Search Results (2,787)

Breast cancer continues to be the leading cancer diagnosis among women worldwide, affecting populations in both industrialized and developing regions. Given the rising number of diagnosed cases each year, there is an urgent need to explore novel compounds with potential anticancer properties. One group of such candidates includes cationic peptides, which have shown promise due to their unique membrane-targeting mechanisms that are difficult for cancer cells to resist. This study presents an initial biophysical assessment of NA-CATH:ATRA-1-ATRA-1, a synthetic peptide modeled after NA-CATH, originally sourced from the venom of the Chinese cobra (Naja atra). The peptide’s interactions with lipid bilayers mimicking cancerous and healthy cell membranes were examined using differential scanning calorimetry and Fourier-transform infrared spectroscopy. Findings revealed a pronounced affinity of NA-CATH:ATRA-1-ATRA-1 for eukaryotic membrane lipids, particularly phosphatidylserine, indicating that its mechanism likely involves electrostatic attraction to negatively charged lipids characteristic of cancer cell membranes. Such biophysical insights are vital for understanding how membrane-active peptides could be harnessed in future cancer therapies. Full article

Ischemia–reperfusion (I/R) injury is a complex pathological process underlying numerous acute organ failures and is a significant cause of morbidity and mortality in diseases such as myocardial infarction, stroke, thrombosis, and organ transplantation. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have demonstrated considerable therapeutic potential, but their broad tropism and general repair signaling may limit their efficacy. This review addresses the emerging paradigm of using organ-specific EVs for the treatment of I/R injury in the respective organs. We summarize the existing studies performed on experimental animals showing that these native EVs could possess tissue tropism and carry a specialized cargo of proteins, miRNAs, and lipids tailored to the unique regenerative needs of their organ of origin, enabling them to precisely modulate key processes, including inflammation, apoptosis, oxidative stress, and angiogenesis. However, their clinical translation faces challenges related to scalable production, standardization, and the dualistic nature of their effects, which can be either protective or detrimental, depending on the cellular source and pathophysiological context. Future developments need to focus on overcoming these obstacles through rigorous isolation protocols, engineering strategies such as cargo enrichment and hybrid vesicle creation, and validation in large-animal models. Overall, organ-specific EVs offer a novel, cell-free therapeutic strategy with the potential to significantly improve outcomes in I/R injury. Full article

Lignocellulosic agricultural residues represent a rich source of potential feedstock for biorefinery applications, but their valorization remains challenging. The white-rot fungus Irpex lacteus J2 exhibited a promising degradation effect, but its molecular mechanisms of lignocellulose degradation remained largely uncharacterized. Here, we performed high-quality whole-genome sequencing and untargeted metabolomic profiling of I. lacteus J2 during the degradation of corn straw as the sole carbon source. The assembled I. lacteus J2 genome contained 14,647 protein-coding genes, revealing a rich genetic repertoire for biomass degradation and secondary metabolite synthesis. Comparative genomics showed high synteny (mean amino acid sequence identity 92.28%) with I. lacteus Irplac1. Untargeted metabolomic analysis unveiled a dynamic metabolic landscape during corn straw fermentation. Dominant metabolite classes included organic acids and derivatives (27.32%) and lipids and lipid-like molecules (25.40%), as well as heterocyclic compounds (20.41%). KEGG pathway-enrichment analysis highlighted significant activation of core metabolic pathways, with prominent enrichment in global metabolism (160 metabolites), amino acid metabolism (99 metabolites), carbohydrate metabolism (24 metabolites), and lipid metabolism (19 metabolites). Fermentation profiles at 3 and 15 days demonstrated substantial metabolic reprogramming, with up to 210 upregulated and 166 downregulated metabolites. Correlation analyses further revealed complex metabolic interdependencies and potential regulatory roles of key compounds. These integrated multi-omics insights significantly expand our understanding of the genetic basis and metabolic versatility, enabling I. lacteus J2 to efficiently utilize lignocellulose. Our findings position I. lacteus J2 as a robust model strain and provide a valuable foundation for developing advanced fungus-based strategies for sustainable bioprocessing and valorization of agricultural residues. Full article

