Search Results (13,960)

Cellulose nanocrystals (CNCs) are renewable and biodegradable nanomaterials that can stabilize Pickering emulsions through steric hindrance and electrostatic repulsion. However, pristine CNCs show limited interfacial anchoring because of their strong hydrophilicity and high surface charge density, making the emulsions susceptible to coalescence, phase separation, and structural instability under environmental stresses. This review summarizes two major strategies for stabilizing and functionally regulating CNC-based Pickering emulsions: chemical modification and synergistic stabilization. Chemical modification regulates CNC surface charge, wettability, interfacial anchoring, and functional group composition through oxidation, amination, esterification, graft copolymerization, desulfation, and etherification, whereas synergistic stabilization constructs composite interfacial films or continuous-phase networks through noncovalent interactions between CNCs and proteins, polysaccharides, cyclodextrins, surfactants, inorganic nanomaterials, or functional molecules. The ability of these emulsion systems to compartmentalize oil-soluble bioactives within structured droplets also provides a basis for improving bioactive stability and release behavior in food-related formulations. These strategies improve emulsion stability and introduce antibacterial, antioxidant, responsive, and controlled-release properties, highlighting the potential of CNC-based Pickering emulsions in active food systems, including food preservation, active packaging, and the stabilization, protection, and release regulation of food bioactives. Remaining challenges in green preparation, structural regulation, release mechanisms, scalable production, and practical evaluation are also discussed. Full article

Sweet basil is a medicinal herb valued for its culinary and therapeutic applications, primarily due to its secondary metabolite content. Therefore, optimizing its cultivation is essential for growers seeking to improve both the quality and nutritional value of the plants. Two cultivars of Ocimum basilicum L., ‘Lettuce Leaf’ (LL) and ‘Purple Opal’ (PO), were evaluated under various nutritional regimes (mineral, organic, and organo-mineral). The assessment included measurements of total protein, fat, and ash content, as well as total polyphenol levels, phenolic acid content, and antioxidant activity. HPLC analysis was performed to evaluate the composition of selected phenolic and chlorogenic acids, flavonoids, and catechins. Additionally, mineral content was analyzed using OES-ICP. Gene expression of key genes involved in the phenylpropanoid pathway (PAL, C4H, 4Cl, CAD, and CVOMT) and the transcription factor OscWRKY1 was analyzed through RT-qPCR. The key findings indicated that the nutritional variants significantly impacted both primary and secondary metabolism in the assessed plants. Additionally, there was a significant (p < 0.05) cultivar-specific response to the different nutritional variants. The results suggest that the optimal nutritional strategy may vary depending on the target metabolite. Variant 4 was associated with the most favorable overall response in basil, including increased protein levels, higher total polyphenol content, and a balanced mineral composition. However, variant 5 showed the highest antioxidant activity for both cultivars. Rutin and protocatechuic acid were detected only in PO, and cryptochlorogenic acid was detected only in LL. A marked varietal difference was observed in gallocatechin content, with the LL variety containing more than fourfold higher levels than the PP variety. The results of RT-qPCR were fluctuating and strongly dependent on the cultivar. Full article

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are critical modulators of male reproductive health, influencing sperm function, hormonal regulation, and overall fertility. While physiological levels of ROS and RNS are essential for processes such as sperm capacitation and acrosome reaction, their overproduction leads to oxidative and nitrosative stress, contributing to male infertility. Excessive ROS and RNS can damage sperm DNA, proteins, and lipids, impairing motility, viability, and fertilizing capacity. Moreover, these reactive species disrupt the hypothalamic-pituitary-gonadal (HPG) axis, leading to hormonal imbalances that further compromise reproductive function. Environmental factors, lifestyle choices, and underlying health conditions exacerbate the production of ROS and RNS, highlighting the need for preventive and therapeutic strategies. Clinically, ROS- and RNS-mediated redox imbalance has been implicated in several male reproductive disorders, including varicocele, genital tract infection and inflammation, obesity, diabetes and other metabolic disorders, and toxicant-related reproductive dysfunction. Antioxidant supplementation has shown promise in mitigating oxidative stress; however, its efficacy varies, and further research is necessary to establish standardized treatment protocols. These findings underscore the clinical relevance of integrating oxidative stress assessment with conventional semen analysis to improve risk stratification and guide targeted interventions in male infertility. This review synthesizes current knowledge on the molecular mechanisms by which ROS and RNS affect male reproduction and discusses potential clinical interventions to address oxidative and nitrosative stress in male infertility. Full article

