Search Results (13,228)

Heat stress (HS) is known to cause liver injury through mechanisms involving oxidative stress and inflammation, thereby highlighting the need for effective therapeutic interventions. This study evaluated the efficacy of sprouted black quinoa extract (SBQE) in mitigating HS-induced liver injury in a rat model. SBQE was obtained through an ultrasonication-assisted ethanol–water extraction process from black quinoa germinated for 48 h. Sprague Dawley rats (male) were administered via oral gavage SBQE at doses of 200, 400, or 800 mg/kg prior to each HS exposure (40 °C for 2 h per day over a period of 8 days). Pretreatment with SBQE resulted in a dose-dependent reduction in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, with the high dose (800 mg/kg) reducing these enzyme levels (p < 0.001 vs. HS group) and alleviating histopathological damage, including a significant decrease in hepatocyte vacuolization and inflammatory cell infiltration (histopathological scores were reduced by p < 0.001 in the 800 mg/kg SBQE group vs. HS group). SBQE also dose-dependently inhibited the accumulation of mitochondrial reactive oxygen species (mean fluorescence intensity decreased by p < 0.001 at 800 mg/kg) and the formation of malondialdehyde while restoring the activities of antioxidant enzymes such as superoxide dismutase (p < 0.01 at 800 mg/kg), catalase (p < 0.05 at 800 mg/kg), and glutathione peroxidase (p < 0.001 at 800 mg/kg), as well as replenishing glutathione levels (p < 0.001 at 800 mg/kg). Furthermore, the levels of proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, interleukin-1β, and interleukin-18) in liver tissue were significantly reduced (with the high dose leading to p < 0.001 vs. HS group), which was associated with enhanced nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2; p < 0.05 at 800 mg/kg) and decreased phosphorylation of nuclear factor-κB p65 (NF-κB; p < 0.001 at 800 mg/kg). Additionally, the protein expression of NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome components and markers of apoptosis were diminished. The results demonstrated that SBQE alleviated HS-induced liver injury by concurrently activating the Nrf2 antioxidant pathway and suppressing NF-κB/NLRP3 inflammasome signaling, suggesting its potential as a nutraceutical intervention for HS-related hepatotoxicity. Full article

In this study, astaxanthin, which has previously been shown to have antiviral effects, was examined for its dose-dependent potency to inhibit cellular SARS-CoV-2 infections. Naturally occurring astaxanthin is obtained and orally administered as ASX-oleoresin, a composition of different astaxanthin fatty acid esters. We therefore hypothesized that the compound’s beneficial effects are not only related to astaxanthin. Thus, a “green” algae extract (i.e., poor astaxanthin content < 0.2%; ASX^p) of the microalgae Haematococcus pluvialis, as well as an astaxanthin-rich algae extract (astaxanthin content = 20%; ASX^r), were tested in in vitro cellular viral infection assays. Thereby, it was found that both extracts reduced viral infections significantly. As a potential mode of inhibitory action, the binding of ASX-oleoresin to the viral spike protein was investigated by isothermal fluorescence titration, revealing binding affinities of Kd = 1.05 µM for ASX^r and Kd = 1.42 µM for ASX^p. Based on our data, we conclude that several ASX-oleoresin fractions from H. pluvialis exhibit antiviral activity, which extends beyond the known antioxidant activity of astaxanthin. From a molecular dynamic simulation of ASX-oleoresin, fatty acid domains could be considered as activity-chaperoning factors of ASX. Therefore, microalgae biomass should be considered in the future for further antiviral activities. Full article

