PubMed

Food Chem. 2025 Mar 25;481:144039. doi: 10.1016/j.foodchem.2025.144039. Online ahead of print.ABSTRACTThe flavor evolution of unsweetened green tea beverage (USGTB) under actual storage is critical for quality control yet remains unclear. Unlike previous studies conducted by accelerated shelf-life testing, this research investigated sensory-chemical changes in naturally stored USGTB (0-7 months) through multi-omics integrating metabolomics and sensomics. Results identified the 5-month as a critical point for flavor preservation. The EC-EGCG dimer emerged as a novel aging marker, contrasting with freshness indicators (ascorbic acid and other antioxidants). Protocatechuic acid and 2-furoic acid served as multi-flavor contributors (yellowish, sweetness and astringency), whereas L-tartaric acid and malic acid enhanced sourness. Concurrently, aroma deterioration was driven by the diminished (E)-β-ionone and accumulated methyl salicylate. Mechanistically, oxidations of ascorbic acid, catechins, and fresh aroma-related volatiles, flavonoid glycosylation, and oligosaccharides hydrolysis collectively drove color darkening, astringency enhancement, sweetness intensification, and cooked-off flavor development. These findings provided targeted quality control points for USGTB during actual shelf-life.PMID:40157108 | DOI:10.1016/j.foodchem.2025.144039

Food Chem. 2025 Mar 21;480:143913. doi: 10.1016/j.foodchem.2025.143913. Online ahead of print.ABSTRACTCarotenoids are vital pigments influencing both the coloration and health of aquatic organisms, particularly in species such as the Pacific abalone (Haliotis discus hannai). In this study, we identified the major carotenoids in abalone foot muscle using targeted metabolomics. Through differential metabolite analysis, we selected metabolites that met the following criteria: p-value <0.05, variable importance in projection (VIP) score ≥ 1, and fold change (FC) ≥ 2 or FC ≤ 0.5. The results showed that zeaxanthin had the highest content among all foot muscle colors, with the most significant p-value of 0.0079. Thus, we confirmed that zeaxanthin is the predominant carotenoid contributing to the distinct coloration of the foot muscle. We then used a deep learning model to predict carotenoid content based on color measurements in the CIELAB color space, defined by the Commission Internationale de l'Eclairage (CIE), which includes three dimensions: lightness (L*), redness-greenness (a*), and yellowness-blueness (b*). Performance evaluation of 344 abalone samples showed that the Long Short-Term Memory (LSTM) model provided the best prediction results, with a root mean square error (RMSE) of 6.692 and a coefficient of determination (R2) of 0.415. Furthermore, we developed the Color-Based Carotenoid Estimation Suite (CCES). This software features a user-friendly graphical interface, enabling users to input colorimetric data, train models, and predict carotenoid content. Compared to traditional methods, CCES offers non-destructive, rapid carotenoid estimation, improving efficiency by 450 times and reducing costs by 47 to 77 times. This method provides an efficient and scalable tool for aquaculture breeding and quality control, with applications extending beyond abalone to other aquatic and terrestrial species.PMID:40157001 | DOI:10.1016/j.foodchem.2025.143913

Water Res. 2025 Mar 25;281:123557. doi: 10.1016/j.watres.2025.123557. Online ahead of print.ABSTRACTOxygenic photogranules mainly composed of cyanobacteria and heterotrophic bacteria, have gained attention for their ability to treat wastewater (removal of C, N, and P) without external aeration. Currently, the metabolic dynamics of photogranules to varying nutrient and light conditions in wastewater treatment systems remains poorly studied. However, understanding how quickly the photogranule metabolism changes, and whether this change is temporary or permanent is important for the optimal use of photogranules. Here, an NMR-based metabolomics approach was applied to investigate the temporal dynamics of photogranule metabolism in the presence or absence of acetate and with or without light. Our findings revealed that under carbon-limited conditions, photogranules relied on alternative carbon sources, such as N-acetylneuraminate (a constituent of EPS) and amino acids like hypotaurine and L-alanine. This adaptation affected key metabolic pathways, including glycolysis, taurine and hypotaurine metabolism, and the tricarboxylic acid cycle. When acetate was provided, both heterotrophic and phototrophic activities were maintained. Notably, the history of carbon supply influenced how photogranules responded to light shifts. Metabolic indicators showed that the lag in carbon addition altered fatty acid metabolism and carbon fixation, leading to shifts in amino acid concentrations and distinct metabolic profiles when the light was turned off. Thus, NMR metabolomics identified metabolic changes, induced by contrasting carbon conditions, lasting for several hours, and significantly affecting the photogranule response to light fluctuations. These results suggest that the history of carbon supplementation may shape metabolic responses of photogranules to other environmental changes or stressors.PMID:40156996 | DOI:10.1016/j.watres.2025.123557

