PubMed

Nat Cell Biol. 2025 Apr 21. doi: 10.1038/s41556-025-01650-9. Online ahead of print.ABSTRACTNutrient stress represents an important barrier for anti-tumour immunity, and tumour interstitial fluid often contains metabolites that hinder immune function. However, it is difficult to isolate the effects of tumour nutrient stress from other suppressive factors. Thus, we used a chemically defined cell culture medium based on the metabolomic profile of tumour interstitial fluid: tumour interstitial fluid medium (TIFM). Culture of CD8+ T cells in TIFM limited cell expansion and impaired CD8+ T cell effector functions upon restimulation, suggesting that tumour nutrient stress alone is sufficient to drive T cell dysfunction. We identified phosphoethanolamine (pEtn), a phospholipid intermediate, as a driver of T cell dysfunction. pEtn dampened T cell receptor signalling by depleting T cells of diacylglycerol required for T cell receptor signal transduction. The reduction of pEtn accumulation in tumours improved intratumoural T cell function and tumour control, suggesting that pEtn accumulation plays a dominant role in immunosuppression in the tumour microenvironment.PMID:40258951 | DOI:10.1038/s41556-025-01650-9

Sci Rep. 2025 Apr 21;15(1):10980. doi: 10.1038/s41598-025-95403-1.ABSTRACTSleep disorders have become a global social problem that increases the risk of developing mental illnesses and metabolic diseases. We aimed to identify biomarkers with which to non-invasively and objectively evaluate chronic sleep disorders. We used capillary electrophoresis-Fourier transform mass spectrometry (CE-FTMS) to analyze metabolomes in saliva collected from 50 persons each with good (≤ 2) and poor (≥ 6) sleep quality scored according to the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J) self-report questionnaire. The levels of five metabolites including glycerol and hippuric acid and eight including 2-hydroxybutyric acid (2HB), were respectively decreased and increased in participants with poor sleep quality. We established a random forest model consisting of six metabolites, including glycerol and hippuric acid, with a prediction accuracy of 0.866. Correlations between metabolites and sleep satisfaction were assessed using the Oguri-Shirakawa-Azumi sleep inventory, middle-age and aged version (OSA-MA) questionnaire. The results showed that 2'-deoxyguanosine, N1-acetylspermine, and 2,4-dihydroxybenzoic acid correlated positively, whereas glucosamine 6-phosphate and trimethylamine N-oxide correlated negatively with sleep quality. These findings suggested that changes in salivary metabolites reflect pathophysiological mechanisms of chronic sleep disorders, and that saliva samples could serve as non-invasive and objective diagnostic targets for predicting habitual sleep quality.PMID:40258870 | DOI:10.1038/s41598-025-95403-1

Sci Rep. 2025 Apr 21;15(1):13748. doi: 10.1038/s41598-025-94701-y.ABSTRACTSepsis after trauma and trauma-induced SIRS have similar symptoms, making their differentiation challenging. Therefore, biomarkers are needed to differentiate between sepsis after trauma and trauma-induced SIRS. We hypothesized that sepsis following trauma induces distinct alterations in blood metabolism compared to trauma-induced SIRS and sought to identify metabolite biomarkers in blood that could differentiate between the two. In this retrospective study, the existing blood metabolomics data from 60 patients without trauma-induced SIRS, 40 patients with trauma-induced SIRS, and 50 non-trauma control cases were analyzed. Among 40 traumatic patients with SIRS, 16 developed sepsis (SDS group), 24 did not develop sepsis (SDDS group) within the subsequent two-week period after trauma. A pairwise comparison between SDS group and SDDS group was used to screen the differential metabolites as biomarkers distinguishing sepsis after trauma from trauma-induced SIRS. Using partial least‑squares discriminant analysis, we demonstrated that SDS group was metabolically distinct from the SDDS group. A total of 37 differential metabolites were found between SDS group and SDDS group. We selected 5 most significantly different metabolites between SDS and SDDS groups as biomarkers to discriminate sepsis after trauma from trauma-induced SIRS, which were 7-alpha-carboxy-17-alpha-carboxyethylandrostan lactone phenyl ester, docosatrienoic acid, SM 8:1;2O/26:1, SM 34:2;2O, and N1-[1-(3-isopropenylphenyl)-1-methylethyl]-3-oxobutanamide. Our study has identified the potential of these biomarkers for differentiating sepsis after trauma from trauma-induced SIRS. This not only provides a new approach for the early diagnosis of sepsis after trauma but also lays a solid foundation for further research based on targeted metabolomics, which may lead to the development of more effective treatment strategies in the future.PMID:40258847 | DOI:10.1038/s41598-025-94701-y