Acetaminophen (APAP) overdose is a major cause of drug-induced liver injury and remains a widely used model of xenobiotic-induced hepatotoxicity. Oxidative stress, mitochondrial dysfunction, and ferroptosis are key events in APAP-mediated liver damage. In this study, we investigated whether L-menthol pretreatment protects against APAP-induced acute liver injury and explored the underlying mechanisms in vivo and in vitro. Male C57BL/6 mice were pretreated with L-menthol (100 mg/kg/day) for 7 days before APAP challenge (300 mg/kg). L-menthol markedly attenuated hepatic necrosis, inflammatory infiltration, and hepatocyte injury, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, suppressed IL-1β, IL-6, and TNF-α production, restored hepatic glutathione and superoxide dismutase levels, and decreased malondialdehyde accumulation. Transcriptomic analysis revealed significant enrichment of differentially expressed genes in reactive oxygen species- and ferroptosis-related pathways. In APAP-challenged HepG2 cells, L-menthol improved cell viability, preserved mitochondrial ultrastructure, reduced ferrous iron accumulation, was associated with upregulation of Keap1/Nrf2/HO-1/NQO1 pathway-related proteins, and restored GPX4 expression. Collectively, these findings indicate that L-menthol pretreatment attenuates APAP-induced hepatotoxicity, possibly through enhancement of antioxidant defenses and attenuation of ferroptosis-associated changes, supporting its potential as a preventive hepatoprotective small molecule against xenobiotic-induced liver injury. Full article

Metabolic and cardiometabolic diseases are closely associated with mitochondrial dysfunction and redox imbalance. Ubiquinol–cytochrome c reductase core protein 2 (UQCRC2), a non-catalytic structural core subunit of mitochondrial respiratory chain Complex III, is increasingly recognized as a regulator of Complex III integrity, electron transfer, oxidative phosphorylation, and mitochondrial redox homeostasis. Under metabolic stress, reduced expression or functional impairment of UQCRC2 may promote electron leakage, mitochondrial reactive oxygen species (mtROS) generation, lipid peroxidation, impaired antioxidant defense, and disrupted glucose–lipid metabolism. These alterations may contribute to insulin resistance (IR), metabolic dysfunction-associated steatotic liver disease (MASLD), obesity, and cardiovascular disease (CVD). This review summarizes current evidence linking UQCRC2 dysfunction to mitochondrial bioenergetic failure, oxidative stress, inflammatory signaling, and cardiometabolic injury. We further discuss redox-regulatory pathways, including Nrf2, AMPK–SIRT1–PGC-1α, glutathione metabolism, and mitophagy, as well as pharmacological agents and natural compounds that may modulate UQCRC2-related mitochondrial responses. Collectively, these findings highlight UQCRC2 as a redox-sensitive mitochondrial node linking Complex III dysfunction to cardiometabolic injury and targeted redox-based interventions. Full article

