PubMed

Sci Rep. 2024 Dec 30;14(1):31635. doi: 10.1038/s41598-024-80544-6.ABSTRACTTriphala is a traditional Ayurvedic herbal formulation composed of three fruits: amla (Phyllanthus emblica), bibhitaki (Terminalia bellerica), and haritaki (Terminalia chebula). Triphala is a potent Ayurvedic remedy that promotes digestion, detoxification, and overall wellness, while also providing antioxidant benefits through its trio of nutrient-rich fruits. In order to elucidate the individual contributions of the three ingredients of Triphala from molecular perspective, the individual ingredients were used for the untargeted LCMS/MS analysis. Fresh fruits (PE, TC, and TB) were collected, processed into coarse powders, and sequentially extracted {hexane, chloroform, and ethyl acetate}. LCMS/MS data analysis was performed on the resultant metabolites, with bioinformatics tools employed for pathway enrichment, target prediction, and classification of identified compounds. Additionally, polyphenols were identified as key compounds with potential health benefits. LCMS analysis of the individual extracts identified a total of 10227 features, resulting in 2515 annotated metabolites, with PE contributing the highest number at 1286. Comparative analysis revealed 408 non-redundant metabolites, with 74.2% being unique to individual fruits, underscoring the complementary phytochemical profiles. Pathway enrichment analysis highlighted dominant phenylpropanoid biosynthesis pathways across all extracts, while a comprehensive polyphenol classification identified 71 polyphenols, with significant interactions predicted between polyphenols and gut microbiota. Additionally, five common polyphenols showed potential human targets related to antioxidant activity. These findings provide a deeper understanding of the phytochemical diversity and potential health benefits of Triphala, supporting its traditional use in promoting health.PMID:39738152 | DOI:10.1038/s41598-024-80544-6

Sci Rep. 2024 Dec 30;14(1):31620. doi: 10.1038/s41598-024-80176-w.ABSTRACTResearch has shown various hydrolyzed proteins possessed beneficial physiological functions; however, the mechanism of how hydrolysates influence metabolism is unclear. Therefore, the current study aimed to examine the effects of different sources of protein hydrolysates, being the main dietary protein source in extruded diets, on metabolism in healthy adult dogs. Three complete and balanced extruded canine diets were formulated: control chicken meal diet (CONd), chicken liver and heart hydrolysate diet (CLHd), mechanically separated chicken hydrolysate diet (CHd). A replicated 3 × 5 Latin rectangle design was used with 10 adult beagles. Within each period, the assigned diets were fed to the beagles for 28 days after a 7-day wash out period. Plasma and fresh fecal samples were collected at day 28. Samples of diets, plasma, and feces were analyzed for global metabolomics with ultra-performance liquid chromatography and quadrupole-Orbitrap high-resolution mass spectrometer interfaced with a heated electrospray ionization source and mass analyzer. In general, there were lower fecal concentrations of dipeptides and protein degradation metabolites, indicating higher protein digestibility, in dogs fed protein hydrolysate diets in contrast with CONd (q < 0.05). Higher plasma pipecolate and glutamate, higher fecal spermidine and indole propionate, and lower phenol-derived products in both plasma and feces were found in CLHd group than CONd (q < 0.05), indicating lower oxidative stress and inflammation levels. The main difference in lipid metabolism between CHd and CONd was the bile acid metabolism, showing lower circulating bile acid, lower unconjugated bile acid excretion and higher taurine-conjugated bile acid excretion in the CHd group (q < 0.05). In conclusion, using chicken hydrolysates as the main protein source in extruded canine diets showed potential for physiological benefits in healthy adult dogs, especially protein hydrolysate from chicken heart and liver demonstrated effects on lowering inflammation and oxidation levels.PMID:39738132 | DOI:10.1038/s41598-024-80176-w

Nat Commun. 2024 Dec 30;15(1):10878. doi: 10.1038/s41467-024-55231-9.ABSTRACTAcute myeloid leukemia (AML) is an aggressive disease with a high relapse rate. In this study, we map the metabolic profile of CD34+(CD38low/-) AML cells and the extracellular vesicle signatures in circulation from AML patients at diagnosis. CD34+ AML cells display high antioxidant glutathione levels and enhanced mitochondrial functionality, both associated with poor clinical outcomes. Although CD34+ AML cells are highly dependent on glucose oxidation and glycolysis for energy, those from intermediate- and adverse-risk patients reveal increased mitochondrial dependence. Extracellular vesicles from AML are mainly enriched in stem cell markers and express antioxidant GPX3, with their profiles showing potential prognostic value. Extracellular vesicles enhance mitochondrial functionality and dependence on CD34+ AML cells via the glutathione/GPX4 axis. Notably, extracellular vesicles from adverse-risk patients enhance leukemia cell engraftment in vivo. Here, we show a potential noninvasive approach based on liquid 'cell-extracellular vesicle' biopsy toward a redefined metabolic stratification in AML.PMID:39738118 | DOI:10.1038/s41467-024-55231-9

