Search Results (1,387)

Radiation therapy is widely used for cancer treatment. To improve therapeutic efficacy, traditional radiosensitizers are often used in combination. However, their toxic side effects necessitate urgent development of safer alternative biogenic radiosensitizers. Herein, a green approach was used to synthesise ZnO NPs, CuO NPs, and ZnO-CuO NCs using S. africana Luteus, and their ability to enhance the radiosensitizing effect of proton irradiation on Michigan Cancer Foundation-7 (MCF7) breast cancer cell line was evaluated. The biogenic nanoparticles are characterised in detail through several analytical techniques, including Ultraviolet-visible (UV-Vis) spectroscopy, X-ray diffraction (XRD), Fourier Transform Infrared (FTIR) spectroscopy, and Scanning Electron Microscopy (SEM). Interestingly, the NPs showed concentration-dependent effects on MCF7 viability, with CuO NPs exhibiting the strongest effect (IC₅₀ = 42.90 µg/mL), followed by ZnO-CuO NCs (71.12 µg/mL) and ZnO NPs (103.43 µg/mL). Proton irradiation produced a dose-dependent decrease in clonogenic survival of MCF7 cells, and ZnO-CuO NCs displayed the highest enhancement of proton-induced cell death, with a Dose Enhancement Factor (DEF) of 1.69, compared with CuO NPs (1.46) and ZnO NPs (1.09). Holotomographic microscopy (HTM) data further confirmed that ZnO-CuO NCs impaired cellular macromolecules more than the individual NPs. Findings from this study suggest that the biogenic NPs are promising radiosensitizers for cancer radiotherapy. Full article

Background/Objectives: Exposure to particulate matter (PM) containing bacterial endotoxins triggers inflammation and oxidative stress in the respiratory epithelium. In this study, we investigated chitosan nanoparticle-loaded Cordyceps militaris grown on germinated Rhynchosia nulubilis (GCN) as a potential functional food-derived ingredient against PM- and lipopolysaccharide (LPS)-induced cellular damage in human lung epithelial cells. Methods: This study employed an integrative approach combining GCN analysis with bioinformatics methods using a PM- and LPS-induced pulmonary cellular inflammation model. Gene Expression Omnibus (GEO) transcriptomic datasets and Cytoscape-based network analysis were utilized to identify key hub genes and signaling pathways associated with PM- and LPS-induced pulmonary inflammation, which were subsequently validated by RT-PCR and Western blotting. Results: Nano-encapsulation significantly improved the antioxidant capacity and storage stability of the extract compared with non-encapsulated Cordyceps militaris grown on germinated Rhynchosia nulubilis (GRC). GCN markedly attenuated PM- and LPS-induced cytotoxicity and intracellular reactive oxygen species (ROS) production in a dose-dependent manner, resulting in a therapeutic index approximately 4.5-fold higher than that of GRC under PM and LPS co-exposure. Bioinformatics analysis identified inflammation-related genes and pathways associated with PM- and LPS-induced pulmonary responses, primarily enriched in tumor necrosis factor (TNF)-related inflammatory pathways, Toll-like receptor signaling, and cytokine signaling. Consistent with these findings, GCN suppressed the expression of C-X-C motif chemokine ligand 2 (CXCL-2) and tumor necrosis factor-alpha (TNF-α) mRNA and inhibited mitogen-activated protein kinase (MAPK)-mediated activator protein-1 (AP-1) and nuclear factor-kappa B (NF-κB) signaling pathways in human type II alveolar epithelial cells (A549). Conclusions: Collectively, nano-encapsulation enhanced the stability and bioactivity of Cordyceps militaris-based extracts, suggesting that GCN may have potential as a functional food-derived candidate ingredient to protect airway epithelial cells against inflammation and oxidative stress induced by PM and LPS. As this study was conducted using an in vitro A549 epithelial cell model, further validation in physiologically relevant systems is needed to confirm its translational applicability. Full article