Dev Comp Immunol. 2025 Apr 19:105373. doi: 10.1016/j.dci.2025.105373. Online ahead of print.ABSTRACTTrionyx sinensis Hemorrhagic Syndrome Virus(TSHSV)seriously hinders the aquaculture of Chinese soft-shell turtle (Trionyx sinensis) due to its high mortality. However, the pathogenic mechanisms of TSHSV in T. sinensis are still unclear. In present study, transcriptomic and metabolomic analyses were performed on turtle livers following TSHSV infection. 734 up-regulated and 770 down-regulated differentially expressed genes (DEGs) were identified in different TSHSV challenge groups. These DEGs were categorized into 12 pathways related to virus infection and host immunity. Moreover, 27, 2679, and 4341 differentially expressed metabolites (DEMs) were identified in the D1, D3, and D5 groups, respectively. These DEMs were mapped into the pathways of energy metabolism, amino acid metabolism and fatty acid metabolism. Association analysis revealed TSHSV induced inflammatory responses, hepatocyte apoptosis, and ultimately led to liver tissue damage. Taurine supplementation promoted the survival rate of turtle after TSHSV infection and reduced the inflammatory response of liver by regulating the production of interferons, antioxidases, and the pro-inflammatory cytokine TNF-α. Collectively, our results provide comprehensive profiles of the transcriptome and metabolome in Chinese soft-shell turtle liver after TSHSV invasion, shedding light on the underlying pathogenic mechanism. The method of taurine supplementation might be a promising therapeutic strategy for protecting turtles from TSHSV.PMID:40258577 | DOI:10.1016/j.dci.2025.105373

J Ethnopharmacol. 2025 Apr 19:119843. doi: 10.1016/j.jep.2025.119843. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: The Shenlingcao oral liquid (SLC), derived from traditional clinical formulations, can enhance physical strength and vitality during chemotherapy for malignant tumors. Previous studies have indicated that SLC can enhance the quality of life and daily functioning of patients with non-small cell lung cancer (NSCLC) within 6 months after adjuvant chemotherapy following radical surgery. Nevertheless, its precise mechanism of action is unclear.AIM OF THE STUDY: To elucidate the function and underlying mechanism of SLC in enhancing the effect of cisplatin in treating NSCLC.MATERIALS AND METHODS: UPLC-Q-Exactive Plus-MS/MS was used to characterize the chemical constituents of SLC. The main gene targets and the pathways of SLC that impact NSCLC were predicted using network pharmacology. A mouse model of Lewis lung cancer and the combination of transcriptomics, metabolomics, and 16S rRNA analysis were used to investigate the underlying mechanisms of the SLC-cisplatin combination in influencing the pathology of NSCLC.RESULTS: The SLC-cisplatin combination significantly reduced tumor volume and weight (P<0.01), boosted T lymphocytes (P<0.05), increased cleaved-caspase-3/caspase-3 expression (P<0.05), and decreased p-PI3K/PI3K, p-AKT/AKT, and Bcl-2/Bax protein levels (P<0.05) compared with cisplatin monotherapy. It also improved the gut flora by enriching the abundance of Bacteroidaceae, S24-7, and Porphyromonadaceae, while modulating metabolic pathways, including caffeine metabolism and fatty acid degradation.CONCLUSIONS: SLC enhanced the effect of cisplatin in inhibiting NSCLC by inducing cell apoptosis, augmenting immune responses, balancing the gut microbiota, and regulating key metabolic pathways. Our findings highlight the potential of SLC as an effective adjuvant therapy for NSCLC.PMID:40258526 | DOI:10.1016/j.jep.2025.119843

