PubMed

Front Vet Sci. 2025 Jan 28;12:1498703. doi: 10.3389/fvets.2025.1498703. eCollection 2025.ABSTRACTINTRODUCTION: In this study, we investigated the metabolic profiles of yak (Bos grunniens) follicles during the development period from the perspective of metabolomics, aiming to screen out the differential metabolites of yak follicles in different sizes and potential pathways during yak follicle development and to provide a basis for the study of follicle development and developmental mechanisms in the further stage of development.METHODS: A total of 20 four-year-old female yaks were selected, and follicles of different sizes were collected after slaughter and divided into d < 3 mm, 3-6 mm and d > 6 mm. The follicular fluid was collected, 6 replicates per group and subjected to LC-MS assay, combined with multidimensional and unidimensional statistical analyses to screen the differential metabolites between follicles of different sizes. Differential metabolites enriched KEGG pathways to screen the pathways that might be related to follicle development.RESULTS: We found that most of the metabolites were mainly enriched in amino acid metabolism pathways, energy metabolism pathways and other pathways of cofactor synthesis, and that during the development of the small follicle to the large follicle, 2-Lysophosphatidylcholine, PC (17:0/0:0), PC (16:0/0:0), and LysoPC (18:0/0:0) were down-regulated; Dioctyl succinate, P-Coumaraldehyde, ISOPRENE, L-Isoleucine, Dioctyl succinate up-regulated.CONCLUSION: These results suggest that amino acid metabolism, the production of steroid hormones and their metabolites, and the metabolic activity of granulosa cells play important roles in follicle development. The results provide a theoretical basis for further exploration of follicular development in yak.PMID:39936077 | PMC:PMC11811112 | DOI:10.3389/fvets.2025.1498703

Front Vet Sci. 2025 Jan 28;12:1510617. doi: 10.3389/fvets.2025.1510617. eCollection 2025.ABSTRACTThis study aimed to investigate the effects of niacin supplementation to a high-concentrate diet (ratio of concentrate supplement to forage = 70:30) on the growth performance, rumen fermentation, rumen microbiota, and metabolomics of sheep. Twelve sheep were randomly divided into two groups: (1) a control group (CON, n = 6) fed a basal diet and (2) a niacin group (NA, n = 6) fed a basal diet supplemented with 130 mg/day niacin for 35 days: days 1-14 were the adaptation period, days 15-35 were the experiment period. On days 15 and 35 of the experiment period, all trial sheep were weighed before the morning feed (07:30 am). Ruminal fluid samples were collected from all trial sheep on days 34 and 35. The results showed that (1) the dry matter feed intake of the NA group was higher than that of the CON group (p < 0.05). (2) The ruminal pH of the NA was significantly higher than that of the CON group at 3, 5, and 7 h after feeding (p < 0.01). The concentrations of NH3-N (p < 0.01), propionate (p < 0.01), and butyrate (p < 0.05) in the NA group were significantly higher than those in the CON group. (3) Compared to the CON group, the ruminal pyruvate content in the NA group was significantly increased at 0 h before feeding (p < 0.05), and lactic acid (p < 0.05) was significantly decreased at 1 and 3 h after feeding, lactate dehydrogenase activities was significantly decreased (p < 0.01) at 3 and 5 h after feeding. (4) The number of specific operational taxonomic units (OTUs) in the CON and NA groups were 26 and 37, respectively, for a total of 1,178 OTUs; principal coordinate analysis (R 2 = 0.172, p-value = 0.007) and non-metric multidimensional scaling (stress = 0.1646) results showed that the two groups of samples were significantly separated. (5) The species distribution bar graph shows that at the phylum level, the relative abundances of Bacteroidetes, Firmicutes, and Proteobacteria were 43.70, 36.25, and 12.77%, respectively. (6) Orthogonal projection to latent structure-discriminant analysis results showed that the two groups of samples were clearly separated in the positive and negative ionization modes, with R 2 Y and Q 2 Y values of 0.705, 0.857, 0.695, and 0.28, respectively. There were 72 metabolic pathways, mainly citric acid cycle, pyruvate metabolism, and cysteine and methionine metabolism. (7) Correlation analysis showed that a number of microorganisms (such as Succinivibrio and Prevotella) and differential metabolites (such as L-malic acid, propionic acid, succinic acid, and pyruvic acid) participated in tricarboxylic acid cycle metabolism. In summary, supplementing niacin to high-concentrate diets can significantly improve the growth performance of sheep, improve rumen fermentation and the rumen microbial community structure, and affect rumen metabolites, thus alleviating the symptoms of rumen acidosis.PMID:39936076 | PMC:PMC11812060 | DOI:10.3389/fvets.2025.1510617

