PubMed

Ultrasound Obstet Gynecol. 2025 May 8. doi: 10.1002/uog.29238. Online ahead of print.ABSTRACTOBJECTIVE: Previous research has identified an association between maternal stress, fetal growth and the expression of glucocorticoid-related genes in the placenta, particularly 11-beta hydroxysteroid dehydrogenase-2 (HSD11β2). However, to date, no studies have simultaneously explored the relationships between maternal stress, placental expression and methylation of HSD11β2, and fetal cortisol metabolites according to fetal growth. The aim of the present study was to evaluate the association between perceived antenatal maternal stress, the expression and methylation of the placental HSD11β2 gene, fetal cortisol metabolites in amniotic fluid and birth weight.METHODS: This nested case-control study, which was part of a large prospective cohort study, was conducted at two maternofetal medicine units in Barcelona, Spain (BCNatal: Hospitals Clinic and Sant Joan de Déu). We enrolled singleton pregnancies and classified neonates as small-for-gestational-age (SGA) if their birth weight was below the 10th percentile (n = 343) or as appropriate-for-gestational-age (AGA) controls (n = 399). The Perceived Stress Scale (PSS) and the State-Trait Anxiety Inventory (STAI) scores were obtained to assess maternal stress and anxiety levels. We analyzed placental HSD11β2 RNA expression (n = 44 SGA and 28 AGA) and DNA methylation levels (n = 89 SGA and 34 AGA), and fetal cortisol metabolites and the activity of metabolizing enzymes in amniotic fluid (n = 135 SGA and 78 AGA) using liquid chromatography-tandem mass spectrometry.RESULTS: Median maternal perceived stress (PSS, 23 (interquartile range (IQR), 17-28) vs 20 (IQR, 15-26); P < 0.001) and median anxiety state (STAI-state, 19.0 (IQR, 14.0-29.0) vs 16.0 (IQR, 11.0-24.0); P < 0.001) scores were significantly higher in the SGA group compared with the control group. SGA cases showed lower median placental HSD11β2 RNA expression (Δ Ct, 50.5 (IQR, 21.6-106.0) vs 92.7 (IQR, 62.3-118.0); P = 0.013) with similar DNA methylation levels (mean ± SD, 10.7 ± 3.0% vs 11.0 ± 2.8%; P = 0.648) compared with AGA controls. Analysis of amniotic fluid revealed altered cortisol metabolism in SGA fetuses, with increased median 5α-tetrahydrocortisol concentration (SGA, 0.09% (IQR, 0.06-0.15%) vs controls, 0.07% (IQR, 0.05-0.11%); P = 0.020) and activity of its related enzyme (5α-reductase activity in SGA, 0.19% (IQR, 0.14-0.31%) vs controls, 0.17% (IQR, 0.12-0.22%); P = 0.007), together with a decrease in median 6-hydroxycortisol concentration (SGA, 0.09% (IQR, 0.06-0.11%) vs controls, 0.11% (IQR, 0.08-0.12%); P < 0.001) and activity of its related enzyme (CYP3A7 activity in SGA, 0.19% (IQR, 0.11-0.25%) vs controls, 0.24% (IQR, 0.17-0.33%); P < 0.001).CONCLUSIONS: SGA pregnancy is associated with high perceived maternal stress and dysregulated fetoplacental cortisol metabolism. These results deepen our understanding of the pathophysiology of SGA and highlight the potential benefit of intervention to mitigate maternal stress. © 2025 International Society of Ultrasound in Obstetrics and Gynecology.PMID:40344310 | DOI:10.1002/uog.29238

