Search Results (441)

Microplastics (MPs) represent an emerging pollutant capable of entering the human body through the respiratory and digestive systems, thereby posing significant health risks. Systemic lupus erythematosus (SLE) is a complex autoimmune disease that affects multiple organ systems, often presenting with polyarticular joint manifestations. Despite its relevance, there is currently limited research on the impact of MPs on lupus arthritis. This study aims to investigate the effects of MPs on joint inflammation in SLE. MRL/lpr mice exhibit SLE similar to that of humans. We administered either 0.5 mg/kg or 5 mg/kg of MPs to 8-week-old female MRL/lpr mice via oral ingestion. Our findings indicate that exposure to MPs can lead to synovial damage, adversely affecting the morphology and function of the knee joint, along with increased oxidative stress, apoptosis, synovial fibrosis, and the secretion of inflammatory cytokines. Notably, MPs significantly enhanced synovial cell pyroptosis by upregulating the expression of NLRP3, CASPASE-1, GSDMD, IL-1β, and IL-18. Mechanistic analyses further demonstrated that MPs exposure activates the NF-κB and NRF2/KEAP1 signaling pathways. Overall, our in vivo findings suggest that MPs exposure promotes synovial cell pyroptosis through increased oxidative stress and NF-κB signaling, thereby disrupting the structure and function of synovial tissue. This research provides new insights into the synovial damage associated with MPs exposure. Full article

The effects of starvation and refeeding on the gut condition of juvenile largemouth bass (Micropterus salmoides) remain unclear. Therefore, our research aimed to explore these effects. Amylase and lipase activities were remarkably decreased in the starvation (ST) group, yet prominently increased in the refeeding (RE) group (p < 0.05). In addition to the malondialdehyde (MDA) level, catalase (CAT) and superoxide dismutase (SOD) activities were significantly upregulated in the ST group (p < 0.05) in marked contrast to those in the controls; however, the RE group showed no substantial variations in CAT and SOD activities or the MDA level (p > 0.05). During starvation, the expression of Nrf2-Keap1 pathway-associated genes was significantly upregulated (p < 0.05). The comparative levels of TNF-α, IL-1β, and IL-15 were highly increased, with the levels of TGF-β1 and IL-10 apparently downregulated in the ST group; in contrast, these levels were restored to their original values in the RE group (p < 0.05). In contrast to the controls, the ST group showed significantly lower height and width of the villi, muscle thickness, and crypt depth and a higher goblet cell number; however, these values were recovered to some extent in the RE group (p < 0.05). The dominant bacterial phyla in the intestines of both groups were Proteobacteria, Firmicutes, Bacteroidetes, Acidobacteria, and Actinobacteria, with marked inter-group differences in the genera Serratia and Lactobacillus. Metabolomics analysis showed that amino acid metabolism is disrupted during starvation and is restored after refeeding. In summary, this study expands our comprehension of the interaction between oxidative stress and antioxidant defenses among juvenile largemouth bass subjected to starvation and refeeding. Full article

Oenobiol Sun Expert, a food formulation designed to enhance skin health prior to sun exposure, has been optimized by incorporating the OenoGrape Advanced Complex, which includes grape pomace extract, increased selenium content and 10% lycopene-rich tomato extract, with these constituents exhibiting high antioxidant potential. To evaluate the effects of these individual ingredients and the overall formulation at the cellular level, the AOP1 cell antioxidant efficacy assay was employed to measure the intracellular free radical scavenging activity, while the Cell Antioxidant Assay (CAA or DCFH-DA) assay was used to assess peroxidation scavenging at the plasma membrane level. The indirect antioxidant activity was examined using stably transfected cell lines containing a luciferase reporter gene controlled by the Antioxidant Response Element (ARE), which activates the endogenous antioxidant system via the Nrf2/Keap1-ARE pathway. Our results indicate that among the individual components, grape pomace extract and sodium selenite possess high and complementary antioxidant properties. Grape pomace extract was particularly effective in inhibiting free radicals (AOP1 EC₅₀ = 6.80 μg/mL) and activating the ARE pathway (ARE EC₅₀ = 231.1 μg/mL), whereas sodium selenite exerted its effects through potent ARE activation at sub-microgram levels (EC₅₀ = 0.367 μg/mL). In contrast, the lycopene-rich tomato extract did not show a notable contribution to the antioxidant effects. The antiradical activity of the OenoGrape Advanced Complex, comprising these three ingredients, was very efficient and consistent with the results obtained for the individual components (AOP1 EC₅₀ = 15.78 µg/mL and ARE EC₅₀ of 707.7 μg/mL). Similarly, the free radical scavenging activity still persisted in the Oenobiol Sun Expert formulation (AOP1 EC₅₀ = 36.63 µg/mL). Next, in vitro intestinal transepithelial transfer experiments were performed. The basolateral compartments of cells exposed to the ingredients were collected and assessed using the same antioxidant cell assays. The direct and indirect antioxidant activities were measured on both hepatocytes and keratinocytes, demonstrating the bioavailability and bioactivity of grape pomace extract and sodium selenite. These finding suggest that the ingredients of this food supplement contribute to enhanced cytoprotection following ingestion. Full article