Microb Pathog. 2025 Apr 19:107621. doi: 10.1016/j.micpath.2025.107621. Online ahead of print.ABSTRACTBACKGROUND: Traditional Chinese Medicine (TCM) theory posits a close relationship between an individual's constitutional types and the overall health. Variations in metabolic processes and microbial composition have been observed across different constitution types. This study aims to explore the relationship between TCM constitutions, intestinal flora, and metabolites to devise personalized TCM treatment strategies, enhancing evidence-based guidance for clinical practice.METHODS: The research investigated differences in microbial diversity and composition among three TCM constitution types: yin-deficiency constitution (PA), balanced constitution (PH), and yang-deficiency constitution (PI). A significant elevation of the Chao1 metric was noted in the PH group compared to the PI group.RESULTS: PCoA and CPCoA analyses demonstrated distinct group separation based on floral samples. Dominant phyla included Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Fusobacteria, with varying abundance at the genus level. Metabolic pathway analysis unveiled disparities in metabolites associated with different pathways among constitution groups. KEGG pathway enrichment analysis emphasized pathways such as steroid hormone biosynthesis, ovarian steroidogenesis, and tryptophan metabolism. Furthermore, correlation analysis revealed associations between specific bacterial taxa and metabolites.CONCLUSION: This study delineated the variations in intestinal flora and metabolic profiles among individuals with PA, PH, and PI constitution types, providing valuable insights for the development of personalized TCM treatment approaches.PMID:40258500 | DOI:10.1016/j.micpath.2025.107621

J Microbiol Methods. 2025 Apr 19:107135. doi: 10.1016/j.mimet.2025.107135. Online ahead of print.ABSTRACTThe application of omics technologies in combination with bench investigations has brought about a significant transformation in the field of probiotics, enabling a thorough investigation of the basic elements contributing to the probiotic activity. Genomics studies have decoded the complete set of genes of probiotic organisms, shedding light on beneficial traits and mechanisms of probiotic action. Transcriptomics analyses focus on gene expression patterns and investigate probiotic adaptation and functionality. Proteomic studies have revealed the intricate connections between proteins in probiotic cells and their relationship with the host environment. Metabolomic profiling has provided a comprehensive perspective on the metabolic pathways related to probiotic metabolism and the production of bioactive substances. The ongoing development of omics technology presents exciting opportunities for probiotic research, as it allows for a deeper exploration of probiotic-host interactions and the creation of advanced and tailored probiotics that offer specific health advantages. A comprehensive analysis of recent progress in genomics, transcriptomics, proteomics, and metabolomics related to probiotics is presented in this review.PMID:40258404 | DOI:10.1016/j.mimet.2025.107135

Redox Biol. 2025 Apr 17;83:103639. doi: 10.1016/j.redox.2025.103639. Online ahead of print.ABSTRACTAcrolein (ACR) is an endogenous reactive unsaturated aldehyde that can be detoxified by the aldo-keto reductase (AKR) enzyme system. While it has been shown that accumulation of ACR is associated with several health problems, including inflammation, oxidative stress, and cardiovascular disease the study aimed to analyze whether an endogenous accumulation of ACR is causal for vascular dysfunction in an akr7a3 mutant zebrafish model. Enlargement of the hyaloid and retinal vasculature, as well as alterations in the larval pronephros and thickening of the glomerular basement membrane in the adult kidney were found upon ACR accumulation. Transcriptomic and metabolomic analyses, followed by functional validation, revealed that the up-regulation of genes controlling the arachidonic acid metabolism and activation of the leukotriene pathway are responsible for the observed microvascular changes. In conclusion, the data have identified an intrinsic function of ACR in akr7a3 mutants that activates the arachidonic acid metabolism and subsequently disrupts vascular integrity by promoting an inflammatory response. Thus, ACR is causal in the development of vascular disease.PMID:40258306 | DOI:10.1016/j.redox.2025.103639

