Search Results (12,134)

Background: Gallic acid (GA) is a dietary polyphenol widely found in walnuts, tea leaves, and grapes, and it is recognized for its potent antioxidant and anti-inflammatory properties. Chronic sleep deprivation (CSD) is known to disrupt redox balance, promote neuroinflammation, and impair cognition, while effective nutritional strategies to mitigate these effects remain scarce. This study was designed to evaluate the protective potential of GA against CSD-induced cognitive deficits in mice and to elucidate the underlying mechanisms. Methods: Seventy-two male ICR mice were randomly allocated to six groups, including control, CSD model, Ginkgo biloba extract, and GA at three doses (50, 100, and 200 mg/kg). After 28 days of treatment, cognitive performance was assessed using the open field test (OFT), novel object recognition (NOR), step-through passive avoidance (ST), and Morris water maze (MWM). Redox status and inflammatory mediators were determined by ELISA, while the hippocampal expression of proteins related to antioxidant defense and NF-κB signaling was analyzed by Western blotting. Results: GA supplementation improved exploratory activity, recognition memory, and spatial learning in the CSD mice. Biochemical evaluation revealed that total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity were restored, while malondialdehyde (MDA) levels, an indicator of lipid peroxidation, were reduced. These changes were accompanied by decreased circulating concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). At the molecular level, GA enhanced the expression of Nrf2, HO-1, and NQO1, while inhibiting p-p65, iNOS, and COX2 in the hippocampus. Conclusions: These findings demonstrate that GA alleviates CSD-induced cognitive deficits through the activation of the Nrf2/HO-1 antioxidant pathway and inhibition of NF-κB–mediated inflammatory responses. Thus, GA may represent a promising nutraceutical candidate for maintaining cognitive health under chronic sleep loss. Full article

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by its aggressive clinical behavior and intricate microenvironment regulation, leading to dismal prognosis. Elucidating the molecular mechanisms underlying PDAC pathogenesis is crucial for developing improved therapeutic approaches. The functional significance and molecular basis of transcobalamin 1 (TCN1) in PDAC remain largely unexplored. Methods and Results: Through integrated analysis of TCGA and GTEx datasets combined with 80 clinical specimens, we identified significant TCN1 overexpression in PDAC, showing a positive association with tumor stage and negative associations with histological differentiation and overall survival. Functional investigations showed that TCN1 enhanced pancreatic cancer cell proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) in both in vitro and in vivo models. Mechanistically, TCN1 physically interacts with signal transducer and activator of transcription 4 (STAT4) to enhance its transcriptional activity. Chromatin immunoprecipitation (ChIP) assays showed that STAT4-mediated transcriptional activation of dual oxidase 2 (DUOX2) occurs through direct promoter binding. As a pivotal reactive oxygen species (ROS)-generating enzyme, DUOX2 overexpression elevates intracellular ROS levels, thereby promoting EMT progression and activating proliferation-related signaling cascades. Antioxidant treatment effectively abrogated TCN1-driven oncogenic phenotypes, establishing ROS as the critical downstream mediator. Conclusions: Collectively, our findings reveal a novel TCN1/STAT4/DUOX2 regulatory axis that exacerbates PDAC progression by remodeling redox homeostasis. This signaling cascade may serve as a prognostic biomarker and a potential therapeutic target for ROS-directed precision therapy in PDAC. Full article

Corbicula fluminea protein (CFP) and cyanidin-3-O-glucoside (C3G) are natural nutrient fortifiers. During consumption or processing, they may interact with each other, inducing alternations in their structural and functional properties. However, nothing was known about the mechanism of their interaction and their synergistic antioxidant effect. In this research, C3G was physically mixed with CFP to simulate practical scenarios. The impact of the presence of C3G on the multispectral characteristics, antioxidant activity, and particle properties of CFP was examined and compared to chemically fabricated C3G-CFP covalent conjugates. The results indicate that C3G tended to spontaneously bind to CFP and formed compact non-covalent complex, with hydrophobic forces predominantly governing the interaction. This binding resulted in the statically quenched intrinsic fluorescence of CFP, accompanied by a dynamic model. Moreover, C3G preferentially induced Trp residue in CFP exposed to a more polar microenvironment, yet it exerted nearly no effects on CFP when analyzed using ultraviolet–visible (UV-Vis) spectroscopy and synchronous fluorescence spectroscopy (SFS). Additionally, although the formed non-covalent complex demonstrated strengthened antioxidant capacity, C3G displayed an antagonistic effect with CFP, whereas lower C3G concentrations led to synergistic effects in covalent conjugates. These findings provide new insights into the effective application of C3G and CFP as nutritional antioxidants. Full article