Rapid Commun Mass Spectrom. 2025 Aug 30;39(16):e10068. doi: 10.1002/rcm.10068.ABSTRACTRATIONALE: The emergence of computational metabolomics tools such as molecular networking and machine learning-based platforms like SIRIUS has significantly advanced MS-based metabolomics studies. These tools enable rapid metabolite identification by deciphering complex fragmentation patterns and chemical transformations occurring during mass spectrometry analysis.METHODS: In this study, methanolic extracts of Viscum combreticola, a plant recently shown to contain a rich composition of cinnamic acid-quinates conjugates, were analyzed using the LC-qTOF-MS in combination with a molecular networking approach to explore the chemical complexity of quinate conjugates.RESULTS: Findings of this study through molecular networking topology revealed that quinic acid undergoes a series of in-gas chemical transformations, including dehydration (-H2O) and decarboxylation (-CO2). These transformations yield unique product ions, some of which are associated with other organic acids, such as isocitric acid. By employing the MS2 search option on the GNPS2 platform, molecules exhibiting these product ions were readily identified in this study. Therefore, highlighting the potential of this function in GNPS2 for tracing unique fragmentation patterns synonymous with certain molecules that can be used to confirm their identity visually.CONCLUSION: The MS2 search function can aid in the discovery of new compounds containing the diagnostic ions of interest that could otherwise be easily missed with manual annotation. This study presents a potential validation approach of looking at multiple product ions to confirm the identity of a molecule, particularly in the presence of other compounds with similar fragmentation pathways or shared fragment ions.PMID:40344267 | DOI:10.1002/rcm.10068

J Appl Toxicol. 2025 May 8. doi: 10.1002/jat.4808. Online ahead of print.ABSTRACTExposure to agricultural dust containing antimicrobial-resistant pathogens poses significant health risks for workers in animal agriculture production. Beyond causing severe airway inflammation, pollutants are linked to intestinal diseases. Swine farm dust is rich in ultrafine particles, gram-positive and gram-negative bacteria, and bacterial components such as lipopolysaccharides (LPS; endotoxins). In our previous study, we demonstrated that intranasal exposure of male and female C57BL/6J mice to 12.5% hog dust extract (HDE, containing 22.1-91.1 EU/mL) for 3 weeks resulted in elevated total cell and neutrophil counts in bronchoalveolar lavage fluid and increased intestinal permeability compared to saline controls. Now, we report that 16S and metagenomic analyses of Week 3 stool samples from HDE-treated mice indicate a reduced abundance of the beneficial species Akkermansia muciniphila and Clostridium sp. ASF356 and Lachnospiraceae bacterium. Bacterial alpha diversity showed increased species evenness in fecal samples from HDE-treated mice (Pielou's evenness, p = 0.047, n = 5-6/group). Metabolomic analysis also indicated significant reductions in key metabolites involved in energy metabolism, including riboflavin (p = 0.027, n = 11) and nicotinic acid (p = 0.049, n = 11), as well as essential amino acids, such as inosine (p = 0.043, n = 11) and leucine (p = 0.018, n = 11). While HDE exposure does not robustly alter overall microbial abundance or community structure, it leads to specific reductions in beneficial bacterial species and critical metabolites necessary for maintaining intestinal homeostasis by supporting energy metabolism, gut barrier function, microbiota balance, and immune regulation. The results of this study underscore the potential risks for gut health posed by inhalation of agricultural dust.PMID:40344252 | DOI:10.1002/jat.4808

PLoS Genet. 2025 May 9;21(5):e1011679. doi: 10.1371/journal.pgen.1011679. Online ahead of print.ABSTRACTNonhost resistance (NHR) serves as a fundamental defense response in plants against non-adapted pathogens, yet its underlying molecular mechanisms remain poorly understood. This study investigates the rice-Pst (Puccinia striiformis f. sp. tritici) interaction using integrated transcriptomic and metabolomic analyses to unravel the temporal dynamics of gene expression and metabolite changes associated with NHR. Our findings reveal a temporally coordinated activation of defense responses, with early induction of receptor-like kinases (RLKs) and hypersensitive response proteins, followed by later activation of jasmonic acid and systemic acquired resistance pathways, along with the accumulation of amino acids and other phenolic compounds. Notably, metabolic pathways related to cell wall reinforcement were significantly upregulated during Pst infection, highlighted by enhanced lignin biosynthesis (phenylpropanoid pathway), nucleotide sugar metabolism, and tryptophan pathways. Rice mutants deficient in genes involved in lignin biosynthesis (OsPAL3, Os4CL3, Os4CL5, and OsCCoAOMT) displayed reduced lignin deposition at infection sites and compromised resistance to Pst, underscoring a critical role of lignin-based physical barriers in NHR. This study provides novel insights into the molecular framework of rice NHR, emphasizing the pivotal role of structural defenses in plant immunity.PMID:40344090 | DOI:10.1371/journal.pgen.1011679