Infect Drug Resist. 2025 Feb 7;18:731-744. doi: 10.2147/IDR.S491358. eCollection 2025.ABSTRACTPURPOSE: The purpose of this study was to evaluate the antibacterial activity and mechanism of linalool against Methicillin-resistant Staphylococcus aureus (MRSA).METHODS: The determination of the antibacterial activity of linalool against clinically isolated MRSA strains was based on the minimum inhibitory concentration (MIC) and growth curve analysis. Finally, the inhibition mechanism of linalool was elucidated through metabolomic analysis and molecular docking.RESULTS: Among the isolated strains, penicillin resistance was found to be the highest, while resistance to daptomycin/quinupristin-dalfopristin, linezolid, vancomycin, tetracycline, telithromycin, and levofloxacin was not observed. The MIC range of linalool was 211.24-1.65 μg/mL, with MIC50 and MIC90 values of 13.2 μg/mL and 105.62 μg/mL, respectively. Metabolomic analysis revealed that linalool interferes with various substance metabolisms and energy metabolism in MRSA, with the glutathione pathway potentially being a key pathway affected by linalool. Molecular docking revealed that linalool exhibited good binding potential to the target glutathione.CONCLUSION: This study suggests that linalool could be developed as a drug or preservative to inhibit MRSA growth.PMID:39936039 | PMC:PMC11812441 | DOI:10.2147/IDR.S491358

ArXiv [Preprint]. 2024 Nov 26:arXiv:2411.17910v1.ABSTRACTIn epidemiological research, causal models incorporating potential mediators along a pathway are crucial for understanding how exposures influence health outcomes. This work is motivated by integrated epidemiological and blood biomarker studies, investigating the relationship between long-term adherence to a Mediterranean diet and cardiometabolic health, with plasma metabolomes as potential mediators. Analyzing causal mediation in such high-dimensional omics data presents substantial challenges, including complex dependencies among mediators and the need for advanced regularization or Bayesian techniques to ensure stable and interpretable estimation and selection of indirect effects. To this end, we propose a novel Bayesian framework for identifying active pathways and estimating indirect effects in the presence of high-dimensional multivariate mediators. Our approach adopts a multivariate stochastic search variable selection method, tailored for such complex mediation scenarios. Central to our method is the introduction of a set of priors for the selection: a Markov random field prior and sequential subsetting Bernoulli priors. The first prior's Markov property leverages the inherent correlations among mediators, thereby increasing power to detect mediated effects. The sequential subsetting aspect of the second prior encourages the simultaneous selection of relevant mediators and their corresponding indirect effects from the two model parts, providing a more coherent and efficient variable selection framework, specific to mediation analysis. Comprehensive simulation studies demonstrate that the proposed method provides superior power in detecting active mediating pathways. We further illustrate the practical utility of the method through its application to metabolome data from two cohort studies, highlighting its effectiveness in real data setting.PMID:39936029 | PMC:PMC11812595

Front Plant Sci. 2025 Jan 28;16:1509126. doi: 10.3389/fpls.2025.1509126. eCollection 2025.ABSTRACTThrips are one of the most challenging pests in agricultural crops, including Chrysanthemum. In this study we tested via two plant assays whether solutions containing sticky rice germ oil (RGO) droplets could effectively trap thrips and lower thrips damage on Chrysanthemum. In the first assay, we additionally assessed the metabolomic effects of these RGO droplet sprays and thrips presence on plant chemistry via 1H NMR and headspace GC-MS on multiple timepoints to investigate which plant metabolites were affected by spraying and their potential relation to plant resistance against thrips. In the second assay, we tested the individual RGO solution constituents against thrips. Our results suggested that the adhesive RGO droplets were not effective as a physical trap as only three out of 600 adult thrips were caught at the achieved coverage. However, average thrips damage was still reduced up to 50% and no negative effects on plant growth were observed up to 25 days. Results from the second plant assay indicated that the individual constituents of the solution containing RGO droplets may have direct effects against thrips. Metabolomics analysis of sprayed leaves via headspace GC-MS and 1H NMR indicated that fatty acids and several volatile compounds such as 4(10)-thujene (sabinene), eucalyptol, cis-4-thujanol, and isocaryophyllene were highest on day 10, while sucrose, malic acid, o-Cymene, and 3-Methyl-2-butenoic acid were highest on day 25. Plants with thrips showed higher flavonoid, carbohydrate and glutamine acetic acid levels, and lower fatty acids and malic acid levels. RGO application increased the levels of fatty acids and alcohols present on top of and inside the Chrysanthemum leaves, while decreasing the concentrations of volatile compounds such as eucalyptol, chrysanthenone and eugenol in the Chrysanthemum leaves. Most interestingly, the thrips effect on the plant metabolome was no longer visible in RGO treated plants at the later harvesttime, suggesting that RGO application may overrule or prevent the metabolomic effects of thrips infestation. In conclusion, our study provides new information on how the application of a new plant-based plant protection product affects insect herbivores and alters crop phytochemistry for improved herbivore resistance.PMID:39935947 | PMC:PMC11811490 | DOI:10.3389/fpls.2025.1509126