This study aimed to develop an environmentally friendly and relatively efficient method for extracting natural antioxidants from avocado by-products while investigating the antioxidant mechanisms of their core bioactive components on multiple dimensions. In vitro antioxidant assays (ABTS, FRAP, SAFR, SFR, ORAC, DPPH) demonstrated that flavonoid procyanidin was the primary antioxidant component in avocado seeds, exhibiting the strongest activity (DPPH EC₅₀ = 3.6 µg/mL). The Hill model indicated a positive synergistic effect (n = 3.1). Chemical and molecular mechanism analyses revealed that avocado seeds exert antioxidant activity predominantly through hydrogen atom transfer (HAT) and electron transfer (ET) pathways. The model predictions suggested procyanidins may stably bind to protein targets in the Keap1-Nrf2 pathway and NOX2 via hydrogen bonding, hydrophobic interactions, and π-cation interactions. Furthermore, response surface methodology (RSM) was employed to optimize the extraction process of avocado seed antioxidants in an ethanol-water system. This study underscores the considerable health benefits and antioxidant capacity of avocado by-products, supporting their promising application in functional foods formulations. Full article

Drought limits plant growth, development and productivity, leading to more than 50% crop loss globally. Drought-induced oxidative stress disturbs the plant’s metabolism; however, plants activate signaling pathways to respond and adapt to drought stress. Although drought response mechanisms are well reported in several crops, these mechanisms are poorly understood in Amaranthus. As a highly nutritious crop, rich in antioxidants with the ability to survive in extreme agro-climatic environments, Amaranthus has the potential to serve as a climate-smart future crop. This review provides evidence of some drought response traits in grain and vegetable Amaranthus species. Grain amaranths are the most tolerant species, mainly through improved osmoregulation, antioxidant capacity, and gene expression. While biomass partitioning, efficient water use, and membrane stability have been reported in both grain and vegetable amaranth, the molecular response of vegetable amaranth remains limited. Thus, future research must focus on integrated biochemical, molecular, and multi-omics applications to screen and identify resilient Amaranthus genotypes under drought for sustainable agriculture. Full article

Ferroptosis, an iron-dependent form of regulated cell death marked by lipid peroxidation, has emerged as a promising therapeutic target in breast cancer, particularly in aggressive subtypes such as triple-negative breast cancer (TNBC). This systematic review explores the molecular mechanisms underlying ferroptosis sensitivity and resistance, focusing on the interplay between iron metabolism, antioxidant defenses, and tumor microenvironmental factors. Literature retrieved from PubMed and Scopus up to May was analyzed in accordance with PRISMA guidelines, including mechanistic studies, preclinical experiments, and ongoing clinical trials. Findings reveal that breast cancer cells evade ferroptosis through enhanced glutathione synthesis, upregulation of GPX4 and system Xc- and adaptive metabolic reprogramming; yet these same mechanisms create exploitable vulnerabilities, including dependence on cystine, polyunsaturated lipids, and dysregulated iron handling. Therapeutic strategies that target key ferroptosis regulators, such as GPX4, ACSL4, and SLC7A11, or that harness agents like statins, sulfasalazine, and nanoparticle-based iron complexes demonstrate strong potential to overcome chemoresistance and selectively eliminate therapy-resistant cancer cell populations. Taken together, the evidence highlights ferroptosis as a critical Achilles’ heel of breast cancer biology and supports further clinical translation of ferroptosis-inducing therapies to improve outcomes in otherwise refractory breast cancer subtypes. Full article

Objectives: This review examines the role of oxidative stress in the survival, apoptosis, and therapy resistance of head and neck squamous cell carcinoma (HNSCC) cells, with a focus on how redox imbalance influences tumour progression and treatment outcomes. Methods: A literature search was conducted in Scopus using the keywords head and neck squamous cell carcinoma, oxidative stress, reactive oxygen species (ROS), and antioxidant systems. Articles published in English were included, without restrictions on publication year. Reviews, clinical studies, and experimental research addressing oxidative stress mechanisms in HNSCC were considered, while non-English papers and studies unrelated to HNSCC were excluded. Key Findings: ROS exhibit dual effects in HNSCC, promoting tumour growth and DNA damage while also inducing apoptosis through molecular interactions. Elevated ROS contribute to drug resistance by inhibiting apoptosis, altering autophagy, and enhancing proliferation. Cancer cells counteract this via adaptive antioxidant responses involving transcriptional regulation and upregulation of enzymatic defences. Major risk factors for HNSCC—alcohol, tobacco, and high-risk HPV infection—disrupt redox homeostasis, underscoring the central role of oxidative stress in both carcinogenesis and therapy response. Conclusions: Oxidative stress plays a context-dependent role in HNSCC progression and treatment resistance. Targeting redox-regulatory pathways may provide therapeutic benefit. This review synthesizes recent insights on ROS-mediated mechanisms, highlighting potential strategies for improving HNSCC management beyond existing literature. Full article

