Search Results (620)

The spleen is essential for immunity, mediating host defense against pathogens and regulating immunological homeostasis. Western-style diets commonly cause the aggregation of body fat and the emergence of obesity. This state might lead to damage to the spleen’s functions. However, the effects of Western-style diets on gene expression and metabolic regulation in the spleen have not yet been fully explored. In this study, C57BL/6 mice were fed either a high-fat diet (HFD) or standard chow (CHFD) for 10 weeks starting at 8 weeks old. Weekly weights were recorded, and spleens were weighed at 18 weeks. The results showed that HFD mice had significantly higher body weights from 12 weeks (p < 0.05) and a higher splenic index at 18 weeks (p < 0.01). HE staining revealed disrupted spleen structures and infarcted areas in the HFD group. Transcriptome sequencing highlighted immune-related pathways, including inflammatory response and interleukin-6 production. Among the differentially expressed genes (DEGs), PCK1, ALDH9A1, and ALDH7A1 were significantly upregulated in the HFD group, whereas PLA2G2F and PLA2G4F exhibited significant downregulation. APOB emerged as a key hub gene in PPI analysis. Metabolomics analysis identified significantly different metabolites (SDMs), including Rifamycins, 7-Ketodeoxycholic Acid, Folinic Acid, and Lotaustralin, as key biomarkers for an HFD, while 1-Methylnicotinamide and Prostaglandin E1 were significant for CHFD. KEGG enrichment linked glycerophospholipid and arachidonic acid metabolism to both transcriptome and metabolome results. The joint analysis of transcriptome and metabolome data revealed that SLC22A8 was negatively correlated with Biliverdin and 1-methylnicotinamide, and MCPT1 was inversely correlated with 7-Ketodeoxycholic Acid. These findings offer insights into the molecular mechanisms and metabolites that influence spleen immunity and systemic immune homeostasis. Full article

Constrained by site conditions and water resources, pear tree cultivation faces increasing drought stress. Paecilomyces variotii extract (PVE), a novel biostimulant extracted from wild sea buckthorn root-isolated strains and containing chitin, humic/fulvic acids, and beneficial microbes, has gained attention due to its high activity and efficacy in alleviating plant stresses (e.g., drought). In this study, Pyrus pyrifolia ‘Qiu Yue’ was used as the experimental material, and pot experiments were conducted to examine the drought-mitigating effects of different PVE concentrations. Drought stress was achieved by maintaining soil water content at 35–45% of water holding capacity for 45 days under natural evaporation conditions in rain shelters. The growth status of pear trees, soil enzyme activity, and metabolite levels were analyzed. The results showed that the application of 5 ng/mL PVE promoted pear tree growth, enhanced leaf antioxidant enzyme activity, and improved photosynthetic capacity and soil enzyme activity. Under normal water conditions, the shoot growth length, plant height, stem diameter, and root system activity of the 5 ng/mL PVE group were 31.91%, 12.05%, 3.54%, and 10.94% higher than those of the control group, respectively. Under drought stress, these values increased by 25.12%, 8.87%, 12.21%, and 16.98%, respectively. The addition of 5 ng/mL PVE facilitates trehalose release and upregulates starch-sucrose, glycerophospholipid, and galactose metabolic pathways, thereby potentiating drought stress tolerance in pear trees. However, at 20 ng/mL, reductions were observed in pear tree growth indicators, leaf antioxidant enzyme activity, soil enzyme activity, and trehalose content in root exudates compared to the 5 ng/mL PVE treatment. Overall, 5 ng/mL PVE effectively promotes pear tree growth and enhances drought resistance, making it suitable for broader use in pear cultivation practices. Full article

To investigate the impacts of dietary Bacillus-based probiotics and yeast-derived prebiotics on the hepatic transcriptome profile, 500 Hisex White laying hens were randomly allotted into five dietary treatments from 37 to 52 weeks of age: control; control + Bacillus subtilis; control + Bacillus subtilis and Bacillus licheniformis; control + Bacillus coagulans; and control + Saccharomyces cerevisiae yeast cell wall. Transcriptome analysis revealed a substantial number of differentially expressed genes exclusively between the control and prebiotic groups, identifying 2221 genes (FDR ≤ 0.05), with 980 genes upregulated (log₂ fold change 0.69 to 24.62) and 1241 downregulated (log₂ fold change −0.74 to −26.46). The top 10 upregulated KEGG pathways included protein export, glycerophospholipid metabolism, tryptophan metabolism, amino acid biosynthesis, alanine, aspartate, and glutamate metabolism, cofactor biosynthesis, propanoate metabolism, ABC transporters, 2-oxocarboxylic acid metabolism, and protein processing within the endoplasmic reticulum. In contrast, the most prominently downregulated pathways encompassed fructose and mannose metabolism, hedgehog signaling, PPAR signaling, Notch signaling, GnRH signaling, cell adhesion molecules, cytokine–cytokine receptor interactions, apelin signaling, glycosaminoglycan degradation, and RIG-I-like receptor signaling. These findings advance understanding of the hepatic transcriptomic response to yeast-derived prebiotics and identify key molecular pathways that could be targeted to enhance metabolic function in laying hens. Full article

