Search Results (1,054)

Interest in sustainable protein sources is increasing because of environmental concerns related to animal agriculture and the growing burden of chronic non-communicable diseases. Plant-derived bioactive peptides (PDBAPs), amino acid sequences released from dietary proteins, are gaining attention because experimental studies have reported activities relevant to hypertension, type 2 diabetes, and cancer-associated processes. Although animal proteins have long been major sources of bioactive peptides, plant materials may offer advantages such as abundance, potentially lower production costs, and broad cultural acceptability; however, these benefits depend on the source, processing requirements, safety, and scale-up conditions. This review integrates plant sources, processing technologies, proposed mechanisms of action, and translational barriers. Current research covers traditional sources, including legumes and cereals, as well as agro-industrial by-products such as potato peels, spent coffee grounds, and broccoli stems. Modern processing strategies increasingly combine enzymatic hydrolysis or microbial fermentation with process-assisting technologies, including ultrasound treatment and subcritical water processing, to improve protein recovery or peptide release. Recent studies also examine proposed mechanisms of PDBAP activity, including Keap1/Nrf2-associated responses and inhibition of enzymes involved in metabolic disorders. Evidence is interpreted according to the stage of experimental validation, from computational prediction and cell-free assays to cellular, animal, and human studies. Key challenges remain, particularly digestive instability, uncertain systemic bioavailability, bitterness, safety standardization, and limited human clinical evidence. Future work should prioritize standardized extraction and analytical methods, optimized delivery systems, and robust clinical trials. Full article

Precision nutrigenomics requires a diet–microbiome–host perspective because microorganisms can transform feed substrates, generate bioactive metabolites, compete with pathogens, and modify intestinal and systemic gene regulation. This structured narrative review synthesizes representative controlled feeding trials, transcriptomic and targeted gene-expression studies, microbiome analyses, and complementary multi-omic evidence concerning dietary regulations in cultured finfish. The available evidence is concentrated particularly on soybean-derived proteins, lipid-source replacements, selected amino acids and micronutrients, functional additives, probiotics, and fermented ingredients in a limited range of cultured finfish species; therefore, the synthesis is not intended to provide exhaustive coverage of every dietary intervention or finfish taxon. Recurrent host responses involve intestinal inflammation and barrier integrity, nutrient transport, lipid and bile-acid metabolism, long-chain polyunsaturated fatty-acid biosynthesis, targets of rapamycin/insulin-like growth factor (TOR/IGF) signaling, and nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) antioxidant defense. The expanded microorganism-centered synthesis shows that dietary effects depend on microbial niche, substrate availability, community succession, metabolite production, and strain-specific probiotic or pathobiont activity. Lactic-acid bacteria, Bacillus-associated interventions, butyrate-generating strategies, fermented ingredients, and microbial biomass may support digestion, immune balance, and disease resistance, but taxonomic shifts alone do not demonstrate functional benefit. Current evidence is limited by extensive reliance on 16S ribosomal RNA (16S rRNA) relative-abundance data, inconsistent digesta-versus-mucosa sampling, inadequate feed and water controls, and weak causal validation. Future precision aquafeed studies should combine host transcriptomics with absolute microbial quantification, shotgun metagenomics, metatranscriptomics, metabolomics, culturomics, histology, and pathogen challenge. Integrating microbial function with host phenotype can improve sustainable feed design, intestinal health, and resilience. Full article

Background Aflatoxin B1 (AFB1) is a potent hepatotoxic mycotoxin that induces severe oxidative liver damage. Kaempferol (Kae), a natural flavonoid with known antioxidant properties, has unclear protective effects against AFB1-induced hepatotoxicity. This study aimed to evaluate the hepatoprotective role of Kae and elucidate its underlying mechanism using integrated in vivo, in silico, and in vitro approaches. Methods: In vivo (AFB1-challenged mice) and in vitro (hepatocyte) models were employed, combined with network pharmacology, molecular docking, and molecular dynamics simulations. Liver injury indices, oxidative stress markers, antioxidant enzyme activities, and Keap1/Nrf2 pathway expression were assessed. Results: Kae co-treatment reversed AFB1-induced increases in liver index, serum ALT/AST, histological lesions, and reduced antioxidant capacity in mice. Network pharmacology revealed 59 common targets, with NFE2L2 (Nrf2) as a key node. In vitro, Kae pretreatment significantly lowered AFB1-elevated ROS, MDA, ALT, and AST, while restoring GSH and total antioxidant capacity. Kae reversed AFB1-induced Keap1 upregulation and Nrf2 downregulation, and increased mRNA levels of HO-1, NQO1, SOD, GPX1, and CAT. Molecular docking and simulation showed stable Kae–Keap1 binding (−9.6 kcal/mol) with critical hydrogen bonds (VAL-606) and van der Waals contacts. Conclusions: Kae directly binds Keap1, activates Nrf2 signaling, upregulates antioxidant gene expression, and mitigates AFB1-induced oxidative liver injury. These findings support Kae as a promising candidate for preventing AFB1 hepatotoxicity. Full article