Background/Objectives: Ischemic stroke is a leading cause of disability and mortality worldwide, with current therapies limited in addressing its complex pathophysiological mechanisms, such as inflammation, oxidative stress, apoptosis, and impaired autophagy. Glycyrrhizic acid (GA), a bioactive compound from licorice (Glycyrrhiza glabra L.), has demonstrated neuroprotective properties in preclinical studies. This review consolidates current evidence on GA’s pharmacological mechanisms and assesses its potential as a therapeutic agent for ischemic stroke. Methods: This review examines findings from recent preclinical studies and reviews on GA’s neuroprotective effects, focusing on its modulation of inflammation, oxidative stress, apoptosis, and autophagy. Studies were identified from major scientific databases, including PubMed, Web of Science, and Embase, covering research from January 2000 to August 2024. Results: GA has demonstrated significant neuroprotective effects through the modulation of key pathways, including HMGB1/TLR4/NF-κB and Keap1/Nrf2, thereby reducing neuroinflammation, oxidative stress, and apoptosis. Additionally, GA promotes autophagy and modulates immune responses, suggesting it could serve as an adjunct therapy to enhance the efficacy and safety of existing treatments, such as thrombolysis. Conclusions: Current findings underscore GA’s potential as a multi-targeted neuroprotective agent in ischemic stroke, highlighting its anti-inflammatory, antioxidant, and anti-apoptotic properties. However, while preclinical data are promising, further clinical trials are necessary to validate GA’s therapeutic potential in humans. This review provides a comprehensive overview of GA’s mechanisms of action, proposing directions for future research to explore its role in ischemic stroke management. Full article

Lung cancer is the leading cause of cancer-related mortality worldwide, primarily driven by genetic mutations. The most common genetic alterations implicated in lung cancer include mutations in TP53, KRAS, KEAP1, NF1, EGFR, NRF2, ATM, ALK, Rb1, BRAF, MET, and ERBB2. Targeted therapies have been developed to inhibit cancer growth by focusing on these specific genetic mutations. However, either the mutations are undruggable or the efficacy of these therapies is often compromised over time due to the emergence of drug resistance, which can occur through additional mutations in the targeted protein or alternative growth signaling pathways. In recent years, immunotherapy has emerged as a promising approach to enhance the effectiveness of cancer treatment by leveraging the body’s immune system. Notable advancements include immune checkpoint inhibitors, monoclonal antibodies targeting cell surface receptors, antibody–drug conjugates, and bispecific antibodies. This review provides an overview of the mechanisms of FDA-approved immunotherapeutic drugs, offering an updated perspective on the current state and future developments in lung cancer therapy. More importantly, the factors that positively and negatively impact the immunotherapy’s efficacy will also be discussed. Full article

PTD-FNK, a synthetic anti-apoptotic protein, has been shown to potently alleviate cellular injuries. However, the effects of PTD-FNK on oxidative defense in boar testicular Sertoli cells (SCs) against oxidative injury has not been explored. In this study, we show that exposure of SCs to 100 mg/L lipopolysaccharide (LPS) for 12 h leads to decreased survival rate, superoxide dismutase (SOD) activity, and increased malondialdehyde (MDA). Treatment with 0.01 nmol/L PTD-FNK for 4 h significantly enhanced the activity of SOD, catalase (CAT), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) in SCs. Concurrently, PTD-FNK treatment effectively reduced the production of reactive oxygen species (ROS) and the levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG) in SCs. Moreover, using His pull-down and LC-MS techniques, we identified PTD-FNK-interacting proteins and confirmed that this protective effect may be mediated by the regulation of the Keap1-Nrf2 signaling pathway by PTD-FNK. Therefore, PTD-FNK alleviates LPS-induced oxidative stress via the Keap1/Nrf2 pathway, providing novel insights for the development of therapeutic agents targeting testicular oxidative damage. Full article