To assess the influence of dietary bile acid (BA) on the phenotype associated with hepatic lipid metabolism and its regulation of lipid homeostasis in gibel carp (Carassius auratus gibelio) under high-fat diet (HFD) conditions, five HFDs were designed using soybean oil (SO) as the single lipid source and supplemented with 0, 200, 400, 600, and 800 mg/kg BA (designated as BA0, BA200, BA400, BA600, and BA800, respectively). Juvenile fish (32.37 ± 0.13 g) were fed five BA-added HFDs (12% SO) for 8 weeks. Considerably lower levels of aspartate transaminase, alanine aminotransferase, low-density lipoprotein, triglyceride, and total cholesterol in the serum were observed in gibel carp fed with HFDs with 400–600 mg/kg BA (p < 0.05). The hepatocytes of the BA400 and BA600 groups were intact without abnormal architecture or histopathological changes, compared to other groups. The presence of most genes related to fatty acid biosynthesis decreased significantly with the addition of 400–600 mg/kg BA (p < 0.05), while the gene expressions of hormone-sensitive lipase, adiponectin receptor 2, and peroxisome proliferator-activated receptor α were variably up-regulated, along with the elevation of dietary BA (p < 0.05). Critical genes involved in bile acid and cholesterol synthesis were obviously down-regulated in gibel carp receiving 600–800 mg/kg dietary BA (p < 0.05), despite the sterol 27-hydroxylase (cyp27a1) gene in the BA800 group (p < 0.05). Moreover, hepatopancreas from the BA0 and BA600 groups were isolated for transcriptome sequencing, identifying 7040 differentially expressed genes (DEGs). The enriched KEGG pathways of DEGs mainly included steroid biosynthesis, protein digestion and absorption, etc. Seven randomly selected DEGs were validated using qRT-PCR and were in agreement with the RNA-seq results. Consequently, the appropriate supplementation of dietary BA for juvenile gibel carp is recommended at doses of 400–600 mg/kg in SO-based HFDs, which could contribute to the amelioration of HFD-induced excessive fat deposition in the hepatopancreas of gibel carp by both inhibiting fatty acid intake, biosynthesis, and steroid production and enhancing lipid decomposition. The findings may elucidate the physiological role of exogenous BA in fish and its underlying mechanism, providing references for the reasonable application of BA in aquafeeds and the prevention of HFD-induced metabolic dysfunction in fish. Full article

Background/Objectives: Watermelon (Citrullus lanatus) is a natural dietary source of L-citrulline and L-arginine, the two amino acids involved in nitric oxide (NO) production and vasodilation. Pre-clinical and clinical studies using isolated amino acids or watermelon extracts suggest blood pressure (BP)-lowering potential; however, limited research has been conducted on the impact of watermelon flesh (WM) on BP in adults at risk for hypertension. Therefore, the primary objective of this study was to assess the effect of daily WM intake for four weeks on 24 h ambulatory BP in adults with elevated blood pressure. The secondary outcomes of this study include changes in glucose and insulin markers, lipid profile, NO, L-citrulline, L-arginine, asymmetric dimethylarginine (ADMA) concentrations, and the L-arginine/ADMA ratio. Methods: In this randomized, placebo controlled parallel study design, 39 adults (age: 41 ± 14 years, BMI: 31 ± 6 kg/m², mean ± SD) with elevated BP were randomly assigned to one of three groups for a 4-week intervention: control (0 g WM), WM-1 cup (152 g/day), or WM-2 cups (304 g/day). Ambulatory BP was measured over 24 h at baseline and the end of the intervention period. Fasting plasma samples were analyzed for metabolic biomarkers on a clinical analyzer and NO using a colorimetric assay. L-citrulline, L-arginine, and ADMA were analyzed using an ultra-high-performance liquid chromatography triple quadrupole mass spectrometer (UHPLC-QQQ-MS/MS). Statistical analyses were conducted using SPSS software (IBM SPSS Statistics, Version 29.0.0). Results: After 4 weeks, mean 24 h ambulatory BP was 130.2 ± 3.9 mm Hg (control), 130 ± 3.2 mm Hg (WM-1 cup), and 124.9 ± 3.9 mm Hg (WM-2 cups), with no statistically significant differences between study interventions (p > 0.05). Similarly, no significant changes were observed in fasting plasma glucose, insulin, lipid profile, or NO concentrations. However, plasma L-arginine concentrations and L-arginine/ADMA ratios significantly increased in the WM groups compared to the control (p = 0.009) after adjusting for age, BMI, race, and gender in the statistical model. Conclusion: Overall, BP was not significantly different after two different doses of watermelon compared to control; however, improvements in NO synthesis pathway precursors (L-arginine, ADMA) suggest potential for dietary modulation to support endothelial function and BP regulation. Full article

