Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Comprehensive chemical profiling of wild Coffea racemosa, C. Zanguebariae, C. arabica, and C. canephora: A Metabolomic approach using LC-MS(n) and multivariate analysis

Tue, 01/04/2025 - 12:00
Food Chem. 2025 Mar 26;481:144062. doi: 10.1016/j.foodchem.2025.144062. Online ahead of print.ABSTRACTBesides the need to adapt coffee cultivation to climate change, the growing demand for high-quality and exotic coffee has increased interest in species such as Coffea racemosa and C. zanguebariae. These species offer drought and pest resistance, fast maturation, and distinct sensory profiles. However, there is a lack of information regarding their chemical profile. Therefore, this study employed a metabolomic approach using LC-MS, ESI(±)MS, and multivariate analysis to assess the chemical profiles of these species and compare them with C. arabica and C. canephora cv. Conilon. Sixty-four compounds were identified, including chlorogenic acids, lipids, carbohydrates, amino acids, and glycosylated diterpenes. The results indicate that C. racemosa shares chemical similarities with C. arabica, particularly in their trigonelline and amino acid abundance, while C. zanguebariae is characterized by a high phospholipid content, which may influence mouthfeel. Additionally, LC-MS allows isomer separation, whereas ESI(±)MS emerged as a fast alternative for chemometric modeling.PMID:40168870 | DOI:10.1016/j.foodchem.2025.144062

Integrated transcriptomics and metabolomics elucidate additive inhibitory effects of combined salinity-waterlogging stress on soybean growth and metabolic adaptations

Tue, 01/04/2025 - 12:00
Plant Physiol Biochem. 2025 Mar 27;223:109847. doi: 10.1016/j.plaphy.2025.109847. Online ahead of print.ABSTRACTSalinity and waterlogging are major abiotic stresses constraining soybean productivity, with their combined effects often surpassing individual impacts. However, the nature of these combined effects-whether additive, synergistic, or antagonistic-remains unclear. In this study, we quantitatively demonstrated that combined salinity-waterlogging stress exerts additive inhibitory effects on soybean (Glycine max L. cv. Qihuang 34) growth, surpassing individual stresses without reaching synergistic severity. Physiological analysis revealed additive inhibition, as reflected by a 38.8 % reduction in leaf area, 36.8 % decrease in dry matter accumulation, and a 63.4 % decline in net photosynthetic rate under combined stress conditions, closely aligning with theoretical additive predictions (e.g., observed vs. predicted values: 38.8 % vs. 40.8 % for leaf area; 36.8 % vs. 37.7 % for biomass). Integrated transcriptomic and metabolomic analysis identified hypoxia-induced ATP depletion as a key driver, disrupting Na+/K+ homeostasis (277.9 % increase in Na+/K+ ratio) despite upregulation of key ion transporters (SOS1: +84.3 %, NHX1a: +54.0 % and NHX1b: +68.7 %). Additive activation of flavonoid biosynthesis genes (CHI, CHR) and metabolites (prunin, chalcone 2'-O-glucoside) mitigated oxidative damage through cumulative metabolite accumulation rather than synergistic interactions. Downregulation of photosynthesis-related genes (e.g., PsbO, PsaA) and ATP synthesis collapse explained energy deficits. Crucially, cutin/suberine biosynthesis emerged as a novel adaptive signature under combined stress. This study provides mechanistic insights into additive salt-waterlogging interactions, identifying targets for stress-resilient soybean breeding.PMID:40168856 | DOI:10.1016/j.plaphy.2025.109847

The preemptive control strategy for invasive plant seed banks triggering ecological threats through synchronized germination