J Appl Microbiol. 2025 Mar 28:lxaf078. doi: 10.1093/jambio/lxaf078. Online ahead of print.ABSTRACTAlmonds, a nutrient-dense food rich in dietary fiber, polyphenols, and unsaturated fatty acids, exhibit significant potential as a functional food with prebiotic effects. Prebiotics selectively stimulate the growth and activity of beneficial gut microbiota, leading to improved gut and systemic health. This review synthesizes evidence from in vitro studies, clinical trials, and systematic reviews to elucidate the prebiotic effects of almond consumption. Almonds enhance gut microbiota diversity and composition, particularly increasing beneficial bacteria such as Bifidobacterium and Roseburia, while promoting the production of short-chain fatty acids (SCFAs), such as butyrate, which are critical for gut barrier integrity and inflammation modulation. The presence of polyphenols, such as proanthocyanidins, contributes to their antioxidative and antimicrobial properties, further supporting microbiome health. Despite variability in study outcomes, likely due to differences in population health status, study design, and almond preparation methods, the cumulative findings underscore almonds' role as a potential prebiotic food with the potential to improve cardiovascular health. Continued research focusing on individualized responses and standardized methodologies is essential to fully harness the health benefits of almond consumption.PMID:40156575 | DOI:10.1093/jambio/lxaf078

Birth Defects Res. 2025 Apr;117(4):e2467. doi: 10.1002/bdr2.2467.ABSTRACTBACKGROUND: Cleft palate is a congenital malformation influenced by both genetic and environmental factors. Although environmental contributors have been extensively studied, the placenta-an essential organ that mediates maternal-fetal interactions and offers protection against environmental insults-remains poorly understood in this context. This study aimed to explore transcriptomic and metabolomic alterations in the placenta following maternal exposure to corticosteroids, using a dexamethasone-induced cleft palate rabbit model.METHODS: Untargeted metabolomics and transcriptomics analyses were conducted on placental and amniotic fluid samples from fetuses with and without dexamethasone-induced cleft palate. Histopathological examination was performed to assess structural abnormalities in the placenta.RESULTS: The cleft palate group exhibited marked placental pathologies, including fibrosis, calcification, and necrosis. Transcriptomic analysis identified 4744 differentially expressed genes, enriched in pathways related to hormone signaling, vascular development, and inflammation. Metabolomic profiling revealed significant changes in both placenta and amniotic fluid, especially in the urea cycle, aspartate metabolism, and nicotinate and nicotinamide metabolism. The urea cycle was particularly disrupted in the cleft palate group.CONCLUSION: These findings reveal a strong association between placental structural and functional abnormalities and cleft palate formation in the dexamethasone-induced model, offering novel insights into the potential role of the placenta in cleft palate pathogenesis.PMID:40156440 | DOI:10.1002/bdr2.2467