Sleep disturbances are linked to metabolic and neurological dysregulation. Moringa oleifera leaves, rich in bioactive compounds, may improve sleep via gut–brain axis modulation. This study investigated the sleep-enhancing effects of fermented Moringa oleifera leaf extract (FM) in mice using metabolomics, gut microbiota analysis, network pharmacology, and molecular docking. A 1:1 combination of Lactobacillus plantarum GDMCC 1.2685 and L. swissii GDMCC 1.791 optimally fermented FM, increasing GABA by 1.67-fold and total amino acids to 46,058.20 ± 845.53 μg/g. FM shortened sleep latency, increased sleep duration, and elevated brain GABA while reducing glutamate (Glu) and Glu/GABA ratios. Hypothalamic metabolomics identified seven sleep-related metabolites, implicating glycerophospholipid, tryptophan, and purine metabolism pathways. FM also reduced Mycobacterium anisopliae (a gut bacterium associated with insomnia) and increased the Firmicutes/Bacteroidetes ratio. Network pharmacology revealed that FM’s effects were mediated via GABA, Glu, and serotonin (5-HT) pathways. These findings demonstrate that FM improves sleep by modulating hypothalamic neurotransmitters and gut microbiota, exerting sedative-hypnotic effects through amino acid, purine, and energy metabolism. Full article

Lactobacillus-enriched yogurt is in increasingly high demand due to its health benefits, but the product stability requires an understanding of the microbial dynamics during fermentation and storage. This study investigated the interactions between probiotic pairs (L. paracasei L9 and L. acidophilus LAC) and starter culture (HYY) through fermentation kinetics, microbial viability, organic acid profiles, and metabolomics. The results demonstrated that L. paracasei L9 significantly increased the titratable acidity from 25.20 ± 7.01 °T to 36.56 ± 3.47 °T at 3 h and reduced the fermentation time by 0.5 h, whereas L. acidophilus LAC showed minimal effects. L. paracasei L9 achieved higher viability (8.4 lg CFU/g) via the high-affinity lactose transport and Leloir pathway, whereas the L. acidophilus LAC growth remained limited (6.9 lg CFU/g). The metabolomic investigation revealed the L9 + HYY upregulated glycerophospholipid metabolism and pantothenate/CoA biosynthesis to support rapid biomass accumulation. In contrast, LAC + HYY modulated the arginine and branched-chain amino acid metabolism for acid tolerance. During 21 days of storage, there were no significant differences in final TA values and lactic acid content among the probiotic supplementation groups. L9 + HYY remained stable (>9.0 lg CFU/g) by upregulating the aromatic amino acid biosynthesis and suppressing the purine/sulfur metabolism, whereas L. acidophilus LAC decreased to 6.02 lg CFU/g. These findings demonstrate the dual role of L. paracasei L9 in accelerating the fermentation and maintaining the microbial stability through metabolic reprogramming, which guides the development of improved probiotic yogurts. Full article