Seeds of Cucurbitaceae crops represent a promising yet underexplored source of bioactive compounds with potential applications beyond nutrition, particularly in the cosmetics industry. This review examines the seeds of Citrullus lanatus (watermelon), Cucumis melo (melon), and Cucurbita pepo (pumpkin), focusing on their biochemical composition and evaluating their functional value in natural cosmetic development. Although these fruits are widely consumed, industrial processing generates substantial seed by-products that are often discarded. These seeds are rich in polyunsaturated fatty acids, proteins, carbohydrates, and phytochemicals, positioning them as sustainable raw materials for value-added applications. The incorporation of seed-derived extracts into cosmetic formulations offers multiple skin and hair benefits, including antioxidant activity, hydration, and support in managing conditions such as hyperpigmentation, acne, and psoriasis. They also contribute to hair care by improving oil balance, reducing frizz, and enhancing strand nourishment. However, challenges such as environmental instability and low dermal permeability of seed oils have prompted interest in nanoencapsulation technologies to improve delivery, stability, and efficacy. This review summarizes current scientific findings and highlights the potential of Cucurbitaceae seeds as innovative and sustainable ingredients for cosmetic and personal care applications. Full article

The pathophysiological mechanism linking oxidative stress and cardiovascular disease (CVD) is not completely elucidated, especially in young individuals. This study aimed to examine redox status in an adolescent Montenegrin population in relation to cardiovascular risk score (CVRS). A cohort of 182 adolescents (76% girls) aged between 16 and 19 was examined. Total antioxidant status (TAS), superoxide dismutase (SOD), advanced oxidation protein products (AOPPs), malondialdehyde (MDA), and total oxidant status (TOS) were determined. Pro-oxy score, anti-oxy score, and oxy score were calculated as comprehensive parameters of overall redox homeostasis status. CVRS was calculated by summarizing several risk factors (i.e., sex, age, obesity, hypertension, dyslipidemia, impaired fasting glucose, and smoking). A significant positive correlation between CVRS and TOS (rho = 0.246, p = 0.001) and AOPP (rho = 0.231, p = 0.002) and MDA (rho = 0.339, p < 0.001), respectively, and a negative correlation with the TAS/TOS ratio (rho= −0.208, p = 0.005) was observed. An increase in pro-oxy scores as well as oxy scores with CVRS risk increase were observed. Anti-oxy scores did not differ between CVRS subgroups. There is a significant relationship between cardiovascular risk score and oxidative stress in the adolescent Montenegrin population. These findings support the possibility for improvement of age-specific CVD risk algorithms by adding redox homeostasis parameters in addition to conventional ones. Full article

With increasing interest in natural therapeutic strategies for skin aging, plant-derived compounds have gained attention for their potential to protect against oxidative stress and inflammation. In this study, we investigated the anti-aging and anti-inflammatory effects of flavonoids isolated from Cercidiphyllum japonicum using a tumor necrosis factor-alpha (TNF-α)-stimulated normal human dermal fibroblast (NHDF) model. The aerial parts of C. japonicum were extracted and analyzed by high-performance liquid chromatography (HPLC), leading to the identification of four major compounds: maltol, chlorogenic acid, ellagic acid, and quercitrin. Each compound was evaluated for its antioxidant and anti-aging activities in TNF-α-stimulated NHDFs. Among them, ellagic acid exhibited the most potent biological activity and was selected for further mechanistic analysis. Ellagic acid significantly suppressed intracellular reactive oxygen species (ROS) generation and matrix metalloproteinase-1 (MMP-1) secretion (both p < 0.001), while markedly increasing type I procollagen production (p < 0.01). Mechanistic studies demonstrated that ellagic acid inhibited TNF-α-induced phosphorylation of mitogen-activated protein kinases (MAPKs), downregulated cyclooxygenase-2 (COX-2), and upregulated heme oxygenase-1 (HO-1), a key antioxidant enzyme. Additionally, ellagic acid attenuated the mRNA expression of inflammatory cytokines, including interleukin-6 (IL-6) and interleukin-8 (IL-8), indicating its broad modulatory effects on oxidative and inflammatory pathways. Collectively, these findings suggest that ellagic acid is a promising plant-derived bioactive compound with strong antioxidant and anti-inflammatory properties, offering potential as a therapeutic agent for the prevention and treatment of skin aging. Full article