Silver nanoparticles (AgNPs) have attracted significant attention in recent years in diverse fields owing to their broad mechanisms of action. In particular, the wound healing process has become one of the main fields where the therapeutic potential of AgNPs is highlighted. AgNPs can be used as monotherapy or incorporated into composite structures in various formulations such as nanogels, hydrogels, powders, ointments, and sprays, for the treatment of a wide range of wound types including burns, excisional and incisional wounds, bone defects, surgical wounds, and diabetic ulcers. This widespread use is attributed to the strong antibacterial, anti-inflammatory, antioxidant, and cell proliferation-promoting biological properties of AgNPs. Moreover, AgNPs exhibit synergistic effects when combined with conventional antibiotics, enhancing their efficiency against resistant bacterial strains or even restoring the lost antibacterial activity. These biological properties enable AgNPs to reduce infection risk while simultaneously promoting high-quality healing by accelerating tissue regeneration. The therapeutic effectiveness of AgNPs is influenced by their physicochemical properties, including particle size, shape, and surface chemistry. In particular, synthesis methods play a significant role in determining both the biological activity and the safety profile of AgNPs. Among various methods, green synthesis approaches stand out for enabling the production of environmentally friendly, non-toxic, and highly biocompatible AgNPs. In this review, the mechanisms of action of AgNPs in wound healing are examined in detail, and recent scientific developments in this field are evaluated based on current in vitro, in vivo, and clinical studies. Full article

Cannabidiol (CBD) and its derivatives show interesting therapeutic potential, including antioxidant, anti-inflammatory, and anticancer properties; however, their clinical translation remains a complex task due to physicochemical restrictions such as low water solubility, high lipophilicity, and instability under light, oxygen, and high temperatures. Polymeric encapsulation has emerged as a promising strategy to overcome these challenges, offering protection against environmental degradation, improved bioavailability, and controlled release. Natural and synthetic polymers, both biocompatible and biodegradable, provide versatile matrices for CBD delivery, enabling nanoparticle formation, targeted transport, and enhanced pharmacokinetics. This review highlights the structural characteristics of CBD, its interaction mechanisms with polymeric matrices such as hydrogels, electrospun nanofibers, biodegradable microparticles, thin films, and lipid-polymer hybrid systems, and the principal encapsulation techniques, such as emulsion solvent evaporation, electrospinning, and supercritical fluid technologies, that facilitate stability and scalability. Furthermore, material characterization approaches, including microscopy, thermal, and degradation analyses, are discussed as tools for optimizing encapsulation systems. While notable advances have been made, key challenges remain in achieving reproducible large-scale production, ensuring regulatory compliance, and designing smart polymeric carriers personalized for specific therapeutic contexts. By addressing these gaps, polymer-based encapsulation may unlock new opportunities for CBD in pharmaceutical, nutraceutical, and therapeutic applications, providing a guide for future innovation and translation into effective patient-centered products. Full article

Maize (Zea mays L.), as a globally significant cereal crop, exhibits high sensitivity to salt stress during early seedling stages. Although melatonin (MT) has demonstrated potential in mitigating abiotic stresses, the specific mechanisms underlying MT-mediated alleviation of salt stress in maize seedlings remain unclear. In this study, we established four treatment groups: control (CK), melatonin treatment (MT), salt stress (NaCl), and combined treatment (NaCl_MT). Metabolomic and proteomic analyses were performed, supplemented by photosynthesis-related experiments as well as antioxidant-related experiments. Metabolomic analysis identified key metabolites in MT-mediated salt stress mitigation. Both metabolomic and proteomic analyses underscored the critical roles of photosynthetic and antioxidant pathways. Salt stress significantly decreased the net photosynthetic rate (Pn) by 67.7%, disrupted chloroplast ultrastructure, and reduced chlorophyll content by 41.6%. Conversely, MT treatment notably mitigated these detrimental effects. Moreover, MT enhanced the activities of antioxidant enzymes by approximately 10–20% and reduced the accumulation of oxidative stress markers by around 10–25% in maize seedlings under salt stress. In conclusion, this study conducted a systematic and multidimensional investigation into the mitigation of salt stress in maize seedlings by MT. Our results revealed that MT enhances antioxidant systems, increases chlorophyll content, and alleviates damage to chloroplast ultrastructure, thereby improving photosystem II performance and strengthening photosynthesis. This ultimately manifests as improved seedling phenotypes under salt stress. These findings provide a meaningful entry point for breeding salt-tolerant maize varieties and mitigating the adverse effects of salinized soil on maize growth and yield. Full article