Tue, 01/04/2025 - 12:00
J Environ Manage. 2025 Mar 31;380:125187. doi: 10.1016/j.jenvman.2025.125187. Online ahead of print.ABSTRACTInvasive alien plants threaten global ecosystems by disrupting biodiversity and degrading ecological functions. Soil seed banks-the reservoirs of viable seeds in the soil-play a crucial role in the persistence and spread of plant populations. However, current control measures for invasive plants predominantly target above-ground vegetation, neglecting these underground seed reserves, thereby allowing invasive plants to re-establish their populations. Inducing synchronous germination to deplete seed banks offers a potential preemptive control strategy. This study hypothesizes that seeds of invasive plants secrete secondary metabolites to promote the synchronous germination of conspecific seeds. Focusing on Ambrosia trifida L., a globally harmful annual invasive plant, where the soil seed bank plays a crucial role in its continued impact. We used metabolomics to identify such metabolites and found that Angelicin significantly enhances germination rates by up to 116.9 % (P < 0.01). Field experiments conducted in the native habitat demonstrated that applying Angelicin at concentrations of 0.015 μg ml-1 or higher depleted over 85 % of the seed bank (P < 0.01) without harming indigenous plant communities. These findings confirm the feasibility of depleting underground seed banks through induced germination. Integrating this strategy with traditional above-ground control methods can develop a comprehensive management system, offering a promising new approach for the widespread control of invasive plants.PMID:40168826 | DOI:10.1016/j.jenvman.2025.125187

Molecular and genomic insights into the pathogenicity of Sarocladium zeae causing maize stalk rot disease

Tue, 01/04/2025 - 12:00
Microbiol Res. 2025 Mar 28;296:128146. doi: 10.1016/j.micres.2025.128146. Online ahead of print.ABSTRACTPost-flowering stalk rot (PFSR) of maize has been traditionally associated with Fusarium verticillioides. Conversely, this study reveals Sarocladium zeae as a new phytopathogen responsible for the disease. This research was conducted to gain a comprehensive understanding of S. zeae by investigating its pathogenic mechanisms, profiling its metabolome, and deciphering its genomic characteristics. Maize stalks displaying stalk rot symptoms were collected from various regions of India. S. zeae was isolated and characterized using ITS and TEF-1α sequencing. Cultures of S. zeae exhibited slower growth on PDA medium compared to F. verticillioides, which dominated due to its rapid growth rate. Pathogenicity was confirmed through a toothpick inoculation assay. The symptoms induced by S. zeae was characterized by powdery, dry, pale brown-black discoloration, were distinct from the typical dark-brown lesions of Fusarium stalk rot. Enzymatic assays revealed increased activity of β-glucosidase, cellulase, and pectate lyase in infected stalks, while qPCR analysis showed the upregulation of endoglucanase and β-glucosidase genes in infected stalks underscored the critical roles of cellulase and β-glucosidase in pathogenicity Metagenomic analysis identified S. zeae as the predominant species in infected stalk samples. Genome assembly revealed the pathogen's complete genetic repertoire, including genes encoding effector proteins and CAZymes involved in cell wall degradation. Moreover, we have demonstrated that the S. zeae as a causal agent of maize stalk rot and further shedding light on its transition from an endophytic to a pathogenic lifestyle. Taken together, this research represents the first report to attribute maize stalk rot to S. zeae and to present its complete genome assembly, significantly advancing the understanding of its biology and pathogenic potential.PMID:40168814 | DOI:10.1016/j.micres.2025.128146

Therapeutic Potential of Raspberry Extract in High-Fat Diet-Induced Liver Injury via Apoptosis and AMPK/PPARα Pathways

Tue, 01/04/2025 - 12:00
J Agric Food Chem. 2025 Apr 1. doi: 10.1021/acs.jafc.4c09593. Online ahead of print.ABSTRACTThis study aimed to explore the efficacy and mechanisms of raspberry (Rubus idaeus L. fruit) aqueous extract (RE) in alleviating high-fat diet (HFD)-induced metabolic-associated fatty liver disease (MAFLD). The MAFLD mouse model was established to examine the effects of RE through liver transcriptome and metabolomics analysis. In this study, RE supplementation significantly alleviated HFD-induced liver injury, hepatosteatosis, inflammation, and insulin resistance. Liver transcriptome analysis demonstrated that RE supplementation favorably regulated signaling pathways involved in fatty acid metabolism and inflammation, including the AMPK signaling pathway, PPAR signaling pathway, apoptosis, etc. Furthermore, the injection of compound C, an antagonist of AMPK, notably reversed the hepatoprotective effects of RE, evidenced by increased lipid profile levels, accelerated fatty acid-related gene disorder, and increased positive tunnel staining area. Furthermore, liver metabolomics analysis demonstrated that RE treatment led to substantial enrichment of the liver tissue metabolite umbelliferone (UMB), which has the potential to ameliorate lipid accumulation and hepatocyte injury through the AMPK signaling pathway. In summary, RE intervention mitigated HFD-induced liver dysfunction in mice, with UMB likely being the primary component responsible for its therapeutic efficacy in the liver. In addition, this study provided new insights, suggesting that RE could be used as a promising therapeutic approach for modulating MAFLD via apoptosis and the AMPK/PPARα signaling pathway.PMID:40168586 | DOI:10.1021/acs.jafc.4c09593

