The islet amyloid polypeptide (IAPP) is a 37-residue peptide hormone secreted by pancreatic β-cells that is known to aggregate into amyloid fibrils. These fibrils accumulate in the pancreatic islets of individuals afflicted with type 2 diabetes and are implicated in β-cell dysfunction. Metal ions such as copper and zinc are known to modulate IAPP fibrillization, yet the role of metal-induced oxidative modifications in this process remains largely unexplored. This study examines the non-enzymatic post-translational oxidation of IAPP and its effects on aggregation using the biologically relevant Cu/O2/ascorbate system. Mass spectrometry identified residues within the amyloidogenic region (residues 20–29) as the primary targets of oxidation. These oxidative modifications impaired the formation of cross-β-sheet amyloid fibrils and promoted the accumulation of amorphous aggregates. The H18A IAPP derivative, lacking the key metal-binding histidine, was also examined to assess the impact of sequence variation on oxidation and aggregation. Copper-mediated oxidation of H18A resulted in a broader distribution of oxidation sites and impacts fibril formation. These findings provide preliminary mechanistic insights into copper-induced oxidation and its impact on IAPP aggregation pathways.

Prunella vulgaris L. (PV) is a versatile plant with medicinal and culinary applications globally. Its mature fruit-spikes (red-brown) are the primary source of traditional medicine and herbal tea. However, large-scale cultivation and harvesting inevitably leads to the unintended inclusion of immature green fruit-spikes, which are considered substandard medicinal parts. To explore the medicinal and nutraceutical potential of green fruit-spikes, our study systematically compared green and red-brown samples. The distinctions between the two fruit-spikes were characterized by determination of total water-soluble extract content, comprehensive chemical difference analysis, and quantitation of six phenolic acids, including Danshensu, caffeic acid, protocatechuic acid, protocatechualdehyde, salviaflaside, and rosmarinic acid. Additionally, variations in antioxidant activity were evaluated by DPPH and ABTS assays. As a result, 106 compounds were identified from the PV samples. Green spikes exhibited higher total water extract yield and contents of the six phenolic acids than the red-brown ones. Moreover, green samples showed greater accumulations of phenolic acids, flavonoids, and triterpenes. Concomitantly, stronger antioxidant activity was displayed in green spikes in both assay models. Caffeic acid, danshensu, rosmarinic acid, and protocatechualdehyde were identified as major contributors by Pearson correlation analysis. Our findings reveal that green fruit-spikes possess advantages in accumulating specific chemical profiles and exhibiting antioxidant activity, highlighting their untapped pharmaceutical and nutraceutical potential.

Fulfilling the demand for functional food with cost safety and environmental sustainability, our novel anthocyanin-enriched functional drink containing the purple waxy corn cob-derived functional ingredient “MP1” showed cognitive enhancing effects with safety in bilaterally ovariectomized rats, a validated model of menopause. Since no clinical evidence that confirms the mentioned effect was available until now, we conducted a two-arm, randomized, double-blind, placebo-controlled, crossover study to confirm the benefits mentioned above. A total of 32 menopausal participants were divided into placebo and MP1 (400 mg) groups, and were subject to a 2-month study period. Safety parameters, working memory and brain components, especially N100 and P300, the negative and positive potentials derived from the event-related potential (ERP) which indicated attention and cognitive processing, together with oxidative stress markers acetylcholinesterase (AChE) and monoamine oxidase (MAO), were assessed at baseline and every month. No serious side effects or toxicity signs were observed. Subjects who consumed MP1 also had decreased N100 and P300 latency, improved working memory and decreased oxidative stress status. Therefore, a byproduct of purple corn can successfully serve as a novel functional ingredient for developing a cognitive enhancer drink with the qualities of safety, cost reduction, and environmental sustainability promotion.

Background: Premature ovarian insufficiency (POI) poses a significant challenge for women. The effects of Cucumaria frondosa tentacles hydrolysates (CFTH) on POI remain to be fully elucidated. Purpose: This study aimed to determine whether CFTH exerts a beneficial effect on ovarian function using a POI mouse model and to investigate the underlying mechanisms of action. Methods: In this study, we characterized the amino acid composition and physicochemical properties of CFTH. The POI model was established by administering 100 mg/kg of cyclophosphamide (CP). We assessed the regulation of the estrous cycle, hormone levels, ovarian cell apoptosis, and oxidative stress markers in POI mice. Differences in ovarian and uterine morphology among the different groups were observed. Furthermore, metabolomics analysis was employed to explore potential mechanisms. Results: CFTH treatment reversed the dysregulation of the estrous cycle and hormone levels. TUNEL analysis revealed that CFTH treatment significantly reduced apoptosis in granulosa cells and altered the expression levels of apoptosis-related genes at the mRNA level. Additionally, CFTH significantly increased superoxide dismutase activity and decreased malondialdehyde levels, thereby mitigating oxidative stress. Metabolomics analysis suggested that CFTH may ameliorate ovarian dysfunction by regulating steroid biosynthesis and the cGMP-PKG signaling pathway. Conclusions: These findings suggest that CFTH may serve as an effective strategy for alleviating POI. Further research is warranted to verify the long-term safety and effectiveness of CFTH in humans.