Front Oncol. 2025 Jan 28;15:1510018. doi: 10.3389/fonc.2025.1510018. eCollection 2025.ABSTRACTINTRODUCTION: Diagnosing the types of malignant lymphoma could help determine the most suitable treatment, anticipate the probability of recurrence and guide long-term monitoring and follow-up care.METHODS: We evaluated the differences in benign, lymphoma and metastasis superficial lymph nodes using ultrasonography and tissue metabolomics.RESULTS: Our findings indicated that three ultrasonographic features, blood supply pattern, cortical echo, and cortex elasticity, hold potential in differentiating malignant lymph nodes from benign ones, and the shape and corticomedullary boundary emerged as significant indicators for distinguishing between metastatic and lymphoma groups. Metabolomics revealed the difference in metabolic profiles among lymph nodes. We observed significant increases in many amino acids, organic acids, lipids, and nucleosides in both lymphoma and metastasis groups, compared to the benign group. Specifically, the lymphoma group exhibited higher levels of nucleotides (inosine monophosphate and adenosine diphosphate) as well as glutamic acid, and the metastasis group was characterized by higher levels of carbohydrates, acylcarnitines, glycerophospholipids, and uric acid. Linear discriminant analysis coupled with these metabolites could be used for differentiating lymph nodes, achieving recognition rates ranging from 87.4% to 89.3%, outperforming ultrasonography (63.1% to 75.4%).DISCUSSION: Our findings could contribute to a better understanding of malignant lymph node development and provide novel targets for therapeutic interventions.PMID:39935832 | PMC:PMC11810734 | DOI:10.3389/fonc.2025.1510018

Front Cell Dev Biol. 2025 Jan 28;12:1472338. doi: 10.3389/fcell.2024.1472338. eCollection 2024.ABSTRACTINTRODUCTION: This study explores the effects of moderate-intensity exercise on protein lactylation in mouse muscle tissue metabolism.METHODS: Healthy adult mice running for 6 weeks as an exercise model and sedentary mice as the control were used to perform transcriptomic, proteomic, lactylation-proteomic, and metabolomic analyses. Correlation analysis between transcriptome and proteome and between proteome and metabolome was also conducted.RESULTS: In this study, 159 lactylation sites of 78 proteins were identified as being differentially regulated by moderate-intensity exercise. Enrichment analysis showed that the lactylation of proteins Atp5mg, and Atp5po exhibited ATP hydrolysis activity. Mtatp8 and Atp5po were involved in biological processes such as mitochondrial transmembrane transport, and Mtatp8, Atp5mg, and Atp5po participate in oxidative phosphorylation and thermogenesis pathways. The lactylation levels of Mtatp8, Atp5mg, and Atp5po proteins in the exercise group were significantly decreased, while their protein levels were significantly increased. The combined analysis of proteomics and metabolomics showed that the oxocarboxylic acid metabolism and sphingolipid signaling pathways had significant changes under the influence of moderate-intensity exercise.DISCUSSION: Our results indicate that moderate-intensity exercise has an effect on the lactylation level of mice, possibly by reducing the lactylation levels of Mtatp8, Atp5mg, and Atp5po and increasing the expression of their protein levels, thereby regulating the oxidative phosphorylation pathway and participating in energy metabolism. Further exploration is needed into the 2-oxocarboxylic acid metabolism pathway and the sphingolipid signaling pathway.PMID:39935788 | PMC:PMC11810897 | DOI:10.3389/fcell.2024.1472338

Front Mol Biosci. 2025 Jan 28;11:1449226. doi: 10.3389/fmolb.2024.1449226. eCollection 2024.ABSTRACTINTRODUCTION: This study applies NMR-based metabolomics to investigate neovascular age-related macular degeneration (nAMD), addressing challenges in patient management, disease progression evaluation, and treatment response assessment. A two-year follow-up of 29 nAMD patients undergoing treatment provided 231 time points for analysis.METHODS: Over the two-year period, 11 males and 18 females (aged 61-92 years) were monitored, yielding 231 time points. At each time point, blood samples for NMR metabolomics analysis, clinical measurements (e.g., lactate, glucose levels, HDL/LDL cholesterol, and blood pH), and optical coherence tomography (OCT) images were collected to evaluate the progression of choroidal neovascularization. 1H-NMR metabolomic analysis led to the quantification of over 60 metabolites and of the major lipoprotein fractions. Both multivariate and univariate statistical approaches tailored for longitudinal data were employed to identify biomarkers correlating metabolomic changes with ocular alterations during disease progression.RESULTS AND DISCUSSION: Despite a rigorous analytical workflow enabling precise quantification of over 60 metabolites and the application of advanced statistical tools for longitudinal data, achieving consistent results across the cohort proved challenging. The dataset's heterogeneity, reflecting real-world clinical practice, complicated the derivation of global conclusions. Personalized analyses on a patient-by-patient basis successfully identified individual correlation models, but a universal model remained elusive. This study highlights the inherent challenges of translating findings from controlled settings into clinical practice, where factors such as visit frequency, treatment variability, and disease heterogeneity limit data uniformity. We emphasize the importance of experimental design in longitudinal studies, particularly when dealing with incomplete and variable datasets. We are therefore confident that, considering both the challenges and difficulties identified in this work and the preliminary results presented here, it is possible to develop predictive and individualized models for monitoring patients with nAMD. Such models could greatly assist clinicians in providing better care for these patients.PMID:39935708 | PMC:PMC11811626 | DOI:10.3389/fmolb.2024.1449226