Am J Respir Crit Care Med. 2025 May 9. Online ahead of print.ABSTRACTRATIONALE: Pulmonary hypertension (PH) poses a significant health threat. Current biomarkers for PH lack specificity and have poor prognostic capabilities.OBJECTIVES: To develop better biomarkers for PH that are useful for patient identification and management.METHODS: Explorative analysis of a broad spectrum of metabolites in PH patients, healthy controls and disease controls in a training and a validation cohort and in vitro studies on human pulmonary arteries.MEASUREMENTS: High resolution mass spectrometry in 233 subjects coupled with machine learning analysis. Histologic and gene expression analysis with focus on lipid metabolism in human pulmonary arteries (PA) of idiopathic pulmonary arterial hypertension lungs (IPAH) and assessment of the acute effects of extrinsic fatty acids (FAs).RESULTS: We enrolled a training cohort of 74 PH patients, 30 disease controls without PH, and 65 healthy controls, and an independent validation cohort of 64 subjects. Among other metabolites, the FAs were significantly increased. Machine learning showed a high diagnostic potential for PH. Additionally, we developed fully explainable lipid ratios with exceptional diagnostic accuracy for PH (AUC 0.89 training cohort, 0.90 external validation cohort), outperforming machine learning results. These ratios were also prognostic and complemented established clinical markers and scores, significantly increasing their hazard ratios for mortality risk. IPAH lungs showed lipid accumulation and altered expression of lipid homeostasis-related genes. In human PA smooth muscle and endothelial cells, FAs caused excessive proliferation and barrier dysfunction, respectively.CONCLUSION: Our metabolomics approach suggests that lipid alterations in PH provide diagnostic and prognostic information, complementing established markers. These alterations may reflect pathologic changes in the pulmonary arteries of PH patients.PMID:40343938

Am J Respir Cell Mol Biol. 2025 May 9. doi: 10.1165/rcmb.2024-0507MA. Online ahead of print.ABSTRACTChronic obstructive pulmonary disease (COPD) is a severe progressive lung disease, often caused by prolonged exposure to cigarette smoke and environmental factors. Pre-clinical COPD research predominately relies on chronic smoke or elastase animal models, each with their own advantages and limitations, such as limited pathophysiological insights or long treatment times. Here we describe a novel and time efficient mouse model of COPD based on bacterial lipopolysaccharide (LPS) and the reactive aldehyde acrolein (Acro). Mice were treated once per week for four weeks with a combination of both LPS and Acro. Histological, inflammatory, and metabolomic alterations were analysed by histological quantification, multicolour flow cytometry, and nuclear magnetic resonance (NMR). Acro/LPS treatment induced moderate airspace enlargement and bronchial remodelling. These structural changes were associated with a distinct inflammatory profile marked by an increase in macrophages, and T-helper cells, as well as increased cytokines, including CXCL11, IL-17a, and TNF-α. Strong inflammation, consisting of T-helper and B-cells was detected in the perivascular and peribronchial space, and increased macrophages in the alveolar regions. Additionally, intervention with the steroid dexamethasone induced a strong reduction in T-cells and macrophages and partially ameliorated histological alterations. Furthermore, we could detect alterations in the metabolome of serum and tissue, including an increase in COPD associated metabolites like trimethylamine N-oxide, as well as a misbalance in energy related metabolites and several amino acids. In summary, we can describe a practical, representative, and time efficient mouse model of COPD, with the potential to study the immunological and pathophysiological development of the disease.PMID:40343865 | DOI:10.1165/rcmb.2024-0507MA

