Search Results (2,674)

This study aimed to investigate the regulatory mechanisms underlying the relationship between cardiac structure and function and plasma metabolic characteristics in Yili horses participating in an 80-km endurance, by integrating echocardiography, lipidomics, and energy metabolomics analyses. Twenty four competing Yili horses were selected and divided based on competition outcomes: Pre-Completion Group: PCG (n = 6); Post-Completion Group: PoCG (n = 6); Overtime Completion Group: OCG (n = 6); and Non-Completion Group: NCG (n = 6). Cardiac structural and functional parameters were assessed via echocardiography, and intergroup differences were analyzed using one-way ANOVA with a significance threshold of p < 0.05. Plasma lipids and energy metabolites were quantified using UPLC–MS/MS, applying screening criteria of variable importance in projection (VIP) > 1, p < 0.05, and fold change (FC) > 1.2 or FC < 0.833. Bioinformatics analyses were subsequently conducted to identify intergroup variations and correlations. Specifically, associations between cardiac structure/function and metabolites were examined using Pearson correlation analysis, with screening criteria of p < 0.05 and correlation coefficient > 0.8. The results revealed the following: (1) Regarding cardiac structure and function, the PCG group exhibited significantly superior indices, including End-diastolic left ventricular diameter (LVIDd), End-diastolic left ventricular volume (EDV), stroke volume (SV), and ejection fraction (EF), compared with OCG and NCG, and LVIDd showed a highly significant negative correlation with competition completion time. (2) In metabolomic analyses, few differential metabolites were found among groups before the competition (only 60 between PCG and NCG), whereas 234 differential lipids were detected between PoCG and PCG, mainly enriched in sphingolipid metabolism and fatty acid degradation pathways. Energy metabolites showed distinct exercise-responsive patterns, with 22 differential metabolites between PCG and NCG and 21 between PoCG and PCG, significantly enriched in amino sugar and nucleotide sugar metabolism and TCA pathways. Dynamic changes in key TCA intermediates, such as citrate and succinate, reflected enhanced aerobic oxidative metabolism during endurance exercise. (3) Carnitine C18:1, Carnitine C10:2, FFA (20:3), Cer (t17:2/23:0) and 3-phenyllactic acid were significantly correlated with cardiac indicators such as LVLD and LVFWs (p < 0.05). In summary, performance in the 80-km endurance of Yili horses was primarily influenced by enlarged LVIDd and EDV, as well as the regulation of sphingolipid–fatty acid metabolic pathways. Triglycerides, specific acyl compounds, and ceramides may serve as potential biomarkers for evaluating endurance performance, providing a theoretical basis for scientific training and breeding of endurance horses. Full article

Acylpyruvate derivatives represent a promising yet underexplored class of compounds for modulating microalgal growth and metabolism. Inspired by the metabolic role of pyruvate and the diverse bioactivity of its acylated analogs, this study investigates the structure–activity relationship of a diverse library of 55 acylpyruvate-derived compounds for stimulation of the green microalga Chlorella vulgaris. The library, encompassing 12 chemotypes including acylpyruvic acids, their esters, and various heterocyclic derivatives, was screened for effects on C. vulgaris growth. Six compounds were identified as active ones that enhanced biomass production in a preliminary microassay. Notably, four of these active compounds were direct acylpyruvate derivatives, highlighting this scaffold as the most promising one. Conversely, a specific subclass, 1,4-benzoxazin-2-ones, exhibited potent, dose-dependent algicidal activity. Detailed assessment of the active compounds under scaled-up culture conditions revealed that while their effect on overall cell density was limited, several compounds significantly enhanced the intracellular content of valuable metabolites: one increased chlorophyll content by 17%, another elevated carotenoids by 40%, and a third boosted neutral lipid accumulation by 44%. Furthermore, control experiments confirmed that the bioactivity of p-ethoxybenzoylpyruvates, which showed the best biological activity, is inherent in the intact framework and is not mediated by their hydrolysis products. Our findings underscore the potential of acylpyruvates as versatile tools for the enhancement of metabolite production in microalgae and as potent candidates for the development of algicides. Full article

