Search Results (2,008)

Ulcerative colitis (UC), a chronic inflammatory bowel disease, is closely associated with disturbances in the gut microbiota. Natural polysaccharides, owing to their unique “indigestibility” and prebiotic properties, represent a potential strategy for intervening in UC by remodeling the gut microecology. This review summarizes the mechanisms by which natural polysaccharides alleviate UC through modulation of the gut microbiota, with a particular focus on the structure–activity relationship between the structural features of natural polysaccharides and their microbiota-regulating functions. Analytical studies indicate that polysaccharides with distinct structures can be recognized and degraded by specific carbohydrate-active enzymes (CAZymes) in the gut microorganisms, leading to the targeted enrichment of beneficial genera such as Roseburia, Lactobacillus, and Akkermansia, while simultaneously suppressing pro-inflammatory genera such as Escherichia–Shigella and Helicobacter. This structure-dependent microbial remodeling ultimately enhances the production of key metabolites and exerts comprehensive therapeutic effects, including repair of the intestinal barrier, suppression of excessive inflammation, and alleviation of oxidative stress, via activation of signaling pathways such as AMP-activated protein kinase (AMPK) and nuclear factor erythroid 2-related factor 2 (Nrf2) and inhibition of pathways such as nuclear factor kappa-B (NF-κB). By exploring the paradigm of “Structure–Decoding–Conversion–Effect” based on precise microecological regulation of polysaccharide structures, this paper provides a crucial theoretical foundation and design strategy for developing targeted microecological interventions. Full article

Resveratrol (RSV), a bioactive polyphenol, has emerged as a pleiotropic modulator within the integrated pathophysiology of cardiovascular disease (CVD) across the life course. Effective CVD management requires a transition from organ-centric frameworks to systems-level models that acknowledge dynamic crosstalk among metabolic, renal, and cardiovascular networks. Oxidative stress constitutes a central unifying axis in this interconnected biology, propagating cross-organ injury from early developmental stages onward. Mechanistically, RSV acts as a redox-responsive gene regulator by activating the Nrf2–ARE pathway, restoring nitric oxide bioavailability, and orchestrating SIRT1, AMPK, and NF-κB signaling to recalibrate mitochondrial function, inflammatory tone, and endothelial integrity. Within the Developmental Origins of Health and Disease (DOHaD) paradigm, RSV exhibits reprogramming potential that attenuates the intergenerational transmission of hypertension, kidney disease, and metabolic dysfunction. Although clinical translation is constrained by limited bioavailability and rapid metabolism, advanced delivery systems and artificial intelligence-enabled optimization strategies provide promising avenues to enhance therapeutic precision and scalability. This narrative review integrates mechanistic and translational insights to position RSV as a systems-oriented life-course intervention with sustained and intergenerational relevance in CVD. Full article

Tumor oxygenation is a key determinant of cancer biology and treatment response, correlating with angiogenesis, recurrence, and malignant progression. Hypoxia is a defining feature of glioblastoma (GBM) and adult diffuse gliomas, generating low-oxygen niches that promote invasion, stem-like states, immune suppression, and resistance to radiotherapy and temozolomide, contributing to poor outcomes. Measuring tissue partial pressure of oxygen (pO₂) and mapping its spatial heterogeneity can, therefore, inform mechanistic understanding and therapeutic development, including hypoxia-activated prodrugs, hypoxia-responsive gene therapy, and optimized radiotherapy planning. Although direct pO₂ assessment is challenging, invasive probes and multimodal imaging can characterize regional hypoxia pre-operatively, support patient stratification, monitor treatment effects, and improve outcome prediction. This review summarizes oxygen dynamics in GBM; analyzes causes of hypoxia (rapid growth outpacing supply, diffusion-limited hypoxia, and abnormal/chaotic vasculature); compares methods to quantify oxygenation from direct measurements to noninvasive imaging surrogates; and evaluates preclinical and clinical strategies that target hypoxia to enhance standard therapy, including barriers to translation. We further integrate oxygenation with cell signaling and redox biology: oxygen gradients are transduced via hypoxia-inducible factor programs and redox-sensitive pathways (NRF2/KEAP1, NOX-derived ROS, nitric oxide/S-nitrosylation, and sulfur metabolic routes), shaping mesenchymal-like transitions and cell-death programs such as ferroptosis. Framing oxygenation as both a microenvironmental and redox-signaling variable positions oxygen imaging as an entry point to biomarker-guided therapies that exploit oxidative vulnerabilities. Full article