J Cosmet Dermatol. 2025 Jan;24(1):e16763. doi: 10.1111/jocd.16763.ABSTRACTBACKGROUND: Acne is a common skin disorder that may be linked to metabolic dysfunction. However, the causal impact of blood metabolites on acne has not been thoroughly investigated.METHODS: We performed a metabolome-wide Mendelian randomization (MR) analysis on 486 blood metabolites and acne using a genome-wide association dataset. The study included preliminary inverse-variance weighted (IVW) analysis, multivariable MR analysis, linkage disequilibrium score (LDSC) analysis, and colocalization analysis, along with reverse MR to address potential reverse causation.RESULTS: Our analysis identified 12 metabolites significantly associated with acne. LDSC analysis revealed a genetic correlation between nonanoylcarnitine and acne. Colocalization analysis confirmed shared genetic variants, and metabolic pathway analysis implicated the arginine biosynthesis pathway and the selenocompound metabolism pathway in the development of acne.CONCLUSION: This study offers a comprehensive understanding of the causal relationships between plasma metabolites and acne. The findings provide insights into potential biomarkers and therapeutic targets for acne treatment, underscoring the need for further research.PMID:39737744 | DOI:10.1111/jocd.16763

Brief Bioinform. 2024 Nov 22;26(1):bbae679. doi: 10.1093/bib/bbae679.ABSTRACTAccurate and rapid taxonomic classifications are essential for systematically exploring organisms and metabolites in diverse environments. Many tools have been developed for biological taxonomic trees, but limitations apply, and a streamlined method for constructing chemical taxonomic trees is notably absent. We present the iPhylo suite (https://www.iphylo.net/), a comprehensive, automated, and interactive platform for biological and chemical taxonomic analysis. The iPhylo suite features web-based modules for the interactive construction and annotation of taxonomic trees and a stand-alone command-line interface (CLI) for local operation or deployment on high-performance computing (HPC) clusters. iPhylo supports National Center for Biotechnology Information (NCBI) taxonomy for biologicals and ChemOnt and NPClassifier for chemical classifications. The iPhylo visualization module, fully implemented in R, allows users to save progress locally and customize the underlying R code. Finally, the CLI module facilitates analysis across all hierarchical relational databases. We showcase the iPhylo suite's capabilities for visualizing environmental microbiomes, analyzing gut microbial metabolite synthesis preferences, and discovering novel correlations between microbiome and metabolome in humans and environment. Overall, the iPhylo suite is distinguished by its unified and interactive framework for in-depth taxonomic and integrative analyses of biological and chemical features and beyond.PMID:39737565 | DOI:10.1093/bib/bbae679

Curr Res Food Sci. 2024 Dec 5;10:100939. doi: 10.1016/j.crfs.2024.100939. eCollection 2025.ABSTRACTBlack oilseed crops are rich in diverse phenolic compounds and have excellent antioxidant activities, as reported in traditional Chinese medicine. Testa (seed coat) and peeled seeds (cotyledon, embryo, and other structures) are the seed's crucial components, contributing to the variation in phytonutrient, phenol content, bioactive component, and protective and pharmacological effects. However, comprehensive and comparative information on total phenol, flavonoid, antioxidant, and metabolic profiles in black seed testa and peeled sesame, soybean, peanut, and rapeseed seeds is rare. Here, we investigated the metabolic profiles, phenolic contents, and antioxidant activities of four black oilseed crop testas and peeled seeds. This study revealed that testa has higher total phenol, flavonoid, and antioxidant activities than peeled seeds. A total of 1847 metabolites were identified across all samples and categorized into 17 major classes: flavonoids (20.02%), phenolic acids (15.15%), lipids (11.47%), amino acids and derivatives (9.36%), alkaloids (7.47%), organic acids (5.79%), terpenoids (5.68%), lignans (5.57%), saccharides (4.27%), and nucleotides and derivatives (4.17%) among the top ten. Primary class metabolites such as amino acids, saccharides, and vitamins were higher in the peeled seeds than in the testa, signifying the role of energy reservoirs and nutritive potential. However, flavonoids, phenolic acids, coumarins, chromones, lignans, terpenoids, tannins, organic acids, and lipids were abundant in the testa. Interestingly, the diversity and content of secondary metabolites were more abundant in the testa than in the peeled seeds of each crop, explaining their potential for phenol content, bioactivity, antioxidant activity, and pharmacological potential. The bioactivity of peeled seeds and testas may be associated with the phytochemical composition and content of flavonoids, phenolic acids, terpenoids, alkaloids, lipids, terpenoids, lignans, amino acids, and saccharides. Therefore, according to our results, peeled seeds offer higher nutritional value, and the testa has medicinal and protective properties. This study provides insights into the variations in phytochemical composition, phenolic content, and antioxidant activity of testa and peeled black sesame, soybean, peanut, and rapeseed seeds for further application of oilseeds in food products and to maximize nutritional benefits.PMID:39737385 | PMC:PMC11683268 | DOI:10.1016/j.crfs.2024.100939