Mycotoxin Res. 2025 May 9. doi: 10.1007/s12550-025-00593-2. Online ahead of print.ABSTRACTRice is a sigsnificant source of both nutritional and economic sustenance in Nigeria, but contamination by fungi and their toxic metabolites in addition to naturally occurring phytotoxins may pose significant challenges to grain quality and consumer health. This study assessed the safety of 80 rice samples retailed in open markets in two Nigerian states by identifying fungal contaminants using phenotypic and molecular techniques and quantifying the secondary metabolites present in the grains through liquid chromatography tandem mass spectrometry. A total of 101 distinct colonies were recovered and identified as nine species belonging to six genera: Aspergillus, Cladosporium, Fusarium, Monascus, Penicillium and Talaromyces. At least one third (30.4%) of the identified species were Aspergillus flavus, while A. montevidensis, Cladosporium halotolerans, Monascus purpureus, Talaromyces islandicus and T. purpureogenus recorded the least incidences of 4.3%. Sixteen mycotoxins and 48 other secondary metabolites including diverse fungal and lichen metabolites, plant toxins and phytoestrogenic phenols were detected in the rice samples. Moniliformin (MON) and beauvericin were the most common mycotoxins, present in 43% of samples, with MON reaching a maximum concentration of 19,391 µg/kg. Aflatoxins contaminated 18% of samples, generally below Nigeria's 10 µg/kg regulatory limit but in one case exceeding the European Union's threshold of 4 µg/kg. This study emphasizes the need to expand chemical contaminant monitoring in foods beyond the regular aflatoxin detection to include a wider spectrum of secondary metabolites and also to comprehensively review and enhance grain handling and retail practices in local/open markets to protect consumer health.PMID:40343616 | DOI:10.1007/s12550-025-00593-2

Anal Bioanal Chem. 2025 May 9. doi: 10.1007/s00216-025-05890-4. Online ahead of print.ABSTRACTInterest in the role of bis(monoacylglycero)phosphate (BMP) lipids in lysosomal function has significantly grown in recent years. Emerging evidence highlights BMPs as critical players not only in Niemann-Pick disease type C (NPC) but also in other pathologies such as neurodegeneration, cardiovascular diseases, and cancers. However, the selective analysis of BMPs is significantly hindered by isomeric phosphatidylglycerol (PG) lipids. While this can be addressed by chromatographic separation, it poses a significant challenge for shotgun lipidomics approaches. Here, we present a shotgun lipidomics strategy to detect and separate BMPs from PGs using differential fragmentation of sodiated ions. This approach, including isotope correction, is integrated into an existing quantitative shotgun lipidomics workflow (Lipidyzer combined with Shotgun Lipidomics Assistant software) that simultaneously quantifies >1400 lipids. Validation using K-562 cell extracts demonstrated acceptable linearity, trueness, repeatability, and a limit of quantification of 0.12 µM, confirming robust analytical performance. Finally, characteristic accumulation of BMP lipids is shown in bone marrow-derived macrophages from NPC mice, demonstrating its applicability. Our method presents a quantitative, selective, rapid, and robust solution for shotgun-based BMP analysis without the need for extensive chromatographic separation or derivatization. The integration of BMP lipid detection into the Lipidyzer platform, alongside the recently launched iSODA data visualization tool, empowers chemists and biologists to gain deeper insights into BMP lipid biology.PMID:40343460 | DOI:10.1007/s00216-025-05890-4

Phytother Res. 2025 May 8. doi: 10.1002/ptr.8447. Online ahead of print.ABSTRACTBenign prostatic hyperplasia (BPH) is a common proliferative disease in older males. PuleanPian, containing rape pollen (RP), is a certified BPH medicine, but its main active compound and mechanism are unknown. This study aims to identify the main active compound of RP for the treatment of BPH. BPH rat models were induced with estradiol/testosterone (E2/T) and treated with RP or its alcohol extract (ALRP). RNA-seq and metabolomics were conducted, and RP compounds were identified via liquid chromatography-mass spectrometry (LC-MS). In vitro experiments used BPH-1 and RWPE-1 cells. E2/T induced BPH symptoms, alleviated by RP and ALRP treatment. RP possibly acts through phosphatidylinositol-3-kinase (PI3K)/AKT pathways, promoting autophagy. LC-MS identified five main RP compounds, with sinigrin implicated in BPH treatment via the PI3K/AKT(AKT Serine/Threonine Kinase 1)/mammalian target of rapamycin (mTOR) axis. Sinigrin may be the active compound in RP for BPH treatment, acting through the PI3K/AKT/mTOR axis.PMID:40343383 | DOI:10.1002/ptr.8447