This narrative review proposes the ‘Brain Health Triad’ as a novel integrative framework for neurorehabilitation and cognitive enhancement, built upon three interdependent biological pillars: neurostimulation, neurotrophy, and neuroprotection. We illustrate how the synergistic interplay between a ‘core triad’ composed of Hericium erinaceus, Bacopa monnieri, and L-Theanine targets these pillars with high specificity. Hericium erinaceus fosters neurotrophy by inducing Nerve Growth Factor (NGF) and Brain-derived neurotrophic factor (BDNF) synthesis through erinacines and hericenones; Bacopa monnieri complements this by enhancing neurostimulation and synaptic plasticity via bacosides; and L-Theanine regulates neurotransmitter balance and alpha-wave activity to stabilize the neural signaling environment. This core architecture is further reinforced by adjunctive nootropic clusters—including withanolides, ginkgolides, citicoline, cordycepin, macamides, and fulvic acid—which provide essential support for mitochondrial resilience and the mitigation of amyloid-β and tau toxicities. By synthesizing molecular evidence from the BDNF/TrkB/CREB signaling axis and the Nrf2/NF-κB homeostatic switch, we demonstrate that this multi-target strategy offers a more robust path to neuronal resilience than traditional single-target approaches. We conclude that this integrated model provides a solid framework for future clinical applications in the management of age-related cognitive decline and neurodegenerative diseases. Full article

Vaccinium bracteatum Thunb. leaves (VBTL), a traditional medicinal plant historically consumed as food in certain regions of China, have been documented to possess potent in vitro antioxidant activity. However, its in vivo anti-aging effects and underlying mechanisms remain to be fully elucidated. Therefore, this study aimed to evaluate its anti-aging efficacy to support its potential value as a functional food constituent for healthy aging. Anti-aging efficacy was systematically assessed using D-galactose-induced aging mice, a Caenorhabditis elegans model, and an H₂O₂-induced cellular senescence model. Key active constituents were identified via untargeted metabolomics. In D-galactose-induced aging mice, VBTL extracts effectively ameliorated oxidative stress, significantly increasing the activities of endogenous antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT), while reducing malondialdehyde (MDA) levels. In Caenorhabditis elegans, VBTL extended lifespan, reduced lipofuscin accumulation, and demonstrated no reproductive toxicity. Untargeted metabolomics identified xanthotoxol as a key active constituent, which was then selected for mechanistic investigation. In a cellular senescence model, xanthotoxol alleviated H₂O₂-induced oxidative stress, significantly enhanced SOD activity, reduced reactive oxygen species (ROS) and MDA levels, inhibited senescence-associated β-galactosidase (SA-β-gal) activity and the expression of senescence-associated secretory phenotype (SASP) factors (IL-6, MMP1, MMP3), and downregulated the expression of genes in the P53/P21/P16 signaling pathway. Mechanistically, xanthotoxol activated the Nrf2 signaling pathway, promoting the expression of its downstream targets heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). This study demonstrates that VBTL and its active compound xanthotoxol exert anti-aging effects across multiple models by modulating the Nrf2 pathway, providing both theoretical and experimental foundations for developing VBTL as a novel, safe, and effective natural ingredient in anti-aging functional foods. Full article