Front Microbiol. 2025 Jan 28;16:1519552. doi: 10.3389/fmicb.2025.1519552. eCollection 2025.ABSTRACTGut microbiota can digest and ferment feed into metabolites to influence the meat quality. Probiotics are used to regulate the gut microbiota. In this study, a total of 360 broilers were assigned to 4 treatments (10 broilers per cage): control (Con), low dose of Lactiplantibacillus plantarum HW1 (Lp_L), medium dose of Lp (Lp_M) and high dose of Lp (Lp_H) for a 42-day experimental period. Results showed that the Lp treatments improved the growth performance, carcass traits, breast meat quality, and also influenced the fatty acids composition, including the decrease of n-6PUFA/n-3PUFA, and the increase of C18:3n3, ∑n-3PUFA and PUFA/SFA. The lipid metabolism-related gene expressions in the liver showed that Lp treatments increased the expression of AMPK, CPT-1α, PPARα, ATGL and also decreased the expression of PPARγ, SREBP-1c, ACC, FAS, LPL, and SCD. Moreover, the abundances of gut microbiota, such as Synergistaceae and Synergistes were influenced by the Lp treatments. Functional prediction of the gut microbiota indicated that pathways, including pancreatic secretion and spliceosome were enriched by the Lp treatments. Untargeted metabolomics revealed that the Lp treatments altered the content of metabolites, such as 6-ketomyristic acid and indole-3-acetamide. These metabolites were enriched in pathways including fatty acid metabolism. Correlation analyses revealed potential interactions between growth performance and meat quality, as well as gut microbiota (Synergistes, etc.) and metabolites (6-ketomyristic acid, etc.). Overall, our data show that the Lp treatments significantly improved the growth performance, carcass traits and meat quality of broilers by regulating fatty acids, gut microbiota and metabolites.PMID:39935642 | PMC:PMC11811115 | DOI:10.3389/fmicb.2025.1519552

J Exp Biol. 2025 Feb 12:jeb.249365. doi: 10.1242/jeb.249365. Online ahead of print.ABSTRACTGlobal warming leads to an increase in extreme heat events, posing significant challenges for insects. Sitobion avenae, Metopolophium dirhodum, and Rhopalosiphum padi are important co-existing aphid species known to cause damage to cereal crops worldwide. The three species differ in thermal tolerance, with R. padi being much more heat tolerant than the other two species. However, it remains unclear whether interspecific variation in heat tolerance is due to differences in metabolic responses to heat stress. Here, we compared their metabolic signatures during and after recovery from the same injury level of heat stress (at 34°C for half and full durations to cause 50% mortality in each species), as well as the identical duration of heat stress. Using quantitative GC-MS, we found that after the same injury level of heat exposure, the three species showed similar changes in most metabolites. However, the heat-tolerant species, R. padi, had higher levels of polyols and amino acids, and uniquely accumulated glycerol. In addition, after the same duration of heat exposure, R. padi maintained a relatively stable metabolic profile, while the less tolerant species showed marked alterations with shift from aerobic to anaerobic metabolism. We suggest that polyols and amino acids play a pivotal role in protecting R. padi from heat damage, conferring its superior thermal tolerance. Overall, this comparative metabolomics study provides insight into the relationship between metabolic responses and heat tolerance of co-existing species, which helps to understand the underlying mechanism of heat tolerance.PMID:39935388 | DOI:10.1242/jeb.249365

