PubMed

Food Nutr Res. 2025 Jan 22;69. doi: 10.29219/fnr.v69.10677. eCollection 2025.ABSTRACTOBJECTIVE: Myricetin is a bioactive compound in many edible plants. We have previously demonstrated that myricetin could significantly protect mice against colitis by regulating Treg/Th17 balance, while underlying mechanism remains unclear. The current study aimed to unravel the potential regulating mechanism of myricetin.METHODS: The concentrations of 22 amino acids in colon were determined using HPLC-MS/MS and principal component analysis (PCA) was performed on the data. MetaboAnalyst was used to detect potential biological pathway influenced by myricetin. The results were further verified using qPCR, molecular docking method, and AhR inhibitor.RESULTS: Studies had found that the biosynthesis of phenylalanine, tyrosine, and tryptophan; phenylalanine metabolism; and histidine metabolism were the most important pathways related to myricetin. Therefore, the aryl hydrocarbon receptor (AhR), which is closely related to the metabolism of tryptophan, phenylalanine, and tyrosine, was postulated to be the underlying signaling pathways. Furthermore, administration of myricet in significantly increased the relative expressions of CYP1A1 and CYP1B1, whereas AhR inhibitor abolished the amelioration of myricetin on DSS-induced colitis. Moreover, AhR inhibitor weakened the regulatory effect of myricetin on Treg/Th17 balance. Furthermore, the results obtained by the molecular docking method speculated that myricetin could bind to AhR as a ligand and activate AhR.CONCLUSION: The results suggested that myricetin could exert its protection against dextran sulfate sodium (DSS)-induced colitis by activating AhR signaling pathway.PMID:39974840 | PMC:PMC11836776 | DOI:10.29219/fnr.v69.10677

Front Med (Lausanne). 2025 Feb 5;11:1492383. doi: 10.3389/fmed.2024.1492383. eCollection 2024.ABSTRACTOBJECTIVES: To explore the mechanism underlying the effect of Fructus Akebiae (FAE) against hepatic fibrosis in mice through combined network pharmacology, liver metabolomics, and 16S rDNA analyses of the gut microbiota.METHODS: In this study, we randomly divided mice into the control, model, FAE high-dose, FAE medium-dose, and FAE low-dose groups to analyze the pathological changes in the hepatic fibrosis and levels of the α-SMA, collagen 1, Nuclear Factor Kappa B (NF-κ B), Toll Like Receptor 4 (TLR4). The gut microbiota was analyzed through 16S rDNA sequencing analysis of liver metabolites using liquid chromatography-mass spectrometry. Furthermore, network pharmacology was used to determine the specific molecular regulation mechanism of FAE in hepatic fibrosis treatment.RESULTS: FAE treatment markedly improved the pathological changes in the hepatic fibrosis. Analysis revealed that FAE administration reversed the carbon tetrachloride (CCl4)-induced dysbiosis by increasing the abundance of Akkermansia and reducing that of Cyanobacteria. Additionally, metabolomic analysis showed that FAE treatment reversed the CCl4-induced metabolic disorders by regulating amino and nucleotide sugar metabolism. Furthermore, correlation analysis showed that Akkermansia and Verrucomicobiota were closely related to D-tolasaccharide and maltotetraose saccharide. Moreover, network pharmacology indicated that FAE might regulate the signaling pathway through the JUN/CASP3/NOS3/PTGS2/HSP90AA1 during treatment.CONCLUSION: FAE may be a promising treatment for hepatic fibrosis, and its protective effects are associated with improvements in the microbiome and metabolic disorders.PMID:39974825 | PMC:PMC11835924 | DOI:10.3389/fmed.2024.1492383

Front Endocrinol (Lausanne). 2025 Feb 5;16:1558561. doi: 10.3389/fendo.2025.1558561. eCollection 2025.NO ABSTRACTPMID:39974823 | PMC:PMC11835697 | DOI:10.3389/fendo.2025.1558561

J Anim Sci Technol. 2025 Jan;67(1):164-178. doi: 10.5187/jast.2023.e135. Epub 2025 Jan 31.ABSTRACTTraditionally, velvet antler (VA) has been used as a medicine or dietary supplement in East Asia. It contains biologically active compounds that exert anti-inflammatory, anti-fatigue, anti-aging, and anticancer effects. Although demand for VA has increased globally, its supply and consumption are limited due to the low recovery of its bioactive compounds from traditional decoctions. Therefore, alternative extraction methods are required to enrich the active compounds and enhance their biological efficacy. The extract has been reported to protect against neuropathological conditions in brain cells and suppress oxidative stress and neuroinflammation-crucial for the initiation or progression of neurodegenerative diseases. Therefore, VA is a potential therapeutic agent for neurodegenerative diseases. However, the beneficial effects of VA on astrocytes, which are the predominant glial cells in the brain, remain unclear. In the present study, we investigated the protective effects of enzymatically digested VA extract (YC-1101) on the mitochondria in astrocytes, which are essential organelles regulating oxidative stress. Proteomic and metabolomic results using liquid chromatography-mass spectrometry (LC-MS/MS) identified enriched bioactive ingredients in YC-1101 compared to hot water extract of VA. YC-1101 displayed significant protective effects against mitochondrial stressors in astrocytes compared with other health functional ingredients. Altogether, our results showed improved bioactive efficacy of YC-1101 and its protective role against mitochondrial stressors in astrocytes.PMID:39974783 | PMC:PMC11833196 | DOI:10.5187/jast.2023.e135