J Immunol. 2025 Mar 28:vkaf027. doi: 10.1093/jimmun/vkaf027. Online ahead of print.ABSTRACTMacrophages and natural killer (NK) cells can effectively kill tumor cells in the presence of anti-cancer IgG monoclonal antibodies (mAbs), but neutrophils are less effective. We previously showed that IgG1 bispecific antibodies (BsAb), which target the IgA Fc receptor (FcαRI, CD89) and a tumor associated antigen induce effective neutrophil recruitment and tumor cell killing in vivo. Here we investigated if the efficacy of an anti-EGFR (CetuximAb)/FcαRI-bispecific antibody could be further improved by implementing glycoengineering of the IgG-Fc, aimed at increasing FcγRIIIa/b binding and/or complement activity. Fc afucosylation was introduced to enhance antibody-dependent cellular cytotoxicity (ADCC) by FcγRIIIa on NK/macrophages, which can also reduce neutrophil-mediated ADCC through their GPI-linked FcγRIIIb. Fc galactylation was found to enhance antibody hexamerization and thereby complement dependent cytotoxicity (CDC). Low fucosylated BsAbs moderately increased NK cell-mediated tumor cell killing, but did not affect neutrophil-mediated tumor cell killing nor phagocytosis by macrophages. Glycoengineering of these EGFR-specific BsAb, which normally are devoid of CDC-activity, did not enable their complement activities. In conclusion, glycoengineered FcαRI BsAbs increased ADCC by NK cells but had little effect on neutrophil or macrophage mediated tumor killing.PMID:40156381 | DOI:10.1093/jimmun/vkaf027

Int J Surg Pathol. 2025 Mar 29:10668969251327748. doi: 10.1177/10668969251327748. Online ahead of print.ABSTRACTPancreatic neuroendocrine tumors are a heterogeneous group of rare clinical tumors, which can be classified into functional pancreatic neuroendocrine tumor (insulinoma is the most common) and noninsulinoma. Insulinoma and noninsulinoma have different mutation profiles. In noninsulinoma, ATRX/DAXX mutation is associated with alternative lengthening of telomeres-positive phenotype and positively correlated with poor prognosis. Copy number variation is also a prognostic marker for a high risk of recurrence. Scholars have used epigenetics as well as a multiomics approach (combining epigenetics, metabolomics, proteomics, etc) to molecularly type noninsulinoma, and there are huge differences in molecular expression and patient prognosis between different groups. In this manuscript, we summarize the published studies that utilized genome, epigenome, transcriptome, and proteome data to classify noninsulinoma.PMID:40156271 | DOI:10.1177/10668969251327748

J Sci Food Agric. 2025 Mar 29. doi: 10.1002/jsfa.14258. Online ahead of print.ABSTRACTBACKGROUND: Diabetes mellitus is a chronic metabolic disorder posing a significant public health challenge. Dendrobium officinale is a valuable edible-medicinal homologous plant. Phenolic extracts from fermented D. officinale leaves (DOLP) demonstrate a hypoglycemic effect. However, the effects of DOLP on physiological metabolism and gut microbiota under diabetic conditions remain unknown.RESULTS: Untargeted metabolomics analysis revealed that DOLP reversed 98 significantly differential metabolites (SDMs) in diabetic mice. Indoxyl sulfate and palmitoyl sphingomyelin were identified as the primary candidate biomarkers associated with the hypoglycemic effect. KEGG pathway enrichment analysis underscored the significance of arginine and proline metabolism, ascorbate and aldarate metabolism, and fatty acid metabolism in the regulatory effects of DOLP. Furthermore, DOLP reversed the dysbiosis of the gut microbiota in diabetic mice, significantly influencing the relative abundance of the genera Intestinimonas, GCA_900066575, Muribaculum, and Enterorhabdus. These differential genera exhibited various correlations with SDMs, including l-hydroxyarginine, γ-guanidinobutyrate, l-threonate, d-galactarate, l-ascorbic acid, palmitic acid, cis-9-palmitoleic acid, octadecanoic acid, and oleic acid.CONCLUSION: The protective effect of DOLP against diabetes mellitus is closely linked to its regulation of physiological metabolism and gut microbiota. DOLP may serve as a promising agent for the prevention and treatment of diabetes mellitus. © 2025 Society of Chemical Industry.PMID:40156225 | DOI:10.1002/jsfa.14258