Effects of SGLT2 Inhibitors on Modulating Protein-Bound Uremic Toxins and Gut Microbiota in Pre-Dialysis CKD Patients: A Matched Case-Control Study

Tue, 01/04/2025 - 12:00
Kidney360. 2025 Apr 1. doi: 10.34067/KID.0000000792. Online ahead of print.ABSTRACTBACKGROUND: The intricate interplay between chronic kidney disease (CKD) and intestinal microbiota has gained increasing attention, with gut dysbiosis being implicated in uremic toxin accumulation and CKD progression. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are now transforming CKD management but pose uncertain effects on shaping gut microbiota. This study aimed to elucidate the impact of SGLT2 inhibitors on perturbations of gut microbial composition and metabolic responses in CKD patients.METHODS: Analysis of fecal microbiota and targeted profiling of serum short-chain fatty acids (SCFAs) and gut-derived uremic toxins were conducted in a matched case-control study, including 60 CKD patients (treated: n=30; untreated: n=30) and 30 non-CKD controls.RESULTS: Gut microbial composition differed significantly among three study groups. CKD patients receiving SGLT2 inhibitors exhibited distinctive taxonomic profiles, such as enrichment of Bacteroides stercoris and Bacteroides coprocola. Surveys of metabolomic profiles revealed a reduction of two uremic solutes, indoxyl sulfate (IS) and p-cresyl sulfate (pCS), and several SCFAs (formic, acetic, propionic, valeric, and 2-methylbutanoic acid) in SGLT2 inhibitor-treated CKD patients. Co-occurrence analysis demonstrated a set of intestinal microbes that is positively or negatively correlated with the levels of pCS, and the abundance of these pCS-associated intestinal microorganisms was correlated with the levels of IS and isovaleric acids in the same and opposite direction, respectively. Further functional prediction indicated attenuated pathways related to protein and carbohydrate metabolism.CONCLUSIONS: Treatment with SGLT2 inhibitors in CKD patients is associated with distinct gut microbial composition and metabolite profiles, suggesting potential modulation of gut dysbiosis and metabolic pathways. Further studies are warranted to elucidate the clinical implications of these findings in CKD management.PMID:40168088 | DOI:10.34067/KID.0000000792

Cerebrospinal Fluid Metabolomics and Proteomics Integration in Neurological Syndromes

Tue, 01/04/2025 - 12:00
Methods Mol Biol. 2025;2914:303-321. doi: 10.1007/978-1-0716-4462-1_21.ABSTRACTThe integration of multi-omics data has increasingly been recognized as an effective approach to addressing complex problems and advancing precision medicine. Metabolomics and proteomics are closely related, and their integration provides complementary insights and enables cross-validation of experimental results. The integration of proteomics and metabolomics in cerebrospinal fluid is expected to reconstruct the complex biological networks underlying nervous system diseases, enhance understanding of molecular mechanisms, and aid in disease classification and prognosis prediction. However, integrating multi-omics data still faces numerous challenges, limiting the application of combined proteomic and metabolomic analyses in neurological diseases. Based on the advantages of integrated proteomics and metabolomics, this chapter introduces, for the first time, common strategies for the integrated analyses of omics data. Furthermore, we review advances in cerebrospinal fluid proteomics and metabolomics for neurological syndromes, highlighting current challenges and future directions.PMID:40167926 | DOI:10.1007/978-1-0716-4462-1_21

An LC-MS/MS Multiplexed Method to Quantify 14 Sphingolipids in Human Cerebrospinal Fluid (CSF)