Aliment Pharmacol Ther. 2025 Feb 11. doi: 10.1111/apt.70012. Online ahead of print.ABSTRACTBACKGROUND: The recent consensus statement redefined steatotic liver diseases. Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction and alcohol-related liver disease (MetALD) now represent distinct disease entities. However, biomarkers that differentiate MASLD and MetALD remain largely unknown.AIMS: To identify lipidomic biomarkers with discriminatory potential for distinguishing MetALD from MASLD.METHODS: Using the UK Biobank dataset, 40,534 people with available MRI liver scans were analysed. A total of, 11,217 cases with a proton density fat fraction (PDFF) ≥ 5% were identified as having steatotic liver disease. Among these, lipidomic profiles were obtained for 5539 MASLD and 462 MetALD cases. A total of, 250 plasma lipidomic and metabolomic parameters were analysed. Mendelian randomisation (MR) analysis was used to confirm the association between alcohol consumption and the lipidomic biomarkers.RESULTS: When comparing the top 30 differentially expressed lipidomic biomarkers predicting MetALD compared to MASLD, the majority were related to HDL and were significantly overrepresented at both analysed time points. The top five metabolites were: acetoacetate, 3-hydroxybutyrate, phospholipids in Large HDL, concentration of large HDL particles, free cholesterol in large HDL. The sensitivity analysis comparing alcohol-related liver disease to MASLD revealed similar associations, suggesting that the HDL signature is stable over time. Additionally, MR analysis further confirmed that alcohol consumption was associated with increased levels of HDL-related metabolites.CONCLUSION: Our findings indicate that HDL-centric lipidomic markers, particularly those within the larger and medium HDL subfraction, may differentiate MetALD from MASLD. Further longitudinal and experimental studies are warranted to validate these findings and assess their clinical implications.PMID:39935287 | DOI:10.1111/apt.70012

Plant J. 2025 Feb;121(3):e17235. doi: 10.1111/tpj.17235.ABSTRACTRhododendron species have the potential to be rich in secondary metabolites with pharmaceutical or industrial value. However, there is a lack of comprehensive metabolome studies at the genome level, particularly for unique and rare species like Rhododendron bailiense, which exclusively grows in karst environments in Guizhou, southwest China. Recently, genome assembly data for this species was available. In this study, nontargeted metabolomics was employed to investigate the secondary metabolites profile of R. bailiense callus. The callus of R. bailiense was induced using 0.2 mg L-1 TDZ (Thidiazuron) + 0.1 mg L-1 IBA (3-Indole butyric acid). A comparison between light-treated calli and dark-cultured calli revealed differential accumulation of metabolites, particularly in flavonoids, terpenoids, coumarins, and hydroxycinnamic acids, known for their beneficial effects such as antioxidant, anticancer, and anti-inflammatory properties. Proanthocyanidins, with various health-promoting effects, were found to accumulate significantly in dark-cultured calli. Light conditions promoted diterpene and triterpene products, whereas darkness favored sesquiterpene products. Additionally, the study demonstrated the potential of utilizing Agrobacterium transformation technology on callus suspension cells to enhance secondary metabolite production. Comparison with the genome of Rhododendron molle revealed that the R. bailiense genome exhibited active 'glycosyltransferase activity,' possessed a higher number of copies of monoterpene and sesquiterpene terpene synthases, and contained high copies of specific cytochrome P450 members (CYP71, CYP76, CYP79, CYP82, CYP736). This study offers valuable insights and potential strategies for the biosynthesis and production of Rhododendron secondary metabolites with pharmaceutical or industrial significance.PMID:39935165 | DOI:10.1111/tpj.17235

Nat Prod Res. 2025 Feb 11:1-10. doi: 10.1080/14786419.2025.2463119. Online ahead of print.ABSTRACTLippia origanoides Kunth is a perennial shrub widely used in Brazilian folk medicine while extracts of its leaves have been shown to possess several therapeutic properties. We investigated this species' non-volatile compounds through a LC-MS-based untargeted metabolomics approach to evaluate the influence of genetic and developmental factors on L. origanoides metabolism. We compared five adult plants and eight leaf developmental stages separately; the chemical analyses were performed via UHPLC-ESI-QTOF-MS/MS and the resulting data were processed in Progenesis QI 2.0 and in MetaboAnalyst 6.0 for statistical analysis. Luteolin-7-O-glucoside and kaempferol/luteolin were the most intense components in the negative and positive ion modes, respectively. A subtle chemical variation between individuals was found while the leaf development, conversely, strongly affected the chemical profile, which may ultimately result in variation in bioactivity. Altogether, we reported herein new perspectives on L. origanoides non-volatile components and the impact of intraspecific factors on this species' metabolism.PMID:39934998 | DOI:10.1080/14786419.2025.2463119