Background/Objectives: mRNA display technology has emerged as a powerful platform for discovering macrocyclic peptides against intractable proteins. However, direct screening against the “undruggable” transcription factor MYC using this approach remains largely unexplored. In this study, we aimed to integrate tyrosinase-mediated cyclization with mRNA display to identify novel macrocyclic peptide inhibitors targeting MYC. Methods: We performed mRNA display combined with tyrosinase-mediated cyclization to generate macrocyclic peptides targeting MYC. Antiproliferative activity was assessed in MYC-dependent tumor cells using CCK8 assay. C-terminal fusions with a TAT-derived cell-penetrating peptide were generated to enhance cell membrane permeability. Binding affinities were measured by bio-layer interferometry (BLI). MYC transcriptional activity was evaluated by RNA sequencing (RNA-seq) analysis of canonical MYC target genes. Results: The identified macrocyclic peptides exhibited potent antiproliferative activity against MYC-dependent tumor cells, with half-maximal inhibitory concentration (IC₅₀) values in the micromolar range. Fusion with the TAT peptide improved antiproliferative potency, yielding IC₅₀ values of 1–3 μM in MYC-dependent cell lines. BLI assays confirmed dose-dependent binding of the peptides to MYC, with dissociation constants (Kd) in the micromolar range. Furthermore, RNA-seq analysis revealed significant downregulation of canonical MYC target genes upon treatment with the TAT-fusion macrocyclic peptide, indicating specific suppression of MYC transcriptional activity. Conclusions: This work establishes the feasibility of using mRNA display to target the “undruggable” protein MYC and identifies a panel of macrocyclic peptides as promising lead candidates for further optimization toward targeted therapies for MYC-driven cancers. Full article

UVA radiation affects communication between the cells that create the human skin. To prevent UVA-induced damage, there is a constant search for compounds protecting all skin cells and homeostasis in their communication. Therefore, the aim of this study was to evaluate the effect of 24 h incubation with 3-O-ethyl ascorbic acid (EAA; 150 µM) on the intracellular proteome of co-cultured keratinocytes and fibroblasts after UVA irradiation (total dose 15 J/cm²), and on the protein profiles released into the medium by both cell types. A proteomic approach (nanoHPLC/QOrbiTrap) allowed the identification of proteins significantly modified by UVA and EAA. In keratinocytes, UVA radiation enhanced expression of pro-inflammatory and pro-proliferative/keratinizing proteins and decreased expression of antiapoptotic and antioxidant proteins, while in fibroblasts, UVA radiation induced expression mainly of pro-inflammatory proteins, simultaneously decreasing levels of proteins involved in the antioxidant response and growth factors. Increased pro-inflammatory protein and decreased growth factor levels were also observed in the medium. EAA restored the levels of these proteins compared to control cultures. The results of this study show that EAA may protect epidermal and dermal cells by reducing levels of pro-inflammatory proteins, increasing antioxidant system activity in skin keratinocytes and fibroblasts, and normalizing intercellular signaling. Full article

Pediatric drug therapy remains fundamentally challenged by profound interindividual variability driven by dynamic development, genetic, and environmental factors. Although dosing strategies based on age, body weight, or body surface area remain important starting points in pediatric pharmacotherapy, they may not fully capture ontogeny-dependent variability in drug disposition and response. Consequently, clinically relevant differences in efficacy and toxicity may still occur among children receiving similar weight-adjusted doses. Pharmacogenomics offers a promising framework for individualized therapy; however, its clinical translation in pediatrics is limited by developmental variability in gene expression and enzyme activity. Emerging evidence highlights the pivotal role of epigenetic regulation, including DNA methylation, histone modifications, and microRNAs, in modulating pharmacogenetic expression across developmental stages, thereby reshaping drug response trajectories. Concurrently, advances in artificial intelligence and next-generation sequencing enable integration of multidimensional datasets, facilitating predictive modeling of drug efficacy and toxicity. This narrative review provides a comprehensive synthesis of developmental pharmacology, pharmacogenomics, and epigenetic mechanisms, while critically evaluating current translational gaps and implementation challenges. Importantly, it proposes an integrative precision framework that incorporates genetic, epigenetic, and computational insights to optimize pediatric pharmacotherapy. By bridging mechanistic biology with emerging digital health technologies, this work advances a paradigm shift from empirical prescribing toward predictive, adaptive, and individualized therapeutic strategies. The proposed approach holds significant potential to enhance clinical outcomes, minimize adverse effects, and accelerate the realization of precision medicine in pediatric populations. Full article

