPH free radical scavenging rate, cell viability, testosterone level, hydrogen peroxide (H₂O₂) content, senescence-associated β-galactosidase (SA-β-gal) activity, 8-hydroxy-2′-deoxyguanosine (8-OHDG) level, and 4-hydroxynonenal (4-HNE) level, were evaluated. The mitochondrial function and structural indicators, such as mitochondrial membrane potential, ATP production, mitochondrial morphology, and mitochondrial DNA (mtDNA) copy number, were subsequently tested. Results: In vitro experiments confirmed that C248 could scavenge DPPH free radicals in a dose-dependent manner, reduce the levels of reactive oxygen species, and increase antioxidant enzyme activity in LCs (p < 0.01). Both C248 and NMN increased testosterone secretion and improved cell viability (p < 0.01). Both C248 and NMN increased mitochondrial morphology and quantity, mitochondrial membrane potential (p < 0.01), ATP production (p < 0.01), and mitochondrial DNA (mtDNA) copy number (p < 0.01). Conclusion: This study reveals that the small molecular C248, a bioactive peptide of PRDX4, is a new candidate molecule for intervening in LC senescence and confirms that mitochondrial protection is a key strategy for improving age-related testicular dysfunction. Full article

Over the past decade, oxidative stress and neuroinflammation have been increasingly recognized as part of the pathology of Alzheimer’s disease (AD). This observation has led to extensive efforts and attempts to apply antioxidant compounds as therapeutic agents for AD and other pathologies. However, most, if not all, of these attempts have failed in preclinical or clinical trials. A tentative explanation for this failure is radical scavengers’ intrinsic lack of specificity in either their mode or district of action. The lack of specificity has been thought by some to be a source of so-called “reductive stress”, another form of redox imbalance that might be just as toxic as oxidative stress. Thus, research interest is shifting from developing simple radical scavengers to designing and refining compounds targeting the overproduction of Reactive Oxygen Species (ROS) in specific pathological conditions. This can be achieved, for instance, by targeting the enzymes that are mainly responsible for their production, namely NADPH oxidases (NOX). In this review, we will discuss, from the point of view of medicinal chemistry, the main innovations in the development of NOX inhibitors and their potential employment for AD therapy. We will also discuss the experimental hurdles that slow down research in this field and possible solutions. Full article

Bryophytes, as early land plants, have evolved and developed a wide array of enzymatic and non-enzymatic antioxidant defense mechanisms to cope with oxidative stress. This review explores the intricate biochemical pathways of bryophyte antioxidant defense including their secondary metabolite (SM) systems and protective enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione transferases (GSTs), glutathione peroxidase (GPx), and glutathione reductase (GR). These metabolic components function through species-specific regulatory mechanisms related to expression way. The pharmacological significance of bryophyte-derived compounds is also highlighted, supported by recent discoveries of numerous bioactive molecules, such as melatonin, cannabinoids, and specific chemical marker compounds. Most current biochemical studies on bryophytes focus on their desiccation tolerance and their utility as pollution indicators; however, another aim of this review is to underscore their broader pharmacological promise. Furthermore, this paper explores the biotechnological applications of bryophytes in drug discovery and the need for bioreactor cultivation of the species used. It also emphasizes the need for further investigation into bryophyte biochemistry and enzymology, particularly their unique enzyme systems, to fully unlock their therapeutic potential. Full article