Stem Cell Res Ther. 2025 Mar 28;16(1):153. doi: 10.1186/s13287-025-04277-7.ABSTRACTBACKGROUND: Adipose-derived mesenchymal stem cells (ASCs) represent a valid therapeutic option for clinical application in several diseases, mostly due to the paracrine activity of their secretome, exerting pro-angiogenic, antinflammatory and immunosuppressive effects. Recently, 3D culturing models has been shown to significantly influence the intrinsic characteristics of these cells, their gene expression and the secretome's composition, thus affecting ASC paracrine effects and clinical potential. This study aims to investigate the feasibility of exploiting 3D culturing as a tool to improve ASC secretome therapeutic efficacy.METHODS: ASCs were cultured in monolayers via conventional two-dimensional (2D) methods or induced to form 3D spheroids by seeding them on 96-well ultra-low attachment (ULA) plates. The phenotypical characterization of 3D-ASCs was performed through immunofluorescence analyses. The composition and angiogenic potential of 3D-ASC-derived secretome was assessed by means of protein array and functional tube formation assay, respectively. We analyzed the expression profile of 92 angiogenesis-related genes in 2D versus 3D cultures through a qRT-PCR array, and GO term enrichment analysis followed by network analysis was applied to identify the top hub genes. The expression of specific angiomiRs in 3D-ASCs and their secretome was assessed by qRT-PCR. The role of miR-145-5p was investigated through transfection with specific mimics/anti-miR.RESULTS: 3D-ASCs showed increased stemness, cell-cell and cell-ECM interactions with respect to 2D-cultured cells. 3D culturing increased the secretion of cytokines involved in the promotion of angiogenesis, resulting in improved angiogenic effects on HUVEC cells. Mechanistically, qRT-PCR array data indicated downregulation of angiopoietin-2 (ANGPT2) as a key factor in the 3D-ASC-secretome-induced angiogenesis. In addition, ANGPT2 was recognized as a predicted target of miR-145-5p, one of the angiomiRs found upregulated in 3D-ASCs. Depletion of miR-145-5p significantly altered ASC secretome angiogenic potential and ANGPT2 expression on HUVEC cells.CONCLUSIONS: All these findings corroborate our hypothesis that 3D culturing is able to positively modulate ASC gene expression and secretome composition in terms of pro-angiogenic potential. Indeed, our study contributes to shed light on the role of the miR-145-5p/ANGPT2 axis in this process, opening the way to innovative potentiation strategies to implement secretome-based therapies, with broad clinical applications.PMID:40155988 | DOI:10.1186/s13287-025-04277-7

BMC Bioinformatics. 2025 Mar 28;26(1):94. doi: 10.1186/s12859-025-06111-6.ABSTRACTThe advent of high-throughput sequencing technologies, such as DNA microarray and DNA sequencing, has enabled effective analysis of cancer subtypes and targeted treatment. Furthermore, numerous studies have highlighted the capability of graph neural networks (GNN) to model complex biological systems and capture non-linear interactions in high-throughput data. GNN has proven to be useful in leveraging multiple types of omics data, including prior biological knowledge from various sources, such as transcriptomics, genomics, proteomics, and metabolomics, to improve cancer classification. However, current works do not fully utilize the non-linear learning potential of GNN and lack of the integration ability to analyse high-throughput multi-omics data simultaneously with prior biological knowledge. Nevertheless, relying on limited prior knowledge in generating gene graphs might lead to less accurate classification due to undiscovered significant gene-gene interactions, which may require expert intervention and can be time-consuming. Hence, this study proposes a graph classification model called associative multi-omics graph embedding learning (AMOGEL) to effectively integrate multi-omics datasets and prior knowledge through GNN coupled with association rule mining (ARM). AMOGEL employs an early fusion technique using ARM to mine intra-omics and inter-omics relationships, forming a multi-omics synthetic information graph before the model training. Moreover, AMOGEL introduces multi-dimensional edges, with multi-omics gene associations or edges as the main contributors and prior knowledge edges as auxiliary contributors. Additionally, it uses a gene ranking technique based on attention scores, considering the relationships between neighbouring genes. Several experiments were performed on BRCA and KIPAN cancer subtypes to demonstrate the integration of multi-omics datasets (miRNA, mRNA, and DNA methylation) with prior biological knowledge of protein-protein interactions, KEGG pathways and Gene Ontology. The experimental results showed that the AMOGEL outperformed the current state-of-the-art models in terms of classification accuracy, F1 score and AUC score. The findings of this study represent a crucial step forward in advancing the effective integration of multi-omics data and prior knowledge to improve cancer subtype classification.PMID:40155814 | DOI:10.1186/s12859-025-06111-6