Background: Eleutherococcus senticosus (Rupr. et Maxim.) Maxim., widely used in Russian and Chinese traditional medicine for its anti-inflammatory activity, contains bioactive compounds capable of stabilizing epithelial function and reducing inflammation. Despite prior research on its effects in the colon, the impact and mechanism of action of E. senticosus fruit extract on epithelial tissues of the upper digestive and respiratory tract remains unexplored. Objectives: This study aimed to evaluate the influence of E. senticosus fruit extract on the transepithelial electrical potential and resistance in the tracheal and small intestinal epithelium of rabbits. In addition, the chemical composition of the extract was also profiled by the means of UHPLC-DAD-MS. Methods: Tissue segments from the trachea and small intestine of New Zealand white male rabbits were examined using the Ussing chamber technique. Three concentrations of E. senticosus fruit extract (0.001, 0.1, 10 mg/100 mL) were applied, and changes in transepithelial electrical potential (dPD) and resistance (R) were recorded. Chemical analysis of the extract was conducted using UHPLC-DAD-MS. Results: For the first time, we have discovered that the E. senticosus extract increased membrane resistance in tracheal tissue, suggesting enhanced barrier integrity. In contrast, a slight decrease in resistance was observed in small intestinal tissue. UHPLC-DAD-MS confirmed the presence of chlorogenic acid, dicaffeoylquinic acids, quercetin derivatives, and myo-inositol, compounds known for their antioxidant, anti-inflammatory, and membrane-stabilizing effects. Conclusions: The differential response of respiratory and intestinal epithelium to the E. senticosus extract highlights its tissue-specific action and supports its traditional use in the prevention and treatment of diseases characterized by epithelial barrier dysfunction, such as asthma, COPD, and Crohn’s disease. Full article

Peptides are widely used in cosmetic formulations to stimulate extracellular matrix (ECM) synthesis, while silybin (a flavonolignan from Silybum marianum) offers retinol-like benefits through antioxidant and photoprotective activity. This study evaluated a novel anti-aging cream combining seven bioactive peptides with silybin to assess synergistic effects on ECM regeneration and clinical skin rejuvenation. In vitro assays in human dermal fibroblasts and keratinocytes revealed that the formulation rapidly upregulated gene and protein expression of collagen types I, III, IV, and XVII and lysyl oxidase (LOX) within 4–16 h. Ex-vivo, ultraviolet (UV)-damaged skin explants treated with the peptide–silybin complex showed enhanced recovery of collagen, elastic fibers, and LOX versus untreated controls. A 56-day clinical study (n = 31) demonstrated significant improvements in wrinkle area and volume, elasticity (+12.5%), firmness (+20.7%), and dermal density (+78%, all p < 0.001). No adverse effects were reported, and over 80% of participants noted improved skin texture and firmness. These findings highlight a novel synergy between peptides and silybin, with rapid ECM activation and clinical efficacy. To our knowledge, this is the first evidence of a cosmetic peptide formulation significantly upregulating LOX expression, suggesting a new mechanism for strengthening dermal architecture and improving skin resilience. Future studies should elucidate the mechanisms underlying these effects and assess whether other botanicals confer complementary benefits when combined with peptide blends. Full article