Background: Apoptosis is a fundamental process for maintaining tissue homeostasis, and its dysregulation is closely linked to the development of numerous diseases, including colorectal cancer. In recent years, dietary polyphenols have gained interest due to their antioxidant, pro-apoptotic, and chemopreventive properties. Artichoke (Cynara scolymus L.) by-products are rich source of hydroxycinnamic acids and flavonoids, making them promising source of bioactive compounds. Methods: In this study we evaluated the cytotoxic and pro-apoptotic activity of four aqueous extracts obtained from artichoke bract by-products, including one commercial hybrid (CAPB) and three local Apulian varieties (BriB, VaMB, LMTB), in human colorectal adenocarcinoma cell lines (Caco-2 and HT29). The extracts were characterized according to their total polyphenol content and phenolic profile. Results: The selected artichoke by-product extracts exhibited significant cytotoxic effects both in a concentration- and time-dependent manner, with concentrations ≥ 2 mg/mL significantly reducing cell viability and nearly abolishing it at 4 mg/mL after 48 h. Moreover, treatment with the extracts modulated the expression of apoptosis-related proteins, characterized by an increase in pro-apoptotic markers (Bax, caspase-9, caspase-3) and a decrease in the anti-apoptotic protein Bcl-2, suggesting activation of the mitochondrial apoptotic pathway. In particular, the BriB extract was able to induce an apoptosis rate higher than 80% in Caco-2 cells and achieved comparable rates in HT29 cells at concentrations of 2–3 mg/mL. Conclusions: Overall, these findings demonstrate that artichoke by-product extracts exert significant pro-apoptotic effects in colorectal cancer cells and highlight their potential as sustainable sources of bioactive compounds for nutraceutical or adjuvant anticancer applications. Full article

Litchi chinensis seeds are rich in flavonoids and exhibit potent antioxidant activity. This study constructed a D-galactose-induced oxidative stress model in mice and applied ultra-high performance liquid chromatography–mass spectrometry (UHPLC-MS), network pharmacology, and molecular docking to clarify the antioxidant activity and material basis of ethanolic litchi seed extract. Litchi seed extract was orally given by gavage at 100 and 200 mg/kg in antioxidant tests, whereas a dosage of 500 mg/kg was adopted for the detection of absorbed constituents in plasma. The results showed that the total flavonoid content of litchi seed extract reached 68.37%. The extract could markedly reduce malondialdehyde (MDA) levels and elevate superoxide dismutase (SOD) activity in the serum, liver and kidney tissues of model mice, thereby mitigating oxidative damage. Thirteen prototype compounds absorbed into blood were characterized by UHPLC-MS. Most of these substances were flavonoids, with isorhamnetin, quercetin and naringenin as the major representatives. Core targets including IGF1R, PIK3R1, EGFR, PIK3CA, ERBB2 and proto-oncogene tyrosine-protein kinase Src (SRC) were screened using network pharmacology, among which SRC was identified as the pivotal hub target. Molecular docking results revealed that isorhamnetin, quercetin, naringenin, and diosmetin were able to bind stably to the SRC protein. The present study demonstrated that litchi seed extract exhibits remarkable antioxidant activity, with isorhamnetin, quercetin, naringenin, and diosmetin as the main bioactive antioxidant components. Full article

Background: The kidney is an organ rich in peroxisomes, which play a pivotal role in fatty acid oxidation and ROS decomposition. Importantly, peroxisomal dysfunction contributes to the development and progression of various renal diseases. Therefore, we aimed to elucidate whether peroxisomes affect renal damage and fibrosis over time using a unilateral ureteral obstruction (UUO) mouse model. Methods: Expression levels of peroxisome-related factors and ROS- and hypoxia-related genes in UUO mice were measured in a time-dependent manner. Results: UUO led to renal damage and fibrosis progression over time; it significantly increased the protein expression levels of ATG5 and ATG7, while it decreased PMP70 and PEX14 protein expression. In particular, UUO increased the protein expression level of pexophagy receptor NBR1. Although the number of peroxisomes decreased, the protein expression levels of peroxisomal biogenesis-related proteins such as PEX11b, PEX16, and PEX19 remained constant. Decreased lipid metabolism due to reductions in ACOX1, DBP, and catalase caused by UUO and increased ROS production through peroxisomal degradation and mitochondrial antioxidant enzyme dysfunction were observed. Additionally, HIF-1α protein levels gradually increased in the UUO mice, whereas those of HIF-2α initially increased and then decreased. Conclusions: UUO is characterized by a progressive, chronological reduction in peroxisomal markers. Our findings indicate that peroxisomal degradation and associated metabolic dysfunction are tightly correlated with the progression of kidney injury and fibrosis, suggesting a potential involvement of compromised peroxisomal homeostasis in renal pathogenesis rather than proving a direct causal mechanism. Maintaining peroxisomal quality control may nevertheless represent a potential therapeutic avenue for chronic kidney disease. Full article