Oat seeds contain peroxygenase, a heme enzyme localized in both the microsomal and the lipid droplet fractions, which are usually separated by multiple ultracentrifugation steps. In this work, it was shown that peroxygenase activity is retained in the lipid fraction (LF) of oat seeds, which is obtained by simple extraction of flour with organic solvents. The enzymatic activity of this crude preparation was tested in the oxidation of thioanisole in comparison with a peroxygenase-containing microsome preparation (MP) from the same plant source in both aqueous medium and pure organic solvents. In most cases, higher activity was observed in the LF preparation, which proved to be stable in organic solvents for at least 24 h, thus offering a good option for the oxidation of highly water-insoluble substrates. LF-peroxygenase maintained the same stereoselectivity features observed with MP, as also demonstrated in the epoxidation reaction of limonene. A protocol for the oxidation of thioanisole in CH₃CN was set up on a preparative scale, and the corresponding sulfoxide was obtained at concentration of 1.7 M and with 84% ee. Full article

Deoxynivalenol (DON) is one of the most common trichothecene mycotoxins found in cereals, posing a significant hazard to food and feed safety. Insects, especially the yellow mealworm (Tenebrio molitor), offer promising alternative protein sources; however, their capacity to metabolise mycotoxins and the nutritional implications are still not fully understood. In this study, T. molitor larvae were reared for two weeks on diets containing DON at 663 or 913 µg/kg, and their biomass was analysed using Liquid Chromatography–Quadrupole Time-of-Flight Mass Spectrometry (LC-QTOF) for DON metabolites and free amino acids, as well as Gas Chromatography–Flame Ionization Detector (GC-FID) for fatty acid profiles. Larvae metabolised DON via multiple pathways, including sulfonation, glucuronidation, sulfation, glucosylation, and de-epoxidation, with a time- and dose-dependent shift towards glucosylation and de-epoxidation. DON exposure significantly reduced the levels of essential amino acids such as methionine, lysine, phenylalanine, and isoleucine, and lowered metabolic intermediates like aspartic and glutamic acid. Conversely, prolonged DON exposure increased linoleic acid levels in larval fat, indicating altered lipid metabolism. These findings demonstrate that T. molitor larvae detoxify DON but incur measurable metabolic costs, leading to changes in amino acid and fatty acid profiles. The dual effect—reduction of toxin levels and nutritional shifts—highlights both the potential and the challenges of using insects for sustainable feed production. Full article