Sci Rep. 2025 Mar 28;15(1):10798. doi: 10.1038/s41598-025-95714-3.ABSTRACTAgaricus bisporus is a widely cultivated edible fungus globally. However, the mechanisms underlying the differences in flavor and nutritional traits between wild-type (W) and cultivated-type (C) strains remain unclear, which hinders the artificial breeding of high-quality varieties. This study systematically revealed, for the first time, the molecular and metabolic basis of flavor divergence between wild and cultivated A. bisporus by integrating transcriptomics and metabolomics. A total of 43 strains (23 wild-type and 20 cultivated-type) were analyzed using high-throughput sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to dissect differences in gene expression and metabolite profiles. Results showed that although total protein and amino acid contents exhibited no significant differences, transcriptomic analysis identified significant upregulation of AGABI2DRAFT_188981 and AGABI2DRAFT_191000 (genes associated with high-affinity methionine permease MUP1) in cultivated strains, suggesting their indirect regulation of flavor formation via methionine metabolism. Metabolomic analysis further revealed a marked increase in uridine levels in cultivated strains (3.2-fold higher than wild-type, p < 0.01), indicating potential medicinal value, while wild strains were enriched with flavor precursors such as fumaric acid and isoleucine (fold change ≥ 2.5). In contrast, cultivated strains accumulated metabolites like 2-hydroxybutyric acid and α-ketoglutarate (VIP > 1.5). This study pioneered the construction of a gene-metabolite correlation network, identifying a strong positive correlation between AGABI2DRAFT_191352 (6-phosphofructokinase) and 2-hydroxybutyric acid (r = 0.82), highlighting the regulatory role of glycolytic flux in flavor metabolism. These findings not only elucidate the impact of artificial cultivation on metabolic reprogramming in A. bisporus but also provide critical molecular targets for targeted breeding of strains with enhanced flavor and nutritional value, offering practical significance for advancing the edible fungi industry.PMID:40155773 | DOI:10.1038/s41598-025-95714-3

Nat Methods. 2025 Mar 28. doi: 10.1038/s41592-025-02646-x. Online ahead of print.ABSTRACTChemical exposures may affect human metabolism and contribute to the etiology of neurodegenerative disorders such as Alzheimer's disease. Identifying these small metabolites involves matching experimental spectra to reference spectra in databases. However, environmental chemicals or physiologically active metabolites are usually present at low concentrations in human specimens. The presence of noise ions can substantially degrade spectral quality, leading to false negatives and reduced identification rates. In response to this challenge, the Spectral Denoising algorithm removes both chemical and electronic noise. Spectral Denoising outperformed alternative methods in benchmarking studies on 240 tested metabolites. It improved high confident compound identifications at an average 35-fold lower concentrations than previously achievable. Spectral Denoising proved highly robust against varying levels of both chemical and electronic noise even with a greater than 150-fold higher intensity of noise ions than true fragment ions. For human plasma samples from patients with Alzheimer's disease that were analyzed on the Orbitrap Astral mass spectrometer, Denoising Search detected 2.5-fold more annotated compounds compared to the Exploris 240 Orbitrap instrument, including drug metabolites, household and industrial chemicals, and pesticides.PMID:40155721 | DOI:10.1038/s41592-025-02646-x

Sci Rep. 2025 Mar 28;15(1):10749. doi: 10.1038/s41598-025-94996-x.ABSTRACTThe level of balance can play an essential role in a soldier's performance. For a Special Forces soldier, the footwear used or extra weight may be important factors affecting their balance level during combat operations or trainings. Therefore, the purpose of the study was to assess the level of static balance of Special Forces Operators and to determine the influence of select elements of a soldier's combat uniform and equipment on balance levels. The study group consisted of 37 Polish Special Forces Operators. To assess the level of static balance, the Romberg test was used in three variants (barefoot, with shoes, and with shoes, helmet, and vest). The measurements were made using the AMTI AccuGait portable force platform. The results of the analysis showed that the calculated average values of selected static balance parameters of soldiers differed depending on the variant of the Romberg test used, and in most cases, those differences were statistically significant ( α < 0.05 ). The lowest average values of parameters characterizing the level of static balance of Special Forces soldiers were calculated for barefoot measurements. The measurements with shoes and additional loads showed a statistically significant increase in almost all analysed parameters compared to barefoot measurements.PMID:40155464 | DOI:10.1038/s41598-025-94996-x