Tue, 01/04/2025 - 12:00
Methods Mol Biol. 2025;2914:251-258. doi: 10.1007/978-1-0716-4462-1_18.ABSTRACTSphingolipids are bioactive lipids comprised of a sphingoid base linked to various long-chain fatty acids and phosphocholine and, in some cases, may also contain one or more sugars. A few species of sphingolipids share similar structures and may even have identical chemical composition but differ in their biological function. For this reason, they can only be accurately quantified using liquid chromatography coupled with mass spectrometry (LC-MS). This technique can separate sphingolipids based on their hydrophobicity and quantify them based on their mass-to-charge ratio (m/z). This is especially important when measuring isomeric species that have identical m/z but differ in their retention time. Here, we describe the development of a new LC-MS method to measure 14 sphingolipid species, including 7 ceramides (C14, C16, C18, C20, C24, C18:1, C24:1), 4 glycosphingolipids (C16 Glucosyl(ß) Ceramide (d18:1/16:0, C16 Galactosyl(ß) Ceramide (d18:1/16:0), C16 Lac Cer, C18 Lac Cer) and 3 sphingosines (Sphingosine (Sph), Glucosyl(ß) Sphingosine (d18:1), Galactosyl(ß) Sphingosine (d18:1)) in human cerebrospinal fluid (CSF). Using this 7-min method, chromatographic resolution of isomeric species glucosylceramide (Glc Cer) and galactosylceramide (Gal Cer) was achieved. This resolution is important as these two sphingolipid classes have distinct biological functions with important implications in neurological diseases like multiple sclerosis.PMID:40167923 | DOI:10.1007/978-1-0716-4462-1_18

Elucidation of the Human Cerebrospinal Fluid Metabolome by Ion Mobility Mass Spectrometry and NMR Spectroscopy

Tue, 01/04/2025 - 12:00
Methods Mol Biol. 2025;2914:229-250. doi: 10.1007/978-1-0716-4462-1_17.ABSTRACTIn the last decades, the prevalence of neurodegenerative disorders such as Parkinson's disease, dementia and stroke has significantly increased. The lack of early-stage biomarkers hereby is a major reason for poor outcomes and limited treatment options. Metabolism alterations are a major driver and readout of neurological implications; however, it can be assessed only to a very minor extent by non-invasive imaging technologies. By contrast, typical diagnostic biofluids like serum or urine reflect metabolic changes on the systemic scale and are not specific to the brain. That's why the analysis of cerebrospinal fluid (CSF) using metabolomic techniques offers a great perspective to better stratify patients with neurological implications. However, as metabolites can readily degrade and CSF collection in a clinical environment is challenging, several confounders have to be considered. Furthermore, no single technique can measure the full CSF metabolome. Hence in this work we used directly collected and quenched CSF for a multi-modal metabolomics profiling approach to define the ex vivo baseline of the human CSF metabolome by robust Nuclear Magnetic Resonance (NMR) spectroscopy and latest state of the art liquid chromatography (LC) ion mobility spectrometry mass spectrometry (IMS-MS).PMID:40167922 | DOI:10.1007/978-1-0716-4462-1_17

Mass Spectrometry Applied to Human Cerebrospinal Fluid Lipidome (II)

Tue, 01/04/2025 - 12:00
Methods Mol Biol. 2025;2914:203-212. doi: 10.1007/978-1-0716-4462-1_15.ABSTRACTLipidomics aims at characterizing lipid profiles and their biological role with respect to protein expression involved in lipid metabolism. Specifically, cerebrospinal fluid (CSF) lipidomics is offering a new perspective in the search for surrogate biomarkers to facilitate early diagnosis of psychiatric and neurodegenerative diseases. In this chapter, we describe a nontargeted approach to profile lipid molecular species present in human CSF using ultrahigh-performance liquid chromatography-electrospray ionization-time-of-flight mass spectrometry (UPLC-ESI-ToF-MS). This workflow complements the toolbox useful for the exploration and monitoring of neurodegenerative mechanisms associated with dysregulation in lipid metabolism.PMID:40167920 | DOI:10.1007/978-1-0716-4462-1_15

Correction: Metabolomic heterogeneity of ageing with ethnic diversity: a step closer to healthy ageing