Tomato is one of the most important vegetable crops worldwide, with about one quarter of the yearly production of fresh fruits dispatched to the processing industry. Paste, canned tomatoes, and sauces represent the three leading categories. Background/Objectives: The metabolic profile of processed tomatoes can be modified by several production steps, affecting the nutritional and sensory profile of the finished product. Despite this, a detailed metabolomic profiling of transformed tomatoes is currently missing. The goal of this investigation is to provide qualitative metabolomic profiling of tomato purees with two main advances: first, the use of a more sustainable analytical approach based on a single extraction protocol and one-shot analysis for multiple information retrieval on different compound classes; second, the achievement of a curated database consolidated over a wide collection of commercial samples representative of the Italian market. Methods: A non-selective ethanol extraction was applied to collect the main polar metabolites followed by untargeted high-resolution MS/MS analysis and software-based compound identification. Results: A list of more than five hundred features was collected and assigned to specific compounds or compound groups with different confidence levels. The results confirmed the persistence in processed tomatoes of the main primary and secondary metabolites already reported in fresh fruits, such as essential amino acids, sugar, organic acids, vitamins, fatty acyls, and phytohormones. Moreover, new insight on specific components never traced before in similar finished samples is provided. Bioactive compounds were detected in all samples, such as oligopeptides with ACE-inhibitor activity, ɣ-aminobutyric acid, alkaloids, and polyphenols (flavonoids, coumarins, and cinnamic acids). Many of these compounds have antioxidant activities, proving the relevance of transformed tomatoes as a source of health-promoting compounds for the human diet. Conclusions: A detailed metabolic profile of commercial tomato puree samples was obtained, and a curated database of metabolites was compiled, which can be useful for multiple purposes, for example, authentication, quality, or nutritional assessments. Full article

Plasmalogens, as natural dietary lipids, are a unique class of glycerophospholipids with distinct structural and functional properties. They are unstable due to the vinyl ether linkage and the unsaturated fatty chains. Hence, plasmalogen changes are closely connected to their beneficial bioactivities and health-related applications. This narrative review focuses on their structural modifications, particularly oxidation of the vinyl-ether and sn-2 acyl chains, enzymatic degradation, and molecular remodeling. The oxidative susceptibility of plasmalogens renders them particularly vulnerable under inflammatory or oxidative stress, contributing to a measurable reduction in total plasmalogen content. Plasmalogen deficiency has been observed in various diseases and applied in clinical applications, including physiological and a variety of pathological conditions. Moreover, plasmalogens have been recognized as not only disease biomarkers but also therapeutic targets. In addition, recent findings in nutrition were discussed, aiming to find that underutilized animal byproducts and microbial lipids are promising new sources of plasmalogens. To conclude, it is crucial to establish practical dynamic monitoring systems of plasmalogens for health promotion and disease prevention interventions. Integrating biochemical pathways, clinical diagnosis, and nutritional interventions remains to be clarified. Full article

Plasma-activated water (PAW) is an emerging disinfectant; however, its potential as a quorum sensing inhibitor (QSI) for biofilm control remains underexplored, and its action mechanisms have not been elucidated. This study investigated the effects of PAW on biofilm formation and spoilage factors secretion in Pseudomonas fluorescens under sub-inhibitory conditions. PAW generated by treating water for 60 s (PAW-60) reduced biofilm biomass by up to 1.29 log CFU/mL after 12 h incubation. It also completely inhibited protease production (100%) and decreased siderophore production by 31.87%. N-butyryl-homoserine lactone (C₄-HSL) was identified as the dominant signaling molecule, with its production decreasing by 34.34–84.07% following PAW treatments. Meanwhile, C₄-HSL activity was significantly suppressed by 42.58–65.38%. An FTIR analysis revealed the formation of a new C=O group, indicating oxidative degradation of acyl homoserine lactones (AHLs). Exogenous C₄-HSL progressively restored the biofilm biomass, spoilage factors production, and QS-related gene expression levels, with no significant difference observed compared with the control at 0.05 µg/mL (p < 0.05). The results suggest that the inhibitory effects of PAW are primarily due to the disruption of AHLs transduction in the QS pathway. Molecular docking showed that the long-lived reactive species in PAW could bind to AHLs’ synthetic protein (FadD1) and receptor protein (LuxR) via hydrogen bonding. PAW-60 reduced the spoilage activity of P. fluorescens inoculated into fish muscle juice and extended its shelf life from 8 to 10 days during storage at 4 °C. A strong positive correlation was observed between AHLs accumulation and the spoilage process. These findings demonstrate that PAW mitigates biofilm formation and food spoilage by blocking signaling transduction, which involves suppression of AHLs production, oxidative degradation of AHLs molecules, and disruption of AHLs recognition. Full article