Artemisia ordosica polysaccharides (AOP) can promote animal growth, improve intestinal morphology, regulate immunity, and enhance antioxidant capacity. To investigate the antioxidant capacity of AOP, three experiments were conducted. (1) Different concentrations of AOP (0, 50, 100, 150, 200, and 250 μg/mL) and 1 µg/mL VA on peripheral blood lymphocytes (PBLs) treated with/without lipopolysaccharides (LPS) were investigated to select the optimum concentration. The results showed that 150 μg/mL AOP had significant antioxidation activity. (2) The PBLs was randomly divided into eight treatments with six replicates, namely CON, AOP, LPS, ML385 (Nrf2 inhibitor), AOP + LPS, AOP + ML385, LPS + ML385 and LPS + ML385 + AOP. The results showed that under a normal condition or stress condition, AOP presented antioxidation activity via upregulating Nrf2/Keap1 pathway-related gene expression. (3) The PBLs was randomly divided into eight treatments with six replicates, namely CON, AOP, LPS, PDTC (NF-κB inhibitor), AOP + LPS, AOP + PDTC, LPS + PDTC and LPS + PDTC + AOP. The results showed that under a normal condition, AOP presented antioxidation activity via increasing TLR4/NF-κB pathway-related gene expression; under a stress condition, AOP alleviated oxidative damage caused by LPS via suppressing TLR4/NF-κB pathway-related gene expression. Full article

Periodontitis affects up to 40% of adults over 60 years old and is a consequence of gingivitis. Periodontitis is characterized by a chronic inflammation, periodontal damage, and alveolar bone resorption. The nuclear factor erythroid 2-related factor 2 (NFE2L2 or NRF2)/Kelch-like ECH-Associated Protein 1 (KEAP1) (NRF2/KEAP1) signaling pathway plays a key role in periodontitis by modulating redox balance and inflammation of the periodontium. However, NRF2 expression is decreased in gingival tissues of patients with periodontitis while oxidative stress is significantly increased in this pathology. Oxidative stress and lipopolysaccharide (LPS) produced by gram-negative bacteria favor the production of inflammatory causing periodontal inflammation and favoring alveolar bone. In this review, we analyzed the current literature regarding the role of natural and synthetic compounds in modulating the NRF2/KEAP1 pathway in in vitro and in vivo models of periodontitis in order to evaluate new potential treatments of periodontitis that can improve the outcome of this disease. Full article

Background/Objectives: The beneficial effects of the flavonoid chrysin can be reduced by its poor oral bioavailability. It has been shown that chrysin-8-C-glucoside (1) has a better absorption capability. The aim of this study was to evaluate the antioxidant and anti-inflammatory activity of this glucoside, as well as the respective hexa-acetate derivative 1a and the hexa-ethyl carbonate derivative 1b since the inclusion of moieties in bioactive molecules may increase or modify their biological effects. Methods: THP-1 macrophages were used to determine the viability in the presence of chrysin derivatives, and non-cytotoxic concentrations were selected. Subsequently, lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) production and inflammatory mediators were examined. The involvement of chrysin derivatives with the Keap1 and Nrf2 antioxidant system was determined by docking and Western blotting studies. Results: Our data demonstrated, for the first time, that pretreatment with the three compounds caused a significant reduction in LPS-induced reactive oxygen species (ROS) production and pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin 1β (IL-1β) levels, as well as in cyclooxygenase 2 (COX-2) expression. The mechanisms underlying these protective effects were related, at least in part, to the competitive molecular interactions of these phenolic compounds with Kelch-like ECH-associated protein 1 (Keap1)–nuclear factor erythroid 2-related factor 2 (Nrf2), which would allow the dissociation of Nrf2 and its translocation into the nucleus and the subsequent up-regulation of hemo-oxygenase 1 (HO-1) expression. Conclusions: Compared to the 8-C-glucoside parent chrysin, compound 1a exhibited the strongest antioxidant and anti-inflammatory activity. We hypothesized that the incorporation of an acetate group (1a) may reduce its polarity and, thus, increase membrane permeability, leading to better pharmacological activity. These findings support the potential use of these phenolic compounds as Nrf2 activators against oxidative-stress-related inflammatory diseases. Full article