Cold exposure severely impairs intestinal homeostasis and growth in young lambs. This study investigated the protective effects of Artemisia argyi polysaccharides (AAPs) on intestinal health in cold-exposed suckling lambs. Twenty-four 7-day-old lambs were randomly allocated to receive a milk replacer supplemented with 0 (Control, C), 0.5 (Low-dose, LA), 1.0 (Medium-dose, MA), or 2.0 g/kg (High-dose, HA) of AAPs for 14 days under cold conditions (−8 °C to −5 °C). The results showed that the MA group significantly increased ADG and decreased the F/G (p < 0.05) compared to the control. Both LA and MA groups significantly improved EE and Ca digestibility, while the MA group further increased CP and P digestibility (p < 0.05). The LA group enhanced jejunal chymotrypsin and lipase activities, whereas the MA group elevated chymotrypsin, lipase, and α-amylase activities (p < 0.05). Additionally, both LA and MA upregulated Nrf2 mRNA expression (and downregulated Keap1 mRNA expression in the jejunum), suggesting activation of the Nrf2/Keap1 pathway; the MA group significantly upregulated CAT, GSH-Px, and SOD1 mRNA expressions, enhanced SOD and CAT activities, and reduced colonic MDA content (p < 0.05). The MA group also significantly elevated the VH/CD across the small intestine, upregulated tight junction genes (Claudin-1 and Claudin-4 in jejunum; ZO-1 and Claudin-1 in colon), and decreased serum D-LA and DAO levels (p < 0.05). Cecal microbiota sequencing showed that AAPs enriched the relative abundance of Anaerofilum and reduced Akkermansia. In conclusion, 1.0 g/kg AAP supplementation effectively mitigates intestinal oxidative stress, improves barrier integrity, and modulates gut microbiota, thereby enhancing nutrient digestibility and growth performance in cold-stressed suckling lambs. Full article

Oxidative stress plays an important role in systemic lupus erythematosus (SLE). To elucidate whether it is already present in early phases, we investigate oxidative stress-related genes in incomplete SLE (iSLE) and quiescent SLE (qSLE, inactive disease), as well as the effect of nuclear factor erythroid-derived 2-like 2 (NRF2) activators on NRF2-related genes in peripheral blood mononuclear cells (PBMCs) and HaCaT keratinocytes. In total, 28 qSLE patients, 29 iSLE patients and 21 age- and sex-matched healthy controls (HCs) were included. Serum free thiols, reactive oxygen species (ROS) levels and NRF2-related antioxidant gene expression were measured. Furthermore, PBMCs and HaCaT keratinocytes were treated with the NRF2 activators sulforaphane (SFN) and dimethyl fumarate (DMF) in vitro to assess expression of antioxidant genes. Finally, NRF2 and Heme oxygenase-1 (HMOX1) proteins in non-sun-exposed skin sections were assessed. Thiols were significantly lower in qSLE patients compared to HCs. In whole blood, Kelch-like ECH-associating protein 1 (KEAP1) and catalase (CAT) mRNA levels were significantly reduced in iSLE and qSLE. Treatment with SFN or DMF in PBMCs upregulated HMOX1 and NAD(P)H quinone dehydrogenase-1 (NQO1) mRNA expression and downregulated CAT expression. In HaCaT cells, mRNA expression of HMOX1, NQO1 and thioredoxin was upregulated. There were no differences in protein expression of NRF2 and HMOX1 in skin tissues. In conclusion, in qSLE patients, oxidative stress is elevated, while antioxidant capacity is decreased. A similar trend, although not significant, is seen in iSLE patients, which indicates that redox imbalances are already present in early phases, but not as obvious as in established SLE. NRF2 activators upregulate antioxidant gene expression in PBMCs and HaCaT cells, highlighting their potential role to modulate oxidative stress pathways in SLE. Full article