Background/Objectives: Esterases are widely used in various industrial fields. This study aimed to isolate and characterize esterase genes from Laceyella sacchari HS49-1, a thermophilic bacterium from a hot spring, which can survive at 45–60 °C and pH 5-10 with robust esterase activity. Methods: A genomic shotgun library was constructed to identify three esterase genes: two in family XII (Est2 and Est7) and one in family VIII (Est1). Sequence analysis revealed significant divergence from other genera. Only Est1 was successfully expressed in Escherichia coli. Its activity, optimal conditions, thermostability, and structure were investigated using p-NP butyrate, temperature/pH assays, heating pre-treatment, and fluorescence quenching. Results: Est1 demonstrated high activity (57.43 ± 0.04 U/mg) towards short-chain p-NP butyrate (C4). Molecular-docking analyses revealed that Est1’s catalytic motif (GXSXG) interacts with various p-NP esters, with binding energy and interaction types varying by acyl chain length. The optimal temperature was 60 °C, and the optimal pH was 8. Est1 exhibited excellent thermostability, retaining 90% of its activity after pre-treatment at 50 °C for 8 h and 69.8% after pre-treatment at 80 °C for the same duration. Fluorescence quenching showed that after 1 h at 80 °C, the fluorescence was reduced by only 16.6%, indicating remarkable heat resistance. Additionally, Est1 did not require metal ions as cofactors and maintained 74.8% of its activity in the presence of 0.1% SDS. Conclusions: The unique properties of Est1 from L. sacchari HS49-1 highlight its potential for industrial applications. Further exploration of this thermophilic bacterium could uncover more valuable genes. Full article

The ability of ultrasound/peracetic acid (US/PAA) to degrade the azo dye Sunset Yellow FCF (SSY) was evaluated considering the impacts of power, pH, inorganic carbon, common salts, radical scavengers, and real water matrices. Pseudo-first-order rate constants revealed synergy indices of 2.90, 3.28, 2.22, and 2.03 at electrical powers of 40, 60, 80, and 100 W, respectively. Selective scavenger assays revealed a mixed radical regime. ^•OH radical involvement was confirmed by inhibition with alcohols (tert-butanol, 2-propanol), benzoic acid, nitrobenzene, sodium azide, and phenol, while suppression by TEMPO highlighted the key role of PAA-derived acyl and peroxyl radicals. Nitrobenzene caused pronounced inhibition at elevated doses, while nitrite acted as a decisive quencher by converting ^•OH and other oxidants into less reactive species. Carbonate alkalinity exerted dual effects: at acidic pH (3.7–4.4) it diverted ^•OH radicals to carbonate radicals and reduced cavitation through dissolved CO₂, whereas at near-neutral pH it buffered conditions toward the optimum (pH 9) and enhanced degradation. Common anions (chloride, sulfate, nitrate) at ≤10 mM produced minor effects. Tests in environmental waters revealed the following reactivity order: seawater > ultrapure water > tap water ≈ Zamzam water > tertiary effluent. Enhanced performance in seawater was attributed to halide-mediated formation of reactive chlorine and bromine species, while inhibition in effluent was linked to organic matter scavenging. Overall, US/PAA emerges as a robust and adaptable advanced oxidation process for azo dye abatement across diverse water matrices. Full article