Front Plant Sci. 2024 Dec 16;15:1520543. doi: 10.3389/fpls.2024.1520543. eCollection 2024.ABSTRACTINTRODUCTION: UV-B can be used as an additional technique for nutrient accumulation in blue-grained wheat, which has special nutritional properties due to its blue starch layer. The concentration of flavonoids in blue-grained wheat under UV-B irradiation is extremely important for further investigation and exploitation of the nutritional properties of blue-grained wheat.METHODS: This investigation focuses on the expression of flavonoids and associated genes in blue-grained wheat using transcriptomic and metabolomic analyzes.RESULTS: The metabolome revealed 1846 compounds and 340 flavonoids after UV-B irradiation. Under UV-B irradiation, the amount of flavonoid metabolites decreased over time, but flavones and flavanols increased, and flavones and flavanols were more diverse and abundant. The content of some flavonoids of blue-grain wheat in period 2 was significantly higher under UV-B irradiation than its check and other periods of different treatments. There are 42344 differentially expressed genes identified from transcriptomic analysis, including 151 genes associated with the flavonoid pathway. The genes for the enzymes FLS, ANR, HCT, CYP75A and CYP73A are more abundant, with F3H and FLS showing higher expression levels.DISCUSSION: The expression of these genes decreased after early UV-B irradiation, but increased later. In the joint WGCNA study of the two groups, the FLS enzyme gene LOC123125079 plays an important role in the response of blue-grained wheat to UV-B irradiation. Our findings help to identify essential genes and processes that allow blue-grained wheat to respond appropriately to UV-B irradiation, which is critical for the accumulation of flavonoids and other bioactive compounds in colored wheat, maximising its nutritional properties.PMID:39737375 | PMC:PMC11684391 | DOI:10.3389/fpls.2024.1520543

Front Nutr. 2024 Dec 16;11:1509577. doi: 10.3389/fnut.2024.1509577. eCollection 2024.ABSTRACTBACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality globally. Hypercholesterolemia accelerates atherosclerotic development and is an independent modifiable risk factor for ASCVD. Reducing cholesterol levels is effective in preventing ASCVD. Acetyl-L-carnitine (ALC) is an endogenous molecule that plays a primary role in energy metabolism; however, its effect on cholesterol metabolism remains unclear.METHODS: We collected plasma samples and clinical data from 494 individuals with hyperlipidemia. Targeted metabolomics were used to measure plasma ALC levels and explore the association of ALC with clinical cholesterol levels. Additionally, we explored the effects of ALC in cholesterol levels and cholesterol metabolism in a murine hypercholesterolemia model. An LDLR-/- mouse-based atherosclerotic model was established to investigate the roles of ALC on atherosclerotic progression.RESULTS: Plasma ALC concentrations were significantly negatively correlated with plasma total cholesterol (TC) levels (r = -0.43, p < 0.0001) and low-density lipoprotein cholesterol (LDL-C; r = -0.53, p < 0.0001). Incorporating ALC into the diet significantly reduced plasma TC and LDL-C levels, downregulated genes involved in cholesterol synthesis, such as sterol regulatory element-binding protein 2 (SREBP2) and 3-hydroxy-3-methyl-glutaryl-CoA reductase, and upregulated low-density lipoprotein receptor expression. ALC supplementation substantially lowered plasma TC levels and inhibited atherosclerosis in LDLR-/- mice.CONCLUSION: ALC reduced atherosclerotic plaque formation by lowering plasma cholesterol levels via suppression of SREBP2-mediated cholesterol synthesis, thus suggesting that ALC is a potential therapeutic target for ASCVD.PMID:39737151 | PMC:PMC11684389 | DOI:10.3389/fnut.2024.1509577

Front Microbiol. 2024 Dec 16;15:1462491. doi: 10.3389/fmicb.2024.1462491. eCollection 2024.ABSTRACTINTRODUCTION: Atopic dermatitis (AD) is an allergic disease caused by various factors that can affect an individual's appearance and cause psychological stress. Therefore, it is necessary to investigate the underlying mechanisms and develop effective treatment strategies. The gut microbiota and bacterial metabolism play crucial roles in human diseases. However, their specific role in AD remains unclear.METHODS: In this study, we established a mouse model of AD and found that 2,4-dinitrofluorobenzene disrupted the skin barrier in mice. The species composition of intestinal bacteria was then analyzed by fecal 16s rRNA sequencing. The metabolic level of mice was analyzed by untargeted and targeted metabolomics in stool.RESULTS: The levels of filaggrin and aquaporin 3 proteins in the model mice and total superoxide dismutase, catalase and malondialdehyde levels were significantly altered. Additionally, inflammatory factors such as tumor necrosis factor-alpha showed a significant increase. Using 16S rRNA gene sequencing, we identified 270 bacterial species with altered abundances of Ruminococcaceae and Bifidobacteriaceae. The untargeted metabolomic analysis detected 1,299 metabolites. Targeted analysis of free fatty acids revealed 49 metabolites with notable increases in linoleic and linolenic acid levels. Fecal bacterial transplantation experiments have demonstrated that oxidative stress, inflammation, and skin barrier damage were alleviated after transplantation.DISCUSSION: These findings suggested that the metabolite linoleic acid negatively correlated with Ruminococcaceae and Bifidobacteriaceae may influence AD development. Perturbations in the intestinal bacteria and flora contributed to the development of AD, and the mouse model could serve as a valuable tool for further investigation of therapeutic approaches for managing ADS.PMID:39736988 | PMC:PMC11683101 | DOI:10.3389/fmicb.2024.1462491