Antioxidant peptides show significant activity and can be developed into functional foods for treating chronic diseases. Cigarette smoke components can cause damage or even apoptosis of lung cells, eventually leading to chronic lung diseases. Therefore, this study aimed to investigate the protective effects and mechanisms of Skipjack tuna peptides against in vitro cigarette smoke extract (CSE)-induced chronic obstructive pulmonary disease (COPD). The results demonstrated that tuna peptides DVGRG (S1), PHPR (S5), GRVPR (S6), and SVTEV (S7) significantly enhanced the activities of SOD, CAT, and GSH-Px by upregulating the mRNA transcription levels of Keap1 and Nrf2, consequently reducing ROS and MDA levels in CSE-induced COPD model of MLE-12 cells. Molecular docking analysis revealed that S1, S6, and S7 competitively inhibited the Keap1-Nrf2 interaction by binding to the Kelch domain of Keap1, whereas S5 operated through a non-competitive mechanism. These peptides also downregulated p65 mRNA expression and upregulated IκBα mRNA expression, leading to a significant reduction in inflammatory cytokines of IL-1β, IL-6, and TNF-α, thereby alleviating inflammatory responses. Furthermore, these peptides significantly inhibited CSE-induced apoptosis by restoring mitochondrial membrane potential and upregulating the Bcl-2/Bax ratio. Additionally, S1, S5, S6, and S7 promoted MLE-12 cell migration in a concentration-dependent manner, suggesting a role in lung epithelial repair and regeneration. In conclusion, tuna peptides S1, S5, S6, and S7 exert antioxidant, anti-inflammatory, anti-apoptotic, and cell migration-promoting effects through the regulation of the Keap1/Nrf2 and NF-κB signaling pathways, as well as Bcl-2/Bax apoptotic balance, providing a promising strategy for mitigating CSE-induced lung injury. Full article

Liver diseases, including fatty liver, hepatitis, and cirrhosis, remain major global health challenges due to their disruption of metabolic homeostasis and detoxification processes. Redox imbalance plays a central role in liver disease progression by promoting inflammation, hepatic stellate cell activation, mitochondrial dysfunction, and fibrogenesis. Although flavonoids have historically been considered direct reactive oxygen species (ROS) scavengers, emerging evidence indicates that their biological effect at physiological concentrations are primarily mediated through modulation of intracellular redox signalling rather than simple radical neutralisation. This review highlights flavonoids as redox-modulating agents capable of restoring hepatic redox homeostasis through coordinated regulation of molecular pathways. Mechanistically, flavonoids activate the Nrf2-Keap1 axis to enhance endogenous antioxidant defences, including heme oxygenase-1 and glutathione biosynthesis enzyme, while suppressing NF-κB-mediated pro-inflammatory signalling and modulating MAPK and PI3K/Akt pathways. They also regulate mitochondrial redox balance, supporting mitophagy, metabolic adaptation, and cellular resilience to oxidative stress. In addition, flavonoid biotransformation by the gut microbiome improves intestinal barrier integrity, reduces endotoxin-driven hepatic inflammation, and contributes to gut–liver crosstalk. Collectively, these mechanisms position dietary flavonoids as multi-target redox modulators with promising therapeutic potential in chronic liver disease, although further studies are needed to improve their bioavailability and clinical translation. Full article

Introduction: Oxidative stress and inflammation are major factors linked to obesity and metabolic dysfunction, leading to a significantly higher risk of related diseases. Atorvastatin and liraglutide possess lipid-lowering, antioxidant, and anti-inflammatory effects that could synergistically improve obesity-related perturbations through modulation of the Nrf2/HO-1 signaling pathway. Methodology: We assessed liraglutide’s pharmacological potential in extending atorvastatin’s benefit on obesity, hyperlipidemia, and fatty liver in rats fed a high-fat diet (HFD) for 12 weeks. We specifically evaluated the effects of liraglutide treatment on atorvastatin-induced anti-inflammatory and antioxidant mechanisms, with a particular focus on Nrf2/HO 1 modulation in adipose and hepatic tissue. In silico analyses, including molecular docking and AlphaFold- Multimer modeling, evaluated the binding affinities of atorvastatin and liraglutide to Nrf2 and HO 1. Results: Compared to ND, the HFD-fed rats had a significantly higher final body weight (362.4 ± 12.7 g vs. 245.6 ± 9.8 g in ND, p < 0.05). There was a marked increase in serum total cholesterol (178.6 ± 9.2 mg/dL vs. 98.3 ± 6.4), fasting glucose (340.1 ± 8.2 mg/dL vs. 82.3 ± 3.1), HbA1c (7.8 ± 0.3 vs. 4.5 ± 0.2), and hepatic COX-2 expression (99.9 ± 6.3 vs 19.6 ± 2.4). The oxidative stress markers were also disturbed, as indicated by SOD (42.5 ± 3.1 vs. 95.2 ± 4.6 U/mg protein), GSH (18.3 ± 1.5 vs. 42.7 ± 2.8 nmol/mg), and p62 (0.005 ± 0.001 vs. 0.125 ± 0.01). Atorvastatin lowered cholesterol (121.2 ± 7.5 mg/dL), COX-2 (61.3 ± 3.3), and body weight (301.7 ± 11.5 g) compared to HFD. Meanwhile, liraglutide caused a greater reduction in body weight (268.5 ± 10.3 g), glucose (112.5 ± 6.7 mg/dL), and COX-2 (42.2 ± 2.9) than atorvastatin. The combination therapy produced the most significant effects, returning body weight (253.6 ± 9.1 g) to baseline, normalizing glucose and lipids, reducing COX-2 to 22.9 ± 2.0, and reactivating the Nrf2/HO-1 pathway, as shown by increased HO-1 expression and the restoration of p62 levels (0.078 ± 0.004). In silico analyses suggest that atorvastatin favorably binds to Nrf2 and HO-1, while liraglutide interacts with structurally relevant interfaces on these proteins, providing a mechanistic basis for their complementary antioxidant and cytoprotective effects. Conclusions: Our findings support targeting the Nrf2/HO-1 signaling pathway as a potential therapy for reversing hyperlipidemia and preventing mediators of inflammation and oxidative stress damage in the liver tissue. The evidence of increased efficacy observed with the combined atorvastatin and liraglutide supports a potential novel understanding of the complementary effects of atorvastatin and liraglutide. This finding requires further investigation to elucidate the combination’s therapeutic advantages in treating metabolic disorder scenarios. Full article