The Salmonella enterica serovar Typhimurium (ST) mutant lacking the msbB gene (ΔmsbB) has been widely studied as a candidate for attenuated bacterial vectors in therapeutic applications. Deletion of msbB results in LPS with under-acylated lipid A, which lowers endotoxicity while maintaining structural integrity. This attenuation has traditionally been attributed to reduced TLR4 activation due to weaker interaction between the modified lipid A and TLR4. In our study, we confirmed that ΔmsbB ST was less lethal than wild-type (WT) ST in a mouse sepsis model. However, this difference persisted even in TLR4- and caspase-11-deficient mice, suggesting that LPS signaling is not the primary determinant of virulence. In vitro, bone marrow–derived macrophages (BMDMs) from TLR4- or caspase-11-deficient mice showed only modest reductions in ST-induced cell death and cytokine production. Importantly, ΔmsbB ST behaved similarly to WT ST in these assays, further indicating that LPS-mediated signaling is not central to the observed attenuation. Our previous studies showed that ST-induced mortality in mice is primarily mediated through NLRC4 activation. Using qPCR and immunoblotting, we found that expression of NLRC4 activators was diminished in the ΔmsbB strain. Additionally, the mutant exhibited increased outer membrane permeability—likely contributing to its heightened antibiotic sensitivity—and reduced motility due to lower flagellin protein levels. In summary, the attenuation of virulence observed in the ΔmsbB strain is not directly due to altered LPS–TLR4 interactions, but rather an indirect effect of diminished expression of virulence factors that activate the NLRC4 inflammasome. Full article

Background/Objectives: Ferroptosis, an iron-dependent form of regulated cell death characterized by excessive lipid peroxidation, has been implicated in various acute and chronic brain disorders, including epilepsy. Although 1,4-naphthoquinone derivatives have been reported to regulate ferroptosis, their mechanistic roles in the nervous system remain underexplored. Here, we investigated the protective effects of 8-hydroxy-2-anilino-1,4-naphthoquinone (8-HANQ) on ferroptotic neuronal death in vitro and seizure behaviors in vivo. Methods: HT22 hippocampal cells were exposed to ferroptosis inducers including glutamate, glutamate plus iron, or RSL3. Lipid reactive oxygen species (ROS), ferroptosis markers, and its related molecules were assessed by flow cytometry and Western blotting. In a kainate (KA)-induced seizure model, 8-HANQ was delivered intracerebroventricularly, followed by behavioral seizure scoring and analysis of hippocampal levels of PSD95, cathepsin-B, and FGFR1 at 72 h post-seizure. Results: 8-HANQ attenuated ferroptotic death in HT22 cells, reducing lipid ROS accumulation and abnormal acyl-coA synthetase long chain family member 4 (ACSL4), suggesting 8-HANQ’s anti-ferroptotic action. Moreover, 8-HANQ also prevented aberrant STAT3-dependent cathepsin-B overexpression while modulating soluble N-cadherin-mediated FGFR1 activation. In vivo, 8-HANQ decreased KA-induced seizure behavior, restored hippocampal cathepsin-B and PSD95 expression, and partially alleviated dysregulation of FGFR1 activation. Conclusions: 8-HANQ prevents ferroptotic neuronal death and synaptic deficits involving FGFR1/STAT3/cathepsin-B-driven ferroptosis while lowering seizure severity, suggesting that 8-HANQ may serve as a potential anti-ferroptotic and anti-seizure agent. Full article

Acid mine drainage (AMD) environments feature extreme acidity (pH ≤ 2) and high heavy metal concentrations. Acidophiles survive these conditions through unique genetic adaptations and secondary metabolite (SM) pathways. Leptospirillum ferriphilum, known for its acid and heavy metal resistance, serves as a model for AMD bioremediation, though systematic multi-omics studies on its key SMs and biosynthesis pathways remain underexplored. In this study, L. ferriphilum YR01 was isolated and identified from the AMD of the Zijinshan copper mine, China. Pangenomic analysis revealed that YR01 possesses the largest number of genes (2623) among the eight sequenced L. ferriphilum strains. Comparative genomics, antiSMASH, BiG-SCAPE, and metabolomic analyses (LC-MS and HPLC-MS) were integrated to comprehensively explore its biosynthetic capacity. A total of 39 biosynthetic gene clusters (BGCs) were identified, of which 60% shared <50% similarity with known clusters, indicating substantial novel biosynthetic potential. The sequence alignment of SM biosynthetic gene clusters (BGCs) demonstrated the potential of L. ferriphilum to synthesize conserved clusters for ectoine, choline, carotenoids, terpenoids, and terpene precursors. YR01 harbors complete BGCs for all five SM types. Notably, key nonribosomal peptide synthetase (NRPS) modules implicated in N-acyl homoserine lactone (AHL) synthesis were identified. Untargeted metabolomics (LC-MS) revealed the production of diverse SMs (18 types) putatively involved in environmental adaptation, including phosphocholine, carotenoids (e.g., anteraxanthin), cholera autoinducer-1 (CAI-1), and multiple AHLs. Targeted detection (HPLC-MS) further confirmed that YR01 could produce ectoine (0.10 ng/mL) and specific AHLs (C₁₄-HSL, C₁₂-HSL, C₁₂-OH-HSL), which were beneficial for the survival of the strain in extremely acidic environments and interspecies communication through SMs. This study represents the first comprehensive multi-omics characterization of BGCs in L. ferriphilum and experimentally validates the production of key SMs. Collectively, this study provides a comprehensive elucidation of the SM biosynthetic repertoire and environmental adaptation strategies in L. ferriphilum, advancing our understanding of microbial adaptation and interspecies communication in AMD systems, and offering potential implications for biomining applications. Full article