Microbiome. 2025 Feb 11;13(1):51. doi: 10.1186/s40168-025-02028-7.ABSTRACTBACKGROUND: Cytotoxic T-lymphocyte-associated protein 4 deficiency (CTLA4-D) is an inborn error of immunity (IEI) caused by heterozygous mutations, and characterized by immune cell infiltration into the gut and other organs, leading to intestinal disease, immune dysregulation and autoimmunity. While regulatory T-cell dysfunction remains central to CTLA4-D immunopathogenesis, mechanisms driving disease severity and intestinal pathology are unknown but likely involve intestinal dysbiosis. We determined whether the intestinal microbiome and metabolome could distinguish individuals with severe CTLA4-D and identify biomarkers of disease severity.RESULTS: The genera Veillonella and Streptococcus emerged as biomarkers that distinguished CTLA4-D from healthy cohorts from both the National Institutes of Health (NIH) Clinical Center, USA (NIH; CTLA-D, n = 32; healthy controls, n = 16), and a geographically distinct cohort from the Center for Chronic Immunodeficiency (CCI) of the Medical Center - University of Freiburg, Germany (CCI; CTLA4-D, n = 25; healthy controls, n = 24). Since IEIs in general may be associated with perturbations of the microbiota, a disease control cohort of individuals with common variable immunodeficiency (CVID, n = 20) was included to evaluate for a CTLA4-D-specific microbial signature. Despite common IEI-associated microbiome changes, the two bacterial genera retained their specificity as biomarkers for CTLA4-D. We further identified intestinal microbiome and metabolomic signatures that distinguished patients with CTLA4-D having severe vs. mild disease. Microbiome changes were associated with distinct stool metabolomic profiles and predicted changes in metabolic pathways. These differences were impacted by the presence of gastrointestinal manifestations and were partially reversed by treatment with abatacept and/or sirolimus.CONCLUSIONS: Loss of intestinal microbial diversity and dysbiosis causing metabolomic changes was observed in CTLA4-D. Albeit some of these features were shared with CVID, the distinct changes associated with CTLA4-D highlight the fact that IEI-associated microbiome changes likely reflect the underlying immune dysregulation. Identified candidate intestinal microbial and metabolic biomarkers distinguishing individuals with CTLA4-D based on severity should be studied prospectively to determine their predictive value, and investigated as potential therapeutic ta. Video Abstract.PMID:39934899 | DOI:10.1186/s40168-025-02028-7

Biomark Res. 2025 Feb 11;13(1):26. doi: 10.1186/s40364-025-00732-y.ABSTRACTOsteoarthritis (OA), a ubiquitous degenerative joint disorder, is marked by pain and disability, profoundly impacting patients' quality of life. As the population ages, the global prevalence of OA is escalating. Omics technologies have become instrumental in investigating complex diseases like OA, offering comprehensive insights into its pathogenesis and progression by uncovering disease-specific alterations across genomics, transcriptomics, proteomics, and metabolomics levels. In this review, we systematically analyzed and summarized the application and recent achievements of omics technologies in OA research by scouring relevant literature in databases such as PubMed. These studies have shed light on new potential therapeutic targets and biomarkers, charting fresh avenues for OA diagnosis and treatment. Furthermore, in our discussion, we highlighted the immense potential of spatial omics technologies in unraveling the molecular mechanisms of OA and in the development of novel therapeutic strategies, proposing future research directions and challenges. Collectively, this study encapsulates the pivotal advances in current OA research and prospects for future investigation, providing invaluable references for a deeper understanding and treatment of OA. This review aims to synthesize the recent progress of omics technologies in the realm of OA, aspiring to furnish theoretical foundations and research orientations for more profound studies of OA in the future.PMID:39934890 | DOI:10.1186/s40364-025-00732-y

Cancer Metab. 2025 Feb 11;13(1):8. doi: 10.1186/s40170-025-00378-2.ABSTRACTBACKGROUND: Melanoma is a highly aggressive skin cancer with a poor prognosis. The endocannabinoids 2-arachidonoylgylcerol (2-AG) and anandamide have been linked to melanoma progression, though their roles remain unclear. We hypothesized that the 2-AG-arachidonate-prostaglandin axis could drive aggressive melanoma progression.METHODS: The genetically engineered melanoma mouse model B6-Tyr::CreERT2; BRafCA; PtenloxP was characterized by targeted metabolomics. Functionally expressed serine hydrolases in the tumor tissue were identified by chemoproteomics. Pharmacological inhibition of carboxylesterase 1 (CES1) was achieved through chronic in vivo i.p. treatment with JZL184 (10 mg/kg daily), confirmed by activity-based protein profiling (ABPP) and targeted lipidomics. CES1-mediated 2-AG hydrolysis was further confirmed in radiotracer-based assays using CES1-transfected cell lines.RESULTS: The diacylglycerol and protein kinase C activator 1-stearoyl-2-arachidonoyl-sn-glycerol (SAG) was significantly elevated in the nodular-like melanoma tissues, along with 2-AG and arachidonic acid (ARA), compared to normal skin. AEA and other N-acylethanolamines were decreased, while, notably, prostaglandin levels remained unchanged. Significant changes in the levels of neuromodulators and neurotransmitters, including serotonin and adenosine, were observed. Pronounced differences between serine hydrolase activity in normal skin and melanoma tissue were identified by ABPP. Intriguingly, CES1 was identified as the only 2-AG-hydrolyzing enzyme in this melanoma tissue, as MAGL and ABHD6/12 were not expressed. The MAGL inhibitor JZL184 also efficiently inhibited CES1 in vitro and in vivo, increasing glycerol esters and reducing tumor progression. Additionally, scRNA-seq data from previous studies revealed divergent MAGL/CES1 expression patterns across different human melanoma subtypes.CONCLUSIONS: A role of CES1 expression in skin is demonstrated for the first time. Our study suggests that 2-AG degradation to arachidonate favors melanoma progression, either reflecting the carcinogenic role of ARA or that monoacylglycerols like 2-AG and/or other CES1 substrates may exert antitumor effects, indicating that CES1 could be a potential therapeutic target. CES1 expression and high SAG, 2-AG, and ARA levels may be a signature of specific BRAF-driven malignant melanoma subtypes which are associated with discrete metabolic adaptations.PMID:39934865 | DOI:10.1186/s40170-025-00378-2