Nat Commun. 2025 Mar 28;16(1):3039. doi: 10.1038/s41467-025-58129-2.ABSTRACTMetabolites are small molecules that are useful for estimating disease risk and elucidating disease biology. Here, we perform two-sample Mendelian randomization to systematically infer the potential causal effects of 1099 plasma metabolites measured in 6136 Finnish men from the METSIM study on risk of 2099 binary disease endpoints measured in 309,154 Finnish individuals from FinnGen. We find evidence for 282 putative causal effects of 70 metabolites on 183 disease endpoints. We also identify 25 metabolites with potential causal effects across multiple disease domains, including ascorbic acid 2-sulfate affecting 26 disease endpoints in 12 disease domains. Our study suggests that N-acetyl-2-aminooctanoate and glycocholenate sulfate affect risk of atrial fibrillation through two distinct metabolic pathways and that N-methylpipecolate may mediate the putative causal effect of N6,N6-dimethyllysine on anxious personality disorder.PMID:40155430 | DOI:10.1038/s41467-025-58129-2

Transl Psychiatry. 2025 Mar 28;15(1):105. doi: 10.1038/s41398-025-03323-5.ABSTRACTAlthough lipid biology may play a key role in the pathophysiology of mental health disorders such as schizophrenia (SCZ) and bipolar disorder (BD), the nature of this interplay and how it could shape phenotypic presentation, including cognitive performance is still incompletely understood. To address this question, we analyzed the association of plasma level of different lipid species with cognitive performance in the transdiagnostic PsyCourse Study. Plasma lipidomic profiles of 623 individuals (188 SCZ, 243 BD, 192 healthy controls) belonging to the PsyCourse Study were assessed using liquid chromatography and untargeted mass spectrometry. The association between 364 annotated lipid species from 16 lipid classes and six cognitive tests was evaluated. Likewise, the association of polygenic risk scores (PRS) for SCZ, BD, executive function (EF), and educational attainment (EA) with lipid plasma levels were also investigated. In the regression analysis, three lipid species belonging to phosphatidylethanolamine plasmalogen and one belonging to ceramide class showed significant negative association with Digit-Symbol test scores. Lipid class-based enrichment analysis in LipidR replicated the significance of the phosphatidylethanolamines class for the Digit-Symbol test, which evaluates the processing speed in cognitive tasks. Polygenic load for SCZ, BD, EF, or EA was not associated with lipid levels. Our findings suggest a link between lipids and cognitive performance independent of mental health disorders. Still, independent replication is warranted to better understand if phosphatidylethanolamines could represent an actionable pharmacologic target to tackle cognitive dysfunction, an important unmet clinical need that affects long-term functional outcomes in individuals with severe mental health disorders.PMID:40155381 | DOI:10.1038/s41398-025-03323-5

Anal Chim Acta. 2025 May 8;1350:343874. doi: 10.1016/j.aca.2025.343874. Epub 2025 Feb 26.ABSTRACTBACKGROUND: Triglycerides (TGs) play a crucial role in various physiological processes through the breakdown of their fatty acyl (FA) side chains. It has been demonstrated that not only the total levels of TGs but also the specific composition of FA side chains are vital for biological functions. However, biomedical studies that comprehensively identify FA compositions remain very limited. One of the reasons is the structural heterogeneity of TGs, with variability in their three fatty acyl chains posing significant challenges for TG analysis.RESULTS: This study proposed a pseudotargeted TG analytical workflow that generated a unique dynamic multiple reaction monitoring (dMRM) acquisition list tailored to different biological sample types.TG profiles were acquired in full scan mode using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-qToF), while LC-triple quadrupole mass spectrometry (LC-QqQ) with PIS was applied to identify fatty acyl chains. Finally, dMRM transitions were derived from confirmed ion pairs of TGs with specific FAs. Two demonstration samples, murine type 2 alveolar epithelial cell line, MLE12, with fatty acid synthase deletion, and hypertriglyceridemia plasma, were used to display the capability of the platform. While more TG species were identified in the MLE12 cell samples compared to human plasma samples (53 vs. 47), a more complex and diverse range of FA compositions in TGs was observed in human plasma compared to MLE12 cell samples (379 vs. 167).SIGNIFICANCE: Our results emphasize the need for customized MRM acquisition tailored to different biological samples, and the pseudotargeted TG analytical workflow proves effective in improving the understanding of TG regulation in biological systems. This study offers a novel and effective solution to address the complex challenges of TG analysis, enhancing accuracy, specificity, and interpretative strength.PMID:40155173 | DOI:10.1016/j.aca.2025.343874