Background and Objectives: Oxidative stress plays a central role in numerous pathological and toxicological processes, and in vivo investigations are essential for understanding integrated systemic responses. Methylxanthines have been reported to modulate redox homeostasis through multiple mechanisms, but their effects in aquatic vertebrate models under metal nanoparticle-induced oxidative stress remain poorly characterized. Materials and Methods: In the present study, adult zebrafish were exposed for 15 days to ZnO nanoparticles (0.69 mg/L) as a pro-oxidant model, and to methylxanthines (caffeine, theobromine, theophylline; 50 mg/L). Oxidative stress biomarkers were assessed by measuring the levels of glutathione peroxidase 1 (GPx1), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) in whole-body homogenates using ELISA. Complementary molecular docking was performed to investigate methylxanthine–enzyme interactions. Results: The most substantial change was observed for SOD level, which significant increased compared to the control group (from 0.122 to 1.090 ng/g; p = 0.001), followed by CAT, which rose from 38.3 pg/g to 100.8 pg/g; p = 0.001), and GPX1 which increased from 84.3 pg/g to 142.2 pg/g; p = 0.011). In parallel, GSH levels decreased by 58.7% (p = 0.001). Co-exposure to methylxanthines significantly modulated the ZnO-NPs exposure response, by mitigating the increase in antioxidant enzyme levels and restoring glutathione. Among the tested compounds, theobromine exerted the strongest protective effect on GPx1 and GSH and caffeine primarily influenced CAT and SOD, whereas theophylline showed overall weaker responses. The molecular docking investigation indicated that all tested methylxanthines can attach to different cavities of the antioxidant enzymes. Theophylline and theobromine established hydrogen bonds and π-stacking interactions with the interfacing amino acids, potentially contributing to the modulation of enzymes stabilization and function under physiological conditions. Conclusions: ZnO-NPs trigger a robust systemic response in zebrafish, whereas methylxanthines display distinct compound-specific modulating effects. Full article

Background: Non-alcoholic steatohepatitis (NASH) lacks approved pharmacotherapies despite affecting approximately 25% of the global population. Agrimonia pilosa, a traditional herb with anti-inflammatory and antioxidant properties, remains unexplored for NASH treatment. Objective: This study investigated the hepatoprotective effects and mechanisms of Agrimonia pilosa extract (APE) in NASH models. Methods: HepG2 cells were treated with free fatty acids (0.125 mM) and APE (+12.5–50 μg/mL). C57BL/6J mice received a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) for 12 weeks with APE (25–100 mg/kg/day), silymarin (100 mg/kg/day), or luteolin (20 mg/kg/day). Lipid accumulation, liver enzymes, histopathology, and molecular markers were assessed. Results: APE dose-dependently reduced lipid accumulation in FFA-treated cells, suppressed lipogenic factors (SREBF1, CEBPA, and PPARG), and upregulated fatty acid oxidation enzymes (CPT1A and PPARA) via AMPK/SIRT1 activation. In NASH mice, APE (100 mg/kg) significantly decreased serum ALT (160.0 ± 49.1 vs. 311.2 ± 66.7 U/L) and AST (96.0 ± 18.7 vs. 219.0 ± 55.7 U/L, p < 0.001), reduced hepatic macrophage infiltration by 68%, and substantially attenuated inflammatory markers (Ccl2, Tnf, and IL6), oxidative stress indicators (NRF2, HMOX1, and CYBB), and fibrogenic markers (ACTA2, COL1A1, and TGFB1) by 83–85% (p < 0.001). Collagen deposition decreased from 5.63 ± 0.39% to 1.54 ± 0.03% (p < 0.001). Conclusions: APE exerts potent hepatoprotective effects through multi-targeted modulation of lipid metabolism, inflammation, oxidative stress, and fibrosis via AMPK/SIRT1 pathway activation, supporting its potential as a natural therapeutic intervention for NASH. Full article

Extracellular vesicles (EVs) are promising therapeutic agents due to their role in intercellular communication. This study examined the protective effects of milk-derived EVs (mEVs) on bovine oviductal epithelial cells (BOECs) under cobalt chloride (CoCl₂)-induced oxidative stress (OS), comparing EVs stored at −80 °C or lyophilized. mEVs and algae-derived EVs (aEVs; negative control) were isolated via tangential flow filtration and applied at 10⁷, 10⁹, and 10¹¹ particles/mL in three treatment strategies: pre-treatment, co-incubation, and post-treatment. mEVs specifically enhanced cell viability in all protocols except for post-treatment, where only 10⁷ particles/mL was effective; meanwhile, storage method did not affect EV activity. Enzyme digestion suggested that internal EV cargos are potentially the dominant contributors to the protective response compared to surface-associated molecules. mEVs reduced the expression of the OS markers DDIT4 and HIF1A while promoting cell migration more effectively than aEVs. Pathway enrichment analysis of previously reported mEV miRNAs indicated regulation of cytokine production and glucocorticoid responses, potentially contributing to OS defense. mEV protein cargo analysis showed pathways primarily linked to peptidase and vesicle-related functions, suggesting that protein cargo may also contribute to the observed protective effects. Overall, mEVs protect BOECs against CoCl₂-induced OS and maintain bioactivity after lyophilization. Full article