As a major source of high-quality protein in China, duck meat such as the renowned Beijing Duck plays a critical role in the poultry industry. Sansui duck, a prized native breed, is valued for its tender meat and rich flavor, yet molecular mechanisms underlying its meat quality remain poorly studied. This study employed metabolomics and proteomics techniques to conduct a comprehensive comparative analysis of the breast and thigh muscles from 90-day-old (90X, 90T) and 468-day-old (468X, 468T) Sansui ducks. The meat quality traits indicated that the shear force and redness (a*) were significantly higher in the 468T and 468X groups compared to the 90X and 90T groups (p < 0.05). Similarly, the shear force values of the 90T and 468T groups were significantly higher than those of the 90X and 468X groups (p < 0.05). Quantitative proteomics analysis revealed differentially expressed proteins (DEPs) significantly enriched in oxidative phosphorylation and ribosomal biogenesis pathways. Non-targeted metabolomics identified differentially expressed metabolites (DEMs) concentrated in amino acid and lipid metabolism pathways. Correlation analysis indicated that in the comparison between 90X and 468X, 18 DEPs and 10 DEMs were closely associated with fleshiness, whereas in the comparison between 468X and 468T, 23 DEPs and 19 DEMs were closely associated with fleshiness. Integrating proteomics and metabolomics data analysis, proteins such as A0A8B9TTI1, R0JRM6, and A0A8B9SQI5, along with metabolites including L-lysine, L-pyrrolidone, and γ-aminobutyric acid from lysine degradation, butanoate metabolism, and 2-oxocarboxylic acid metabolism pathways, can be proposed as key factors influencing meat quality through pathways including lysine degradation, butanoate metabolism, and 2-oxocarboxylic acid metabolism in older ducks. In contrast, the protein R0JXJ3 and metabolites choline and L-glutamine may determine meat quality differences between anatomical sites through the ABC transporter pathway. These findings provide molecular insights and potential biomarkers for genetic breeding and meat quality improvement in Sansui ducks. Full article

This study aimed to (i) investigate the effect of using grape water in the production of traditional sourdough; (ii) select seeds for use in laboratory-scale sourdough bread production; and (iii) assess the effect of incorporating fresh germinated seeds into recipe of organic sourdough bread on nutritional, technological, and sensory properties. The pH of both control (CSD, flour only) and boosted (BSD, supplemented with “grape water”) sourdough fell below 4.5 by day 3. After 10 days of back-slopping and fermentation, both sourdoughs harbored 9 log CFU/g of lactic acid bacteria, whereas yeast cell density in the CSD was 1 log cycle higher. Based on their high germination rates (~90%), lentil and wheat seeds were selected as additional ingredients (5%). Bread with germinated lentils (GL) and bread with germinated wheat (GW) were compared with control bread (without seeds). GL and GW breads showed gas cell areas of 28.6% and 18.1%, respectively, which were higher than the control. In addition, GL and GW received higher scores for taste (8.6) and softness (5.6), respectively. Additionally, GL contained more proteins (9.9%) and fewer lipids (0.3%) than the two other bread types, in addition to being potentially labeled as a “source of fiber”. Full article

Diabetes mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia and associated complications such as cardiovascular disease, nephropathy, retinopathy, neuropathy, and chronic non-healing wounds. Current antidiabetic therapies offer only partial glycemic control and are limited by poor bioavailability, adverse effects, and an inability to prevent disease progression. Plant-derived exosome-like nanoparticles (PENPs) have emerged as a promising class of natural nanocarriers with excellent biocompatibility, low immunogenicity, and intrinsic multi-component bioactivity. However, few reviews have addressed recent progress in PENPs for DM therapy. To capture the recent developments in this area, this review provides a systematic synthesis of recent advances in PENPs for DM therapy, covering plant sources, extraction and purification methods, molecular compositions, and therapeutic mechanisms. Preclinical studies have demonstrated that PENPs can improve hyperglycemia, enhance insulin sensitivity, regulate hepatic lipid metabolism, and promote wound healing by modulating oxidative stress, inflammation, gut microbiota, glucose metabolism, and insulin signaling. Additionally, PENPs have been shown to promote angiogenesis via glycolytic reprogramming. Despite these promising findings, challenges including scalable isolation, standardized physicochemical characterization, and clinical translation remain. Future directions include engineering multifunctional PENPs, establishing Good Manufacturing Practice (GMP)-compliant production, and conducting clinical trials to facilitate their integration into precision therapeutics for diabetes management. Full article