Aberrant wound healing in the retina can manifest as proliferative vitreoretinopathy (PVR), which involves the myofibroblast transdifferentiation of retinal pigment epithelial (RPE) cells. In this study, experiments were conducted to examine the structure–activity relationships of endocannabinoid-like compounds, N-acyl dopamines, on the myofibroblast transdifferentiation of RPE cells. The collagen matrix contraction assay was used to assess myofibroblast function. Western blot analysis and immunocytochemistry techniques were used to evaluate myofibroblast markers. N-palmitoyl dopamine (PALDA), N-oleoyl dopamine (OLDA), and N-arachidonoyl dopamine (NADA), in a concentration-dependent manner, inhibited contraction of collagen matrices mediated by either primary porcine RPE cells treated with TGF-β2, or human RPE cells treated with TGF-β2 plus TNFα (TNT). The rank order of potency was PLDA = OLDA > NADA. In contrast, the substitution of dopamine with other polar head groups led to a complete loss of their ability to inhibit myofibroblast transdifferentiation. Western blot analysis demonstrated that PALDA, OLDA, and NADA down-regulated the myofibroblast markers fibronectin and α-SMA. Immunocytochemistry experiments showed that these N-acyl dopamines reduced the incorporation of α-SMA into F-actin stress fibers. Overall, these structure–activity relationship studies demonstrate that the dopamine head group is crucial for N-acyl dopamine to inhibit myofibroblast transdifferentiation of RPE cell, whereas the fatty acid side chain determines the potency of it. This study points to the potential of N-acyl dopamines as a novel class of therapeutic agents for treating retinal fibrotic conditions, such as PVR. Full article

Acetamiprid (ACE), a widely used neonicotinoid insecticide, has raised concerns due to its potential reproductive toxicity. While its adverse effects on animal reproductive systems have been documented, the impact of ACE on mammalian oocytes remains poorly understood. This study aimed to investigate the potential effects of ACE exposure on porcine oocytes and evaluate whether alpha-tocopherol (α-TOC), a fat-soluble antioxidant, could alleviate ACE-induced oocyte damage. Porcine cumulus oocyte complexes (COCs) were exposed to ACE alone or co-treated with α-TOC for 44 h during in vitro maturation. ACE exposure significantly reduced the first polar body (PB1) excretion rate, arrested meiotic progression, and disrupted spindle assembly in porcine oocytes. Furthermore, ACE impaired mitochondrial function, evidenced by decreased mitochondrial membrane potential (MMP), while increasing intracellular reactive oxygen species (ROS) accumulation and lipid peroxidation (LPO). Additionally, ACE exposure induced intracellular iron overload and dysregulated ferroptosis-related genes, downregulating solute carrier family 7 member 11 (SLC7a11) and glutathione peroxidase 4 (GPX4) while upregulating transferrin receptor 1 (TfRC) and acyl-CoA synthetase long-chain family member 4 (ACSL4), contributing to the occurrence of oocyte ferroptosis. Notably, α-TOC co-treatment effectively alleviate oxidative stress and lipid peroxidation, thereby protecting oocytes from ACE-induced ferroptosis. Collectively, these findings indicate that oxidative stress-mediated ferroptosis may be a major contributing pathway through which ACE impairs oocyte maturation and suggest that α-tocopherol may serve as a protective agent against ACE-induced oocyte damage. Full article