This study aimed to investigate the effects of training on cardiac structure and function, as well as plasma metabolite profiles in horses, in order to uncover the molecular regulatory mechanisms and cardiac remodeling under long-term exercise. We hypothesize that long-term standardized training induces physiological cardiac remodeling and differential metabolomic changes in Yili horses, which correlate with improved athletic performance. The study focuses on physiological exercise-induced cardiac remodeling, characterized by increased left ventricular wall thickness and chamber size. A total of 18 Yili horses, a unique Chinese equine breed, were included in the study of equine exercise physiology. Twelve horses underwent six months of standardized training followed by three 1000 m performance tests. Based on final rankings, they were divided into an advanced group (AG, top six horses) and a habitual group (HG, bottom six horses). The remaining six untrained horses served as the untrained group (UG), with only free-range activity. Echocardiographic results revealed significant differences (p < 0.05) between the trained and untrained groups in cardiac parameters such as LVID, LVFW, LVM, AODd, IVSs, HR, EDV, ESV, LADs, LVLD, MVD, PADs, and SV. Further comparison between AG and HG showed significant differences in AODd, EESV, HR, IVSd, LVIDs, LVM, RVDd, and RVDs (p < 0.05). Metabolomic analysis identified 465 differential metabolites between AG and HG, 456 between AG and UG, and 379 between HG and UG, with 106 overlapping metabolites among all three groups. Plasma metabolomics revealed significant negative correlations between specific long-chain lysophosphatidylcholines (LPCs) and cardiac structural parameters (LVIDd, LVFWD, LVIDs, LVLD, MVD, and LADs), whereas LPC (O-18:2) showed an opposite trend. Key metabolites such as 3-hydroxybutanoic acid, carnitine C4:0, carnitine isoC4:0, hippuric acid, and uric acid were significantly lower in AG compared to HG and UG, with uric acid levels negatively correlated with LVID and LVM. Glycerophospholipid metabolism emerged as the core pathway differentiating exercise capacity among all groups. Notably, efferocytosis (vs. HG and UG) and tryptophan metabolism/aromatic amino acid biosynthesis (vs. HG) were specifically enriched in AG. These findings provide a novel theoretical basis and research perspective for optimizing racehorse training strategies and exploring the metabolic regulation of the athletic heart. Full article

The rust disease caused by Melampsora apocyni seriously affects the growth of Poacynum hendersonii. However, the defense mechanisms against rust infection remain unclear. This study explored the regulatory mechanisms of P. hendersonii in response to rust disease through combined physiological, biochemical, and transcriptomic analyses. The results showed that with the increase in disease severity, the chlorophyll content of leaves decreased significantly, while the antioxidant and phenylalanine ammonia lyase activities progressively increased. Mild infection triggered an 11.9-fold surge in salicylic acid levels and a sharp decline in abscisic acid compared to controls, as well as increased synthesis of total phenolics, total flavonoids, chlorogenic acid, cryptochlorogenic acid, isoquercetin, hyperoside, rutin, and astragalin. Transcriptome analysis showed that the “plant–pathogen interaction, plant hormone signal transduction and phenylpropanoid biosynthesis” pathways were significantly up-regulated in the mild infection stage, while “glycerophospholipid metabolism, fatty acid degradation and ABC transporters” were activated in the severe infection stage. In summary, P. hendersonii regulates energy metabolism and phenylpropanoid metabolism through salicylic acid signaling and promotes the accumulation of secondary metabolites and the lignification process of leaves, thereby enhancing rust resistance. Key enzyme genes (COMT, POD, CAD, F5H) and metabolites (chlorogenic acid, isoquercitrin, rutin) can be used as important targets for disease resistance breeding. Our research provides important reference for the prevention and control of M. apocyni in P. hendersonii. Full article

The nutritional value of lipids depends not only on their fatty acid composition but also on their stereospecific positioning on the glycerol backbone. This study investigated the fatty acid composition and sn-2 positional distribution of triacylglycerols (TAG), as well as the composition of major phospholipids in golden pompano (Trachinotus ovatus) juveniles (initial weight: 10 g) fed five diets including graded levels of dietary n-3 highly unsaturated fatty acids (HUFA; 0.64–2.10%) for 56 days. With increasing dietary n-3 HUFA levels, the proportions of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), and total n-3 HUFA in muscle TAG, phosphatidylcholine (PC), and phosphatidylethanolamine (PE) significantly increased. Phospholipids, especially PC and PE, were preferentially enriched with n-3 HUFA, and the sn-2 positions of TAG showed a significantly increased deposition of DHA and reduced n-6/n-3 ratios. RNA-Seq analysis was performed on muscle tissues of T. ovatus subjected to different dietary n-3 HUFA levels to further investigate the molecular mechanisms of lipid compositional and structural changes. A total of 126,792 unigenes were obtained, of which 47.78% were successfully annotated. KEGG pathway enrichment analysis implicated the glycerophospholipid, glycerolipid, and sphingolipid metabolism pathways in lipid composition and distribution regulation, identifying gpat4, agpat3, agpat8, lpeat1, and lpgat1 as potential regulators. These findings offer insights into lipid remodeling in marine fish and support strategies to enhance aquaculture product quality. Full article