Parasit Vectors. 2024 Dec 30;17(1):547. doi: 10.1186/s13071-024-06599-6.ABSTRACTBACKGROUND: Echinococcosis is a zoonotic disease caused by an Echinococcus tapeworm infection. While diagnostic methods for humans often rely on ultrasound imaging and immunodiagnostic techniques, diagnosis in intermediate hosts typically has no widely used diagnostic markers, hampering disease control efforts.METHODS: The differences in serum metabolites of sheep infected with Echinococcus granulosus and a control group were analyzed using ultrahigh-performance liquid chromatography (UHPLC) separation with tandem mass spectrometry (MS/MS) detection. This provided a basis for the early diagnosis and pathogenetic study of cystic echinococcosis (CE) in intermediate hosts at the metabolomics level. Orthogonal projections to latent structures-discriminant analysis (OPLS-DA) were used to analyze different metabolites in the serum of the two groups. The differentially abundant metabolites were entered into the MetaboAnalyst 5.0 online analysis website for processing, and the top-15-ranked metabolic pathways were set to produce bubble plots and differential abundance score plots, with a significant difference of P < 0.05 and a false discovery rate (FDR) < 0.1 as the screening conditions.RESULTS: Data analyses of serum samples from both groups identified a total of 1905 significantly different metabolites, where 841 metabolites were upregulated and 1064 metabolites were downregulated. Twelve metabolites were significantly upregulated and 21 metabolites were significantly downregulated in the experimental group. Then, the 1,7-dihydroxyxanthone, 2-methylbutyrylglycine, 3,3-dimethylglutaric acid, 5,12-dihydroxy-6,8,10,14,17-eicosapentaenoic acid, 9-hydroperoxy-10E,12Z,15Z-octadecatrienoic acid, and trimethylamine N-oxide 6 metabolites were selected as diagnostically valuable candidate biomarkers (area under the curve [AUC] > 0.7). These differential metabolites are involved in various metabolic pathways, including amino acid metabolites (arginine, L-isoleucine, L-valine) and fatty acid metabolism (fenugreek, arachidonic acid, linolenic acid). Compared with the control group, sheep in the CE group had increased serum levels of fenugreek acid, while all other metabolites such as glycine showed significantly reduced serum levels (P < 0.01).CONCLUSIONS: Through non-targeted metabolomic analysis of the serum of CE-infected sheep, differential metabolites closely related to amino acid metabolism and the fatty acid metabolism pathway were identified. These differentially abundant metabolites can serve as biomarkers for diagnosing CE infection in intermediate sheep hosts.PMID:39736799 | DOI:10.1186/s13071-024-06599-6

Pediatr Rheumatol Online J. 2024 Dec 30;22(1):113. doi: 10.1186/s12969-024-01041-8.ABSTRACTBACKGROUND: Juvenile idiopathic arthritis (JIA) is challenging to classify and effectively monitor due to the lack of disease- and subtype-specific biomarkers. A robust molecular signature that tracks with specific JIA features over time is urgently required, and targeted plasma metabolomics may reveal such a signature. The primary aim of this study was to characterise the differences in the plasma metabolome between JIA patients and non-JIA controls and identify specific markers of JIA subtype. We also assessed the extent to which these signatures are due to underlying inflammation as assessed by glycoprotein acetyls (GlycA) and high-sensitivity C-Reactive Protein (hsCRP) levels.METHODS: Targeted nuclear magnetic resonance (NMR) metabolomic profiles of plasma of 72 children with JIA and 18 controls were assessed cross-sectionally. Associations between 71 metabolomic biomarkers and JIA, JIA subtype, disease activity status, and inflammation markers (GlycA and hsCRP) were assessed using multivariable linear regression models.RESULTS: JIA was associated with higher GlycA (mean difference = 0.93 standard deviations, 95% confidence interval = [0.370, 1.494], Padj = 0.039) and docosahexaenoic acid (1.06, [0.51, 1.60], Padj = 0.021), and lower acetate (-0.92, [-1.43, -0.41], Padj = 0.024) relative to controls. This variation was largely driven by systemic JIA (sJIA), with 24 of 71 total biomarkers significantly different (Padj <0.05) relative to controls. There were no specific differences identified in oligoarticular (oJIA) or polyarticular (rheumatoid factor positive or negative) JIA relative to controls. Despite being generally highly correlated with hsCRP (r > 0.70), GlycA, but not hsCRP, was positively associated with active disease in sJIA (0.22, [-0.40, -0.04], Padj = 0.018), and 6 of 24 sJIA-associated markers were associated with GlycA levels. Only 1 sJIA-associated biomarker, histidine, was associated with hsCRP levels.CONCLUSION: Differences in the plasma NMR metabolomic profiles are apparent in children with sJIA, but not other JIA subtypes, relative to non-JIA controls. These findings suggest a potential utility for classifying and monitoring JIA through metabolomic profiling, with chronic inflammation, measured by GlycA, potentially playing a role in at least some of these metabolomic differences.PMID:39736759 | DOI:10.1186/s12969-024-01041-8