Acute liver failure (ALF) is characterized by a rapid decline in liver function, leading to metabolic and organ failure. This study employed liver metabolomics, Nuclear Factor kappa-B (NF-κB) signaling pathway analysis, and inflammatory factor profiling to investigate the therapeutic mechanisms of xanthoxylin in ALF. Xanthoxylin administration led to increased antioxidant levels and reduced markers of inflammation and tissue damage. Xanthoxylin downregulated the messenger RNA (mRNA) expression of Nitric Oxide Synthase (NOS), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α), NF-κB, Inhibitor of NF-κB α (IκBα), and Toll-like receptor 4 (TLR4), and inhibited the protein expression of p-p38 and p-p65 while upregulating B-cell CLL/Lymphoma 2 (Bcl-2) and B-cell Lymphoma-x (Bcl-xl). Metabolomic analysis identified 41 differentially expressed metabolites, 20 of which showed strong correlations with pharmacodynamic parameters. These 20 candidate metabolite signatures are involved in amino acid and carboxylic acid metabolic pathways, with potential links to glycolysis and the tricarboxylic acid (TCA) cycle. Together, these findings suggest that xanthoxylin exerts therapeutic effects against ALF by modulating the IκBα/NF-κB signaling pathway and related metabolic pathways, providing a scientific basis for understanding its multi-target mechanism. Full article

Adequate placental development and function, prerequisites for the development of a healthy fetus, rely on controlled trophoblast invasion into the decidua and remodeling of the spiral arteries. These tightly regulated processes involve epithelial–mesenchymal transition (EMT) and endovascular differentiation of trophoblast cells. Taxifolin (dihydroquercetin), a natural flavonoid with various pharmacological effects, previously showed cytoprotective, antioxidant, and anti-inflammatory activity on trophoblast cells. Given that the literature indicates that this flavonoid suppresses EMT and can affect angiogenesis across different cell types, we investigated the potential of taxifolin (10 and 100 µM) to modulate invasion and endothelial-like differentiation in human extravillous trophoblast HTR-8/SVneo cells by functional tests. Expression of different molecular markers relevant to these processes was evaluated at the mRNA and protein levels. Our results showed that taxifolin inhibited invasion of HTR-8/SVneo cells, involving downregulation of integrin α5 subunit and modulation of MMP-2 and MMP-9 mRNA expression and secretion. No changes in the concentrations of secreted TIMP-1 and TIMP-2 were observed following taxifolin treatment. Furthermore, downregulation of N-cadherin and vimentin in treated trophoblast cells indicated suppression of EMT. Taxifolin inhibited endothelial-like differentiation of HTR-8/SVneo cells, as evidenced by reduced tube formation and downregulation of VE-cadherin in treated cells. Moreover, expression of TGFB1 was upregulated in treated cells, as were levels of phosphorylated SMAD2/3, indicating involvement of TGF-β signaling in TF-induced effects on trophoblast cells. The in vitro effects of taxifolin on suppression of trophoblast invasion, EMT, and endothelial-like differentiation highlight its potential impact on placental development processes. Full article

Intestinal oxidative stress severely compromises the health and growth of weaned piglets. The fly maggot-derived antioxidant peptide FMP was previously identified, but its protective mechanisms remain unclear. Here, we explored how FMP alleviates oxidative intestinal injury. In IPEC-J2 cells, FMP pretreatment significantly attenuated H₂O₂-induced cytotoxicity, ROS accumulation, and apoptosis, while enhancing antioxidant enzyme activities and activating Nrf2 signaling (p < 0.05). Co-treatment with the Nrf2 inhibitor ML385 abolished FMP-mediated mitophagy enhancement and cytoprotection, revealing that FMP enhances PINK1/Parkin-dependent mitophagy via Nrf2 activation. In diquat-challenged weaned piglets, oral FMP administration restored serum SOD and GSH-Px activities, reduced MDA and DAO levels (p < 0.05), upregulated jejunal tight junction proteins, and enriched Lactobacillus populations. These findings demonstrate that FMP targets the Nrf2-mitophagy axis to protect against intestinal oxidative damage, supporting its application as a green feed additive. Full article