Tue, 01/04/2025 - 12:00
Metabolomics. 2025 Apr 1;21(2):48. doi: 10.1007/s11306-025-02247-x.NO ABSTRACTPMID:40167843 | DOI:10.1007/s11306-025-02247-x

A pilot study on hemodynamically stable isolated chest trauma patients reveals dysregulation of oxidative metabolism

Tue, 01/04/2025 - 12:00
Metabolomics. 2025 Apr 1;21(2):49. doi: 10.1007/s11306-025-02241-3.ABSTRACTBACKGROUND: Metabolomic dysregulation precedes clinical deterioration following injury. However, despite receiving comparable treatment, patients with similar injury severity often follow different clinical trajectories and outcomes.METHODS: This prospective cohort study at a level 1 trauma centre screened 4541 acutely injured patients with chest trauma between September 2019 and February 2023. Fifty hemodynamically stable patients with isolated chest trauma were recruited for the final analysis. Urine samples were collected on the injury days 1, 3, and 7. For healthy subjects, the urine sample was collected once. NMR-based metabolomics was performed.RESULTS: The study found that the majority of injured patients were young (median age of 40 years), with road traffic injuries being the most common. The median time to presentation of the patient to the ED was 3.08 h, and 92% of patients had multiple rib fractures, pulmonary contusion (60%), and pleural involvement (88%). No patient died. The study found that twenty metabolites were dysregulated (p-value < 0.001). Twelve metabolites were upregulated, while the other eight showed downregulation. However, only five metabolites showed temporal association. 4-HPA, phenylalanine, aconitate, and carnitine represent a high potential for use as a biomarker in patients with isolated blunt trauma chest patients who remain hemodynamically stable. These differentially regulated metabolites were involved in Glyoxylate and dicarboxylate metabolism pathways, glycine, serine, and threonine metabolism, and the Citrate cycle (TCA cycle).CONCLUSIONS AND RELEVANCE: Metabolomics can accurately characterize metabolism in isolated blunt chest trauma patients, revealing perturbed pathways of traits such as oxidative stress and amino acid metabolisms. These metabolites could serve as biomarkers to detect systemic changes following chest injuries early. Metabolic profiling following an injury can aid in detecting systemic changes early and identifying novel biomarkers, enabling targeted interventions to improve patient outcomes.PMID:40167841 | DOI:10.1007/s11306-025-02241-3

An Interplay Between Hypothalamic Microstructure, Systemic Metabolism and Gut Microbiome Composition in Male Rats at Hyperacute Timepoint Post TBI

Tue, 01/04/2025 - 12:00
J Neurosci Res. 2025 Apr;103(4):e70032. doi: 10.1002/jnr.70032.ABSTRACTTraumatic brain injury (TBI) is an insult to the brain that impacts neuronal and non-neuronal cells/tissues. The study aimed to understand TBI-induced early changes in the brain and systemic physiology. The male rats were subjected to mild and moderate TBI, where serum and urine metabolic fingerprints of mild TBI rats showed a hypermetabolic response with increased energy metabolites, amino acids, and gut metabolites in serum and increased TCA cycle intermediates in urine. In contrast, the moderate TBI rats showed decreased lactate, pyruvate, amino acids (glycine and leucine) and gut metabolites [trimethylamine N OXIDE (TMAO), choline and acetate] in serum. The urine showed increased pyruvate, creatinine, and allantoin levels. To understand the brain's role in altered metabolic physiology, hypothalamus structure was assessed using diffusion tensor imaging (DTI) and stress levels were observed using serum corticosterone. The injured rats exhibited changes in DTI metrics in the hypothalamus, suggesting a potential disruption in the regulation of the hypothalamus-pituitary-adrenal axis (HPA) axis. These alterations were accompanied by increased TNF-α levels after moderate TBI. The injury induced allostatic overload, accompanied by impaired hypothalamic structure, and metabolic physiology also showed gut microbiome dysbiosis. The gut microbiome showed an increased Firmicutes: Bacteroidetes ratio after injury, with variable gut composition after both injuries. Therefore, the present study provides insight into an interplay between the HPA axis, metabolism, and gut microbiome following TBI. Importantly, this crosstalk between the regulatory systems was different after mild and moderate injury, highlighting the need to assess injury phenotype based on the severity.PMID:40167488 | DOI:10.1002/jnr.70032