Background: In this study, the preparation of pea glycopeptides based on the Maillard glycosylation pathway (PPH-M) and its antagonistic mechanism against alcoholic liver injury in zebrafish were studied. Results: The results showed that the conjugation of D-xylose significantly improved the antioxidant activity of pea protein hydrolysates (PPHs). The structural characterization indicated that PPH was successfully covalent binding to D-xylose, which was mainly manifested as a stretching vibration change in Fourier transform infrared spectroscopy (FTIR) and molecular size increase. Scanning electron microscopy (SEM) and zeta potential also confirmed the covalently bound of the two. In addition, a model of alcohol-induced liver injury in zebrafish was established. Through the intervention of different doses of PPH-M, it was found that the intervention of PPH-M could significantly increase superoxide dismutase (SOD) activity, reduce malondialdehyde (MDA) content, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) activity, and significantly improve alcohol-induced liver injury in zebrafish. The protective effect of PPH-M was also confirmed by liver pathology and fluorescence microscopy. Finally, reverse transcription-polymerase chain reaction (qRT-PCR) results indicated that PPH-M could significantly regulate the expression level of antioxidant-related mRNA. PPH-M could also regulate the expression of the Keap1/Nrf2 signaling pathway and up-regulated glutathione synthesis signaling pathway to antagonize alcohol-induced liver injury in zebrafish. Conclusion: This study revealed the mechanism of PPH-M antagonized alcoholic liver injury and laid a theoretical foundation for its development as functional foods. Full article

Parkinson’s disease (PD) is a progressive, multisystemic α-synucleinopathy, recognized as the second most prevalent neurodegenerative disorder globally. Its neuropathology is characterized by the degeneration of dopaminergic neurons, particularly in the substantia nigra pars compacta (SNpc), and the intraneuronal accumulation of α-synuclein-forming Lewy bodies. Oxidative stress is a key contributor to PD pathogenesis. Thioredoxin-interacting protein (TXNIP) is a crucial regulator of cellular redox balance, inhibiting the antioxidant function of thioredoxin. This pilot study aimed to investigate the protein expression and localization of TXNIP in the SNpc of PD patients compared to healthy controls. We performed immunohistochemical analyses on 12 post-mortem human brain sections (formalin-fixed, paraffin-embedded) from six subjects with PD and six healthy controls. The study was performed on PD subjects with Braak stage 6. Our findings revealed that in control samples, TXNIP protein was distinctly and closely associated with neuromelanin (NM) pigment within the cytoplasm of SNpc dopaminergic neurons. Conversely, in PD samples, there was a markedly weak cytoplasmic expression of TXNIP, and critically, this association with NM pigment was absent. Furthermore, PD samples exhibited a significant reduction in both dopaminergic neurons and NM content, consistent with advanced disease. These findings, which mirror previous transcriptomic data showing TXNIP gene under-expression in the same subjects, suggest that altered TXNIP expression and localization in SNpc dopaminergic neurons are features of late-stage PD, potentially reflecting neuronal dysfunction and loss. Full article

(1) Background: The goal of the present study was to evaluate whether the supplementation with a multi-species probiotic in the diet of laying hens can change the microbiota and health status of the oviduct. (2) Methods: A total of 60 cages housing lightweight laying hens (36 weeks old) were randomly assigned to the following two different treatments: a control group fed a diet without probiotic, and a treatment group receiving diets supplemented with 50 g/ton of probiotics. The trial lasted for 26 weeks, after which five layers were slaughtered per treatment for oviduct (magnum) assessment, focusing on microbiome composition, oxidant and antioxidant status, and morphological analyses. Additionally, intestinal (jejunum) samples were collected to determine oxidant and antioxidant status. (3) Results: Probiotic supplementation resulted in lower counts of organisms from the RB41 order (p = 0.039) and Burkholderia genus (p = 0.017), and a total reduction in Bacillus and Corynebacterium (p = 0.050) compared to the control treatment. Genera Burkholderia (p = 0.017), Corynebacterium (p = 0.050), and Bacillus (p = 0.050) were also lower with the probiotic supplementation in relation to the control. Genera Epulopiscium (p = 0.089), Flavobacterium (p = 0.100), Ruminococcus (p = 0.089), and Staphylococcus (p = 0.100) tended to be lower in the probiotic group compared to the control. No significant differences were found between treatments for oviduct lesions. Probiotic treatment resulted in a higher protein thiol level in the intestine compared to the control (p < 0.001). However, the use of probiotics tended to reduce glutathione S-transferase levels in the oviduct compared to the control (p = 0.068). (4) Conclusions: These results suggest that dietary supplementation with probiotics can modulate the oviduct microbiota and improve the antioxidant status of laying hens, without causing tissue damage. Further research is warranted to explore the long-term implications of these changes on reproductive performance and egg quality. Full article