BMC Med. 2025 Feb 11;23(1):79. doi: 10.1186/s12916-025-03920-7.ABSTRACTBACKGROUND: Sepsis-associated acute kidney injury (SA-AKI) is a frequent complication in patients with sepsis and is associated with high mortality. Therefore, early recognition of SA-AKI is essential for administering supportive treatment and preventing further damage. This study aimed to identify and validate metabolite biomarkers of SA-AKI to assist in early clinical diagnosis.METHODS: Untargeted renal proteomic and metabolomic analyses were performed on the renal tissues of LPS-induced SA-AKI and sepsis mice. Glomerular filtration rate (GFR) monitoring technology was used to evaluate real-time renal function in mice. To elucidate the distinctive characteristics of SA-AKI, a multi-omics Spearman correlation network was constructed integrating core metabolites, proteins, and renal function. Subsequently, metabolomics analysis was used to explore the dynamic changes of core metabolites in the serum of SA-AKI mice at 0, 8, and 24 h. Finally, a clinical cohort (28 patients with SA-AKI vs. 28 patients with sepsis) serum quantitative metabolomic analysis was carried out to build a diagnostic model for SA-AKI via logistic regression (LR).RESULTS: Thirteen differential renal metabolites and 112 differential renal proteins were identified through a multi-omics study of SA-AKI mice. Subsequently, a multi-omics correlation network was constructed to highlight five core metabolites, i.e., 3-hydroxybutyric acid, 3-hydroxymethylglutaric acid, creatine, myristic acid, and inosine, the early changes of which were then observed via serum time series experiments of SA-AKI mice. The levels of 3-hydroxybutyric acid, 3-hydroxymethylglutaric acid, and creatine increased significantly at 24 h, myristic acid increased at 8 h, while inosine decreased at 8 h. Ultimately, based on the identified core metabolites, we recruited 56 patients and constructed a diagnostic model named IC3, using inosine, creatine, and 3-hydroxybutyric acid, to early identify SA-AKI (AUC = 0.90).CONCLUSIONS: We proposed a blood metabolite model consisting of inosine, creatine, and 3-hydroxybutyric acid for the early screening of SA-AKI. Future studies will observe the performance of these metabolites in other clinical populations to evaluate their diagnostic role.PMID:39934788 | DOI:10.1186/s12916-025-03920-7

BMC Med. 2025 Feb 11;23(1):78. doi: 10.1186/s12916-025-03914-5.ABSTRACTBACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a key risk factor for cardiovascular disease (CVD), potentially driven by shared metabolic mechanisms. Metabolic perturbations associated with MASLD and CVD remain underexplored in people with HIV (PWH).METHODS: We used data from the longitudinal multicenter 2000HIV study comprising 1895 virally suppressed PWH, out of which 970 had available liver and carotid artery measurements. Transient elastography with controlled attenuation parameter (CAP) was performed for the assessment of liver steatosis (CAP > 263 dB/m) and fibrosis (LSM ≥ 7.0). Historic and future incident CVD within 2-year follow-up, defined as myocardial infarction, stroke, peripheral arterial disease, and angina pectoris, were extracted from the medical files, while atherosclerotic plaque(s) in the carotid arteries were assessed using ultrasonography. Metabolic perturbations were analyzed using mass spectrometry-based untargeted metabolomics (n = 500 metabolites) and nuclear magnetic resonance spectroscopy for targeted lipids and other metabolites (n = 246 metabolites).RESULTS: PWH with liver steatosis were more likely to have arterial plaques (47% vs. 36%; P value = 0.003) and CVD history (11% vs. 6.8%; P value = 0.021) than PWH without liver steatosis. These associations were only significant in lean PWH, in contrast to those with BMI ≥ 25 kg/m2. Metabolic pathways associated with liver steatosis and fibrosis primarily involved lipid and amino acid metabolism, and they were validated by targeted lipoproteomic measurements. Interestingly, metabolomic pathways and lipoproteomic signatures associated with MASLD were mostly distinct from those associated with CVD parameters. However, several metabolic pathways were shared, especially in lean PWH. These include arachidonic acid metabolism and formation of prostaglandin, purine metabolism, cholecalciferol metabolism, and glycine, serine, alanine, and threonine metabolism.CONCLUSION: Metabolic disturbances linked to liver steatosis and CVD diverge across BMI categories in PWH. Lean PWH, unlike their overweight/obese counterparts, show common metabolic perturbations between MASLD and CVD, particularly involving arachidonic acid metabolism. This suggests that lean PWH with liver steatosis may face a heightened risk of CVD due to shared metabolic pathways, potentially opening avenues for targeted interventions, such as aspirin therapy, to mitigate this risk.PMID:39934780 | DOI:10.1186/s12916-025-03914-5