Background: Type 2 diabetes (T2D) has become a serious global public health concern. Liubao tea (LBT) has demonstrated beneficial effects on gut microbiota and glucose-lipid metabolism, holding promising therapeutic potential for T2D; however, its underlying mechanisms remain unclear. This study aims to elucidate the potential mechanisms of Liubao tea extract (LBTE) against T2D. Methods: LC-MS technology was used to identify the chemical components of LBTE and combined with network pharmacology and molecular docking to screen its potential active ingredients and targets for improving T2D. Therapeutic efficacy was assessed in high-fat diet/streptozotocin (HFD/STZ)-induced diabetic mice via serum biochemical analyses and histopathological examinations. Serum metabolomics, 16S rRNA sequencing, quantification of short-chain fatty acids (SCFAs), quantitative real-time PCR (qPCR), and antibiotic-treated pseudo-germ-free models were employed to elucidate the underlying mechanisms. Results: LBTE effectively reduced blood glucose levels and improved lipid metabolism, primarily by promoting hepatic glycogen synthesis and suppressing glycerophospholipid synthesis. LBTE also alleviated hepatic inflammation by modulating inflammatory cytokine expression. Additionally, LBTE reshaped the gut microbiota profiles by decreasing harmful bacteria and increasing SCFA-producing bacteria, resulting in elevated fecal SCFAs. SCFAs contributed to improving hepatic metabolism and inflammation, enhancing intestinal barrier function. Notably, these effects were abolished by antibiotic-induced microbiota depletion, confirming the microbiota-dependent mechanism of LBTE. Quercetin, luteolin, genistein, and kaempferol were considered as potential active ingredients contributing to the antidiabetic effects of LBTE. Conclusions: These findings provide novel perspectives on the viability of LBTE as a complementary strategy for T2D prevention and management. Full article

As the principal dietary source of lipids, edible oils (notably vegetable oils) exist in crude form predominantly as triacylglycerols (about 95%), with the remainder comprising impurities and diverse minor components. Therefore, the refining processes of vegetable oil are particularly important. The application potential of safflower seed oil (SSO) in both nutraceutical and pharmaceutical domains is attributed to its exceptionally high linoleic acid concentration and abundant polyphenolic constituents. However, a systematic analysis of SSO during physical refining has yet to be conducted. This study aims to investigate the effects of refining processes on the fatty acids of SSO compared with flaxseed oil (FSO). In this study, chemical analysis, gas chromatography and ultra-high-performance liquid chromatography were used to analyze and compare the physicochemical indexes, fatty acid composition, and the lipidomics of SSO and FSO. Results indicated that optimized refining significantly enhances quality parameters in both SSO and FSO. A total of 40 and 43 fatty acids were identified in SSO and FSO, respectively. Deacidification significantly altered their fatty acid profiles, particularly polyunsaturated fatty acids, with C18:2 and C18:3 being the most affected. A total of 20 significantly different lipids were screened (variable importance in projection > 1.5, p < 0.05) and were mainly classified as glycerophospholipids and glycerolipids, of which two lipids (C18:2 and C18:3 (9, 12, 15)) demonstrated particularly marked differences, suggesting that these lipid species represent significant discriminators between SSO and FSO groups; these two lipids exhibited significant alterations during the refining processes of SSO and FSO, respectively. Full article

The appressorium is a specialised infection structure formed by Beauveria bassiana during host invasion. This study used sulforaphane to regulate the formation rate of B. bassiana appressoria, evaluated the correlation between appressorium formation and fungal pathogenicity, and explored its impact on insect cuticular metabolism. The results showed that sulforaphane significantly modulated appressorium formation. Spore suspensions with varying appressorium formation rates were injected into Opisina arenosella and Bombyx mori larvae. As the appressorium formation rate increased, B. bassiana exhibited enhanced pathogenicity, leading to accelerated larval mortality. A significant positive correlation (p ≤ 0.05) was observed between appressorium formation and pathogenicity. LC-MS analysis revealed that, prior to appressorium development, larvae activated defence mechanisms involving secondary metabolites, hormone signalling, and toxin metabolism pathways. Following appressorium formation, 61 unique cuticular compounds were identified, along with activation of host lipid metabolism (notably glycerophospholipid degradation), programmed cell death pathways (ferroptosis, necroptosis), and enhanced energy metabolism via the citric acid cycle—collectively indicating disruption of the epidermal defence barrier. Overall, appressorium development by B. bassiana significantly reshapes the metabolic landscape of the larval cuticle, thereby enhancing fungal virulence. This study provides a theoretical foundation for understanding the pathogenic mechanisms of B. bassiana. Full article