Objective: To evaluate whether human adipose-derived mesenchymal stem cells (ADSCs) protect against ᴅ-galactose (ᴅ-gal)-induced aging-like testicular injury and to investigate the involvement of the Keap1/Nrf2 pathway and NLRP3-associated pyroptosis. Methods: A mouse model of aging-like testicular injury was established by subcutaneous administration of ᴅ-gal for 8 weeks, followed by tail vein injection of ADSCs. Testicular morphology, blood–testis barrier (BTB) integrity, and senescence-associated markers (p16, p21) were assessed. In vitro, TM4 Sertoli cells were used to establish a senescence model and Tranwell co-cultured with ADSCs. Oxidative stress, inflammatory responses, and pyroptosis-related markers were evaluated using biochemical assays, immunofluorescence, Western blotting, and RT-qPCR. The involvement of the Keap1/Nrf2-NLRP3 axis was further examined using pharmacological inhibitors. Results: ADSC treatment significantly alleviated ᴅ-gal-induced testicular atrophy and histopathological injury, accompanied by reduced expression of the senescence markers p16 and p21 and partial restoration of BTB-related structures. ADSCs also attenuated oxidative stress, as evidenced by decreased ROS and MDA levels, increased SOD activity, and enhanced expression of Nrf2 and its downstream antioxidant targets, including HO-1 and NQO1. In parallel, ADSC administration suppressed NLRP3 activation, reduced caspase-1 cleavage, and lowered the expression of pro-inflammatory cytokines. In TM4 cells, inhibition of Nrf2 weakened the protective effects of ADSCs and was accompanied by reactivation of NLRP3-associated signaling, whereas inhibition of NLRP3 attenuated senescence- and inflammation-related changes without restoring Nrf2 activity. Conclusions: ADSCs alleviate ᴅ-gal-induced aging-like testicular injury, at least in part, by restoring redox balance, preserving BTB-associated structure, and suppressing NLRP3-associated pyroptosis through the Keap1/Nrf2 pathway. These findings suggest that ADSC-based therapy may represent a promising strategy for age-related male reproductive dysfunction, while further studies using genetic models and functional fertility endpoints are needed to confirm causality and translational relevance. Full article

The largemouth bass (Micropterus salmoides) is an important freshwater aquaculture species in China, but the increasing incidence of disease under intensive production conditions has become a major constraint on its sustainable development. This study evaluated the effects of dietary Eucommia ulmoides extract (ELE) supplementation on growth performance, immune and antioxidant responses, intestinal health, gut microbiota, and resistance to largemouth bass virus (LMBV) in juvenile largemouth bass. During a 56-day feeding trial, fish with an initial body weight of 13.14 ± 0.11 g were fed diets containing 0, 30, 60, 90, 120, or 150 mg ELE/kg, with three replicate nets per treatment. Dietary supplementation with 60–90 mg/kg ELE significantly increased weight gain rate (p < 0.05). ELE also improved selected serum antioxidant and immune indices, with the most pronounced responses generally observed at intermediate supplementation levels. In the intestine, the increased Nrf2 and decreased Keap1 mRNA expression were consistent with the potential involvement of Keap1/Nrf2-related redox regulation. ELE also modulated the expression of inflammation- and apoptosis-related genes and increased the expression of selected tight-junction-related genes, suggesting a potential contribution to intestinal inflammatory regulation and barrier maintenance. In addition, ELE supplementation was associated with shifts in bacterial diversity and community composition, although the responses varied among supplementation levels. Following LMBV challenge, the 90 mg/kg group showed the highest observed protection, accompanied by lower splenic expression of the largemouth bass virus major capsid protein (LMBV-MCP) and proinflammatory gene expression, suggesting reduced viral activity and host inflammatory responses. Overall, dietary supplementation with 60–90 mg/kg ELE elicited the most favorable combined responses and may contribute to the regulation of growth, antioxidant and immune status, and intestinal homeostasis in largemouth bass. Full article