Yi Mai Granule Improves High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease in Mice by Regulating Gut Microbiota and Metabolites

Tue, 01/04/2025 - 12:00
Int J Microbiol. 2025 Mar 23;2025:2273986. doi: 10.1155/ijm/2273986. eCollection 2025.ABSTRACTYi Mai granule (YMG) is a traditional Chinese medicine (TCM) herbal decoction consisting of two TCM formulas: Gua-Lou-Ban-Xia decoction and Si-Jun-Zi decoction. YMG has shown clinical benefit in the treatment of nonalcoholic fatty liver disease (NAFLD), which may be due to its regulatory effects on lipid metabolism. Previous studies have highlighted the importance of the gut microbiota and its metabolites in the use of TCM. However, the effect of YMG on the gut microbiota in the treatment of NAFLD remains unclear. In this study, we established an NAFLD model in ApoE-/- mice and treated them with YMG. High-performance liquid chromatography was adopted to identify the chemical components of YMG. By mapping the candidate targets using network pharmacology, we found that the targets of the main components of YMG were significantly enriched in NAFLD-related pathways. Moreover, 16S rRNA gene sequencing revealed that YMG affected the constitution and metabolism of the gut microbiota in NAFLD model mice, including lipid and carbohydrate metabolism. Similarly, metabolites related to lipid and carbohydrate metabolism in mouse serum were significantly altered by YMG. The correlation heat map and network analyses showed that the gut microbiota and metabolites affected by YMG were closely related to the blood lipid content. Collectively, YMG may exert therapeutic effects by affecting the metabolism of gut microbiota, thus regulating lipid and carbohydrate metabolism. These findings offer novel insight into the pharmacological mechanism of YMG in the treatment of NAFLD and provide theoretical bases for its clinical applications.PMID:40166691 | PMC:PMC11955292 | DOI:10.1155/ijm/2273986

Distinct and Shared Molecular Mechanisms in Pediatric Antrochoanal Polyps and Chronic Rhinosinusitis with Nasal Polyps: A Proteomic and Metabolomic Integrative Analysis

Tue, 01/04/2025 - 12:00
J Inflamm Res. 2025 Mar 26;18:4435-4447. doi: 10.2147/JIR.S507475. eCollection 2025.ABSTRACTPURPOSE: The underlying mechanisms of pediatric antrochoanal polyps (ACP)and chronic rhinosinusitis with nasal polyps (CRSwNP) remain largely unexplored. This study investigates their proteomic and metabolomic profiles to uncover unique and overlapping pathways, shedding light on their underlying causes.METHODS: Specimens were collected from six children with ACP, six with CRSwNP, and six with normal inferior turbinate mucosa (CK) at Shenzhen Children's Hospital. Protein profiles were analyzed using data-independent acquisition (DIA) mass spectrometry, while metabolite profiles were assessed via non-targeted metabolomics (UPLC-MS/MS). Differences in proteins and metabolites were identified through statistical selection and bioinformatics, followed by integrated pathway analysis to explore their roles in disease processes.RESULTS: Proteomic analysis identified 1000 differentially expressed proteins (DEPs) in ACP and 880 in CRSwNP compared to controls. Key DEPs in ACP included PEX1 and LYPD2, while CRSwNP included PEX1, CFAP52, SPAG6 and DHRS9. Metabolomic analysis identified 129 differential metabolites in ACP and 11 in CRSwNP, with 5-HTP showing opposite regulation between the two conditions. Pathway analysis pointed to oxidative stress and lipid metabolism disruptions in ACP, and immune and ciliary dysfunction in CRSwNP. Both conditions shared inflammation and extracellular matrix remodeling, but tryptophan metabolism diverged, with 5-HTP reduced in ACP and elevated in CRSwNP.CONCLUSION: This study highlights oxidative stress and lipid dysregulation as hallmarks of pediatric ACP, distinct from ciliary and immune dysfunction in CRSwNP, with inflammation and matrix remodeling as common features. The opposing regulation of 5-HTP reflects differences in tryptophan metabolism. Key molecules like PEX1, LYPD2, CFAP52, and 5-HTP emerge as potential biomarkers, offering promise for improved diagnosis and targeted therapies in nasal polyp-related conditions, but the small sample size and exploratory design require validation in larger cohorts to ensure clinical applicability.PMID:40166594 | PMC:PMC11955737 | DOI:10.2147/JIR.S507475