Anal Chim Acta. 2025 May 8;1350:343825. doi: 10.1016/j.aca.2025.343825. Epub 2025 Feb 19.ABSTRACTBACKGROUND: Cardiolipins (CL) are a mitochondria-specific family of phospholipids that play central roles in mitochondrial function. Imbalance in CL metabolism, especially excessive CL oxidation, leads to mitochondrial dysfunction, apoptosis, and inflammation, contributing to age-related diseases. As of yet no comprehensive methods have been developed to assess CL, oxidized CL (oxCL), and monolyso-CL (MLCL) species.RESULTS: To fill this critical research gap, we combined untargeted and targeted lipidomic approaches to analyze CL species in human skeletal muscle samples. The method enabled in-depth structural characterization using exact mass measurement followed by multistage fragmentation (MSn) to achieve unequivocal structural elucidation at the molecular species level and sn-position level for some species. This novel methodology identified intact mono- and di-oxygenated L4CL species and allowed the differentiation of isomeric 9/13-HODE-L3CL and 9(10)/12(13)-EpOME-L3CL with unprocessed total lipid extracts. Overall, 220 molecular species (125 CL, 30 oxCL, and 65 MLCL) were detected. Our method includes a quantitation strategy that leveraged on establishing three-leveled matrix-matched calibration curves normalized by using internal standard M4CL and its isotopologues M+1 (13C-M4CL) and M+3 (13C3-M4CL) respectively. The analytical performance was also evaluated and found to be highly sensitive with LLOQs at fmol levels and reproducible with precision RSD <20 % for the majority.SIGNIFICANCE AND NOVELTY: This is the first reported method to simultaneously provide broad coverage of CL, oxCL, and MLCL species from a single injection of total lipid extract in a complex biological sample. This method is also the first to demonstrate the presence of sn-positional isomers of CL in human skeletal muscle. It has been successfully applied to a pilot study of skeletal muscle biopsies and provided meaningful results. We anticipate the methodology will facilitate investigations of the cardiolipin lipidome leading to a better understanding of the complex and highly interactive biological processes that regulate mitochondria function and expand minor cardiolipin targets including oxCL and MLCL for biomarker discovery.PMID:40155162 | DOI:10.1016/j.aca.2025.343825

Anticancer Res. 2025 Apr;45(4):1343-1353. doi: 10.21873/anticanres.17520.ABSTRACTBACKGROUND/AIM: Multimodal treatment is now the primary strategy for managing pancreatic cancer. Blood-based protein markers are sometimes useless for evaluating the real-time disease condition to determine treatment strategies. This study focused on detecting novel exosomal lipid biomarkers, as exosomes contain several biological mediators.MATERIALS AND METHODS: Lipidomic analysis was conducted by liquid chromatography-mass spectrometry (LC-MS) using serum exosome-derived lipid samples from four pancreatic ductal adenocarcinoma (PDAC) patients and four healthy controls. Some candidates were ascertained using multiple time-point blood samples from four additional PDAC patients. Furthermore, we validated them using an additional twelve multimodal-treated PDAC patient cohort.RESULTS: Nontarget LC-MS analysis revealed that lysophosphatidylcholine (LPC) expression levels were significantly decreased in PDAC patients compared to healthy controls. Multiple time-point blood samples demonstrated that LPC (16:0) and LPC (18:1) consistently showed lower levels in relapsed cases than in non-relapsed cases over time. In the validation cohort, a low LPC level before initial treatment was associated with histological lymphatic invasion (p=0.04) and was linked to progressive-free survival (PFS) (p=0.04).CONCLUSION: PDAC patients with initially low LPC levels in the blood exosomes demonstrated an unfavorable PFS. Exosomal lipid markers may serve as potential indicators for disease monitoring in pancreatic cancer patients undergoing multimodal treatment.PMID:40155024 | DOI:10.21873/anticanres.17520