Food Chem X. 2024 Oct 5;24:101871. doi: 10.1016/j.fochx.2024.101871. eCollection 2024 Dec 30.ABSTRACTFeeding sheep with high-concentrate diet (HCD) to shorten production cycle is a well-developed feeding strategy to increase lamb production. Here, metabolomics were performed to explore the mechanism that HCD changes lamb nutrition composition. Differential metabolites were enriched in primary bile acid biosynthesis. Significantly higher content of bile acids including taurodeoxycholic acid sodium salt (TDCA), taurochenodeoxycholic acid sodium salt (TCDCA) and taurocholic acid (TCA) was observed in lamb of HCD, while the content of lithocholic acid (LCA), cholic acid (CA), chenodeoxycholic acid (CDCA) and Chenodeoxycholic acid-3-beta-D-glucuronide (CDCA-3Gln) were higher in the controls. Furthermore, a significantly decreased content of fatty acids was observed in lamb of HCD group. Finally, primary skeletal cells treated with CA or TCA showed a significant decrease in contents of fatty acids, while TCA showed a stronger effect in decreasing fatty acid contents. Collectively, we suggest that HCD decreases lamb fatty acid contents by regulating bile acid composition.PMID:39974716 | PMC:PMC11838137 | DOI:10.1016/j.fochx.2024.101871

Food Chem X. 2024 Oct 9;24:101884. doi: 10.1016/j.fochx.2024.101884. eCollection 2024 Dec 30.ABSTRACTIn order to ensure the quality of saozi and expand its usage scenarios, it is necessary to determine the appropriate dose of irradiation. Non-targeted metabonomics method was used to explore the influence of changes in composition induced by different irradiation doses on the sensory characteristics of saozi. With increased irradiation dose (0, 2, 5, and 8 kGy), the TBARS value of saozi increased, whereas aroma, taste, and overall acceptability scores of saozi significantly decreased (p < 0.05). A total of 147 differential components including amino acids, organic acids, fatty acids, purines, and pyrimidines were screened from different irradiation doses of saozi. Twenty significant change pathways were identified in the KEGG enrichment results, most of which involve amino acids, nucleotide substances, acidic substances, among others, indicating that radiation-induced changes in these substances were one of the main reasons affecting the sensory scores of saozi. Considering the sensory scores and changes in the composition of saozi, when using cobalt 60 for the irradiation treatment of saozi, the optimal irradiation dose should be less than 5 kGy.PMID:39974712 | PMC:PMC11838134 | DOI:10.1016/j.fochx.2024.101884

Med Rev (2021). 2024 Aug 29;5(1):76-82. doi: 10.1515/mr-2024-0056. eCollection 2025 Feb.ABSTRACTAdipose-derived mesenchymal stem cells (ADSCs) and bone marrow-derived mesenchymal stem cells (BMSCs) have shown great potential in clinical applications. However, the similarities and differences between these two cell types have not been fully elucidated. Recent advances in transcriptomic and metabolomic research have provided valuable insight into the characteristics and functions of ADSCs and BMSCs. In this perspective article, we review the key findings from these studies, including cellular heterogeneity as well as differences in metabolic and secretory properties. We discuss how these insights can help guide the selection of the most suitable cell source for the clinic, and the optimization of preconditioning strategies prior to clinical deployment. Furthermore, we analyze the current landscape of products and clinical trials involving ADSCs and BMSCs, highlighting their therapeutic potential. We propose that the integration of multi-omics datasets will be crucial for establishing a comprehensive understanding of ADSC and BMSC identity and potency, and the provision of quality-assured stem cell-derived products for the clinic.PMID:39974562 | PMC:PMC11834745 | DOI:10.1515/mr-2024-0056