Objectives: Neuroinflammation is recognized as a significant characteristic of Alzheimer’s disease (AD). Currently, there is a notable absence of effective pharmacological agents to prevent or treat neuroinflammatory processes associated with AD. Heat shock protein 70 (HSP70) is pivotal in the progression of neuroinflammation. In this study, we explored the potential of maltol, a Maillard reaction product derived from red ginseng, as a therapeutic agent for neuroinflammation. Methods: In vitro, HMC3 microglial cell models were developed to examine the regulatory effects of gradient concentrations of maltol (12.5, 25, 50 μM) on the TLR4/MyD88/NF-κB p65 signaling pathway, neuroinflammation, and pyroptosis. Analyses of the GEO database and Gene Set Enrichment Analysis (GSEA) were performed to identify the core targets of maltol, followed by HSP70 gene silencing experiments to validate the targeted regulatory mechanism. Results: Maltol significantly mitigated LPS-induced neuronal damage and cognitive deficits in mice. It effectively suppressed microglia-mediated neuroinflammation and pyroptosis, reversed oxidative stress-induced neuronal ferroptosis, and inhibited neuronal apoptosis. In vitro experiments demonstrated that maltol obstructed TLR4/MyD88 binding, thereby inhibiting NF-κB p65-mediated neuroinflammation and pyroptosis, while also alleviating excessive ROS accumulation to enhance oxidative stress and ferroptosis. Bioinformatics analysis identified HSP70 as a crucial target for the anti-inflammatory and antioxidant effects of maltol. Subsequent gene silencing experiments confirmed that maltol exerted its inhibitory effects on LPS-induced neuroinflammation and pyroptosis in an HSP70-dependent manner. Conclusions: Maltol exhibits significant protective effects against Alzheimer’s disease-related neuroinflammation, oxidative stress, pyroptosis, and ferroptosis through the targeting of HSP70. This study elucidates the molecular mechanisms by which maltol improves neuroinflammatory injury and provides a novel theoretical foundation and therapeutic strategy for the intervention of Alzheimer’s disease neuroinflammation using traditional Chinese medicine. Full article

The efficacy of enzyme therapy is limited by their poor stability under physiological conditions. Thermostable enzymes, derived from extremophilic organisms or generated by advanced protein engineering, offer a revolutionary solution to this long-standing challenge. They are widely used in industrial biocatalysis. Their therapeutic applications are poorly investigated and spread across diverse disciplines. While most applications are in the preclinical stages, emerging evidence from animal models demonstrates proof-of-concept for thermostable antioxidant enzymes in cardiovascular, neurodegenerative, and inflammatory diseases. This review critically assesses the translational landscape, distinguishing between established therapeutic enzymes (e.g., asparaginase, PEGylated SOD) and emerging experimental candidates. This narrative review consolidates existing knowledge about thermostable enzyme engineering and their emerging functions as molecular therapies, particularly in oxidative stress-related diseases. This review synthesizes recent advances in structural biology, computational protein design, biomaterials engineering, and translational antioxidant strategies, highlighting how breaking down disciplinary barriers is accelerating the development of sustainable and self-regenerating antioxidant platforms. By integrating molecular precision with systems-level therapeutic design, engineered thermostable antioxidant enzymes exemplify the future of biological development, where multidisciplinary collaboration drives innovation against oxidative stress-driven pathologies. Engineered thermostable enzymes provide a versatile basis for next-generation therapeutics, with the potential to address medical needs through improved stability, targeted activity, and multifunctional design. Full article