Res Sq [Preprint]. 2025 Apr 29:rs.3.rs-5960764. doi: 10.21203/rs.3.rs-5960764/v1.ABSTRACTHTLV-1 is an enigmatic retrovirus triggering a debilitating neuroinflammatory disease, HTLV-1-associated myelopathy (HAM), with unknown pathogenesis. Both HTLV-1 infection and HAM predominantly affect women and non-white neglected populations. HAM is lacking disease-modifying treatment, as current treatment is mostly symptomatic and inspired by either HIV-1 or multiple sclerosis therapeutic strategies. We used systems biology analyses of novel and publicly available data comprising (epi)genomics, transcriptomics, metabolomics and proteomics of multi-ancestry cohorts from a total of > 2500 People Living with HTLV-1 from 5 countries (Brazil, Peru, Japan, UK, US). Leveraging an unique admixed Brazilian cohort, genome-wide association study (GWAS) revealed African-specific variants in inflammasome sensor AIM2 with genome-wide significance (p < 5x10 - 8 ). Suggestive loci (p > 5x10 - 8 ) corresponding to metabolic, immune and neuronal genes were validated using published Japanese GWAS. Polygenic risk score and proviral load were independent disease predictors across ancestries. Systems biology analysis revealed neuronal/synaptic signaling, monocyte count, glucose/lipid metabolism, and neurocognition/depression as genetically linked to HAM. In silico drug screening identified estrogen blocker Fulvestrant as the top hit, while also confirming existing (pre)clinical data for HDAC inhibitors and immunosuppressants. Validated GWAS genes were overexpressed in HAM patients' whole blood and CD4 T-cells, as well as in spinal cord astrocytes, oligodendrocytes, and microglia by single-cell RNAseq. We experimentally confirmed decreased ApoA1/lipid/cholesterol levels, higher monocyte levels and lower neurocognitive scores in multi-ancestry cohorts. We found striking biological similarities between retroviral Hbz/Tax overexpression, Hbz interactome and HAM multi-omics findings: enrichment for lipid/cholesterol metabolism, estrogen signaling, neurodegenerative diseases, and viral pathways including EBV, recently identified as the major driver of multiple sclerosis. In conclusion, our data-driven approach uncovers novel disease mechanisms and therapeutic targets, and a validated polygenic risk score allowing targeted surveillance for high-risk individuals. A strong molecular overlap to other neurodegenerative/neuroinflammatory diseases reveals shared neuropathogenic pathways between unrelated viruses.PMID:40343334 | PMC:PMC12060986 | DOI:10.21203/rs.3.rs-5960764/v1

PeerJ. 2025 May 5;13:e19374. doi: 10.7717/peerj.19374. eCollection 2025.ABSTRACTBACKGROUND: Increasing evidence has shown a close relation between the pathogenesis of type 2 diabetes mellitus (T2DM), which is a global health problem with multifactorial etiopathogenesis, and gut microbiota.METHODS: During in-vitro fermentation of Scrophularia ningpoensis (known as Xuanshen) polysaccharide (SNP) by T2DM gut microbiota, effects of SNP on the gas content, production of short-chain fatty acids (SCFAs), metabolite profile and microbiota composition were studied.RESULTS: Analysis of chemical compositions indicates that the total sugar content of SNP was found to be as high as 87.35 ± 0.13% (w/w). SNP treatment significantly improved the gas volume and composition in T2DM fecal matter. Moreover, intestinal flora degraded SNP to produce SCFAs, thus regulating SCFA production and composition. Metabolomic analysis implied that SNP shows potential to regulate the five gut metabolites (L-valine, L-leucine, L-isoleucine, L-alanine, and xylitol) in T2DM fecal matter. Furthermore, dysbiosis of gut microbiota induced by T2DM was reversed by SNP. The evidence includes decreasing Firmicutes/Bacteroidota ratio at phylum level promoting proliferation of the bacterial abundance of Dorea, Parabacteroides, Faecalibacterium, and Lachnospira and decreased bacterial abundance of Escherichia-Shigella. Based on these findings, the action mechanism of SNP against T2DM was clarified by reshaping microbiota and regulating intestinal metabolites, and a novel target was provided for interventions of T2DM.PMID:40343088 | PMC:PMC12060902 | DOI:10.7717/peerj.19374