Oxidative stress induces reactive oxygen species (ROS) accumulation, which compromises sperm DNA integrity, cellular homeostasis, and semen quality in Hainan black goats. This study aimed to mitigate ROS-mediated sperm damage by examining the protective effects of curcumin on metabolic regulation and sperm structural integrity. Semen samples were treated in vitro with varying concentrations of curcumin (5, 25, 50 μmol/L) under oxidative stress conditions. The intermediate concentration (25 μmol/L) was most effective at enhancing sperm quality. Following treatment, sperm motility, membrane integrity, and acrosome stability were significantly improved (p < 0.05), while ROS levels and apoptosis rates decreased. Antioxidant enzyme activities—glutathione peroxidase (GPX, p < 0.05), catalase (CAT, p < 0.05), and superoxide dismutase (SOD, p < 0.05)—were markedly elevated. Metabolomic analysis identified 48 differential metabolites (p < 0.05), including gluconic acid, 3-hydroxybutyric acid, and argininosuccinic acid, which were mainly involved in antioxidant defense, energy metabolism (e.g., the citrate cycle), and osmoregulatory pathways. Lipidomics revealed reduced lipid peroxidation and increased polyunsaturated fatty acid content, correlating with enhanced membrane stability. Transmission and scanning electron microscopy revealed preservation of sperm ultrastructure, with reduced mitochondrial and chromatin damage. Quantitative PCR further indicated curcumin-mediated downregulation of pro-apoptotic genes (BAX, Caspase3, and FAS) and upregulation of the anti-apoptotic gene BCL2 (p < 0.05). These findings demonstrate that Curcumin at 25 μM mitigated menadione-induced oxidative stress in goat sperm in vitro, improving antioxidant status, mitochondrial function and membrane integrity while reducing apoptosis. Multi-omic profiling supported redox and lipid homeostasis restoration. These findings establish proof-of-principle in an acute oxidative model.

Lacmellea edulis, traditionally known as chicle, is a species that has received little attention despite its nutraceutical potential. This study aimed to evaluate the physicochemical characteristics (pH, soluble solids, titratable acidity, moisture, ash, and minerals) and the content of bioactive compounds (vitamin C, organic acids, carotenoids, and phenols) of fruits at different stages of ripeness, as well as their antimicrobial (against Candida albicans, Candida tropicalis, Escherichia coli, Staphylococcus aureus, and Streptococcus mutans), antiproliferative and antihaemolytic activity. Bioactive compounds were quantified using liquid chromatography, while biological activities were assessed via spectrophotometric assays. The results revealed a high concentration of ascorbic acid in the ripe pulp (3.0 mg/100 g DW), higher levels of organic acids in the unripe pulp (3947.6 mg/100 g DW), and a high total phenol content in the ripe peel (10,890.9 mg/100 g DW). The peel exhibited the highest antioxidant activity (63.3 mmol ET/100 g DW). Regarding antimicrobial activity, the pulp exhibited the lowest MIC values against E. coli (2.7 mg/mL) and S. mutans (2.6 mg/mL), the peel against S. aureus (21.3 mg/mL) and C. tropicalis (5.3 mg/mL), and the seeds against C. albicans (20.8 mg/mL). Additionally, the peel exhibited the greatest antiproliferative efficacy against cervical (HeLa) and hepatoma (HepG2) cancer cells. None of the evaluated extracts showed significant haemolytic effects, confirming their safety. Overall, L. edulis appears to be a promising source of bioactive metabolites with potential applications in functional foods and pharmaceutical products.

Selenoprotein thioredoxin reductase 1 (TXNRD1) is frequently upregulated in various cancer cells to sustain cellular redox homeostasis, and its inhibition has emerged as a promising anti-cancer strategy. In this study, we identified PK11007, a thiol-modifying compound previously characterized as a p53 reactivator, as a potent inhibitor of TXNRD1. PK11007 irreversibly inhibited recombinant TXNRD1 in a time- and dose-dependent manner. Using differential scanning fluorimetry (DSF) and LC–MS/MS analysis, we confirmed that PK11007 covalently modifies the C-terminal redox motif (Cys497-Sec498) of TXNRD1. In non-small cell lung cancer (NSCLC) H1299 cells, PK11007-induced TXNRD1 inhibition disrupted cellular redox balance, leading to impaired autophagy flux and cell death. Similar autophagy suppression was observed in TXNRD1-knockdown cells, as well as pharmacological inhibition of TXNRD1 by Auranofin (AF) and TXNRD1 inhibitor 1 (TRi-1). Taken together, these findings highlight that oxidative stress contributes to the cytotoxic effects of PK11007 and uncover autophagy disorder as a downstream consequence of TXNRD1 inhibition.