Hum Genomics. 2024 Dec 31;18(1):141. doi: 10.1186/s40246-024-00704-7.ABSTRACTNeurodegenerative diseases present complex genetic architectures, reflecting a continuum from monogenic to oligogenic and polygenic models. Recent advances in multi-omics data, coupled with systems genetics, have significantly refined our understanding of how these data impact neurodegenerative disease mechanisms. To contextualize these genetic discoveries, we provide a comprehensive critical overview of genetic architecture concepts, from Mendelian inheritance to the latest insights from oligogenic and omnigenic models. We explore the roles of common and rare genetic variants, gene-gene and gene-environment interactions, and epigenetic influences in shaping disease phenotypes. Additionally, we emphasize the importance of multi-omics layers including genomic, transcriptomic, proteomic, epigenetic, and metabolomic data in elucidating the molecular mechanisms underlying neurodegeneration. Special attention is given to missing heritability and the contribution of rare variants, particularly in the context of pleiotropy and network pleiotropy. We examine the application of single-cell omics technologies, transcriptome-wide association studies, and epigenome-wide association studies as key approaches for dissecting disease mechanisms at tissue- and cell-type levels. Our review introduces the OmicPeak Disease Trajectory Model, a conceptual framework for understanding the genetic architecture of neurodegenerative disease progression, which integrates multi-omics data across biological layers and time points. This review highlights the critical importance of adopting a systems genetics approach to unravel the complex genetic architecture of neurodegenerative diseases. Finally, this emerging holistic understanding of multi-omics data and the exploration of the intricate genetic landscape aim to provide a foundation for establishing more refined genetic architectures of these diseases, enhancing diagnostic precision, predicting disease progression, elucidating pathogenic mechanisms, and refining therapeutic strategies for neurodegenerative conditions.PMID:39736681 | DOI:10.1186/s40246-024-00704-7

BMC Pediatr. 2024 Dec 31;24(1):849. doi: 10.1186/s12887-024-05343-4.ABSTRACTBACKGROUND: To compare the impact of two different lipid emulsions, specifically a soybean oil-based emulsion and a multiple oil emulsion (soybean oil, medium-chain triglycerides, olive oil, and fish oil, SMOF), on serum metabolites of very low birth weight (VLBW) infants using untargeted metabolomics analysis.METHODS: A comparative study was conducted on 25 VLBW infants hospitalized in neonatal intensive care units (NICU) of Hangzhou Women's Hospital in 2023. The infants were divided into the SMOF group (13 cases) and the soybean oil group (12 cases) based on the type of lipid emulsion used during parenteral nutrition. Serum samples were collected at birth and 14 days later from both groups. An untargeted metabolomics analysis was conducted on serum samples using Ultra-high Performance Liquid Chromatography - Tandem Mass Spectrometry (UHPLC-MS/MS). Differential metabolites were identified using Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) modeling, with criteria of variable importance in the projection (VIP) > 1 and false discovery rate (FDR) < 0.05. Functional annotation of the top 30 differential metabolites, ranked by VIP value, was conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Subsequently, enrichment and topological analyses were conducted with MetaboAnalyst software to identify key metabolic pathways. Finally, receiver operating characteristic (ROC) analysis was performed on metabolites associated with the identified key metabolic pathways.RESULTS: The metabolomic analysis revealed that, in the OPLS-DA model, no significant metabolite differences were found in umbilical cord blood between the two groups. However, 84 differential metabolites were identified in the 14-day samples from the SMOF group compared to the soybean oil group. According to MetaboAnalyst analysis, glycerophospholipid metabolism emerged as the most significantly altered metabolic pathway following the administration of SMOF lipid emulsion. Additionally, ROC curve analysis confirmed a significant increase in LysoPC(20:5), PE(16:0/20:5), and PE-NMe(22:5/16:0) metabolites in the SMOF group.CONCLUSION: The administration of SMOF lipid emulsion in VLBW infants resulted in significant modifications of serum metabolites compared to traditional soybean oil-based lipid emulsions. Notably, glycerophospholipid metabolism was identified as the most prominently altered metabolic pathway. Metabolites, including LysoPC(20:5), PE(16:0/20:5), and PE-NMe(22:5/16:0), emerged as potential biomarkers.CLINICAL TRIAL NUMBER: Not applicable.PMID:39736612 | DOI:10.1186/s12887-024-05343-4