Background: Hexavalent chromium (Cr(VI)) is a widespread environmental toxic heavy metal with strong oxidative properties; however, its immunotoxicity and metabolic mechanisms in rabbit spleen remain largely unclear. Methods: In this study, New Zealand rabbits were exposed to 0, 12.5, 25, and 50 mg/L Cr(VI) (as potassium dichromate, K₂Cr₂O₇) via drinking water for four weeks to investigate splenic damage and the underlying molecular pathways. Spleen pathological injury was evaluated by hematoxylin and eosin (H&E) staining, and the distribution of T cells, B cells, and macrophages was assessed by immunohistochemistry. Antioxidant enzyme activities and antioxidant substance levels were determined using ELISA, and the relative mRNA expression of immune factor genes, antioxidant-related genes, and ferroptosis-related genes was quantified by quantitative real-time PCR (qRT-PCR). In addition, the distribution of iron in splenic tissue was detected by enhanced Prussian blue staining. Results: Our results demonstrate that high-dose Cr(VI) significantly inhibited body weight gain, induced lymphocyte atrophy, vacuolization, and widening of intercellular spaces in the splenic white pulp. Furthermore, Cr(VI) reduced T and B lymphocyte populations, promoted macrophage infiltration and inflammatory cytokine gene expression in a concentration-dependent manner, impaired total antioxidant capacity, and led to a decrease in glutathione (GSH) levels in the spleen. Additionally, Cr(VI) exposure increased iron accumulation, activated the ACSL4–NOX lipid peroxidation cascade, and downregulated GPX4 expression, ultimately triggering ferroptosis. Conclusions: These findings reveal that Cr(VI) causes splenic immune injury by disrupting oxidative homeostasis and inducing ferroptosis, providing novel insights for evaluating immunotoxicity and identifying metabolic targets under Cr(VI) pollution. Full article

Fish are continuously exposed to stress factors throughout their life cycle, making the use of anaesthetics essential for a wide range of experimental procedures. Currently, the most commonly used and FDA approved anaesthetic for fish research is Tricaine Methanesulfonate (MS-222). However, its use has been associated with several undesirable effects, including hypoxemia, hypercapnia and hypoglycaemia, as well as environmental concerns due to its release through aquaculture effluents. These limitations highlight the need for alternative anaesthetic strategies. Natural compounds such as clove oil, menthol and thymol have been investigated as potential alternatives, demonstrating effective anaesthetic properties. However, their low aqueous solubility, represents a significant challenge, which may be overcome through nanoencapsulation. This approach can enhance solubility, enable controlled release, and reduce the effective dose required. Accordingly, the present study aims to provide an overview of the recent advances in nanoparticle-based encapsulation strategies for anaesthetic delivery in fish, with a focus on their efficacy, safety and environmental impact. Some studies have demonstrated the benefits of nanoencapsulation. In adult zebrafish (Danio rerio), lower concentrations of benzocaine were required when encapsulated in chitosan-PLGA nanoparticles, while lidocaine-loaded lipid NPs reduced bradycardia. In Nile Tilapia (Oreochromis niloticus), clove oil encapsulated in lipid-based nanocapsules enabled effective anaesthesia and prolonged release of the active compound eugenol. Similarly, mucoadhesive zein NPs, reduced the effective concentration of Eugenol by up to 50%. Monoterpenes such as menthol and thymol also show promise for zebrafish anaesthesia, demonstrating efficacy at 50 mg/L. These findings suggest that nanoparticle-based delivery systems can improve the efficacy and safety of fish anaesthetics while reducing required doses and potential environmental impact. Future research should focus on optimizing nanoparticle-anaesthetic systems by combining natural compounds with biocompatible and biodegradable nanocarriers (e.g., zein, chitosan or PLGA) to achieve controlled release, targeted delivery and minimization of side effects. Full article