Background/Objectives: The breast cancer susceptibility gene 1 (BRCA1) is a tumor suppressor gene whose mutations are associated with increased susceptibility to develop breast or ovarian cancer. BRCA1 mainly exerts its protective effects through DNA double-strand break repair. Although not itself a transcriptional factor, BRCA1, through its multiple protein interaction domains, exerts transcriptional coregulation. In addition, BRCA1 expression alters cellular metabolism including inhibition of de novo fatty acid synthesis, changes in cellular bioenergetics, and activation of antioxidant defenses. Some of these actions may contribute to its global oncosuppressive effects. However, the breadth of metabolic pathways reprogrammed by BRCA1 is not fully elucidated. Methods: Breast cancer cells expressing BRCA1 were investigated by multiplatform metabolomics, metabolism-related transcriptomics, and joint metabolomics/transcriptomics data processing techniques, namely two-way orthogonal partial least squares and pathway analysis. Results: Joint analyses revealed the most important metabolites, genes, and pathways of metabolic reprogramming in BRCA1-expressing breast cancer cells. The breadth of metabolic reprogramming included fatty acid synthesis, bioenergetics, HIF-1 signaling pathway, antioxidation, nucleic acid synthesis, and other pathways. Among them, rewiring of glycerophospholipid (including phosphatidylcholine, -serine and -inositol) metabolism and increased arginine metabolism have not been reported yet. Conclusions: Rewired glycerophospholipid and arginine metabolism were identified as components of BRCA1-induced metabolic reprogramming in breast cancer cells. The study helps to identify metabolites that are candidate biomarkers of the BRCA1 genotype and metabolic pathways that can be exploited in targeted therapies. Full article

Background/Objectives: Vitex agnus-castus has been traditionally used to treat hormonal disorders, and recent evidence suggests its potential anticancer properties. However, its effects on gastric cancer remain unclear. Methods: This study examined the cytotoxic, apoptotic, and anti-metastatic effects of hydroalcoholic Vitex agnus-castus seed extract in gastric cancer cells. Antioxidant capacity (DPPH, ABTS) and total phenolic and flavonoid contents were analyzed. Cytotoxicity was assessed using the MTT assay in HGC27, MKN45, and AGS gastric cancer cell lines and CCD-1072Sk fibroblasts. Apoptosis, mitochondrial membrane potential (MMP), and cell cycle changes were evaluated via Annexin V-FITC/PI, Rhodamine 123, and PI staining, respectively. RT-qPCR and gene enrichment analyses were conducted to investigate the molecular mechanisms. Apoptosis-related protein expression was analyzed through enzyme-linked immunosorbent assay (ELISA). Results: The extract exhibited high antioxidant activity and a significant phenolic content. It reduced cell viability in a dose-dependent manner in gastric cancer cells, while exerting low toxicity in fibroblasts. It significantly increased apoptosis, induced G0/G1-phase cell cycle arrest, upregulated pro-apoptotic genes (CASP3, CASP7, TP53, BCL2L11), and downregulated anti-apoptotic genes (XIAP, NOL3). Gene enrichment analysis highlighted pathways like apoptosis, necrosis, and cysteine endopeptidase activity. The extract also disrupted MMP, inhibited migration and spheroid formation, suppressed EMT markers (SNAIL, SLUG, TWIST1, N-CADHERIN), and upregulated E-CADHERIN. The expression of Caspase 3 and Bax proteins increased and Bcl2 protein decreased. Conclusions: These findings suggest that Vitex agnus-castus seed extract exerts strong anticancer effects in gastric cancer cells by promoting apoptosis, reducing proliferation, and inhibiting migration. Further studies are warranted to explore its clinical relevance. Full article