BMC Cardiovasc Disord. 2024 Dec 31;24(1):762. doi: 10.1186/s12872-024-04423-8.ABSTRACTBACKGROUND: Qi Li Qiang Xin (QLQX) capsule has a solid theoretical basis and clinical efficacy in the treatment of chronic heart failure; however, the underlying mechanisms remain obscure. This study was designed to determine the effect of the QLQX on the treatment of heart failure and delineate the underlying mechanisms via a nontargeted metabolomics and lipidomics approach.METHODS: A rat model of heart failure after myocardial infarction (MI) was established via permanent ligation of the anterior descending branch of the left coronary artery. The rats were then randomly divided into the SHAM group, the MI group, the QLQX group (1.3 g/kg/day), and the VAL (valsartan) group (80 mg/kg/day). Cardiac function was measured via echocardiography. The levels of serum NT-proBNP and hs-cTn-I were detected via ELISA. H&E staining and Masson's trichrome staining were used to observe cardiac morphology and myocardial fibrosis. Using the UPLC-QTOF/MS method, metabolomics and lipidomics analyses were performed on the plasma of the rats in each group to identify biomarkers and potential amino acid and lipid therapy mechanisms for heart failure after QLQX administration in rats with heart failure.RESULTS: QLQX capsule improved the heart f unction of rats with heart failure after myocardial infarction by increasing the LVEF and LVFS, decreasing the LVIDd and LVIDs. QLQX capsule reduce the levels of NT-proBNP and hs-cTn-I, which are markers of heart failure, and improve the myocardial infarction area and degree of myocardial fibrosis. In addition, in the metabolomics analysis, a total of 17 plasma metabolites were significantly different between heart failure rats and normal rats, all of which recovered significantly after QLQX treatment. These metabolites mainly participate in the biosynthesis of unsaturated fatty acids; valine, leucine and isoleucine biosynthesis; phenylalanine, tyrosine and tryptophan biosynthesis; and glycerophospholipid metabolism. Lipid analysis revealed that FA18:2, FA18:3, FA20:5, and FA22:6 in the QLQX group were significantly altered (P < 0.01). The peak area contents of FA18:2, FA18:3, FA20:5, and FA22:6 in the sham surgery group and model group also significantly decreased (P < 0.05).CONCLUSION: This study elucidates the therapeutic effect of QLQX on heart failure rats and elucidates its potential mechanisms, which are related mainly to the regulation of amino acid and lipid metabolism in heart failure rats through metabolomics and lipidomics experiments.PMID:39736521 | DOI:10.1186/s12872-024-04423-8

BMC Gastroenterol. 2024 Dec 30;24(1):478. doi: 10.1186/s12876-024-03576-2.ABSTRACTBACKGROUND: Gastric cancer (GC) remains one of the predominant malignant tumors within the digestive tract, yet its underlying biological mechanisms remain elusive. The primary objective of this study is to delineate the causal relationship between circulating metabolites and GC.METHOD: The primary Mendelian randomization (MR) analysis was based on three large GWAS datasets. While the inverse variance weighted served as the primary analysis technique for investigating causal relationships, additional sensitivity analyses were facilitated through methods such as MR-PRESSO, the weighted median, and MR-Egger. Subsequently, replication, meta-analysis, and multivariable MR were executed using another GC GWAS.RESULTS: The results of this study indicated significant associations between three metabolites 3-methyl-2-oxovalerate (OR 5.8, 95%CI: 1.53-22.05, p = 0.0099), piperine (OR 2.05, 95%CI: 1.13-3.7, p = 0.0175), Phe-Phe dipeptide (OR 0.16, 95%CI: 0.03-0.93, p = 0.0409) and GC.CONCLUSION: The present study provides evidence supporting a causal relationship between these three circulating metabolites and GC risk. Elevated levels of 3-methyl-2-oxovalerate and piperine may increase the risk of GC, while Phe-Phe dipeptide may have a protective effect. By integrating genomics and metabolomics, we offer a novel perspective on the biological mechanisms underlying GC. Such insights have the potential to enhance strategies for the screening, prevention, and treatment of GC.PMID:39736510 | DOI:10.1186/s12876-024-03576-2