DNA damage resulting from oxidative stress plays a major role in cancer formation. Despite DNA damage, the inability of cells to enter apoptosis due to irregularities in apoptotic protein levels and the induction of their proliferation as a result of the increase in polyamine levels causes the development and progression of cancer. The anticancer effects of Rhus coriaria L. extracts on lung cancer, colon cancer and fibroblast cell lines were determined by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide). Total antioxidant status (TAS) was analyzed with a commercial kit. The expression levels of genes related to apoptosis and the polyamine pathway in lung and colon cancer cell lines were analyzed by a Real-time Polymerase Chain Reaction (RT-PCR) device. Rhus coriaria L. extracts were found to have anticancer effects selectively on A549 and HT-29 cancer lines. It has also been shown that Rhus coriaria L. extracts have strong antioxidant capacity and can inhibit the Xanthine Oxidase (XO) enzyme in a dose-dependent manner. Afterwards, the interactions of the molecules in extracts of Rhus coriaria L. against various proteins such as colon cancer protein (PDB ID: 3DTC and 4UYA) lung cancer protein (PDB ID: 4ZXT and 5ZMA) were examined, and their activities were compared. MM/GBSA methods of the molecule with the best docking score are calculated as binding free energy. Full article

Chaenomeles speciosa (Sweet) Nakai (CF), a traditional food in East Asia and a recent addition to clinical dietary recommendations, has demonstrated potential for managing hyperuricemia. However, its bioactive components and therapeutic mechanisms remain largely unexplored. In this study, we used an integrative approach incorporating serum pharmacochemistry, metabolomics, bioinformatics, molecular docking, and in vitro/vivo validation to investigate CF’s effects and mechanisms in hyperuricemia. In hyperuricemic mice, CF significantly reduced serum uric acid, creatinine, and blood urea nitrogen (BUN) levels, improved kidney histopathology, and restored redox balance by increasing antioxidant enzyme activities (SOD and GSH-Px) while lowering malondialdehyde (MDA) levels. Metabolomic analysis revealed that CF modulated pathways associated with oxidative stress, including purine metabolism, arachidonic acid metabolism, and α-linolenic acid metabolism, to reverse hyperuricemia-associated metabolic perturbations. Correlation analysis between differential metabolites and serum-absorbed constituents identified androsin, cynaroside, and salicin as potential bioactive compounds. These compounds showed high predicted binding affinities to COX-1, PGE2, and XOD in molecular docking, and these interactions were validated by in vitro assays, where the compounds effectively suppressed inflammatory cytokine production and inhibited XOD activity. Overall, CF exerts anti-hyperuricemic and renoprotective effects through coordinated regulation of purine metabolism, inflammation, and oxidative stress, supporting its potential as a functional food or complementary therapy for hyperuricemia-related conditions. Full article

Agricultural soils surrounding mining areas are often polluted with heavy metals (HMs) due to long-term mining activities and high geological background values. In this study, we investigated the distribution and transport of Cu, Cr, Zn, Cd, Pb, and As in a soil–rice system near a century-old mining site, evaluated their toxic effects on rice (Oryza sativa L.) throughout the growth period, and assessed the associated health risks using the Nemerow index and potential ecological risk index. The results showed that HM contents in rice grown in contaminated soils were significantly higher than in the control. HMs mainly accumulated in roots, with the lowest contents in grains. Cd exhibited the highest enrichment capacity, with bioconcentration factors of 0.79, 1.04, and 1.95 at the tillering, heading, and maturity stages, respectively, and its accumulation increased with rice growth. Transport from stems to leaves was relatively strong. HM exposure significantly inhibited rice growth, reducing plant height, biomass, tiller number, and panicle emergence. In addition, oxidative stress indicators and antioxidant enzyme activities, as well as root amino acid exudation, were markedly altered under HM stress. According to soil–rice HM contents, the pollution level of agricultural soils reached a high class, with As, Pb, Cd, and Zn as the main contributors. The potential ecological risk reached a moderate level, with Cd identified as the dominant factor. Notably, the health risks to children were substantially higher than those to adults, and Monte Carlo simulation indicated a 100% probability of non-carcinogenic and carcinogenic risks for adults and children. The above results highlighting the urgent need for risk management in mining-affected regions. Full article