Background: Alcohol use disorder (AUD) is a grave mental health condition that can result in significant health and social consequences. The medications Naltrexone and Nalmefene are indicated for the treatment of AUD, with Naltrexone having received the most extensive research attention. Methods: The majority of papers assessing universal measures of alcohol consumption employed two primary metrics: total alcohol consumption (TAC) and the number of days per month where individuals engaged in heavy drinking (HDD). Indicators pertaining to the maintenance of complete abstinence were excluded due to the absence of sufficient data. The safety of both substances was also assessed, as were the frequency of side effects and independent patient dropout. The study also incorporated practical factors of the therapy, such as the route of administration, dosage regimen, and the drug’s patient convenience, which can have a significant impact on adherence to therapy. Results: Nalmefene, administered in an “as needed” regimen, demonstrated statistically significant activity in reducing HDD and total alcohol consumption (TAC) among patients with AUD, particularly those with elevated World Health Organization (WHO) DRL risk. Preliminary findings from the ESENSE1 (Efficacy of Nalmefene in Alcohol Dependence; the first phase III study), ESENSE 2 (Efficacy of Nalmefene in Alcohol Dependence, the second phase III study), and SENSE (the final phase III long term-safety and cost-effectiveness study) studies indicate a substantial decrease in HDD and TAC following the initial month of treatment. These effects persist throughout the subsequent follow-up period. Several Japanese studies have corroborated the effectiveness of Nalmefene, demonstrating its efficacy across both short-term and long-term applications. Furthermore, these studies have substantiated its safety profile, indicating that there is no inherent risk of addiction or the emergence of withdrawal symptoms. The mild nature of adverse events (most commonly nausea and dizziness) led to a relatively low discontinuation rate of Nalmefene treatment. A subsequent study, employing a recognized methodology, corroborated the efficacy of psychosocial support in enhancing treatment outcomes. Meta-analyses demonstrate that Naltrexone exhibits comparable efficacy in reducing the frequency and severity of alcohol consumption. In select populations, the injectable form (LAI) of this pharmaceutical agent facilitates less frequent dosing, which is advantageous for the treatment process. A comparison of Nalmefene and Naltrexone reveals that the latter does not demonstrate a significant impact on the likelihood of individuals returning to heavy alcohol consumption. Conclusions: In the treatment of AUD, both naltrexone and nalmefene have been shown to yield positive outcomes, particularly in terms of reducing the HDD and TAC. According to the World Health Organization (WHO) classification, Nalmefene is indicated for individuals with a high risk of developing serious conditions. It has been demonstrated to produce rapid and sustained results while exhibiting a favorable safety profile, characterized by the absence of significant adverse effects. Naltrexone is a medication that has proven to be effective. LAI may have a positive impact on the efficacy of treatment. Full article

The prevalent endocrine disruptor bisphenol A (BPA) is associated with aging-related conditions, including metabolic disorders. It has been shown that BPA promotes bone fragility through oxidative stress-induced apoptosis and impaired osteoblast differentiation. The identification of sustainable bioactive substances that alleviate BPA-induced bone toxicity is thus of biomedical and environmental significance. Wolffia globosa (WG), the world’s smallest flowering aquatic plant, has recently gained attention as a high-protein, antioxidant-rich nutraceutical, yet its impact on BPA-induced osteoblast dysfunction has not been systematically investigated. This study presents a comprehensive assessment of WG ethanolic extract (WGE) in MC3T3-E1 pre-osteoblasts, incorporating thorough phytochemical characterization, acute high-dose and chronic low-dose BPA exposure models, and multi-faceted mechanistic analysis. LC-MS/MS profiling identified luteolin (116.17 ± 0.69 µg/g), rosmarinic acid (54.80 ± 2.12 µg/g), and apigenin (48.77 ± 0.61 µg/g) as the predominant bioactive compounds. WGE exhibited potent antioxidant capacity across DPPH and ABTS radical scavenging assays, complemented by high ORAC and FRAP values, reflecting broad-spectrum antioxidant mechanisms. Treatment with WGE (25 and 50 µg/mL) resulted in significant alleviation of BPA-induced cytotoxicity, decreased intracellular ROS levels, and inhibited apoptosis. WGE (12.5 µg/mL) also modulated autophagy-related markers (LC3-II, Beclin-1, and p62), suggesting potential autophagic participation, although flux verification was not conducted. Treatment with WGE (12.5 µg/mL) also restored BPA-suppressed osteogenesis under chronic exposure, as evidenced by enhanced alkaline phosphatase activity, and increased both mineralization and upregulation of osteogenic genes including runt-related transcription factor2 (Runx2), collagen type I alpha 1 (Colla1), alkaline phosphatase (ALP), and osteocalcin (OCN). These effects were accompanied by partial reactivation of Wnt/β-catenin signaling. This study is the first to demonstrate that WGE protects osteoblasts from BPA toxicity by concurrently strengthening antioxidant defenses, limiting apoptosis, modulating autophagy-related markers, and supporting β-catenin-mediated osteogenesis, highlighting WG as a promising sustainable nutraceutical candidate for the prevention of environmental toxin-related bone fragility. Full article