Metabolomics. 2025 Apr 21;21(3):55. doi: 10.1007/s11306-025-02248-w.ABSTRACTINTRODUCTION: Intestinal helminth parasites trigger the host immune response through epithelial sensory tuft cells, but helminth-derived molecules that may activate tuft cells are poorly characterized.OBJECTIVES: The study aimed to identify small molecules released in vitro by two nematode parasites, that infect rodents (Nippostrongylus brasiliensis) and ruminants (Haemonchus contortus), and to test candidate ligands in an in vivo model of tuft cell differentiation.METHODS: Small molecules were analyzed by hydrophilic interaction liquid chromatography (HILIC) of material released by adult parasites incubated in serum-free media, followed by mass spectrometry; selected molecules were administered to mice and tuft cell expansion enumerated after 5 days.RESULTS: A range of different conditions (culture media, timing, oxygenation) were tested, and comparisons made between the conditions, and between the two nematode species at selected points. Common products across the conditions and species included carboxylic acids (malate, succinate), medium chain fatty acids (such as decanoic and undecanoic acids), purines (guanine, xanthine and their derivatives), and phosphocholine compounds. We selected 19 of the prominent molecules for in vivo testing by oral administration, including succinate, a known activator of tuft cell differentiation. Malate elicited a low but significant level of tuft cell expansion, while undecanoic acids with or without a bromine substitution were also able to induce significant differentiation comparable to succinate. Other molecules including phosphorylcholine had no effect.CONCLUSION: Multiple molecular species including decanoic and undecanoic acids released by helminths may contribute to activation of tuft cells in vivo.PMID:40257648 | DOI:10.1007/s11306-025-02248-w

Metabolomics. 2025 Apr 21;21(3):53. doi: 10.1007/s11306-025-02242-2.ABSTRACTINTRODUCTION/OBJECTIVE: Some Mendelian randomization (MR) studies have found that there may be a genetic causal relationship between circulating metabolites and Alzheimer 's disease (AD), but the strength of evidence and the direction of association are not always consistent. In this study, a systematic review and meta-analysis of all the literature using MR methods to study the causal relationship between metabolites and AD was conducted to enhance the robustness and correlation of predicting genetic causality.METHODS: We conducted a comprehensive review of Mendelian randomization (MR) studies which are within the timeframe of all years to 20 December 2023. Circulating metabolites were considered as the exposure factor, and AD served as the outcome. Two researchers, each with relevant professional backgrounds, independently evaluated study quality and extracted data from the selected studies. Meta-analysis was carried out using R Studio version 4.3.1.RESULTS: In total, 30 studies were included, with 13 selected for meta-analysis. The meta-analysis results revealed that genetically predicted high levels of some metabolites may be associated with a reduced risk of AD. (HDL-C: OR = 0.90, 95% CI 0.83-0.97, p = 0.004; Testosterone: OR = 0.93, 95% CI 0.90-0.97, p = 0.001; Male hormones exclude testosterone: OR = 0.85, 95% CI 0.75-0.96, p = 0.007; Glutamine: OR = 0.85, 95% CI 0.81-0.89, p < 0.001) Meanwhile, genetically predicted high LDL-C levels are associated with an increased risk of AD. (LDL-C: OR = 1.52, 95% CI 1.15-2.00, p = 0.003). There is not enough evidence to prove that there is a genetic causal relationship between diabetes and AD. (OR = 1.02, 95% CI 1.00-1.03, p = 0.12).PMID:40257621 | DOI:10.1007/s11306-025-02242-2

Metabolomics. 2025 Apr 21;21(3):54. doi: 10.1007/s11306-025-02252-0.ABSTRACTINTRODUCTION: The use of large, non-sample specific metabolite reference libraries often results in high proportions of false positive annotations in untargeted metabolomics.OBJECTIVE: This study aimed to measure and curate a library of polar metabolites and lipids present in cardiac microtissues.RESULTS: Untargeted ultra-high performance liquid chromatography-coupled mass spectrometry measurements of cardiac microtissue intracellular extracts were annotated by comparison against four spectral databases and a retention time library. The annotations were combined to create a library of 313 polar metabolites and 1004 lipids.CONCLUSIONS: The curated library will facilitate higher confidence metabolite annotation in mass spectrometry-based untargeted metabolomics of cardiac microtissues.PMID:40257543 | DOI:10.1007/s11306-025-02252-0