Front Cardiovasc Med. 2025 Apr 24;12:1568528. doi: 10.3389/fcvm.2025.1568528. eCollection 2025.ABSTRACTChronic allograft vasculopathy (CAV) is a major cause of late graft failure in heart transplant recipients, characterized by progressive intimal thickening and diffuse narrowing of the coronary arteries. Unlike atherosclerosis, CAV exhibits a distinct cellular composition and lesion distribution, yet its pathogenesis remains incompletely understood. A major challenge in CAV research has been the limited application of advanced "-omics" technologies, which have revolutionized the study of other vascular diseases. Recent advancements in single-cell and spatial transcriptomics, proteomics, and metabolomics have begun to uncover the complex immune-endothelial-stromal interactions driving CAV progression. Notably, single-cell RNA sequencing has identified previously unrecognized immune cell populations and signaling pathways implicated in endothelial injury and vascular remodeling after heart transplantation. Despite these breakthroughs, studies applying these technologies to CAV remain sparse, limiting the translation of these insights into clinical practice. This review aims to bridge this gap by summarizing recent findings from single-cell and multi-omic approaches, highlighting key discoveries, and discussing their implications for understanding CAV pathogenesis.PMID:40342971 | PMC:PMC12058854 | DOI:10.3389/fcvm.2025.1568528

Food Chem X. 2025 Apr 15;27:102434. doi: 10.1016/j.fochx.2025.102434. eCollection 2025 Apr.ABSTRACTThis study employed a widely targeted metabolomics approach combined with flavoromics evaluation to systematically analyze dynamic metabolic variations under four processing techniques: fresh EUL (XY), traditionally dried EUL (HG), green tea processed EUL (GT), and black tea processed EUL (BT). A total of 1839 non-volatile metabolites and 289 volatile metabolites were identified. Key affected metabolites included amino acids (e.g., essential amino acids upregulated 90 % in HG), lipids (oxidized fatty acids elevated in BT), phenolic acids (23 % increase in GT), flavonoids (120+ downregulated in BT), nucleotides, and terpenoids. Each processing method demonstrates unique advantages: HG preserves amino acids, GT enhances catechin content, and BT optimizes secondary metabolites. This study provides the first comprehensive metabolic map of EUL processing, offering a scientific foundation for standardizing product quality and developing functional applications.PMID:40342911 | PMC:PMC12059405 | DOI:10.1016/j.fochx.2025.102434

Front Oncol. 2025 Apr 24;15:1511594. doi: 10.3389/fonc.2025.1511594. eCollection 2025.ABSTRACTThis study focuses on the proteomic analysis of cerebrospinal fluid (CSF) in a patient with stage III retinoblastoma (RB) with the aim to identify molecular changes associated with central nervous system (CNS) relapse. The child received systemic chemotherapy and intrathecal topotecan as CNS prophylaxis, along with enucleation of the left eye. After two chemotherapy cycles, CNS relapse occurred, evidenced by positive CSF findings and magnetic resonance imaging (MRI) showing leptomeningeal involvement at the anterior skull base. The child's condition deteriorated, and two months later, he died due to progressive CNS disease. The aim of the study was to analyze serial CSF samples collected at different stages of treatment, as well as a control sample, to identify differences in CSF protein expression profiles during CNS RB relapse. Using mass spectrometry, a total of 1,029 proteins were identified across all CSF samples, samples were analyzed in duplicate ensuring technical replication. An unsupervised heatmap revealed 46 differentially expressed proteins. Over-regulated proteins in CSF-RB samples were primarily involved in inflammation, extracellular matrix remodeling, epithelial mesenchymal transition initiation, migration, invasion, and cellular metabolism (PON1, RNPEP, MCAM, NEGR1, NID1, SERPINA1, FAT2, RELN, NEGR1, and SEZ6). These processes are key drivers of cancer progression and metastasis. Proteomic analysis could be valuable in identifying proteins modulated in CSF during disease progression in RB patients, offering potential for new prognostic biomarkers.PMID:40342827 | PMC:PMC12058659 | DOI:10.3389/fonc.2025.1511594