During the pathological process of spinal cord injury (SCI), ferroptosis is closely related to mitochondrial homeostasis. Following the occurrence of SCI, the interruption of local blood supply leads to mitochondrial damage within cells and a reduction in Adenosine triphosphate (ATP) production. This results in the loss of transmembrane ion gradients, causing an influx of Ca²⁺ into the cells, which in turn generates a significant amount of Reactive oxygen species (ROS) and reactive nitrogen species. This leads to severe mitochondrial dysfunction and an imbalance in mitochondrial homeostasis. Ferroptosis is a form of programmed cell death that differs from other types of apoptosis, as it is dependent on the accumulation of iron and lipid peroxides, along with their byproducts. The double bond structures in intracellular polyunsaturated fatty acids (PUFA) are particularly susceptible to attack by ROS, leading to the formation of lipid alkyl free radicals. This accumulation of lipid peroxides within the cells triggers ferroptosis. After SCI, the triggering of ferroptosis is closely associated with the “death triangle”—a core network that catalyzes cell death through the interaction of three factors: local iron overload, collapse of antioxidant defenses, and dysregulation of PUFA metabolism (where PUFA are susceptible to attack by reactive ROS leading to lipid peroxidation). These three elements interact to form a central network driving cell death. In the pathological cascade of SCI, mitochondria serve as both a major source of ROS and a primary target of their attack, playing a crucial role in the initiation and execution of cellular ferroptosis. Mitochondrial homeostasis imbalance is not only a key inducer of the “death triangle” (such as the intensification of lipid peroxidation by mitochondrial ROS), but is also reverse-regulated by the “death triangle” (such as the destruction of mitochondrial structure by lipid peroxidation products). Through the cascade reaction of this triangular network, mitochondrial homeostasis imbalance and the “death triangle” jointly drive the progression of secondary damage. This study aims to synthesize the mechanisms by which various therapeutic approaches mitigate SCI through targeted regulation of mitochondrial homeostasis and inhibition of ferroptosis. Unlike previous research, we integrate the bidirectional regulatory relationship between “mitochondrial homeostasis disruption” and “ferroptosis” in SCI, and emphasize their importance as a synergistic therapeutic target. We not only elaborate in detail how mitochondrial homeostasis—including biogenesis, dynamics, and mitophagy—modulates the initiation and execution of ferroptosis, but also summarize recent strategies that simultaneously target both processes to achieve neuroprotection and functional recovery. Furthermore, this review highlights the translational potential of various treatments in blocking the pathological cascade driven by oxidative stress and lipid peroxidation. These insights provide a novel theoretical framework and propose combinatory therapeutic approaches, thereby laying the groundwork for designing precise and effective comprehensive treatment strategies for SCI in clinical settings. Full article

Rice bran, a fiber-rich source of bioactive compounds, has gained attention for its potential health benefits, yet its effects on metabolic syndrome (MetS) remain unclear. This study aimed to evaluate the impact of rice bran consumption on anthropometric measures, blood pressure, glycemic control, and lipid profiles in individuals with MetS. A systematic search of PubMed/Medline, Scopus, Cochrane Library, and Embase was conducted up to 30 January 2025, to identify randomized controlled trials (RCTs) assessing rice bran supplementation. Twenty-six RCTs involving 1255 participants (642 in rice bran groups, 613 in controls) were included in the meta-analysis. Weighted mean differences (WMDs) with corresponding p values were calculated. Rice bran significantly reduced systolic blood pressure (WMD: −3.336 mmHg; p = 0.0006), diastolic blood pressure (WMD: −3.145 mmHg; p = 0.015), and HbA1c (WMD: −0.199%; p = 0.003). Lipid profiles improved, with reductions in total cholesterol (WMD: −13.594 mg/dL; p < 0.0001) and LDL cholesterol (WMD: −14.580 mg/dL; p < 0.0001), and an increase in HDL cholesterol (WMD: 3.074 mg/dL; p = 0.007). These findings suggest rice bran supplementation may be a promising natural dietary strategy for managing and preventing MetS. Full article