Background: Premature ovarian failure (POF) is a common disease among women, which can cause many complications and seriously threaten women’s physical and mental health. Currently, hormone replacement therapy is the primary treatment for premature ovarian failure. However, the side effects are serious and will increase the chance of breast cancer and endometrial cancer. Deer blood hydrolysate (DBH) is the product of enzymatic hydrolysis of deer blood, has antioxidant, anti-ageing, and anti-fatigue effects, and has the potential to improve premature ovarian failure. Methods: In our experiment, a mouse model of premature ovarian failure was established through intraperitoneal injection of 400 mg/kg/d of D-gal for 42 days. At the same time, different doses of DBH were gavaged to observe its ameliorative effect on premature ovarian failure. Results: The experimental findings indicated that DBH could restore the irregular oestrus cycle of POF mice, improve the abnormal amounts in serum hormones follicle-stimulating hormone (FSH), luteinising hormone (LH), progesterone (P) and estradiol (E2), increase the number of primordial follicles and decrease the number of atretic follicles. In addition, DBH also raised the level of superoxide dismutase (SOD) and reduced the level of malondialdehyde (MDA) and reduced the apoptosis of ovarian granulosa cells in mice. The WB assay results showed that gavage of DBH restored the decrease in the indication of nuclear factor erythroid 2-related factor 2 (Nrf2), Heme Oxygenase-1 (Ho-1), and B-cell lymphoma-2 (Bcl-2) proteins and reduced the elevated expression of Kelch-like ECH-associated protein 1 (Keap1), Bcl-2 associated X protein (Bax), and Cysteinyl aspartate specific proteinase-3 (Caspase-3) proteins that were induced by D-gal. Conclusions: To sum up, the present research indicated that DBH can ameliorate D-gal-induced oxidative stress and apoptosis by regulating the Nrf2/HO-1 signalling pathway and the Bcl-2/Bax/caspase-3 apoptosis pathway, which can be used for further development as a nutraceutical product to improve premature ovarian failure. Full article

Overexposure to ultraviolet (UV) radiation can lead to photoaging, which contributes to skin damage. The objective of this study was to evaluate the effects of an antioxidant peptide (SHP2) purified from seahorse (Hippocampus abdominalis) alcalase hydrolysate on UVB-irradiated skin damage in human keratinocyte (HaCaT) and human dermal fibroblast (HDF) cells and a zebrafish model. The data revealed that SHP2 significantly enhanced cell viability by attenuating apoptosis through the reduction of intracellular reactive oxygen species (ROS) levels in UVB-stimulated HaCaT cells. Moreover, SHP2 effectively inhibited ROS, improved collagen synthesis, and suppressed the secretion of matrix metalloproteinases (MMPs) in UVB-irradiated HDF cells. SHP2 restored the protein levels of HO-1, Nrf2, and SOD, while decreasing Keap1 expression in UVB-treated HDF, indicating stimulation of the Keap1/Nrf2/HO-1 signaling pathway. Furthermore, an in vivo study conducted in zebrafish confirmed that SHP2 inhibited photoaging by reducing cell death through the suppression of ROS generation and lipid peroxidation. Particularly, 200 µg/mL of SHP2 exerted a remarkable anti-photoaging effect on both in vitro and in vivo models. These results demonstrate that SHP2 possesses antioxidant properties and regulates skin photoaging activities, suggesting that SHP2 may have the potential for use in the development of cosmetic products. Full article

Zearalenone (ZEA) is a mycotoxin produced by Fusarium spp. fungi and is widely found in moldy corn, wheat, barley, and other grains. ZEA is distributed to the whole body via blood circulation after metabolic transformation in animals. Through oxidative stress, immunosuppression, apoptosis, autophagy, and mitochondrial dysfunction, ZEA leads to hepatitis, neurodegenerative diseases, cancer, abortion, and stillbirth in female animals, and decreased sperm motility in male animals. In recent years, due to the influence of climate, storage facilities, and other factors, the problem of ZEA pollution in global food crops has become particularly prominent, resulting in serious problems for the animal husbandry and feed industries, and threatening human health. Resveratrol (RSV) is a natural product with therapeutic activities such as anti-inflammatory, antioxidant, and anticancer properties. RSV can alleviate ZEA-induced toxic effects by targeting signaling pathways such as NF-κB, Nrf2/Keap1, and PI3K/AKT/mTOR via attenuating oxidative damage, inflammatory response, and apoptosis, and regulating cellular autophagy. Therefore, this paper provides a review of the protective effect of RSV against ZEA-induced toxicity and its molecular mechanism, and discusses the safety and potential clinical applications of RSV in the search for natural mycotoxin detoxification agents. Full article