Front Immunol. 2025 Apr 24;16:1546629. doi: 10.3389/fimmu.2025.1546629. eCollection 2025.ABSTRACTHuman leukocyte antigen (HLA) molecules are pivotal in guiding human adaptive immune responses through their presentation of peptide ligands, collectively known as the immunopeptidome. This process is central to the development of cancer immunotherapies, such as vaccines and T-cell therapies. Profiling the immunopeptidome from plasma and other biofluids has gained increasing traction, as it offers a minimally invasive approach for monitoring disease states and immune responses toward cancer therapy. Here we present the second iteration of SAPrIm, a refined immunopeptidomics tool optimized for soluble HLA analysis. It can process up to 12 samples per batch within a day. In this plasma-focused iteration, we identified approximately 1,200 to 4,000 immunopeptides from 100 µL to 1 mL of plasma, demonstrating high reproducibility across technical replicates, biological replicates, and inter-day analyses. This robust reproducibility highlights the method's strong potential for reliable relative quantification of immunopeptides in plasma-based studies. This workflow is positioned to advance the field of immunopeptidomics by enabling efficient plasma-based comparative analyses and mid-size cohort studies.PMID:40342411 | PMC:PMC12058715 | DOI:10.3389/fimmu.2025.1546629

Turk J Med Sci. 2025 Feb 19;55(2):509-517. doi: 10.55730/1300-0144.5995. eCollection 2025.ABSTRACTBACKGROUND/AIM: The etiology of hypertension in pediatric populations is complex and multifactorial, with metabolic abnormalities playing a fundamental role in the pathogenesis of the condition. This study investigates the therapeutic effects of Benzyl alcohol (BA), identified through metabolomics analysis of pediatric hypertension serum, on Angiotensin II (Ang II)-induced vascular and renal injury in murine models.MATERIALS AND METHODS: Male C57BL/6 mice were used to establish a vascular remodeling model by continuous 4-week Ang II infusion using a subcutaneous osmotic pump. Bioinformatics was used to identify target metabolites. The tail artery, common carotid artery diastolic, and systolic pressures in mice were determined with a blood pressure monitor. Vascular structure changes were assessed with HE and Masson staining, while kidney pathology was examined using HE. Serum urea nitrogen, creatinine, and cystatin C levels were measured with ELISA kit.RESULTS: Metabolomics analysis identified metabolite BA as a potential target for hypertension management. Compared to the Ang II group, BA reduced systolic blood pressure by 11.58% and diastolic blood pressure by 14.62% in the fourth week. After sodium nitroprusside treatment, the Ang II group showed reduced vasodilation reactivity versus the control. BA significantly restored this reactivity, unlike acetylcholine. Furthermore, BA was observed to attenuate Ang II-induced vascular mediator thickening, the mediator-to-lumen ratio, and collagen deposition. Ang II administration resulted in renal structural damage and increased concentrations of urea nitrogen, creatinine, and serum cystatin C, which was reversed by BA treatment.CONCLUSION: BA exhibits potential in enhancing the vasodilatory response, vascular remodeling, and renal injury associated with Ang II.PMID:40342326 | PMC:PMC12058017 | DOI:10.55730/1300-0144.5995

Biotechnol Bioeng. 2025 May 8. doi: 10.1002/bit.29008. Online ahead of print.ABSTRACTThe simultaneous detection of tens to hundreds of metabolites in a single metabolomic timecourse sample offers a unique but often unrealized opportunity for quantification validation. An individual timecourse fit for each metabolite fundamentally convolutes measurement noise with systematic sample bias (stemming from, for example, variable sample dilution, extraction, and normalization). However, since systematic bias, by its definition, influences all metabolites within a sample in a similar fashion, it can be identified and corrected through the simultaneous fit of all detected metabolites in a single timecourse model. This study presents a nonlinear B-spline mixed-effects model as a convenient formulation capable of estimating and correcting such bias. The proposed model was successfully applied to real cell culture data and validated using simulated timecourse data perturbed with varying degrees of random noise and systematic bias. The model was able to accurately correct systematic bias of 3%-10% to within 0.5% on average for typical data. An R package for the correction model has been developed to facilitate model adoption and use. The proposed nonlinear B-spline mixed-effects formulation is general enough for application to a broad range of research areas beyond just cell culture metabolomics.PMID:40342154 | DOI:10.1002/bit.29008