A Large Language Model-Powered Map of Metabolomics Research

Tue, 01/04/2025 - 12:00
bioRxiv [Preprint]. 2025 Mar 19:2025.03.18.643696. doi: 10.1101/2025.03.18.643696.ABSTRACTWe present a comprehensive map of the metabolomics research landscape, synthesizing insights from over 80,000 publications. Using PubMedBERT, we transformed abstracts into 768-dimensional embeddings that capture the nuanced thematic structure of the field. Dimensionality reduction with t-SNE revealed distinct clusters corresponding to key domains such as analytical chemistry, plant biology, pharmacology, and clinical diagnostics. In addition, a neural topic modeling pipeline refined with GPT-4o mini reclassified the corpus into 20 distinct topics-ranging from "Plant Stress Response Mechanisms" and "NMR Spectroscopy Innovations" to "COVID-19 Metabolomic and Immune Responses." Temporal analyses further highlight trends including the rise of deep learning methods post-2015 and a continued focus on biomarker discovery. Integration of metadata such as publication statistics and sample sizes provide additional context to these evolving research dynamics. An interactive web application ( https://metascape.streamlit.app/ ) enables dynamic exploration of these insights. Overall, this study offers a robust framework for literature synthesis that empowers researchers, clinicians, and policymakers to identify emerging research trajectories and address critical challenges in metabolomics, while also sharing our perspectives on key trends shaping the field.PMID:40166287 | PMC:PMC11957067 | DOI:10.1101/2025.03.18.643696

Serum metabolic profiling of patients with diabetic kidney disease based on gas chromatography-mass spectrometry

Tue, 01/04/2025 - 12:00
Front Mol Biosci. 2025 Mar 17;12:1541440. doi: 10.3389/fmolb.2025.1541440. eCollection 2025.ABSTRACTINTRODUCTION: Given the increasing incidence rate of diabetic kidney disease (DKD), there is an urgent need for methods to diagnose and treat DKD in clinics.METHODS: Serum samples were collected from 56 DKD patients and 32 healthy controls (HCs) at the First Affiliated Hospital of Ningbo University, and the metabolic profiles were obtained through untargeted metabolomics using gas chromatography mass spectrometry. The data were then analyzed using principal components analysis, orthogonal partial least-squares discriminant analysis, Pearson correlation analysis, and receiver operating characteristic (ROC) curve.RESULTS: It was found that the serum metabolic profiles of the DKD patients were significantly different from those of the HCs. A total of 68 potential differential metabolites were identified that were involved in arginine biosynthesis, ascorbate and aldarate metabolism, and galactose metabolism, among others; a total of 31 differential metabolites were also identified between early-stage (EDG) and late-stage (LDG) DKD patients. Additionally, 30 significant metabolic differences were observed among the EDG, LDG, and HC groups. Based on Pearson correlation analysis between the abundances of the differential metabolites and clinical markers (estimated glomerular filtration rate, blood urea nitrogen, serum creatinine, and urinary albumin/creatinine ratio) and area under the ROC curve (AUROC) analysis, the AUROC values of myoinositol and gluconic acid were found to be 0.992 and 0.991, respectively, which can be used to distinguish DKD patients from HCs.DISCUSSION: These results indicate that myoinositol and gluconic acid could possibly be used as biomarkers of DKD.PMID:40166083 | PMC:PMC11955480 | DOI:10.3389/fmolb.2025.1541440

Altered milk tryptophan and tryptophan metabolites and health of children born to women with HIV