Food Chem X. 2024 Dec 17;25:102089. doi: 10.1016/j.fochx.2024.102089. eCollection 2025 Jan.ABSTRACTHighland barley β-glucan (HBG) has attracted increasing attention due to its excellent biological activities. However, the effects of HBG on gut flora and metabolites are unknown. Therefore, the effects of HBG on the gut microbiota during fermentation were analyzed by 16 s rRNA sequencing and untargeted metabolomics. The results showed that HBG could enrich microbial diversity, increase the abundance of beneficial bacteria, and inhibit the biology of pathogenic bacteria. In addition, HBG increased the content of short-chain fatty acids and decreased fermentation broth pH. Metabolomics analyses showed that HBG also increased the content of beneficial metabolites such as taurine and affected amino acid metabolism, among other pathways. This study lays the foundation for the application of HBG in functional foods.PMID:39974532 | PMC:PMC11838092 | DOI:10.1016/j.fochx.2024.102089

Food Chem X. 2024 Dec 9;25:102075. doi: 10.1016/j.fochx.2024.102075. eCollection 2025 Jan.ABSTRACTThis study investigated the impact of steaming on the flavor and metabolic profile of Antarctic krill, aiming to elucidate the pathways responsible for flavor development and metabolic shifts during processing. HS-SPME-GC-MS identified key volatile compounds, including alcohols, aldehydes, ketones and so on. The results demonstrated a significant increase in nonanal content from 2.23 ± 0.06 μg/kg to 8.14 ± 1.26 μg/kg after steaming. The formation pathways of two key flavor compounds, nonanal and 1-octen-3-ol, were attributed to fatty acid degradation. Hierarchical clustering and volcano plot showed metabolic shifts between raw and steamed krill, with differential metabolites like hydroquinone and gamma-aminobutyric acid emerging as key contributors to flavor changes. Furthermore, metabolic network further linked these shifts to reactions involving amino acids, nucleotide and other compounds during steaming, impacting the overall taste.PMID:39974529 | PMC:PMC11838135 | DOI:10.1016/j.fochx.2024.102075

Biochem Med (Zagreb). 2025 Feb 15;35(1):010707. doi: 10.11613/BM.2025.010708.ABSTRACTINTRODUCTION: Sphingolipids, essential to trophoblast and endothelial function, may impact inflammation in preeclampsia. However, their specific role in late-onset preeclampsia remains unclear. To address this research gap, we analyzed sphingolipid profiles in pregnancies at high risk for preeclampsia development to identify potential biomarkers and clarify their role in disease pathogenesis.MATERIALS AND METHODS: We monitored 90 pregnant women at high risk for preeclampsia development across four gestational points. These women were later categorized into the group of women with high risk who did not develop preeclampsia (HRG) (70 women) or the preeclampsia group (PG) (20 women). Sphingolipids (sphingosine, sphinganine, sphingosine-1-phosphate (S1P), ceramides C16:0/C24:0, and sphingomyelin C16:0) were quantified via liquid chromatography-tandem mass spectrometry.RESULTS: Sphingolipid profiles revealed distinct patterns between groups. Concentrations of S1P in the HRG increased from the 1st trimester to delivery (P < 0.001). We did not notice significant changes in S1P during pregnancy in the PG but compared with the HRG we found significantly lower concentrations at each test point from the 2nd trimester until delivery (P = 0.020, P = 0.013, P = 0.011, respectively). Ceramides C16:0 and C24:0 demonstrated significant increases over time in HRG (P < 0.001, both). Sphingomyelin C16:0 increased significantly across pregnancy in both groups (P < 0.001 in HRG and P = 0.006 in PG), with no significant differences between groups.CONCLUSIONS: We identified S1P as a potential biomarker for late-onset preeclampsia, with lower concentrations observed in PG compared to HRG. Rising sphingomyelin concentrations in both cohorts might serve as a relevant cardiovascular risk indicator in pregnancies at high risk for preeclampsia.PMID:39974194 | PMC:PMC11838718 | DOI:10.11613/BM.2025.010708

medRxiv [Preprint]. 2025 Jan 25:2025.01.23.25320909. doi: 10.1101/2025.01.23.25320909.ABSTRACTExtracellular vesicles (EVs) released by neurons (nEVs) provide an opportunity to measure biomarkers from the brain circulating in the periphery. No study yet has directly compared molecular cargo in brain tissue to nEVs found in circulation in humans. We compared the levels microRNAs and environmental chemicals because microRNAs are one of the most studied nEV cargoes and offer great potential as biomarkers and environmental chemical load in nEVs is understudied and could reveal levels of chemicals in the brain. To do so, we leveraged matched sets of brain tissue and serum, and isolated serum total EVs and serum nEVs. We also generated and compared metabolomic profiles in a different set of matched serum, serum total EVs, and serum nEVs since metabolite cargo in nEVs is also understudied but could offer potential biomarkers. Highly expressed brain tissue miRNAs showed stronger correlations with nEVs than serum or total EVs. We detected several environmental chemical pollutant classes in nEVs. The chemical pollutant concentrations in nEVs were more strongly correlated with brain tissue levels than those observed between brain tissue and serum or total EVs. We also detected several endogenous metabolite classes in nEVs. Compared to serum and total EVs, there was enrichment of metabolites with known signaling roles, such as bile acids, oleic acid, phosphatidylserine, and isoprenoids. We provide evidence that nEV cargo is closely correlated to brain tissue content, further supporting their utility as a brain liquid biopsy.PMID:39974146 | PMC:PMC11839008 | DOI:10.1101/2025.01.23.25320909