Paracetamol overdose is a major cause of drug-induced acute kidney injury (AKI), driven by oxidative stress, inflammation, mitochondrial dysfunction, and tubular apoptosis. This study evaluated the nephroprotective efficacy of pH-responsive carboxymethyl cellulose-encapsulated hesperidin-stabilized selenium nanoparticles (CMC@HES-SeNPs) against paracetamol-induced AKI in rats. HES-SeNPs were synthesized using hesperidin as a reducing/stabilizing agent and further coated with CMC. The nanoparticles were characterized by DLS, zeta potential, TEM, and in vitro release kinetics at pH 7.4 and 5.5. 42 Male rats were allocated into groups of control, paracetamol (PAR), paracetamol treated with sodium selenite (PAR&Se), paracetamol treated with hesperidin (PAR&HES), paracetamol treated with hesperidin-loaded selenium nanoparticles (PAR&HES-SeNPs), and paracetamol treated with carboxy methyl cellulose-coated hesperidin-loaded selenium nanoparticles (PAR&CMC@HES-SeNPs). Paracetamol markedly impaired renal function, increasing creatinine, urea, NGAL, KIM-1, and cystatin-C, and induced oxidative/nitrosative stress, Keap-1 upregulation, Nrf2 suppression, NF-κB-mediated inflammation, cytochrome-C release, Bax/Bcl-2 imbalance, caspase-3 activation, and severe renal histopathological injury. CMC@HES-SeNPs displayed sustained, pH-enhanced hesperidin release and produced the strongest renoprotective response, restoring renal biomarkers, associated with restoration of Keap-1/Nrf2-related antioxidant markers, reduction in TNF-α, IL-6, NF-κB, and caspase-3, increased IL-10, and preservation of renal architecture. Collectively, these results indicate that CMC@HES-SeNPs represent a promising multifunctional nanoplatform for mitigating paracetamol-induced AKI in association with coordinated modulation of redox, inflammatory, and mitochondrial apoptotic markers, and highlight CMC encapsulation as a rational strategy to enhance selenium–flavonoid delivery and efficacy for future drug-induced AKI management and translation. Full article

Despite the traditional application of Sophora moorcroftiana seeds (SMS) in Tibetan medicine for heat-clearing, damp-drying, anti-inflammatory and detoxifying properties, the anti-inflammatory mechanisms of SMS remain insufficiently understood and warrant systematic investigation. This study evaluated the protective effects of an ethanolic SMS extract against lipopolysaccharide (LPS)-induced oxidative stress and inflammation in RAW 264.7 macrophages, with emphasis on the p62/Keap1/Nrf2 signaling pathway. In vitro, the extract exhibited significant DPPH, ABTS and ·OH radical scavenging activities, as well as ferric-reducing antioxidant power, in a clear concentration dependent manner. An inflammatory model was established by stimulating RAW 264.7 cells with LPS, followed by treatment with graded concentrations of the ethanolic SMS extract. The extract significantly reduced LPS-induced nitric oxide production and decreased the secretion of TNF-α, IL-6 and IL-1β, while suppressing iNOS and COX-2 expression at both mRNA and protein levels. In parallel, the extract alleviated oxidative stress, as evidenced by reduced intracellular reactive oxygen species (ROS) and MDA levels, increased antioxidant defenses including SOD, GSH and CAT, and decreased LDH release. At the protein-expression level, SMS treatment was accompanied by differential changes in p62, Keap1, total Nrf2 and HO-1 expression, suggesting that its effects may involve regulatory processes associated with cellular stress and antioxidant defense. Collectively, the ethanolic extract of SMS attenuated LPS-induced inflammatory and oxidative stress responses in RAW 264.7 macrophages. These effects may be associated with the suppression of inflammatory mediator production, reduction in the cellular oxidative stress burden and modulation of proteins involved in cellular stress responses and antioxidant defense. Full article