Jellyfish stings are the most common type of marine life injuries. However, at present, the treatment measures against jellyfish stings are mostly empirical and supportive, with uncertain therapeutic outcomes, and there is a lack of specific antidotes based on the toxic mechanism of jellyfish venom in clinical practice. In our previous study, polyphenol epigallocatechin-3-gallate (EGCG) was found to neutralize the toxicity of jellyfish Nemopilema nomurai venom (NnV) in vivo and in vitro. Herein we further demonstrated that EGCG exerted its antagonistic effect against NnV through inhibiting the oxidative stress, pro-apoptotic proteins, and systemic inflammatory responses. Subsequently, we constructed a polyethylene glycol (PEG)-EGCG/tetracycline hydrochloride (HTC) co-loaded micellar nanocomplex in order to enhance the stability and bioavailability of EGCG in vivo, which successfully integrated the membrane-repair function of PEG, the enzyme inhibitory effect of HTC and the antioxidant properties of EGCG. Notably, this micellar nanocomplex demonstrated significant protective effects against both functional damage and pathological alterations in a non-lethal NnV-envenomed mouse model. When administered 1 h after NnV envenomation, EGCG (40 mg/kg), HTC and PEG-EGCG (containing 40 mg/kg EGCG) only partially improved abnormal blood biochemical indicators and moderately alleviated histopathologic damage, and PEG-EGCG/HTC containing merely 8 mg/kg EGCG completely mitigated the toxic reactions in envenomed mice. In the preventive regimen, the administration of EGCG, HTC or PEG-EGCG 30 min before exposure showed no significant improvement in abnormal blood biochemical indicators and histopathologic damage, while PEG-EGCG/HTC could still significantly improve the functional impairments and histopathologic damage of the heart and liver in NnV-envenomed mice. These findings suggest the clinical translational potential of PEG-EGCG/HTC against jellyfish envenomation. Full article

Lead (Pb) induces oxidative stress, inflammation, and hepatorenal injury. We evaluated whether fenugreek (Trigonella foenum-graecum) seed powder (200 mg/kg) protects against subchronic Pb-acetate exposure in male albino mice. Sixty mice were randomized to six groups (n = 10): control (G1), fenugreek-only (G2), Pb 150 mg/kg (G3), and three co-exposure groups receiving fenugreek with Pb at 50, 100, and 150 mg/kg (G4–G6), gavaged daily for 8 weeks. LC–DAD–ESI–MS/MS of the seed batch tentatively identified 32 metabolites, dominated by flavonoid C-glycosides, luteolin dihydrogalloyl-glucosyl-pentosyl glucoside (15.90%), vicenin-3 (14.46%), vicenin-2 (9.66%), vicenin-1 (8.80%), kaempferol 7-O-rhamnosyl-glucoside (8.71%), with additional acylated phenolic conjugates. Pb exposure (G3) significantly reduced growth and intake, elevated serum ALT, AST, ALP, urea, and creatinine, raised blood Pb, and produced hepatic necrosis, vacuolation, and inflammation. Molecularly, Pb upregulated Nrf2, HO-1, SCD-1, TNF-α, and IL-6 and suppressed SOD-3. Fenugreek co-treatment attenuated all these changes across the three Pb doses, with greatest effect at the lowest Pb load (G4). Notably, fenugreek co-treatment reduced rather than further increased Nrf2 and HO-1 expression relative to Pb alone, a pattern most consistent with lowering the upstream oxidative stimulus rather than direct induction of these pathways. The seed’s polyphenolic profile—rich in vicenin-type C-glycosides and luteolin and kaempferol derivatives—offers a plausible chemical basis for the antioxidant, anti-inflammatory, and modest Pb-lowering effects observed; however, because whole seed powder was administered and metabolite identifications are tentative, these structure–activity relationships are presented as hypotheses for future bioactivity-guided fractionation rather than as demonstrated mechanisms. These preclinical findings support further investigation of fenugreek as a candidate dietary adjunct against environmental Pb exposure, contingent on protein-level validation, pharmacokinetic characterization, benchmarking against a standard chelator, and bioactivity-guided fractionation. Full article