BMC Cancer. 2025 Feb 11;25(1):234. doi: 10.1186/s12885-025-13522-4.ABSTRACTBACKGROUND: Eukaryotic Initiation Factor 5A1 (EIF5A1) is a translation factor, and its pro-tumorigenic role has been extensively documented across various cancer types. However, its specific function in bladder cancer (BLCA) remains unclear.METHODS: We integrated proteomics and transcriptomics data with clinical data from BLCA patients to investigate the correlation between EIF5A1 expression and BLCA, as well as its potential clinical applications. Transcriptomic data were employed to explore the downstream signaling pathways regulated by EIF5A1. Furthermore, ChIP analysis and luciferase reporter assays were conducted to identify the upstream transcription factors regulating EIF5A1.RESULTS: EIF5A1 expression is significantly upregulated in cancer tissues and cells and is strongly associated with poor prognosis. Silencing EIF5A1 in BLCA cells significantly reduced invasiveness, and proliferative capacity. Mechanistic studies identified YAP/TEAD4 as a transcription factor that regulates EIF5A1, influencing mitochondrial-mediated apoptosis by activating the JAK2/STAT3 signaling pathway, thereby promoting BLCA progression.CONCLUSION: Our research demonstrates that EIF5A1 is upregulated in BLCA and associated with poor prognosis. We identified TEAD4 as a potential transcriptional regulator of EIF5A1 and showed that EIF5A1 expression is associated with changes in JAK2/STAT3 signaling and mitochondrial apoptosis in BLCA.PMID:39934701 | DOI:10.1186/s12885-025-13522-4

BMC Plant Biol. 2025 Feb 12;25(1):185. doi: 10.1186/s12870-025-06192-8.ABSTRACTPine wilt disease (PWD), caused by the pine wood nematode (PWN) Bursaphelenchus xylophilus, threatens Pinus seriously. Pinus koraiensis is one of the most important pine species in China and is the host for PWN. However, our understanding of the defence-regulating process following infection by B. xylophilus at the molecular level remains limited. To understand the mechanisms that P. koraiensis responds to B. xylophilus invasion, P. koraiensis was inoculated with B. xylophilus solutions and observed no obvious symptoms during the early stage; symptoms began to appear at 5 dpi. Therefore, we conducted comparative transcriptomic, metabonomic and proteomic analyses between P. koraiensis 5dpi and 0 dpi. In infected plants, 1574 genes were significantly up-regulated, including 17 terpenoid-, 41 phenylpropanoid- and 22 flavonoid-related genes. According to GO and KEGG enrichment analyses of significantly up-regulated genes, 86 GO terms and 16 KEGG pathways were significantly enriched. Most terms and pathways were associated with terpenoid-, phenylpropanoid-, flavonoid- and carbohydrate-related events. Similarly, the abundance of 36 and 30 metabolites, significantly increased in positive and negative polarity modes, respectively. Among them, naringenin and 3-methyl-2-oxovaleric acid exhibited significant toxic effects on B. xylophilus. According to functional analysis of significantly up-regulated metabolites, most terms were enriched in above pathways, in addition to alkaloid biosynthesis. Although the abundance of few proteins changed, response to stress term was significantly enriched in significant up-regulated proteins. Furthermore, plant receptor-like serine/threonine kinases, pectin methylation modulators, pinosylvin O-methyltransferase and arabinogalactan/proline-rich proteins were significantly up-regulated in the infected P. koraiensis compared to healthy plants. These proteins were not abundant in the healthy plant. Overall, these results indicate that P. koraiensis can actively response to PWN via various defense strategies, including events related to terpenoids, flavonoids, phenylpropanoids, lipids and alkaloids. Particularly, terpenoids and flavonoids are required for the early defence of P. koraiensis against B. xylophilus infection.PMID:39934660 | DOI:10.1186/s12870-025-06192-8