Skin cancer is one of the most common malignancies worldwide. Cold atmospheric pressure Plasma (CAP) is increasingly successful in skin cancer therapy, but further research is needed to understand its selective effects on cancer cells at the molecular level. In this study, A431 (squamous cell carcinoma) and HaCaT (non-malignant) cells cultured under identical conditions revealed similar ROS levels but significantly higher antioxidant levels in unstimulated A431 cells, indicating a higher metabolic turnover typical of tumour cells. HaCaT cells, in contrast, showed increased antioxidant levels upon CAP stimulation, reflecting a robust redox adaptation. Specifically, proteins involved in antioxidant pathways, including NF-κB, IκBα, Nrf2, Keap1, IKK, and pIKK, were quantified, and their translocation level upon stimulation was evaluated. CAP treatment significantly elevated Nrf2 nuclear translocation in non-malignant HaCaT cells, indicating a strong protection against oxidative stress, while selectively inducing NF-κB activation in A431 cells, potentially leading to apoptosis. The expression of pro-inflammatory genes like IL-1B, IL-6, and CXCL8 was downregulated in A431 cells upon CAP treatment. Notably, CAP enhanced the expression of antioxidant response genes HMOX1 and GPX1 in non-malignant cells. The differential response between HaCaT and A431 cells underscores the varied antioxidative capacities, contributing to their distinct molecular responses to CAP-induced oxidative stress. Full article

The discarding of agri-food by-products is a stringent problem due to their high environmental impact. Recovery strategies can lead to a reduction of waste and result in new applications. Agri-food waste represents a source of bioactive molecules, which could promote health benefits. The primary goal of this research has been the assessment of the antioxidant activity of milk permeate, a dairy farm by-product, and the isolation and identification of peptide fractions endowed with antioxidant activity. The chromatographic extraction of the peptide fractions was carried out, and the peptides were identified by mass spectrometry. The fractions showed radical scavenging activity in vitro. Moreover, the results in the Caco-2 cell model demonstrated that the peptide fractions were able to protect from oxidative stress by stimulating the Keap1/Nrf2 antioxidant signaling pathway, increasing the transcription of antioxidant enzymes. In addition, the bioactive peptides can affect cellular metabolism, increasing mitochondrial respiration. The action of the peptide fractions was also assessed in vivo on a zebrafish model and resulted in the protection of the whole organism from the adverse effects of acute cold stress, highlighting their strong capability to protect from an oxidative insult. Altogether, the results unveil novel recovery strategies for food by-products as sources of antioxidant bioactive peptides that might be utilized for the development of functional foods. Full article

Herein, the ultrasound-assisted extraction conditions affecting the yield of EUPS (Eucommia ulmoides polysaccharide) were analyzed using a Box-Behnken response surface design. The alleviation effect of EUPS on diquat-induced oxidative stress in mice was also studied. A maximum EUPS yield of 2.60% was obtained under the following optimized conditions: an extraction temperature of 63 °C, extraction time of 1 h, and ratio of liquid to raw materials of 22:1. EUPS exhibited strong 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical-scavenging ability (87.05%), 2′-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) radical-scavenging ability (101.17%), and hydroxyl radical-scavenging ability (62.92%). The administration of EUPS increased the activities of superoxide dismutase, catalase, and glutathione peroxidase and decreased malondialdehyde levels in the livers of mice exposed to diquat. EUPS may inhibit the downregulation of NAD(P)H:quinoneoxidoreductase 1 and heme oxygenase 1 mRNA expression in the livers of diquat-administered mice through the Nrf2-Keap1 signaling pathway. Moreover, the abundance of Firmicutes and Ligilactobacillus was enhanced, whereas that of Helicobacter decreased in the gut of the remaining groups of mice compared with that of the diquat-treated mice. Therefore, EUPS exhibited an antioxidant effect and improved oxidative stress and intestinal flora abundance in mice. Full article