Background/Objectives: The association between plasma metabolites derived from dietary substrates and inflammatory processes remains underexplored, despite its potential relevance in the prevention of non-communicable diseases. This systematic review aimed to examine the relationship between blood metabolites and the modulation of inflammatory biomarkers. Methods: A total of 25 randomized controlled trials, published between 2019 and 2024, were included from an initial pool of 111 records. These studies investigated the effects of dietary patterns, specific food groups, or nutritional supplements on the human metabolome and their potential links to inflammation. Results: Metabolomic analyses were predominantly performed using mass spectrometry (MS)-based platforms (17 out of 25), with liquid chromatography–mass spectrometry as the most frequently employed method. Both targeted (n = 14) and untargeted (n = 11) approaches were represented, and samples were drawn from plasma, urine, and feces. Across the interventions, 64 metabolites were modulated, including fatty acyls, glycerolipids, benzenoids, and organic acids, reflecting potential changes in pathways related to oxidative stress, lipid and carbohydrate metabolism, and inflammatory signaling. Several studies also assessed classical inflammatory biomarkers such as C-reactive protein (CRP), tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). Interventions involving healthy traditional dietary patterns, improvements in dietary fat quality, or the use of specific probiotic strains were often associated with favorable immunometabolic outcomes. In contrast, some interventions, such as Mohana Choorna, elicited upregulation of immune-related gene expression in adipose tissue without improvements in glucose or lipid metabolism. Conclusions: While metabolomic responses varied across studies, the evidence highlights the value of dietary interventions in modulating systemic metabolism and inflammation. These findings support the integration of metabolomics into clinical nutrition to define more personalized and effective dietary strategies for inflammation-related chronic disease prevention. Full article

Scrophularia aestivalis Griseb. is a Balkan endemic species whose phytochemical composition and medicinal properties have not been previously investigated. The therapeutic potential of Scrophularia species has attracted considerable attention, resulting in extensive studies on their chemical and pharmacological properties, with over 200 secondary metabolites identified to date. The present study aimed to explore the phytochemical composition of Bulgarian-origin S. aestivalis, including isolation and characterization of individual secondary metabolites. From methanol extract of the plant’s aerial parts, aucubin, harpagide, 8-O-acetylharpagide, cis- and trans-harpagoside, 6-O-methyl catalpol, acylated derivatives of catalpol, and linarin were isolated and identified. The anti-obesity activity of the extract and primary fractions was evaluated in a Caenorhabditis elegans model of obesity. Significant lipid-reducing activity was demonstrated in four fractions, indicating promising anti-obesogenic properties. Following chemical profiling and quantitative analysis, the main components of the most active fractions were identified, namely the cis- and trans-harpagoside isomers. Subsequent experiments demonstrated that treatment with harpagoside reduced lipid accumulation and improved mitochondrial function in glucose-supplemented worms, with the data suggesting potential involvement of the SKN-1 signaling pathway. Full article

The distinctive geographical environment of the Qinghai–Tibet Plateau has nurtured a variety of anthocyanin-rich berry plants. This review systematically summarizes the current state of research on anthocyanins obtained from Lycium ruthenicum Murr. (LRAs), Nitraria tangutorun Bobr (NTAs), and Rubus idaeus (RAs) for their potential health benefits and use. The anthocyanins found in these three berries have attracted considerable interest for their significant biological effects, such as their antioxidant, anti-aging, hypoglycemic, anti-inflammatory, and neuroprotective activities, as well as their ability to regulate the gut microbiota and inhibit cancer cells. These anthocyanins have potential applications as natural colorants, packaging materials and smart labels, as well as functional food and health supplements in the food industry. They have diverse molecular architectures with glycosylation and acylation profiles. The structural features of anthocyanins are closely related to their biological activities. This review provides a detailed overview of the chemical structures, synthesis pathways, biological activities, and applications in the food industry of LRAs, NTAs, and RAs. This summary offers a theoretical foundation for exploring plant resources characteristic of the Qinghai–Tibet Plateau and for the development and utilization of high-value-added functional foods, pharmaceuticals, and cosmetics. Full article