Glutinous rice huangjiu, a non-distilled wine variety unique to China, is rich in nutrients. However, systematic research on the differences in its non-volatile functional components remains scarce, despite these variations being key factors influencing its antioxidant effects. This study employed non-targeted metabolomics to systematically analyze the non-volatile metabolite profiles of 16 glutinous rice huangjiu brands, identifying 1450 metabolites. An alcohol-induced hepatocyte injury model was established, combining cell viability and reactive oxygen species (ROS) level assays to screen for samples (G10 and G11) exhibiting significant efficacy across varying alcohol concentrations. Differential metabolite analysis further identified key bioactive compounds including L-proline, dihydroferulic acid, chalcones, and multiple phenolic derivatives. Using molecular docking technology, we preliminarily revealed that these components may exert antioxidant and hepatoprotective effects either by directly scavenging free radicals or indirectly through mechanisms such as participating in glutathione metabolism and regulating the KEAP1-Nrf2 signaling pathway. This study elucidates the differences among glutinous rice huangjiu at the metabolomic and cellular model levels, providing a scientific basis for evaluating the health benefits and developing new products of huangjiu. Full article

Adolescence is a metabolically vulnerable period, during which rapid physiological maturation coincides with the dynamic remodelling of the gut microbiome. This narrative review summarises evidence from 2015 to 2025 to clarify how disturbances to the gut–liver axis driven by dysbiosis contribute to the development and progression of non-alcoholic fatty liver disease (NAFLD) in young people. Based on a systematic search of the databases PubMed, Scopus and Web of Science, we outline the basis of bidirectional communication between the gut and liver and emphasise how microbial imbalance alters the handling of lipids in the liver by enhancing de novo lipogenesis, impairing fatty acid oxidation and disrupting AMPK signalling and mitochondrial function. Consistent findings from clinical and experimental studies show that adolescents with NAFLD exhibit reduced microbial diversity, the enrichment of ethanol- and LPS-producing taxa, and altered short-chain fatty acid profiles. Each of these is associated with hepatic inflammation and metabolic reprogramming. Microbial molecules, including LPS, secondary bile acids and branched-chain amino acid metabolites, activate TLR4–NF-κB pathways, promote Kupffer cell activation and intensify oxidative stress. These mechanisms intersect with factors specific to adolescence, such as increased adiposity, hormonal shifts and diet-induced metabolic strain. Dietary patterns emerge as key modulators of these processes. Westernised diets promote dysbiosis and endotoxemia, whereas Mediterranean, fibre-rich and plant-based diets enhance SCFA production, strengthen epithelial integrity and modulate adiponectin-dependent hepatic metabolism. Micronutrient-sensitive epigenetic regulation, particularly that involving folate, choline and polyphenols, also plays a role in shaping lipid homeostasis and inflammatory tone. We also highlight emerging evidence that the activation of cytoprotective pathways, especially Nrf2, is dependent on lifestyle factors and links antioxidant-rich functional foods and physical activity to improved mitochondrial resilience and microbiome stability. We evaluate therapies targeting the microbiome, including probiotics, prebiotics, synbiotics and postbiotics, which reduce endotoxemia, restore microbial balance and complement dietary strategies. Thus, these findings emphasise the importance of age-specific, mechanistically informed interventions that integrate diet quality, microbial ecology, and the molecular pathways that govern metabolic health in adolescents with NAFLD. Full article