Kalanchoe pinnata, commonly known as the “miracle plant” or “life plant”, is a succulent species traditionally used for various health conditions. Recent research investigations have intensified interest in this species due to its diverse repertoire of bioactive constituents, including flavonoids, alkaloids, triterpenes, and glycosides. These compounds have been associated with multiple therapeutic effects, notably antioxidant, anti-inflammatory, and antidiabetic activities. Although several studies have highlighted the positive effects of the extracts of K. pinnata on key factors contributing to the pathophysiology and complications of diabetes mellitus, a systematic overview focusing on the use of these extracts and their bioactive constituents in the management of the disease is lacking. This literature review summarizes the phytochemical composition, traditional uses, and recent scientific data supporting the antidiabetic potential of K. pinnata, with a particular focus on its effects on glycemic control, as well as inflammatory and oxidative homeostasis, toxicity, safety, and potential clinical implications. The phytochemical constituents discussed include quercetin, kaempferol, apigenin, epigallocatechin gallate (EGCG), avicularin, and bufadienolides, along with a presentation of representative structures. The review also covers the potential mechanisms of action in diabetes mellitus. The survey of available literature highlights the effects of K. pinnata on indices of diabetes mellitus, including enhancing insulin sensitivity, mitigating oxidative stress and inflammation, lowering blood glucose levels, and the potential adverse effects. These results point to the promising prospect for K. pinnata use in the management of diabetes mellitus and its associated complications, while underscoring the need for more rigorous investigations, including well-controlled clinical trials. Full article

Oxidative stress occurs within bovine when exposed to harmful stimuli, accompanied by substantial accumulation of reactive oxygen species. Without timely clearance, these reactive oxygen species attack vascular endothelial cells, concurrently inducing extensive production of lipid peroxides within the vascular endothelium, and thereby triggering ferroptosis. Aspirin eugenol ester (AEE) showed pharmacological activity against oxidative stress-induced vascular endothelial damage. However, whether it could alleviate vascular endothelial damage by inhibiting ferroptosis remains unclear. This study aimed to evaluate the effects of AEE on vascular endothelial ferroptosis and elucidate its underlying molecular mechanisms. This study established vascular endothelial damage models in vitro and in vivo to explore the ability of AEE to inhibit ferroptosis and oxidative stress by measuring ferroptosis- and oxidative stress-related biomarkers. Transcriptomic and network pharmacology analyses were performed to identify AEE-regulated pathways and key targets. Validation of the pathways were conducted using molecular docking, cellular thermal shift assay, and specific protein agonists/inhibitors. AEE inhibited oxidative stress and ferroptosis in bovine aortic endothelial cells induced by hydrogen peroxide (H₂O₂) or RSL3 via suppressing the upregulation of ferroptosis-related genes and enhancing the expression of antioxidant genes. Transcriptomic and network pharmacology analyses identified JNK as a core target of AEE in regulating ferroptosis. JNK agonists enhanced H₂O₂-induced ferritinophagy; on the contrary, JNK inhibitors alleviated it. AEE suppressed H₂O₂-induced phosphorylation of JNK/c-Jun and ferritinophagy. In a carrageenan-induced rat aortic vascular endothelial damage model, AEE alleviated vascular endothelial damage and ferroptosis-related gene changes, promoted antioxidant gene expression, and inhibited JNK/c-Jun phosphorylation and ferritinophagy. AEE inhibited vascular endothelial ferroptosis by enhancing antioxidant ability, blocking downstream ferritinophagy, and reducing ferrous ion release. Full article

The emergence of antibiotic-resistant bacteria has resulted in a lack of available drugs that can be used to treat various diseases. Antimicrobial peptides (AMPs) are green and safe antibiotic alternatives. In 2022, an outbreak of an acute diarrheal disease caused by Gram-negative cocci named Neisseria occurred among domestic geese (Anser cygnoides orientalis) in Northeast China. In this study, we analyzed Neisseria S1, which caused diarrhea in geese, and determined whether AMP R7I designed in our laboratory can be used to treat Neisseria infection. This is the first report and isolation of enteropathogenic Neisseria, as well as the first report of Neisseria infection in Anser cygnoides orientalis. Peptide R7I has the capability to counteract Neisseria S1 infection both in vivo and in vitro. R7I induced the release of intracellular contents, leading to the death of Neisseria. Oral treatment of R7I modulated metabolic levels, antioxidant capacity, and immune responses and inhibited inflammation in Neisseria-infected geese. Furthermore, R7I significantly contributed to the recovery of intestinal homeostasis and regulated intestinal function via a signaling pathway related to metabolism in Neisseria infection. During our study of the mechanism of R7I against Neisseria infection, we preliminary found that R7I regulates lipid metabolism disorder and inflammation caused by Neisseria infection through the PPAR signaling pathway. In conclusion, R7I shows a strong ability against Neisseria infection, and it can be used as an oral antibiotic alternative in animal feed. Full article