This study investigates the effect of walnut green husk extract (WE) on gut microbiota, metabolites, and immune-antioxidant changes in fattening pigs through gut microbiota-metabolite interactions. A total of 60 healthy fattening pigs (Duroc × Landrace × Yorkshire) with an initial body weight of 65.2 ± 3.1 kg were randomly assigned to two groups (n = 30 per group): the control group (NC), which was fed a basal diet, and the WE group, which was fed the basal diet supplemented with 0.1% walnut green husk extract (WE). Dietary supplementation with 0.1% WE significantly increased the relative abundances of beneficial bacteria (e.g., Firmicutes, Lactobacillus) and reduced pathogenic bacteria (e.g., Proteobacteria, Shigella). Untargeted metabolomics identified 170 differentially accumulated metabolites, among which propionic acid—a key short-chain fatty acid with immunomodulatory effects—was significantly upregulated by 1.09-fold (p = 0.03) and showed a positive correlation with beneficial microbial abundances. These metabolites were enriched in glycerophospholipid and α-linolenic acid metabolism pathways, where eicosadienoic acid inhibited the nuclear factor kappa-B (NF-κB) pathway for anti-inflammatory effects, and methyl cinnamate synergistically regulated mitogen-activated protein kinase (MAPK) signaling with Lactobacillus. Serum analyses showed that WE significantly enhanced IgA, IgM, and IgG levels by 3.97-fold, 4.67-fold, and 4.43-fold (p < 0.01), reduced malondialdehyde (MDA) concentration by 82.8% (p < 0.01), and trended to improve antioxidant capacity via glutamine. Mechanistically, WE promoted short-chain fatty acid production by beneficial bacteria, forming a “microbiota–metabolite–immunity” cascade to enhance lipid metabolism and alleviate intestinal inflammation. These findings highlight that WE provides multi-omics evidence for its application as a functional feed additive. Full article

Sulforaphane, a natural isothiocyanate predominantly found in cruciferous vegetables, has shown potential in preventing and treating Helicobacter pylori infection. However, the underlying metabolic mechanisms remain largely unclear. This study employed high-coverage metabolomics and lipidomics methods to comprehensively investigate the effects of sulforaphane on the serum and liver metabolic profiles of H. pylori-infected mice. Metabolomics and lipidomics analysis revealed that H. pylori infection disrupted multiple metabolic pathways, leading to perturbations in amino acids, fatty acids, bile acids, and various lipid species. Sulforaphane treatment can ameliorate these disruptions, notably reversing alterations in serum glycerophospholipids and restoring hepatic levels of amino acids, bile acids, glycerophospholipids, ceramides, and peptides. Key metabolic pathways implicated included glutathione metabolism and glycine and serine metabolism, which are associated with antioxidant defense and host resistance to pathogenic infections. These findings offer a comprehensive metabolic basis for understanding the therapeutic effects of sulforaphane against H. pylori infection. Full article

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

Background/Objectives: In recent years, lipids have emerged as critical regulators of different disease processes, being involved in cancer pathogenesis, progression, and outcome. Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) has significantly expanded the technology’s reach, enabling spatially resolved profiling of lipids directly from tissue, including formalin-fixed paraffin-embedded (FFPE) specimens. In this context, MALDI matrix selection is crucial for lipid extraction and ionization, influencing key aspects such as molecular coverage and sensitivity, especially in such specimens with already depleted lipid content. Thus, in this work, we aim to explore the feasibility of mapping lipid species in FFPE clinical samples with MALDI-MSI using 6-aza-2-thiothymine (ATT) as a matrix of choice. Methods: To do so, ATT performances were first compared to those two other matrices commonly used for lipidomic analyses, 2′,5′-dihydroxybenzoic acid (DHB) and Norharmane (NOR), on lipid standards. Results: As a proof-of-concept, we then assessed ATT’s performance for the MALDI-MSI analysis of lipids in FFPE brain sections, both in positive and negative ion modes, comparing results with those obtained from other commonly used dual-polarity matrices. In this context, ATT enabled the putative annotation of 98 lipids while maintaining a well-balanced detection of glycerophospholipids (60.2%) and sphingolipids (32.7%) in positive ion mode. It outperformed both DHB and NOR in the identification of glycolipids (3%) and fatty acids (4%). Additionally, ATT exceeded DHB in terms of total lipid count (62 vs. 21) and class diversity and demonstrated performance comparable to NOR in negative ion mode. Moreover, ATT was applied to a FFPE glioblastoma tissue microarray (TMA) evaluating the ability of this matrix to reveal biologically relevant lipid features capable of distinguishing normal brain tissue from glioblastoma regions. Conclusions: Altogether, the results presented in this work suggest that ATT is a suitable matrix for pathology imaging applications, even at higher lateral resolutions of 20 μm, not only for proteomic but also for lipidomic analysis. This could enable the use of the same matrix type for the analysis of both lipids and peptides on the same tissue section, offering a unique strategic advantage for multi-omics studies, while also supporting acquisition in both positive and negative ionization modes. Full article