Chronic liver diseases, including fibrosis and hepatocellular carcinoma (HCC), are primarily driven by oxidative stress, yet traditional antioxidant therapies often lack the specificity and efficacy required for clinical success. This review evaluates the emerging therapeutic potential of two atypical globins, cytoglobin (CYGB) and neuroglobin (NGB), exploring their unique hexacoordinated heme structures that enable potent reactive oxygen and nitrogen species (ROS/RNS) scavenging and redox-regulated signaling. We summarize a broad range of in vitro and in vivo evidence demonstrating that these globins deactivate hepatic stellate cells, reduce extracellular matrix accumulation, and function as tumor suppressors by modulating pathways such as Raf/MEK/ERK and NRF2. In human cohorts, CYGB expression levels inversely correlate with the progression of Metabolic Dysfunction-Associated Steatohepatitis (MASH) and HCC, highlighting its potential as a clinical biomarker. Furthermore, recombinant protein therapies involving CYGB and NGB show promise in promoting collagen degradation and inhibiting malignant transformation. We conclude that CYGB and NGB represent sophisticated catalytic redox regulators that offer a novel therapeutic paradigm for restoring redox homeostasis. While delivery and pharmacokinetic barriers remain, these globins are highly promising candidates for first-in-class biologics in hepatology. Full article

Silymarin (Silybum marianum (L.) Gaertn. extract) is a widely used botanical for liver disease, yet clinical results remain inconsistent. Most mechanistic work uses supraphysiological aglycones, whereas humans are exposed predominantly to phase II conjugates that are strongly protein-bound and routed by transporters toward bile and the intestinal mucosa. We reframe silymarin activity through a spatial pharmacology lens, proposing three post-intake windows: early (0–2 h) conjugate-dominant exposure with localised β-glucuronidase-mediated reactivation; intermediate (2–8 h) enterohepatic recirculation pulses; and late (8–48 h) microbial catabolite contributions. Each window engages distinct signalling modules—Keap1/NRF2, NF-κB, and AMPK-mTOR-TFEB—via transient redox events (quinone cycling, micro-H₂O₂ relays) and proteostatic remodelling (autophagy/mitophagy). We synthesise human pharmacokinetic and clinical evidence—with emphasis on MASLD and alcohol-associated liver disease—and show how formulation, meal timing, and microbiome metabotype determine which windows are engaged. Finally, we propose minimum reporting standards and falsifiable hypotheses to reduce between-study heterogeneity and enable precision use of silymarin. Full article

Skin aging and wound healing are the result of intricate and interconnected processes involving chronic inflammation, oxidative stress, cellular senescence and extracellular matrix degradation. Mesenchymal stem cell (MSC)-derived exosomes are rich in bioactive components, particularly microRNAs (miRNAs), which play a crucial role in regulating gene expression and key signaling pathways critical for maintaining skin homeostasis. This article reviews the current evidence regarding the roles of MSC-derived exosomal miRNAs (MSC-Exo-miRNAs) in cutaneous repair and rejuvenation. Specific exosomal miRNAs are analyzed for their ability to modulate inflammatory responses, promote fibroblast proliferation and collagen synthesis, enhance angiogenesis, and facilitate keratinocyte migration and re-epithelialization. Their roles in regulating key signaling pathways are discussed in the context of skin regeneration and aging, including nuclear factor-κB (NF-κB), PI3K/Akt, TGF-β/Smad, Wnt/β-catenin, and nuclear factor erythroid 2-related factor 2 (Nrf2). Additionally, emerging engineering strategies aimed at optimizing miRNA cargo loading, improving delivery efficiency, and advancing clinical translation are highlighted. Overall, MSC-Exo-miRNAs represent a promising cell-free therapeutic strategy for skin repair and rejuvenation; however, further mechanistic investigations and rigorous clinical studies are necessary to fully realize their translational potential. Full article