Sodium p-perfluorous nonenoxybenzenesulfonate (OBS) has been proposed as a substitute for perfluorooctanesulfonic acid (PFOS), yet it has garnered increasing attention due to its environmental persistence and potential toxicity. Despite these concerns, the neurotoxic mechanisms of OBS remain unclear. This study investigates and compares the neurotoxic effects and mechanisms of OBS and PFOS in Caenorhabditis elegans. L4-stage worms were exposed to OBS (0.1–100 μM) or PFOS (100 μM) for 24 h. Neurobehavioral analysis showed that OBS exposure induced concentration-dependent neurobehavioral deficits, with 100 μM OBS significantly reducing pharyngeal pumping rate (29.8%), head swing frequency (23.4%), and body bending frequency (46.6%), surpassing the effects of PFOS. Both compounds decreased the fluorescence intensity of dopaminergic, glutamatergic, and γ-aminobutyric acid neurons and downregulated neurotransmitter-associated genes. They also increased ROS generation and inhibited antioxidant gene expression. Molecular docking revealed that OBS had a stronger binding affinity to p38 MAPK key protein (PMK-1) than PFOS. OBS and PFOS upregulated pmk-1 and skn-1, modulating oxidative stress and neuronal function. pmk-1 mutation differentially affected OBS-induced neurobehavioral changes and gene expression alterations. Our findings indicate that OBS exhibits stronger neurotoxicity than PFOS in Caenorhabditis elegans, mediated through the PMK-1 pathway. These results highlight the need for further investigation into the safety of OBS as a PFOS alternative. Full article

Coffee silverskin (CS), a by-product generated during coffee roasting, contains high levels of xylan hemicellulose and protein, making it a promising substrate for functional ingredient production. This study developed an integrated bioprocess to simultaneously produce bioactive peptides and xylooligosaccharides (CS-XOS) from CS. Conventional alkaline extraction (CAE) under optimized conditions (1.0 M NaOH, 90 °C, 30 min) yielded 80.64 mg of protein per gram of CS and rendered the solid residue suitable for XOS production. Enzymatic hydrolysis of the extracted protein using protease_SE5 generated low-molecular-weight peptides (0.302 ± 0.01 mg/mL), including FLGY, FYDTYY, and FDYGKY. These peptides were non-toxic, exhibited in vitro antioxidant activity (0–50%), and showed ACE-inhibitory activities of 60%, 26%, and 79%, and DPP-IV-inhibitory activities of 19%, 18%, and 0%, respectively. Concurrently, the alkaline-treated CS solid residue (ACSS) was hydrolyzed using recombinant endo-xylanase, yielding 52.5 ± 0.08 mg of CS-XOS per gram of ACSS. The CS-XOS exhibited prebiotic effects by enhancing the growth of probiotic lactic acid bacteria (μ_max 0.100–0.122 h⁻¹), comparable to commercial XOS. This integrated bioprocess eliminates the need for separate processing lines, enhances resource efficiency, and provides a sustainable strategy for valorizing agro-industrial waste. The co-produced peptides and CS-XOS offer significant potential as functional food ingredients and nutraceuticals. Full article

Reactive oxygen species (ROS) are often seen solely as harmful byproducts of oxidative metabolism, yet evidence reveals their paradoxical roles in both promoting and inhibiting cancer progression. Despite advances, precise context-dependent mechanisms by which ROS modulate oncogenic signaling, therapeutic response, and tumor microenvironment dynamics remain unclear. Specifically, the spatial and temporal aspects of ROS regulation (i.e., the distinct effects of mitochondrial versus cytosolic ROS on the PI3K/Akt and NF-κB pathways, and the differential cellular outcomes driven by acute versus chronic ROS exposure) have been underexplored. Additionally, the specific contributions of ROS-generating enzymes, like NOX isoforms and xanthine oxidase, to tumor microenvironment remodeling and immune modulation remain poorly understood. This review synthesizes current findings with a focus on these critical gaps, offering novel mechanistic insights into the dualistic nature of ROS in cancer biology. By systematically integrating data on ROS source-specific functions and redox-sensitive signaling pathways, the complex interplay between ROS concentration, localization, and persistence is elucidated, revealing how these factors dictate the paradoxical support of tumor progression or induction of cancer cell death. Particular attention is given to antioxidant mechanisms, including NRF2-mediated responses, that may undermine the efficacy of ROS-targeted therapies. Recent breakthroughs in redox biosensors (i.e., redox-sensitive fluorescent proteins, HyPer variants, and peroxiredoxin–FRET constructs) enable precise, real-time ROS imaging across subcellular compartments. Translational advances, including redox-modulating drugs and synthetic lethality strategies targeting glutathione or NADPH dependencies, further highlight actionable vulnerabilities. This refined understanding advances the field by highlighting context-specific vulnerabilities in tumor redox biology and guiding more precise therapeutic strategies. Continued research on redox-regulated signaling and its interplay with inflammation and therapy resistance is essential to unravel ROS dynamics in tumors and develop targeted, context-specific interventions harnessing their dual roles. Full article