Front Plant Sci. 2025 Apr 4;16:1560186. doi: 10.3389/fpls.2025.1560186. eCollection 2025.ABSTRACTBee pollination can affect tomato yield and quality. The mechanism of improving the yield and quality of tomatoes by bee pollination is not clear, and few studies have been conducted. To understand how bee pollination affects tomato quality, by using respectively weighing, vernier caliper, handheld refractometer, pH meter to measure single fruit weight, fruit size, the sugar content, and the pH value, enzyme linked immunosorbent assay (ELISA) to determine endogenous hormone content, and LC-MS to perform untargeted metabolomics analysis, we compared these physiological indicators, endogenous hormone levels, and metabolism of tomato fruits pollinated after honeybee, bumblebee, and plan growth regulator (PGR) pollination. Our results indicate that the tomatoes pollinated by bumblebees were heavier and larger than those pollinated by honeybees and PGR. The sugar content of tomatoes pollinated by honeybees and bumblebees significantly respectively increased by 7.96% and 10.18% than that of tomatoes pollinated by PGR. The pH value of tomatoes pollinated by honeybees (3.99 ± 0.02) and bumblebees (3.94 ± 0.03) was significantly lower than that of tomatoes pollinated by PGR (4.19 ± 0.04) (p < 0.05). Different pollination methods significantly affected the content of endogenous hormones in fruits. In five endogenous hormones, the highest content was gibberellin (GA) in honeybee pollination treatment, IAA in bumblebee treatment, and the highest contents were abscisic acid (ABA), zeatin (ZT), and N 6-(Δ2-isopentenyl) adenosine (iPA) in PGR treatment. It is speculated that different pollination methods may regulate the maturity and quality of tomatoes through different hormone levels. There were respectively five different metabolites (three upregulated and two downregulated), 95 different metabolites (59 upregulated and 36 downregulated), and 95 different metabolites (56 upregulated and 39 downregulated) in honeybee pollination vs. bumblebee pollination, honeybee pollination vs. PGR pollination, and bumblebee pollination vs. PGR pollination. Metabolites are mainly involved in phenylpropanoid biosynthesis, flavonoid biosynthesis pathway, and stilbenoid, diarylheptanoid and gingerol biosynthesis. Compared with PGR pollination, the metabolism of amino acids, vitamins, sugars, flavor substances, and organic acids with antioxidant physiological effects in honeybee pollination and bumblebee pollination groups was significantly higher. It can be inferred that the tomato fruit after bee pollination may have a better taste and is favorable to resisting diseases. These results provide valuable insight for uncovering the mechanism of how bee pollination enhances tomato fruit flavor and will enhance our understanding of interactions between bee pollinators and fruit development processes.PMID:40256596 | PMC:PMC12006744 | DOI:10.3389/fpls.2025.1560186

Front Cell Infect Microbiol. 2025 Apr 4;15:1537726. doi: 10.3389/fcimb.2025.1537726. eCollection 2025.ABSTRACTBACKGROUND: This study used a nontargeted metabolomic approach to investigate small molecular metabolites in the peripheral blood of pediatric patients with influenza. By comparing these metabolites with those in healthy children, potential biomarkers for the early detection and diagnosis of influenza were explored.METHODS: Plasma samples were collected from 47 children with H1N1 influenza, 40 with H3N2 influenza, and 40 healthy controls at Xi'an Children's Hospital, Xi'an Jiaotong University Second Affiliated Hospital, and Xi'an Central Hospital between May and September 2023. Nontargeted metabolomic detection and analysis were performed.RESULTS: In the H1N1 group, 14 glycerophospholipid metabolites were significantly altered compared to controls, with 11 (78.5%) markedly downregulated. These downregulated metabolites showed negative correlations with inflammatory markers, including white blood cell (WBC) count, neutrophils, C-reactive protein (CRP), and Procalcitonin (PCT), whereas the upregulated metabolite PC(P-18:1(9Z)/16:0) showed positive correlations with validation markers. In the H3N2 group, 12 glycerophospholipid metabolites were significantly altered, with 9 being downregulated. The downregulated LysoPC(20:0/0:0) showed a positive correlation with alanine aminotransferase (ALT) but a negative correlation with WBC count, while the upregulated metabolite LysoPA(18:1(9Z)0:0) correlated positively with ALT, aspartate aminotransferase (AST), and lactate dehydrogenase (LDH).CONCLUSIONS: Distinct metabolomic profiles were identified in pediatric H1N1 and H3N2 influenza cases compared to healthy controls. Specific glycerophospholipid metabolites were closely associated with inflammatory and liver function markers, highlighting their potential as biomarkers for disease monitoring and early diagnosis.PMID:40256448 | PMC:PMC12006178 | DOI:10.3389/fcimb.2025.1537726