Background: Endocrine therapy with tamoxifen remains a cornerstone in the treatment of estrogen receptor-positive (ER+) breast cancer; however, the emergence of resistance to its active metabolites, 4-hydroxytamoxifen (4-OHTAM) and Endoxifen, represents a major clinical limitation. Increasing evidence suggests that drug efflux transporters, redox-adaptive signaling, and translational control mechanisms may converge to promote chemoresistance. This study aimed to investigate the coordinated expression patterns of ABCC transporters, the eukaryotic initiation factor 4F (eIF4F) complex, and NRF2 signaling in tamoxifen-metabolite-resistant MCF-7 breast cancer cells. Methods: MCF-7 cell variants resistant to 4-OHTAM (Variant B) or Endoxifen (Variant C) were established through prolonged drug exposure. Cytotoxicity assays assessed cellular viability and chemoresistance. Protein expression and molecular interactions were analyzed using Western blotting and co-immunoprecipitation. Flow cytometry was employed to evaluate transporter-associated fluorescence intensity. In silico molecular docking was performed to estimate the binding affinity of tamoxifen metabolites to ABCC transporters. Results: Endoxifen-resistant cells exhibited the most pronounced chemoresistant phenotype. Analysis of ABCC transporters revealed modest but consistent increases in fluorescence intensity across resistant variants; however, these differences did not reach statistical significance. Dysregulation of the eIF4F complex was observed, with increased eIF4E and reduced eIF4A levels, suggesting altered translational control associated with resistant phenotypes. Increased NRF2 protein expression was detected in resistant variants, consistent with enhanced redox-adaptive capacity. Analysis of ABCC transporters revealed modest but consistent increases in fluorescence intensity across resistant variants; however, these differences did not reach statistical significance. Molecular docking demonstrated strong binding affinity between Endoxifen and ABCC2, supporting a potential role for transporter-mediated efflux. Conclusions: Tamoxifen-metabolite resistance in ER+ breast cancer is associated with coordinated trends in ABCC transporter-associated signals, altered eIF4F complex expression, and sustained NRF2 signaling. These findings suggest the presence of a multifactorial adaptive network that may contribute to endocrine resistance. Targeting components of this network warrants further mechanistic investigation. Full article

Styela plicata, an edible ascidian rich in diverse bioactive constituents, represents a promising source of marine natural products for therapeutic discovery. Here, bioactive components from a 95% ethanol extract of S. plicata (ESP) were characterized by HPLC-MS/MS, showing that the major constituents were oxygenated small molecules dominated by fatty acyls and carboxylic acid derivatives. In a mouse model of alcohol-induced liver injury, H-ESP treatment (300 mg/kg) significantly reduced serum levels of AST, ALT, and TG (p < 0.01), while effectively ameliorating pathological changes in liver tissue, reducing lipid accumulation and inflammatory responses. Transcriptome sequencing (H-ESP vs. model group) identified 1097 differentially expressed genes (172 upregulated and 925 downregulated), and KEGG analysis highlighted significant enrichment of the Toll-like receptor signaling pathway. ESP modulated hepatic metabolite expression, suppressed inflammation via TLR-4/NF-κB pathway inhibition, and boosted antioxidant defenses by activating Nrf2/HO-1 signaling, which was further confirmed by RT-qPCR and immunohistochemistry. ESP increased intestinal SCFAs (acetate, propionate, isobutyrate; p < 0.05), improved α-diversity and the Firmicutes/Bacteroidetes ratio, reversed shifts in Lactobacillus and Bifidobacterium, and partly restored Odoribacter, supporting a gut–liver axis mechanism. Overall, these findings indicate that ESP exerts hepatoprotective effects by modulating the gut–liver axis, and they provide insights for developing natural therapeutics against alcoholic liver disease. Full article