Oxidative stress significantly contributes to the exacerbation of brain damage during cerebral ischemia-reperfusion injury (CIR/I). In our previous study, purified cornel iridoid glycoside (PCIG), consisting of morroniside (MOR) and loganin (LOG), showed neuroprotective effects against CIR/I. To further explore the antioxidative effects and underlying molecular mechanisms, we applied PCIG, MOR, and LOG to rats injured by middle cerebral artery occlusion/reperfusion (MCAO/R) as well as H₂O₂-stimulated PC12 cells. Additionally, the molecular docking analysis was performed to assess the interaction between the PCIG constituents and Kelch-like ECH-associated protein 1 (Keap1). The results showed that the treated rats experienced fewer neurological deficits, reduced lesion volumes, and lower cell death accompanied by decreased levels of malondialdehyde (MDA) and protein carbonyl, as well as increased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). In H₂O₂-stimulated PC12 cells, the treatments decreased reactive oxygen species (ROS) production, mitigated mitochondrial dysfunction, and inhibited mitochondrial-dependent apoptosis. Moreover, the treatments facilitated Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) translocation into the nucleus and selectively increased the expression of NAD(P)H quinone oxidoreductase 1 (NQO-1) and heme oxygenase 1 (HO-1) through MOR and LOG, respectively. Both MOR and LOG demonstrated strong binding affinity to Keap1. These findings suggested that PCIG, rather than any individual components, might serve as a valuable treatment for ischemic stroke by activating the Nrf2/NQO-1 and Nrf2/HO-1 signaling pathway. Full article

The present study evaluated the effect of adding 0% (control), 30%, 40% and 50% SPMs (small-peptide chelating trace minerals) to replace ITMs (inorganic trace minerals) in the diets of Litopenaeus vannamei; 720 shrimp were randomly assigned to four treatments (six replicates per group, 30 shrimp per replicate) in a 42-day feeding trial. There were no significant differences (p > 0.05) among the control, 40% SPM and 50% SPM groups in terms of the survival rate, weight gain rate, specific growth rate, hepatosomatic index, condition factor, feed intake, feed conversion ratio, or protein efficiency ratio; however, protein efficiency ratio was reduced in the 30% SPM group (p < 0.05). Glucose, triglyceride, and aspartate aminotransferase levels in the hemolymph of the 30% SPM group were significantly increased (p < 0.05), while the glucose and aspartate aminotransferase levels were also significantly increased in the 40% SPM group (p < 0.05). In the 50% SPM group, the glucose and triglyceride levels were also significantly increased (p < 0.05). Hepatopancreatic alkaline phosphatase activity was elevated at 40% SPM, and alkaline phosphatase, acid phosphatase, glutathione peroxidase, and total antioxidant capacity activities were significantly increased in the 50% SPM group (p < 0.05). The moisture content and drip loss were reduced in both the 40% and 50% SPM groups (p < 0.05). Therefore, replacing 40–50% ITMs with SPMs can maintain growth performance while enhancing physiological functions. In conclusion, the results of this study demonstrate that the incorporation of 30–50% SPMs into one’s diet constitutes a viable alternative to 100% ITMs. Full article