Physiol Mol Biol Plants. 2025 Mar;31(3):453-475. doi: 10.1007/s12298-025-01581-7. Epub 2025 Apr 9.ABSTRACTGlobal omics offer extensive insights into the diversity of essential biomolecules across various plant developmental stages. Despite advancements in high-throughput technologies, the integrated analysis of global omics such as proteomics, transcriptomics, and metabolomics, is yet to be fully explored in fruits of Capsicum species. In this study, we used an integrated omics approach to identify proteins involved in fruit development, and metabolite biosynthesis in the placenta and pericarp tissues of two contrasting genotypes belonging to ghost chili (Capsicum chinense) and C. annuum. The mass spectrometry analysis identified a total of 4,473 and 2,012 proteins from the pericarp and placenta tissues of Capsicum fruits. We observed expression of developmental stage-specific proteins, such as kinases, transferases, ion transporters, F-box proteins, and transcription factors that were enriched in the biosynthesis of primary and secondary metabolites. The abundance of these proteins corresponded with RNAseq data. Key proteins related to capsaicinoids biosynthesis, such as Acyltransferase 3, 3-oxoacyl-[acyl-carrier protein], 4-coumaroyl co-A ligase, and 3-ketoacyl-coA synthase 3, were identified in placenta of highly pungent ghost chili, along with J-domain proteins and transcription factors such as MYB101, MYB 14-like, bHLH112, NAC, and Cyt p450 CYP82D47, suggesting their role in capsaicinoids and secondary metabolites biosynthesis. Further, we observed a correlation of the expression of genes and proteins with the abundance of primary and secondary metabolites, such as carbohydrates, alcohols, fatty acids, phenolics, glycerides, polyamines, and amino acids. Our findings provide a novel multiomics resources for future functional studies, with potential applications in breeding programs.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-025-01581-7.PMID:40256276 | PMC:PMC12006620 | DOI:10.1007/s12298-025-01581-7

Trends Analyt Chem. 2023 Dec;169:117350. doi: 10.1016/j.trac.2023.117350. Epub 2023 Oct 5.ABSTRACTIn the past decade, lipidomics, now recognized as standalone subdiscipline of metabolomics, has gained considerable attention. Due to its sensitivity and unparalleled versatility, mass spectrometry (MS) has emerged as the tool of choice for lipid identification and detection. Traditional MS-based lipidomics are performed on bulk cell samples. While informative, these bulk-scale cellular lipidome measurements mask cellular heterogeneity across seemingly homogeneous populations of cells. Unfortunately, single cell lipidomics methodology and analyses are considerably behind genomics, transcriptomics, and proteomics. Therefore, the cell-to-cell heterogeneity and related function remains largely unexplored for lipidomics. Herein, we review recent advances in MS-based single cell lipidomics. We also explore the root causes for the slow development of single-cell lipidomics techniques. We aim to provide insights on the pivotal knowledge gaps that have been neglected, prohibiting the propulsion of the single-cell lipidomics field forward, while also providing our perspective towards future methodologies that can pave a path forward.PMID:40255629 | PMC:PMC12007889 | DOI:10.1016/j.trac.2023.117350

Front Pharmacol. 2025 Apr 4;16:1517446. doi: 10.3389/fphar.2025.1517446. eCollection 2025.ABSTRACTAMIS: Chemotherapy-induced hepatotoxicity (CIH) is a significant concern in colorectal cancer (CRC) patients treated with the CAPEOX (capecitabine and oxaliplatin) regimen. Identifying predictive factors for CIH is crucial for clinical management.PATIENTS AND METHODS: This study analyzed colorectal tissue (CRT), plasma, and urine samples from CRC patients. Differentially expressed metabolites (DEMs) across these tissues were integrated for multi-omics analysis, and predictive models for CIH susceptibility were developed. An independent set of 75 plasma samples was used for validation.RESULTS: A total of 492 differentially expressed compounds were identified in samples from 63 CRC patients, including 105, 149, and 238 DEMs in CRT, plasma, and urine, respectively. Lipids and lipid-like molecules were predominant in all samples. Among these, urine samples exhibited the highest variability and provided the strongest predictive power for CIH susceptibility. Principal component analysis (PCA) effectively differentiated normal patients from those with CIH. The study revealed steatosis as the primary pathological feature of CIH, with disrupted lipid metabolism emerging as a key characteristic. Predictive models constructed from multi-tissue metabolites profile exhibited high accuracy, with the plasma model achieving an AUC of 0.933 in external validation set. Our study underscores the importance of individual metabolic variations in CIH susceptibility, reflecting the complex interplay of genetic, environmental, and lifestyle factors.CONCLUSION: This study emphasizes the critical role of alterations in lipid, polyamine, and purine metabolism, as well as impaired tissue repair mechanisms, were identified as key endogenous factors underlying CIH susceptibility. The developed predictive models demonstrate potential for clinical application in assessing CIH risk in CRC patients undergoing CAPEOX chemotherapy.PMID:40255576 | PMC:PMC12006014 | DOI:10.3389/fphar.2025.1517446