Tue, 01/04/2025 - 12:00
Res Sq [Preprint]. 2025 Mar 21:rs.3.rs-6229815. doi: 10.21203/rs.3.rs-6229815/v1.ABSTRACTChildren born to women with HIV (WWH) suffer increased morbidity and, in low-income settings, have two to three times the mortality of infants born to women without HIV. The basis for this increase remains elusive. In low-income settings, breastfeeding is recommended because health benefits outweigh the risk of transmission, especially when maternal antiretroviral therapy is provided. We profiled the milk metabolome of 326 women sampled longitudinally for 18 months postpartum using global metabolomics. We identify perturbations in several metabolites, including tryptophan, dimethylarginine, and a recently discovered antiviral ribonucleotide, that are robustly associated with maternal HIV infection. Quantitative tryptophan and kynurenine levels in both milk and plasma reveal that these perturbations reflect systemic depletion of tryptophan and alterations in tryptophan catabolism in WWH. Our findings provide intriguing evidence that decreases in tryptophan availability and perturbations in tryptophan catabolism in children born to WWH may contribute to their increased morbidity and mortality.PMID:40166030 | PMC:PMC11957222 | DOI:10.21203/rs.3.rs-6229815/v1

Integrated multi-omics landscape of non-small cell lung cancer with distant metastasis

Tue, 01/04/2025 - 12:00
Front Immunol. 2025 Mar 17;16:1560724. doi: 10.3389/fimmu.2025.1560724. eCollection 2025.ABSTRACTBACKGROUND: Distant metastasis is one of the important factors affecting the prognosis of lung cancer patients. Extracellular vesicles (EVs) play an important role in the occurrence, development, and metastasis of cancer. However, it is currently unclear whether EVs in BALF are involved in distant tumor metastasis.METHODS: we collected bronchoalveolar lavage fluid (BALF) from patients with metastatic and non-metastatic non-small cell lung cancer (NSCLC) to isolate exosomes, which were then characterized by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM), followed by comprehensive metabolomic and proteomic analysis to ultimately construct a distant metastasis prediction model for non-small cell lung cancer.RESULTS: Our research has found that the BALF of NSCLC patients is rich in EVs, which have typical morphology and size. There are significant differences in protein expression and metabolite types between patients with distant metastasis and those without distant metastasis. Sphingolipid metabolism pathways may be a key factor influencing distant metastasis in NSCLC. Subsequently, we constructed a predictive model for distant metastasis in NSCLC based on differentially expressed proteins identified by proteomics. This model has been proven to have high predictive value.CONCLUSION: The multi-omic analysis generated in this study provided a global overview of the molecular changes, which may provide useful insight into the therapy and prognosis of NSCLC metastasis.PMID:40165954 | PMC:PMC11956740 | DOI:10.3389/fimmu.2025.1560724

Metabolomics Analysis of the Mechanism of Yuquan Capsules in the Treatment of T2DM Rats Using UPLC/MS

Tue, 01/04/2025 - 12:00
Diabetes Metab Syndr Obes. 2025 Mar 27;18:905-916. doi: 10.2147/DMSO.S512089. eCollection 2025.ABSTRACTPURPOSE: Yuquan capsule (YQC) is a well-known proprietary Chinese medicine used for the treatment of type 2 diabetes mellitus. The aim of this study was to investigate the potential mechanism and efficacy of YQC in the treatment of T2DM by means of metabolomics.METHODS: Thirty-two male SD rats were randomly divided into four groups of control, type 2 diabetic mellitus (T2DM), metformin (Met), and YQC. Establishment of the T2DM model by high-fat diet (HFD) and streptozotocin (STZ). Fasting blood glucose (FBG) and weight were measured weekly, urine output was collected and recorded. The blood, kidney, pancreas, and liver tissue samples were collected at the end of the experiment. Blood samples were analyzed with methods of ELISA, pancreas, and liver tissues were analyzed by pathological sections, and serum was analyzed by metabolomics using ultra-performance liquid chromatography quadrupole time-of-flight coupled with mass spectrometry (UPLC-Q/TOF-MS).RESULTS: It was observed that YQC could reduce blood glucose levels by modulating blood lipid and transaminase indices, and by diminishing the concentration of inflammatory factors within hepatic and pancreatic tissues. Furthermore, YQC restores homeostasis by regulating lipid and amino acid metabolism, engaging 21 biomarkers and 10 metabolic pathways.CONCLUSION: YQC has the capacity to enhance blood lipid and transaminase levels, suppress the expression of inflammatory factors, and foster the homeostatic progression of metabolic circulation in rats with T2DM.PMID:40165883 | PMC:PMC11956709 | DOI:10.2147/DMSO.S512089

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