Objectives: To evaluate associations between social vulnerability and rheumatoid arthritis (RA)-related mortality in the United States, with emphasis on domain-specific effects of the Social Vulnerability Index (SVI). Methods: We conducted a county-level ecological study of RA-related mortality from 2010 to 2019 using age-adjusted mortality rates and the Centers for Disease Control and Prevention SVI. Gamma regression models examined associations between RA mortality and overall SVI and four thematic domains, including socioeconomic status, household composition and disability, minority status and language, housing type and transportation by using both continuous and quartile-based measures. Results: Between 2010 and 2019, 354,280 deaths occurred among individuals with RA, corresponding to a mean age-adjusted mortality rate of 9.7 per 100,000 population. In multivariable analyses adjusting for all SVI domains, household composition and disability vulnerability demonstrated the strongest and most consistent positive association with mortality, with a dose–response relationship across quartiles. Housing type and transportation vulnerability showed a modest positive association. Minority status and language vulnerability was inversely associated with mortality, whereas socioeconomic vulnerability was not significant in continuous models but demonstrated an inverse association with mortality in quartile-based analyses. Conclusions: RA mortality is differentially associated with specific domains of social vulnerability rather than overall vulnerability burden. Household composition and disability represent clinically salient risk factors, demonstrating the relevance of functional status and caregiving context in RA outcomes. Domain-specific assessment of social vulnerability may enhance clinical risk stratification and inform more targeted, patient-centered RA management. Full article

Spectrophotometry offers the advantage of low cost and less time consumption, making it still attractive as a method of analysis, especially when coupled with multivariate calibration models. This enhancement solves the majority of the drawbacks of UV–VIS spectrophotometry, which have to do with the entangled spectra of complex mixtures. In this study, a multivariate model was developed and validated for the determination of perindopril erbumine, amlodipine besylate and indapamide, addressing previously unresolved challenges by systematically covering three fixed-dose combinations with differing component ratios and by achieving accuracy suitable for the assay determination. The experimental plan involved a Taguchi orthogonal array design with three factors at five levels. In order to create multivariate calibration models, principal component regression, partial least squares and concentration residual augmented least squares regression algorithms were tested. Principal component regression combined with a genetic algorithm for feature selection was chosen as the optimal model based on prediction performance estimated by nested cross-validation with cluster-based sample splitting. The developed method was also evaluated for its environmentally friendly potential while the analytical method validation procedure confirmed its applicability for the assay testing of the fixed-dose drug combination. Full article

The understanding of oxidative stress is being refined leading to the use of the terms “oxidative distress” and “eustress”. This reflects the dual role of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in both pathology and physiology, emphasizing the complexity of the mechanisms influencing the redox status. This review discusses how these redox mechanisms interact with key signaling pathways, specifically the mammalian/mechanistic target of rapamycin (mTOR) and peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α), which are crucial for mitochondrial health and muscle recovery. During exercise, the contraction of skeletal muscles increases ROS production which, through redox signaling, triggers mitochondrial biogenesis, enhances the antioxidant defenses and stimulates glucose metabolism, contributing to cardiovascular function and health. There is a large consensus about the importance of physical exercise in maintaining the redox homeostasis. However, the redox status could be disturbed after an intense and/or long physical effort, and signs such as markers of oxidative distress were identified. In that context, antioxidant strategies are warranted to prevent oxidative damage and help recovery. Given the many factors influencing the redox status of the body, including the training status, the duration and type of exercises and effort, diet, lifestyle, genetic polymorphisms, and circulating cytokines, a personalized approach is necessary. Targeted therapeutic interventions become important for preventing oxidative damage and helping recovery. In this review, we discuss the potential benefits of micro-immunotherapy (MI), as a multi-target approach utilizing signaling molecules, including cytokines at low doses (LD, typically 3–5 centesimal Hahnemannian CH dilutions) and ultra-low doses (ULD, from 6 CH upwards). We focused specifically on the investigational MI medicine 2LMIREG, and propose its application in preventing oxidative distress and restoring redox balance. Additionally, this review explores how the redox status interplays with the immune system, presenting preclinical data on 2LMIREG as a proof-of-concept for a tailored immunoregulatory strategy to enhance both immune and oxidative adaptations. Full article