Food Sci Nutr. 2025 Apr 18;13(4):e70067. doi: 10.1002/fsn3.70067. eCollection 2025 Apr.ABSTRACTDendrobium chrysotoxum stem is a famous traditional ethnic medicinal, and its flowers have the potential to be used as new food or traditional Chinese medicine resources. However, the chemical composition, edible safety, and antioxidant capacity of D. chrysotoxum flowers are insufficient. In this study, we collected 49 samples of D. chrysotoxum flowers from 49 cultivation sites across five southern provinces in China. The heavy metals and pesticide residues in D. chrysotoxum flowers were determined. Furthermore, this experiment conducted a systematic toxicological safety assessment, analyzed the chemical composition, and evaluated the antioxidant capacity of D. chrysotoxum flowers. The results showed that none of the 49 samples of D. chrysotoxum flowers posed safety risks regarding the five heavy metals and 33 banned pesticide residues. The toxicological safety assessment confirmed that there was no observed toxicity in mice at an acute oral dose of 30.0 g kg-1. The D. chrysotoxum flower extract showed no mutagenic effects on mice. Within the dosage range of 6.67 g kg-1, the D. chrysotoxum flower extract did not induce micronuclei in mouse bone marrow erythrocytes or cause chromosomal aberrations in mouse spermatocytes. Additionally, within the dosage range of 10 g kg-1, the D. chrysotoxum flower extract exhibited no subchronic toxicity in mice. A total of 2,047 metabolites were identified in D. chrysotoxum flowers and classified into 15 superclasses using a widely targeted metabolomics method. Sixteen amino acids were measured using high-performance liquid chromatography. This study demonstrates that D. chrysotoxum flowers are safe for human consumption at recommended dosages. Furthermore, D. chrysotoxum flowers contain a variety of functional compounds with antioxidant properties, making them suitable for development and use as edible flowers.PMID:40255547 | PMC:PMC12006730 | DOI:10.1002/fsn3.70067

Brief Bioinform. 2025 Mar 4;26(2):bbaf141. doi: 10.1093/bib/bbaf141.ABSTRACTFor metaproteomics data derived from the collective protein composition of dynamic multi-organism systems, the proportion of missing values and dimensions of data exceeds that observed in single-organism experiments. Consequently, evaluations of differential analysis strategies in other mass spectrometry (MS) data (such as proteomics and metabolomics) may not be directly applicable to metaproteomics data. In this study, we systematically evaluated five imputation methods [sample minimum, quantile regression, k-nearest neighbors (KNN), Bayesian principal component analysis (bPCA), random forest (RF)] and six imputation-free methods (moderated t-test, two-part t-test, two-part Wilcoxon test, semiparametric differential abundance analysis, differential abundance analysis with Bayes shrinkage estimation of variance method, and Mixture) for differential analysis in simulated metaproteomic datasets based on both data-dependent acquisition MS experiments and emerging data-independent acquisition experiments. The simulation datasets comprised 588 scenarios by considering the impacts of sample size, fold change between case and control, and missing value ratio at random and nonrandom. Compared to imputation-free methods, KNN, bPCA, and RF imputation performed poorly in datasets with a high missingness ratio and large sample size and resulted in a high false-positive risk. We made empirical recommendations based on the balance of sensitivity in analysis and control of false positives. The moderated t-test was optimal in scenarios of large sample size with a low missingness ratio. The two-part Wilcoxon test was recommended in scenarios of small sample size with a low missingness ratio or large sample size with a high missingness ratio. The comprehensive evaluations in our study can provide guidance for the differential abundance analysis in metaproteomics.PMID:40254829 | DOI:10.1093/bib/bbaf141