Rhabdomyolysis-associated acute kidney injury is driven by myoglobin-mediated oxidative stress, inflammation, mitochondrial impairment, and tubular cell death. This study evaluated the nephroprotective activity of green-synthesized Withania somnifera-functionalized selenium nanoparticles (Ws-SeNPs) in glycerol-induced renal injury and compared their efficacy with native W. somnifera extract and sodium selenite. The chemical profile of the plant extract was characterized by LC–MS/MS, and Ws-SeNPs were evaluated using dynamic light scattering, zeta potential analysis, transmission electron microscopy, and FTIR spectroscopy. Thirty-five male rats were assigned to Control, ARF, ARF & Ws, ARF & selenium, and ARF & Ws-SeNPs. ARF was induced by intramuscular injection of 50% glycerol. Glycerol administration induced marked skeletal muscle injury, renal dysfunction, tubular damage, oxidative stress, inflammation, mitochondrial dysregulation, pyroptosis, apoptosis, and histopathological alterations. Both Ws and sodium selenite provided partial protection, whereas Ws-SeNPs produced the greatest improvement in renal function and tissue architecture. Their protective effect was associated with restoration of Nrf2-dependent antioxidant defenses, suppression of NF-κB/NLRP3/GSDMD-associated inflammatory and pyroptotic signaling, preservation of mitochondrial regulatory pathways, and attenuation of apoptosis. These findings indicate that Ws-SeNPs provide multi-target protection against glycerol-induced rhabdomyolysis-associated renal injury and may represent a promising phytochemical-based selenium nanoformulation for further preclinical investigation. Full article

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide and are driven by the interplay between oxidative stress and chronic inflammation. Although these processes have been extensively investigated, their integration into a unified mechanistic framework and their translational relevance for biomarker-guided precision medicine remain insufficiently addressed. This narrative review integrates mechanistic, biomarker, and translational perspectives on the redox–inflammation axis in atherosclerosis and acute ischemic stroke, critically evaluating oxidative and inflammatory biomarkers while highlighting current challenges and emerging therapeutic opportunities. Reactive oxygen and nitrogen species (ROS/RNS) promote endothelial dysfunction, lipid oxidation, and activation of redox-sensitive pathways, including NF-κB, Nrf2/Keap1, JAK/STAT, and the NLRP3 inflammasome, resulting in vascular inflammation and injury. Biomarkers such as hs-CRP, IL-6, MPO, MDA, F2-isoprostanes, oxLDL, and antioxidant enzyme activity have demonstrated associations with cardiovascular risk, disease severity, and clinical outcomes, and therefore show diagnostic and prognostic potential. However, with the exception of selected inflammatory biomarkers, most oxidative stress biomarkers have not yet been sufficiently validated for routine clinical use because of biological variability, limited specificity, and insufficient analytical standardization. Disappointing outcomes of antioxidant supplementation further reflect the complexity of redox biology and the dual physiological and pathological roles of ROS. Here, we highlight that future progress in cardiovascular medicine will require a shift from non-specific antioxidant supplementation to precision redox modulation, integrating multimarker profiling, system biology, multi-omics, and artificial intelligence and machine-learning approaches to improve cardiovascular risk stratification and personalized therapy. Full article

Mammary gland inflammation, clinically expressed as mastitis in dairy ruminants and lactating women, arises from a self-amplifying loop of pathogen sensing, oxidative stress and innate immune activation, and remains a leading driver of antibiotic use, milk-quality loss and morbidity. Mounting pressure to reduce antimicrobial dependence has refocused attention on flavonoids—structurally diverse plant polyphenols with multi-target bioactivity, derived mainly from in vitro and rodent mastitis models. This review integrates contemporary evidence on the six principal flavonoid subclasses within a unifying molecular framework. Across subclasses, flavonoids converge on shared targets: the TLR4–MyD88–NF-κB axis, MAPK cascades, the Keap1–Nrf2–ARE antioxidant pathway, the NLRP3 inflammasome and tight-junction proteins of the blood–milk barrier. Less canonical mechanisms—m⁶A epitranscriptomic regulation, ferroptosis suppression, AhR signalling, anti-virulence binding to bacterial enzymes such as IGPD, and gut-microbiota-driven remodelling of the gut–mammary axis—expand the pharmacological landscape. We additionally appraise the subclasses comparatively, identifying flavanones and the flavone baicalin as carrying the strongest translational evidence, and examine the conflicting findings, model limitations, and delivery, residue and regulatory barriers that currently separate mechanistic promise from on-farm application. We outline structure–activity considerations and translational priorities, and position flavonoids as mechanism-rich, antibiotic-sparing candidates for the prevention and adjunctive management of mammary gland inflammation in dairy ruminants. Full article