Phytother Res. 2025 May 8. doi: 10.1002/ptr.8518. Online ahead of print.ABSTRACT3-Oxo-22α-hydroxy-rotundic acid (ITP3) demonstrated notable hypolipidemic activity. However, the molecular mechanism of its hypolipidemic activity has not been elucidated. The present study aimed to evaluate its lipid-lowering efficacy using in vivo and in vitro hyperlipidemia models and to further elucidate its potential mechanism of action in hyperlipidemia. Endophytic fungi in plants of the genus Ilex were utilized for microbial transformation of rotundic acid (RA) to generate an adequate quantity of ITP3. Free fatty acid (FFA) treatment of HepG2 cells and C57BL/6J mice was used to evaluate the hypolipidemic effects of ITP3 in vivo and in vitro. A metabolomics approach combined with Western blot analysis was used to reveal the potential mechanism of the anti-hyperlipidemia of ITP3. The results showed that ITP3 exhibited good lipid-lowering activity in vivo and in vitro models of hyperlipidemia. In addition, metabolomics analysis revealed significant changes in serum and intracellular metabolite lipid levels, which were restored by ITP3. Mechanistically, ITP3 can inhibit lipid synthesis and activate lipid oxidation via the AMPK-SREBP-1c-PPARα pathway, thereby ameliorating lipid metabolism disorders. ITP3 exhibits a promising lipid-lowering effect via the AMPK-SREBP-1c-PPARα pathway, thereby improving lipid metabolism. This work highlights ITP3 as a potential phytochemical candidate for the treatment of hyperlipidemia.PMID:40341857 | DOI:10.1002/ptr.8518

Clin Transl Med. 2025 May;15(5):e70331. doi: 10.1002/ctm2.70331.ABSTRACTAnalysing the genome, epigenome, transcriptome, proteome, and metabolome within the spatial context of cells has transformed our understanding of tumour spatiotemporal heterogeneity. Advances in spatial multi-omics technologies now reveal complex molecular interactions shaping cellular behaviour and tissue dynamics. This review highlights key technologies and computational methods that have advanced spatial domain identification and their pseudo-relations, as well as inference of intra- and inter-cellular molecular networks that drive disease progression. We also discuss strategies to address major challenges, including data sparsity, high-dimensionality, scalability, and heterogeneity. Furthermore, we outline how spatial multi-omics enables novel insights into disease mechanisms, advancing precision medicine and informing targeted therapies. KEY POINTS: Advancements in spatial multi-omics facilitate our understanding of tumour spatiotemporal heterogeneity. AI-driven multimodal models uncover complex molecular interactions that underlie cellular behaviours and tissue dynamics. Combining multi-omics technologies and AI-enabled bioinformatics tools helps predict critical disease stages, such as pre-cancer, advancing precision medicine, and informing targeted therapeutic strategies.PMID:40341789 | DOI:10.1002/ctm2.70331

Plant Biol (Stuttg). 2025 May 7. doi: 10.1111/plb.70025. Online ahead of print.ABSTRACTA recent paradigm shift in ecology supports that the classic functional trait space should be extended to include the metabolome. Accordingly, metabolomic signatures differ between plant species or genotypes depending on where they grow along ecological gradients. Yet, it remains unclear whether environmental gradients alone induce intraspecific phytochemical shifts in natural populations, and if these differences can be replicated experimentally. To address this gap, we combined an observational and experimental study to explore how elevation drives differences in the diversity, endemism and composition of specialized metabolites within the widely distributed perennial grass Festuca rubra. We show that both natural and experimental populations (consisting of identical sets of unique genotypes) exhibit distinct metabolic profiles, unique to each elevation. While natural populations growing in alpine environments displayed lower phytochemical diversity and endemism than those inhabiting lower elevations, phytochemical diversity and endemism peaked at intermediate elevation for the experimental populations. In addition, elevation caused shifts in overall composition of metabolomic groups for experimental populations, reflected in alterations in the over- and under-representation of metabolites within specific superclasses. Our study demonstrates that elevation plays an important role in shaping the metabolome. Rapid shifts in abiotic and biotic environments following climate change may act to alter the plant metabolome, which can impact future ecosystem-level dynamics.PMID:40341698 | DOI:10.1111/plb.70025