J Ethnopharmacol. 2025 Mar 26:119699. doi: 10.1016/j.jep.2025.119699. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: The Zhimu-Huangbai herb-pair (ZB) is one of the most widely accepted prescriptions for treating Alzheimer's disease (AD) in traditional Chinese medicine. However, the effective components and mechanism of ZB for treating AD have not been fully understood.AIM OF THE STUDY: This study aims to reveal the active components of ZB in the treatment of AD through serum pharmacochemistry, identify the potential targets and pathways of ZB in treating AD through metabolomics, and subsequently verify its mechanism through in vivo experiments.MATERIALS AND METHODS: The components of ZB in both blood and cerebrospinal fluid were determined by using UPLC-Q-TOF-MS. The efficacy of ZB was assessed in a mouse model of AD induced by D-galactose. Metabolomics methods were used for screening and identification of differential metabolites and enrichment analysis of metabolic pathways. The enzyme-linked immunosorbent assay (ELISA) was used to detect the activities of enzyme complexes I-IV, as well as the levels of ATP and ROS in hippocampal mitochondria of mice. Additionally, the expression of key genes and proteins in the signaling pathway was examined by utilizing immunohistochemistry, real-time quantitative PCR, and Western blot.RESULTS: A total of 27 prototype components were identified from the serum of rats given ZB, of which 8 components were simultaneously detected in the cerebrospinal fluid. A total of 20 different metabolites were identified from mouse plasma using a metabolomics technique. The enrichment analysis results revealed that the pathway of ZB treatment for AD mainly involves glycerophospholipid metabolism, arachidonic acid metabolism, and unsaturated fatty acid biosynthesis. In vivo experiments have shown that ZB can improve the energy metabolism of the brain and increase the production of ATP by improving mitochondrial dysfunction. In addition, ZB could promote the release of brain-derived neurotrophic factor (BDNF), increase the density of postsynaptic density protein (PSD95), and enhance the expression of synaptophysin (SYN).CONCLUSION: Our study demonstrates that ZB can improve mitochondrial and synaptic function in AD mice induced by D-gal, providing experimental support for the clinical application and drug development for the prevention and treatment of AD.PMID:40154898 | DOI:10.1016/j.jep.2025.119699

Environ Pollut. 2025 Mar 26:126108. doi: 10.1016/j.envpol.2025.126108. Online ahead of print.ABSTRACTLung cancer poses a significant global burden with rising morbidity and mortality. Coal tar pitch-induced lung cancer is an occupational disease where early detection is crucial but challenging due to unclear pathogenesis. We established a malignant transformation model using BEAS-2B cells treated with coal tar pitch extract (CTPE). Macro- and micro-observations showed CTPE-induced alterations, including changes in cell morphology, enhanced proliferation and migration abilities, upregulated EGFR expression, modified levels of CYP1A1 and GSTM1 metabolizing enzymes, and a transition towards a mesenchymal phenotype. These findings strongly suggest that the cells have undergone malignant transformation. Metabolomics analysis revealed changes in 1120 metabolites, with 31 co-expressed, mainly in energy and amino acid metabolism. Small extracellular vesicles (SEVs) concentrations and EGFR levels were significantly altered. Correlation analysis identified a relationship between these biomarkers, implying their potential significance as early events in the initiation and progression of lung cancer. These findings provide valuable insights and a rationale for lung cancer screening and mechanistic investigations, thereby contributing to a deeper understanding of the disease.PMID:40154873 | DOI:10.1016/j.envpol.2025.126108