This work aimed to promote an integrated valorization approach for recovering lipophilic fractions from whole pisco grape pomace using emerging extraction technologies such as Randall (40 °C, 360 min) and Pressurized Liquid Extraction (PLE: 60 °C, 10 min) to characterize lipid-soluble biocompounds and evaluate their functional quality and antioxidant potential. PLE achieved maximum extraction yields (11–15%). Extraction techniques did not significantly alter fatty acid profiles, with C18:2n6c linoleic acid being most abundant (65–69%), followed by C18:1n9c oleic acid (17–21%), while C20:1 eicosanoid acid was least prevalent (1–2%). The fatty acid profile enabled functional potential evaluation through atherogenicity, thrombogenicity, and hypocholesterolemic/ hypercholesterolemic ratios, showing values comparable to other lipid sources. α-Tocopherol content was significantly influenced by extraction techniques (87–645 μg/g), while polyphenol content showed no significant differences between methods (0.6–0.8 mg GAE/g extract). Randall demonstrated higher DPPH radical scavenging capacity (25–30%), while PLE presented higher ORAC values (68–120 μmolTE/g extract). This represents the first characterization of lipophilic fractions from this pomace type, highlighting how emerging extraction techniques affect recovery of high-quality, antioxidant-rich fractions. Results suggest their potential as functional biocompound sources and candidates for various applications, contributing to grape waste valorization strategies. Full article

Background/Objective: Gallstone disease (cholelithiasis) is a prevalent hepatobiliary disorder with limited non-surgical therapeutic options. Sinapic acid (SINAP), a phenolic compound found in various dietary sources, has demonstrated anti-inflammatory and hepatoprotective effects. However, its role in gallstone dissolution has not been explored. This study was designed to evaluate whether sinapic acid modulates hepatic cholesterol transport and enhances gallstone dissolution using a gallstone dissolution assay in artificial bile solution. Methods: The cytotoxicity of SINAP was assessed in HepG2 cells via the MTT assay. The mRNA and protein expression of lipid transporters (ABCG5, ABCG8, and LXRα) was quantified using qRT-PCR, ELISA, and Western blotting. Additionally, molecular docking was conducted to evaluate SINAP’s interaction with gallstone-related protein targets compared to that for the standard drugs (ursodeoxycholic acid and ezetimibe). Results: SINAP achieved a 53.71% gallstone weight reduction over 12 days, comparable to that with ursodiol (59.24%), and following 24 h of exposure, SINAP demonstrated minimal cytotoxicity, maintaining over 80% cell viability up to 50 µg/mL, with an IC₅₀ value of 28 µg/mL. SINAP significantly upregulated ABCG5, ABCG8, and LXRα expression (p < 0.01), suggesting enhanced bile acid secretion. Docking studies confirmed the strong binding affinities of SINAP to key cholesterol transport proteins. Conclusions: These results indicate that SINAP may serve as a promising natural candidate for non-surgical management of cholelithiasis and support further preclinical investigation. Full article

Due to their high nutritional value and a lower environmental impact, Tenebrio molitor (T. molitor) larvae are regarded as an alternative protein and lipid source in food industries, animal husbandry, and fishery. This study aimed to investigate the effect of ω-3 PUFA intake on the nutritional value and gut microbiota of T. molitor larvae. Tenebrio molitor (T. molitor) larvae were reared with wheat bran at 20–32 °C for 4 weeks to screen for a suitable temperature. EPA ethyl esters (EE), DHA ethyl esters (ED), DHA triglycerides (TG), and krill oil (KO) were supplemented in wheat bran to rear larvae for 4 weeks, and the compositions including moisture, carbohydrates, crude protein, and crude fats were analyzed. Gut microbiome was analyzed using 16S rRNA amplicon sequencing. Larvae reared on wheat bran showed optimal growth at 28 °C. ω-3 PUFA supplements increased crude protein (1.07–1.16 fold) and crude fat (1.12–1.22 fold) contents without affecting survival. Gut microbiota composition shifted significantly in all ω-3 supplemented groups, altering over 10 genera. Bacteria with changed abundance (e.g., Clostridium), known for roles in protein/lipid metabolism, likely contributed to the enhanced nutritional contents. These findings demonstrate the benefits of ω-3 PUFA supplementation in T. molitor rearing and identify associated gut bacteria. Full article