J Ethnopharmacol. 2024 Dec 28:119287. doi: 10.1016/j.jep.2024.119287. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Epimedium Tourn. ex L. is a traditional Chinese medicine used for thousands of years in China to treat forgetfulness. Icariin is a principal component of the genus Epimedium.AIM OF THE STUDY: The metabolic mechanism of icariin treating forgetfulness is explored.MATERIALS AND METHODS: A D-galactose-induced senescent mouse model was employed. The cognitive performance of mice was assessed in the fear conditioning test. Hippocampal pathology was assessed in the immunohistochemistry assay. Plasma metabolome was analyzed using GC-MS method, and the differential metabolites were further identified by UPLC-MS/MS or GC-MS method. The liver function, including ALT and AST, was assessed by enzyme reaction. Icariin was administered intraperitoneally at 50 and 100 mg/kg. Mice were administered five consecutive days per week for 8 weeks.RESULTS: Icariin treatment improved hippocampus-related fear memory but not amygdala-related memory, whereas Pexidartinib (PLX3397), a microglial scavenger, did not. Icariin treatment maintained the TMEM119-positive microglial population and decreased the accumulation of the senescent biomarker p16 in the dorsal hippocampus in senescent mouse brains, whereas PLX3397 did not. Notably, p16 in the CA2 subregion significantly decreased in icariin-treated mice than the other hippocampal subregions. The senescent mice exhibited the circulating metabolic characteristics of mild ketoacidosis, active tricarboxylic acid (TCA) cycle, lactic acidosis, hyperglycemia, active detoxification, active cis-oleic acid metabolism, and inhibitory GABA shut. R-3-hydroxybutyric acid primarily produced in the liver was selectively and robustly decreased by icariin treatment, which was not observed with PLX3397. The TCA cycle was rescued in senescent mice by icariin treatment. Icariin also protected liver function (plasma ALT) in D-gal-induced senescent mice.CONCLUSIONS: Icariin may protect mouse hippocampal cognition from D-gal-induced senescence by protecting microglial homeostasis, and facilitating the utilization of R-3-hydroxybutyric acid is one of the underpins.PMID:39736348 | DOI:10.1016/j.jep.2024.119287

J Ethnopharmacol. 2024 Dec 28:119300. doi: 10.1016/j.jep.2024.119300. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: The Daqinjiao decoction (DQJT), a classical prescription, has been utilized for millennia in stroke management, yet its underlying mechanisms remained obscure.AIM OF THE STUDY: The aim of this study was to elucidate the mechanisms through which DQJT mitigates cerebral ischemia/reperfusion injury (CI/RI).MATERIALS AND METHODS: The quantification of DQJT's primary components were performed by HPLC. Pharmacological assessments were then conducted to ascertain DQJT's efficacy in a Middle Cerebral Artery Occlusion/Reperfusion (MCAO/R) model. Following this, untargeted metabolomics, lipidomics and network pharmacology analyses were undertaken to unveil potential mechanisms, which were subsequently validated. UPLC-Q-TOF/MS was utilized to detect DQJT-derived chemicals in brain tissue, and molecular docking techniques were employed to investigate the bioactive compounds.RESULTS: DQJT treatment reduced brain damage induced by MCAO/R, as evidenced by decreased infarct sizes, enhanced behavioral function scores, and diminished neuronal damages. Untargeted metabolomics and lipidomics revealed that DQJT improved metabolism of unsaturated fatty acids. According to network pharmacology, lipid metabolism, cAMP signaling pathway and toll-like receptor signaling pathway pathways were notably affected, with HSP90AA1, TLR4, and PKA identified as potential targets of DQJT. Immunofluorescence and Western blot analyses further demonstrated that DQJT counteracted necroptosis and ferroptosis by inhibiting the HSP90AA1 and TLR4 pathways and enhancing the PKA pathway. Molecular docking results supported that the possible pharmacodynamic substances of DQJT in protecting against CI/RI.CONCLUSION: This research established that DQJT attenuates brain injury induced by MCAO/R through the modulation of necroptosis and ferroptosis via pathways including HSP90AA1, TLR4, and PKA. It shed light on the potential mechanisms and effective constituents of DQJT in stroke treatment, paving the way for further exploration of this ancient formula.PMID:39736347 | DOI:10.1016/j.jep.2024.119300