This study investigated the role of miR-144 in mitigating oxidized fish oil (OFO)-induced muscle oxidative stress and quality deterioration in Megalobrama amblycephala. The feeding trial was conducted for 5 weeks, and four experimental diets were formulated, namely NC (fresh fish oil), OF (OFO), OF + ago (OFO and miR-144 agomir), and OF + anta (OFO and miR-144 antagomir). Histological results showed that OFO significantly reduced myofiber density (from 758.00 ± 13.69 to 636.57 ± 13.44 N/mm2) and decreased the percentage of myofibers with diameters > 50 μm (from 53.45% to 38.52%). OFO intake significantly increased the content of malondialdehyde (MDA), protein carbonyl (PC), advanced oxidation protein product (AOPP), and 3-nitrotyrosine (3-NT), and significantly decreased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity in muscle. OFO treatment significantly up-regulated the expression of inflammatory factors (NF-κB, TNF-α, HO-1, and IL-6), significantly down-regulated NQO1. Moreover, OFO reduced muscle differentiation and maturation by down-regulating the expression of MyoG, MYHC1, and protein synthesis genes (AKT3, TOR, and S6K1), and up-regulating the expression of protein hydrolysis genes (FoxO3a, MuRF1, HSP70, Beclin-1, P62, and ATG8). Moreover, miR-144 agomir exacerbated OFO-induced muscle damage by suppressing Nrf2, whereas miR-144 antagomir mitigated these effects. Silencing miR-144 re-activates Nrf2, alleviating oxidative damage, enhancing protein deposition, and improving muscle quality. These findings suggest that targeting the miR-144/Nrf2 axis could counteract OFO-induced muscle deterioration.

Lysolecithin, characterized by its superior emulsifying and stabilizing properties, facilitates nutrient absorption and is extensively utilized in aquatic feed formulation. Nevertheless, its precise function in shrimp nutrition and physiology remains inadequately understood. This study aimed to evaluate the feasibility and optimal dosage of replacing 2% soybean lecithin with varying levels of soybean lysolecithin (0–2%) in the diet of Litopenaeus vannamei. Growth performance, antioxidant indices, and lipid metabolism were assessed. The results demonstrated that dietary supplementation with 0.1% lysolecithin had the best growth performance, significantly improved lipid retention and apparent crude fat digestibility, while reducing malondialdehyde (MDA) levels in the hepatopancreas and alleviating endoplasmic reticulum (ER) stress. The 0.1% group also exhibited better hepatopancreatic tissue structure and lipid metabolic homeostasis. In contrast, higher inclusion levels (≥1.5%) led to increased lipid accumulation and enhanced activities of lipid metabolic enzymes but were associated with a risk of oxidative stress and less favorable tissue morphology. No significant differences in antioxidant enzyme activities were observed among groups. It is hypothesized that lysolecithin may regulate lipid metabolism and homeostasis via the Ca2+/CaMKKβ/AMPK signaling pathway; further studies are required to confirm this mechanism. In conclusion, 0.1% soybean lysolecithin is recommended as the optimal dietary level for L. vannamei, supporting its feasibility as a substitute for 2% soybean lecithin in shrimp feed.

The use of antioxidants in the dermatocosmetic industry has become increasingly popular to help protect and stabilize other sensitive active ingredients, prolonging the effectiveness and durability of the cosmetic product. Grape pomace, as the main by-product generated through winemaking, and Polygonum cuspidatum, concentrate bioactive metabolites with high antioxidant activity. Hydroalcoholic extracts obtained from grape pomace (Merlot and Feteasca Neagra varieties) and the root and flower of Japanese knotweed, respectively, alone and in mixtures, were characterized, and preliminary assays were conducted for their incorporation in two gel-based cosmetic formulations. The characterization of the extracts revealed the presence of catechin, vanillic acid, caffeic acid, myricetin, resveratrol, and kaempferol. The hydroalcoholic extract of P. cuspidatum flower and root was found to have the highest content of total phenolic compounds (10.920 ± 0.268 mg GAE/mL, respectively, 4.751 ± 0.072 mg GAE/mL), and the highest antioxidant activity (expressed as DPPH Radical Scavenging Capacity, IC50) by 28.04 ± 1.12 µg GAE/mL and 83.91 ± 1.13 µg GAE/mL, respectively. Catechin was the most abundant polyphenol found in pomace extract (687.87 mg/kg). The type and the concentration of the plant extract used in dermatocosmetic gel formulations influenced their antioxidant activity. Encapsulation of P. cuspidatum flower extract in liposomes prior to their incorporation into the gel formulation demonstrated the role of liposomes in enhancing the stability and modulation of phenolic compound delivery. It is worth noting that this dermatocosmetic formulation, which contains the flower extract of P. cuspidatum, was the subject of a pending patent application.