Tomato (Solanum lycopersicum L.) is the world’s second-most cultivated vegetable. Production reached 192 million tonnes in 2023; approximately 23% is industrially processed, leaving 4.3 to 10.2 million tonnes of pomace each year. Despite its high content of lycopene, tocopherols, polyphenols, dietary fibre, and seed oil, most of this residue is composted, landfilled, or fed without prior processing. This narrative review examines how the chemistry of tomato by-products maps onto their effects in farm animals, and how green-extraction biorefinery fits within the European Green Deal. Reported pomace lycopene runs from 36.7 to 50.2 mg/100 g DM, with phenolics near 161.8 mg GAE/g. Lycopene is an efficient singlet-oxygen quencher; it activates Keap1–Nrf2–ARE signaling while dampening NF-κB. Supercritical CO₂, ultrasound, microwave, pressurized-liquid, and NADES extractions can now recover up to 91% of peel lycopene using green, food-grade solvents. In broilers, 5 to 10% pomace or 30 to 400 mg/kg purified lycopene improves antioxidant status and lessens heat stress; in dairy ruminants, ensiled pomace at 10 to 40% maintains milk yield while improving milk PUFA. In finishing pigs and rabbits, dietary pomace or lycopene improves tissue oxidative stability, with growth benefits reported in heat-stressed rabbits. Standardized bioactive reporting and clearer inclusion limits remain the main research priorities. Full article

Collagen, long regarded as the inert structural scaffold of the extracellular matrix, is now recognised as a source of bioactive signaling molecules: enzymatic hydrolysis releases low-molecular-weight bioactive collagen peptides that act systemically. This narrative review synthesises in vitro, animal-model, and veterinary clinical evidence with explicit differentiation of evidence levels; literature was identified through structured searches of PubMed, Web of Science, and Google Scholar, covering peer-reviewed, English-language reports published between 2000 and January 2026, without a formal systematic protocol. Across rodent, porcine, and human pharmacokinetic studies, orally administered collagen hydrolysate is efficiently absorbed, with a fraction reaching the circulation as intact prolyl-hydroxyproline and hydroxyprolyl-glycine through the conserved PEPT1/PEPT2 transporters; reported bioavailability varies with source, dose, and method, so no single value generalises across species. Native collagen and larger collagen fragments engage structure-dependent receptors in vitro (α2β1 integrins, DDR1/DDR2, GPVI, LAIR-1/2) that require triple-helical or Gly-Pro-Hyp presentation, whereas it is not established that the di- and tripeptides that reach the circulation after oral dosing engage them; their systemic actions are partly attributable to intracellular routes, including the Keap1–Nrf2 axis, HDAC/HAT modulation, and glycine-dependent glutathione synthesis. The gut–collagen peptide axis, a model derived from rodent and cell-culture data, links microbial bile acid remodeling and FXR/TGR5 signaling to systemic effects. Current evidence supports validated use in canine and equine osteoarthritis; species-specific bioavailability studies in dogs and cats remain the priority. Full article

Rice glutelin hydrolysates (RGHs) with different degrees of hydrolysis (DH) were prepared using papain, and the structural characterization, physicochemical stability, and antioxidant activity of RGH were analyzed. Results showed that RGH primarily consisted of low molecular weight (MW) peptides (<3 kDa), with hydrophobic/aromatic amino acid content increasing with DH. Higher DH level led to reduced average particle size and zeta potential of RGH. Structurally, as DH increased, a decrease in α-helix content alongside increased β-sheet/random coil ratios was observed in RGH, indicating a transition towards a more disordered structure in RGH. Furthermore, the antioxidant activity of RGH was significantly enhanced with the increase in DH, with RGH-18 showing the highest bioactivity. RGH maintained stability and antioxidant capacity under gastrointestinal digestion as well as various environmental stresses, including varying pH and temperatures, and the presence of metal ions. Cellular experiments demonstrated that RGH-18 alleviated H₂O₂-induced oxidative damage in HepG2 cells, likely by inhibiting Keap1 and activating Nrf2 via the Keap1/Nrf2 pathway. This study supports the potential of RGH as a functional ingredient and provides insights for targeted rice peptide production. Full article