J Ethnopharmacol. 2024 Dec 28:119293. doi: 10.1016/j.jep.2024.119293. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Cisplatin (CP), a widely used antineoplastic agent, is a leading cause of drug-induced liver injury (DILI) due to its hepatotoxic effects. Licorice (GC), an established remedy in traditional Chinese medicine (TCM), has shown promise in addressing liver diseases and DILI. Nonetheless, the specific active components and underlying mechanisms of GC in mitigating CP-induced liver injury remain inadequately investigated.AIM OF THE STUDY: This study examined the active components and efficacy of GC in addressing CP-induced hepatotoxicity, focusing on its mechanisms related to bile acid metabolism and gut microbiota regulation.MATERIALS AND METHODS: Utilizing a CP-induced rat liver injury model, this study evaluated changes in liver coefficient, liver function indices, and pathological morphology while assessing the efficacy of GC for both prevention and treatment of CP-induced liver injury. Subsequently, UPLC-Q-TOF-MS qualitatively analyzed GC's blood-entering components, elucidating its pharmacodynamic material basis. Network pharmacology analysis identified potential pathways and targets of GC's blood components in relation to CP-induced liver injury. Furthermore, metabolomics and 16S rRNA sequencing were employed to clarify the pharmacodynamic mechanisms of GC in modulating bile acid metabolism and gut microbiota, offering insights into its preventive and therapeutic roles.RESULTS: The pharmacodynamic results revealed that GC significantly reduced liver function biomarkers and improved pathological changes in liver tissue. UPLC-Q-TOF-MS analysis identified 16 blood-entering components as potential pharmacodynamic agents of GC for preventing and treating CP-induced liver injury. Network pharmacology analysis suggested a link between GC's efficacy and the bile acid metabolic pathway. Furthermore, metabolomics analysis, immunoblotting, and 16S rRNA sequencing demonstrated that GC regulated bile acid metabolites in both liver and feces, enhanced FXR and BSEP expressions in the liver, and decreased CYP27A1 expression. Additionally, GC mitigated CP-induced intestinal dysbiosis by altering the abundance of gut microbiota.CONCLUSIONS: UPLC-Q-TOF-MS performed a qualitative analysis of 16 blood-entering components linked to GC, providing a basis for further exploration of the pharmacodynamic material underpinning GC. The protective role of GC in CP-induced liver injury appears connected to enhanced bile acid metabolism and restoration of gut microbiota balance.PMID:39736346 | DOI:10.1016/j.jep.2024.119293

Clin Nutr. 2024 Dec 19;45:31-35. doi: 10.1016/j.clnu.2024.12.016. Online ahead of print.ABSTRACTBACKGROUND&AIMS: Celiac disease (CD) and potential CD (pCD) are immune-mediated disorders triggered by the ingestion of gluten. In non-celiac gluten sensitivity (NCGS) neither allergic nor autoimmune mechanisms are involved. Relationships between NCGS and CD need to be further investigated.METHODS: Serum metabolomics and lipoproteomics, performed via nuclear magnetic resonance spectroscopy, were used to characterize these three gluten-related disorders. Lasso regression models were calculated to discriminate the groups of interest.RESULTS: Several metabolites and lipoprotein-related parameters (particularly those associated with HDL cholesterol) allowed the selective discrimination between CD (and pCD) and NCGS. This evidence pointed to possible alterations of the gut microbiota in NCGS patients. Cross-validated regression models were able to discriminate between CD and NCGS, and pCD and NCGS with AUCs of 0.90 and 0.83, respectively.CONCLUSION: This pilot study suggests changes in the gut microbiota and paves the way to the elucidation of the underlying mechanisms of NCGS.PMID:39736173 | DOI:10.1016/j.clnu.2024.12.016

Mov Disord. 2024 Dec 30. doi: 10.1002/mds.30095. Online ahead of print.ABSTRACTBACKGROUND: Lewy body diseases, including dementia with Lewy bodies (DLB), are characterized by α-synuclein accumulation, leading to dementia. Previous studies suggest distinct epigenetic and metabolomic profiles in DLB.OBJECTIVE: This study aims to identify diagnostic biomarkers by analyzing the methylome and metabolome in the Brodmann area 7 of postmortem brain tissues from DLB patients and control subjects using multiomics approaches.METHODS: Methylation analysis was performed using the Illumina EPIC array, and metabolomics profiling was conducted via 1H nuclear magnetic resonance (NMR) and direct injection/liquid chromatography coupled with mass spectrometry. Differential methylation and metabolite analysis were conducted, followed by pathway enrichment to explore biological relevance.RESULTS: We identified 3478 significantly differentially methylated cytosines, mostly hypermethylated, enriched in CpG islands near transcription start sites. Pathway enrichment analysis showed significant pathways, primarily linked to olfactory and synaptic functions. Metabolomics profiling identified 15 significantly altered metabolites, with Phosphatidylethanolamine (PE) Biosynthesis being the most affected pathway. Key correlations between differentially methylated cytosines and metabolites, particularly in the PE Biosynthesis pathway involving PTDSS1 and PCYT2 genes, were observed.CONCLUSIONS: Notably, sex-specific differences were found, with females exhibiting more epigenetic and metabolomic changes than males. Increased hypermethylation, linked to transcriptional silencing, and disruptions in PE biosynthesis suggest a role in synaptic dysfunction and olfactory deficits. In addition, α-aminoadipic acid was strongly associated with vascular functions, hinting at a possible overlap between vascular health and DLB. This study provides new insights into DLB mechanisms and potential therapeutic targets. © 2024 International Parkinson and Movement Disorder Society.PMID:39736077 | DOI:10.1002/mds.30095