Sci Rep. 2025 Apr 20;15(1):13637. doi: 10.1038/s41598-025-98369-2.ABSTRACTAdenomyosis (AM) is characterized as a chronic and progressive disorder with limited therapeutic strategies available. Myometrial fibrosis is a prominent pathological feature of AM, yet the underlying molecular mechanisms remain elusive. The present study conducted a comparative analysis using proteomics and metabolomics to investigate myometrial fibrosis and its underlying mechanisms. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was utilized to analyze adenomyotic and normal myometrial tissues from ten AM patients who underwent hysterectomy with myometrial fibrosis confirmed by Masson staining. This analysis established comprehensive proteomic and metabolomic profiles of AM patients and revealed widespread alterations in the proteome and metabolome within normal and fibrotic myometrium. Key proteins and signaling pathways linked to myometrial fibrogenesis were identified based on proteomic data. The integrated analysis showed significant associations between proteomic and metabolomic data and highlighted the critical role of the PI3K/AKT signaling pathway. Immunohistochemistry and Spearman's correlation analysis suggested a relationship between myometrial fibrosis and the metaplasia of myometrial stromal cells into myofibroblasts. Subsequent experiments identified crucial proteins and signaling pathways involved in myometrial fibrosis, indicating an association with the activation of the PI3K/AKT signaling pathway in myofibroblasts. Notably, PI3K/AKT inhibitors may contribute to the effective alleviation of myometrial fibrosis. This study is the first to demonstrate that myometrial fibrosis represents a critical pathological mechanism in AM through multi-omics methods and to elucidate the crucial role of the PI3K/AKT signaling pathway in this process. These findings provide valuable insights into the pathophysiology of AM and suggest antifibrotic treatment as a promising therapeutic strategy.PMID:40254638 | DOI:10.1038/s41598-025-98369-2

Stem Cell Res Ther. 2025 Apr 20;16(1):199. doi: 10.1186/s13287-025-04309-2.ABSTRACTBACKGROUND: Cytokine licensing with pro-inflammatory molecules, such as tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), has emerged as a promising strategy to enhance the therapeutic potential of multipotent mesenchymal stromal cells (MSCs). While licensing has demonstrated benefits for immunomodulation, its effects on other key MSC functions, including differentiation and paracrine activity, remain incompletely explored. In this study, we evaluated the transcriptomic, metabolomic, and functional changes induced by short-term TNF-α/IFN-γ priming of Wharton's jelly-derived MSCs (WJ-MSCs).METHODS: WJ-MSCs were expanded and exposed to TNF-α and IFN-γ (10 ng/ml each) for 24 h. Transcriptomic analysis was performed using RNA sequencing to identify differentially expressed genes related to immune modulation and lineage commitment. Metabolomic profiling was conducted using high-resolution mass spectrometry to assess changes in metabolic pathways. Functional assays evaluated the effects of cytokine priming on induced differentiation and growth factor secretion.RESULTS: Cytokine licensing induced notable alterations in gene expression, upregulating pathways linked to immune response, inflammation, and cytokine signalling. However, short-term cytokine treatment significantly attenuated the osteogenic and adipogenic differentiation of MSCs, as evidenced by the reduced expression of RUNX2, ALP, CEBPA, and PPARG. The priming had a negligible effect on EGF, FGF-2, HGF, LIF, and SCF secretion. The production of VEGF-A and VEGF-C was elevated, although the levels remained low. Metabolomic analysis revealed enhanced kynurenine pathway activity, indicative of increased tryptophan catabolism, accompanied by elevated levels of fatty acids and polyamines.CONCLUSIONS: Our findings demonstrate that TNF-α/IFN-γ priming reprograms WJ-MSCs by enhancing their immunomodulatory capacity at the expense of differentiation potential. These results highlight the need for tailored strategies to optimize MSC functionality for specific clinical applications.PMID:40254602 | DOI:10.1186/s13287-025-04309-2