Vascular–osteogenic coupling plays a central regulatory role in bone regeneration, but it is frequently impaired under pathological conditions, including aging, ischemia, and chronic inflammation, which compromises efficient bone repair. Gelatin methacryloyl (GelMA) hydrogels, which combine extracellular matrix-like bioactivity, adjustable mechanical properties, and compatibility with three-dimensional biomanufacturing, have become a widely used material platform for vascularized bone regeneration. From the perspective of vascular–osteogenic coupling, this review reframes and synthesizes GelMA-based approaches for vascularized bone regeneration, grouping existing strategies into three categories: (i) intrinsic material design, in which pore architecture, microchannels, dynamic networks, and interfacial functionalization are used to guide vascular ingrowth; (ii) exogenous bioactive delivery, involving growth factors, extracellular vesicles, cells, and inorganic ions to enhance vascularization; and (iii) smart responsive strategies, including ROS/pH-responsive systems, sequential release, and external stimulation, which aim to recapitulate the evolving microenvironment during bone repair. This review further compares these strategies in terms of evidence level, reproducibility, and translational potential. Exogenous delivery systems currently have the strongest preclinical support, but issues related to dose standardization, burst release, and long-term safety remain unresolved. Intrinsic material programming is less extensively studied, yet may be more compatible with manufacturing consistency, sterilization, and engineering translation. Most stimuli-responsive systems, by contrast, remain largely at the small-animal or proof-of-concept stage. Future GelMA-based systems should therefore shift from increasing functional complexity toward improving predictability, reproducibility, and clinical feasibility. Compositionally defined and structurally controllable GelMA composites that integrate vascular regulation with mechanical support may provide a more realistic path for vascularized bone regeneration. Full article

The coexistence of microplastics (MPs) and heavy metals (Cd, Pb) in agricultural soils has become a global environmental and ecological risk. In this study, a pot experiment was conducted to investigate the effects of different concentrations of polyethylene (PE) microplastics and combined Cd/Pb contamination on the growth and development, heavy metal accumulation, and antioxidant system of tobacco (Nicotiana tabacum L. cv. Yunyan 87). The results showed that low-dose PE and low concentrations of heavy metals had minor impacts on tobacco growth and the antioxidant system; in contrast, high-dose PE and elevated heavy metal treatments markedly induced increases in malondialdehyde content (MDA) and enhanced the activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD). Under co-contaminated conditions, the addition of low-dose PE reduced the translocation capacity of heavy metals, alleviated heavy metal-induced oxidative stress responses, and promoted tobacco growth. Conversely, high-dose PE promoted the translocation of Cd into tobacco plants and increased Cd contents in tobacco leaves, leading to marked decreases in soluble protein and soluble sugar contents, and causing severe reductions in plant height, number of functional leaves, and biomass. Structural equation modeling (SEM) analysis revealed that the direct effect of PE on tobacco growth was not significant; instead, it primarily acted as a regulatory factor, exerting either promotional or inhibitory effects on tobacco growth at different doses. The impact of Cd/Pb on tobacco growth appeared to involve two potential pathways. On the one hand, Cd/Pb induced direct toxicity through their accumulation within tobacco tissues. On the other hand, they exerted indirect regulation primarily by modulating the activities of the tobacco antioxidant system. Full article

As a core nutritional component of milk, casein features excellent digestibility and biocompatibility, making it an ideal carrier for embedding natural bioactive substances in dairy product research. Luteolin, a typical flavonoid compound with superior antioxidant and anti-inflammatory bioactivities, is limited in industrial dairy applications due to poor environmental stability and low biological utilization. Moreover, the dynamic interplay mechanism between luteolin and casein throughout fermentation and cold storage remains unclear. This study hypothesized that luteolin could assemble with casein via non-covalent binding to form stable composite fermentation system, thereby optimizing the overall quality and functional attributes of fermented milk. This work aimed to explore the binding characteristics of luteolin of casein in fermented milk and its regulatory effects on products’ physicochemical properties, antioxidant capacity and nutritional digestibility. Experimental outcomes verified the hypothesis that luteolin bonded with casein through hydrogen bonding and hydrophobic interactions. With increased luteolin supplementation, the fermentation system presented lowered pH and elevated titratable acidity. Compared with control fermentation system without luteolin, the fermentatiuon system containing 0.06% luteolin achieved 31.31% higher DPPH radical scavenging rate, 27.02% higher ABTS clearance capacity, and 26.42% higher in vitro protein digestibility (p < 0.05). Dose-dependent increases in particle size and absolute zeta-potential enhanced system colloidal stability, while FTIR detection confirmed obvious variations in protein secondary structure in fermented milk. This study elucidates the distinctive structure–function correlation of the luteolin–casein fermentation system in fermented dairy matrices, providing original insights and reliable theoretical support for developing novel dairy products rich in functional nutritional factors. Full article