medRxiv [Preprint]. 2025 Feb 4:2025.02.03.25321363. doi: 10.1101/2025.02.03.25321363.ABSTRACTBACKGROUND: Towards improving outcomes for adolescents with obesity, we aimed to define metabolic and microbiome phenotypes at baseline and post-weight loss intervention.METHODS: The Pediatric Obesity Microbiome and Metabolism Study enrolled 220 adolescents aged 10-18 with severe obesity (OB) and 67 healthy weight controls (HWC). Blood, stool, and clinical measures were collected at baseline and after a 6-month intervention for the OB group. Serum metabolomic and fecal microbiome data were analyzed for associations with BMI, insulin resistance, and inflammation. Fecal microbiome transplants were performed on germ-free mice using samples from both groups to assess weight gain and metabolomic changes.RESULTS: Adolescents with OB exhibited elevated serum branched-chain amino acids (BCAA) but reduced ketoacid metabolites (BCKA) compared to HWC. This pattern was sex- and age-dependent, unlike adults with OB, who showed elevated levels of both. The fecal microbiomes of adolescents with OB and HWC had similar diversity but differed in membership and functional potential. FMT from OB and HWC donors had similar effects on mouse body weight, with specific taxa linked to weight gain in FMT recipients. Longitudinal analysis identified metabolic and microbial features correlated with changes in health measures during the intervention.CONCLUSION: Adolescents with OB have unique metabolomic adaptations and microbiome signatures compared to their HWC counterparts and adults with OB.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03139877 (Observational Study) and NCT02959034 (Repository).FUNDING SOURCES: American Heart Association Grants: 17SFRN33670990, 20PRE35180195National Institute of Diabetes and Digestive and Kidney Diseases Grant: R24-DK110492.PMID:39974080 | PMC:PMC11838640 | DOI:10.1101/2025.02.03.25321363

medRxiv [Preprint]. 2025 Feb 6:2025.02.05.25321733. doi: 10.1101/2025.02.05.25321733.ABSTRACTBACKGROUND: Preclinical literature and behavioral human data suggest that diet profoundly impacts the human gut microbiome and energy absorption-a key determinant of energy balance. To determine whether these associations are causal, domiciled controlled feeding studies with precise measurements of dietary intake and energy balance are needed. Metabolomics-a functional readout of microbiome modulation-can help identify putative mechanisms mediating these effects. We previously demonstrated that a high-fiber, minimally processed Microbiome Enhancer Diet (MBD) fed at energy balance decreased energy absorption and increased microbial biomass relative to a calorie-matched fiber-poor, highly processed Western Diet (WD).OBJECTIVE: To identify metabolic signatures distinguishing MBD from WD feeding and potential metabolomic mechanisms mediating the MBD-induced negative energy balance.METHODS: We deployed global metabolomics in feces, serum, and urine using samples collected at the end of a randomized crossover controlled feeding trial delivering 22 days of an MBD and a WD to 17 persons without obesity. Samples were collected while participants were domiciled on a metabolic ward and analyzed using Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy. Linear mixed effects models tested metabolite changes by diet. Weighted gene network correlation analysis identified metabolite modules correlated with energy balance phenotypes.RESULTS: Numerous metabolites consistently altered in the feces, fasting serum, and/or urine may serve as putative dietary biomarkers of MBD feeding. Fecal diet-microbiota co-metabolites decreased by an MBD correlated with reduced energy absorption and increased microbial biomass. An MBD shifted the urinary metabolome from sugar degradation to ketogenesis-evidence of negative energy balance.CONCLUSIONS: Precisely controlled diets disparate in microbiota-accessible substrates led to distinct metabolomic signatures in feces, fasting serum, and/or urine. These diet-microbiota co-metabolites may be biomarkers of a "fed" (MBD) or "starved" (WD) gut microbiota associated with energy balance. These findings lay the foundation for unveiling causal pathways linking diet-microbiota co-metabolism to energy absorption.PMID:39974023 | PMC:PMC11838622 | DOI:10.1101/2025.02.05.25321733

medRxiv [Preprint]. 2025 Feb 3:2025.01.29.25321260. doi: 10.1101/2025.01.29.25321260.ABSTRACTBiological age (BA), shaped by genetics, lifestyle, and environmental exposures, reflects physiological changes and mediates the effects of social determinants of health (SDoH) in diseases other than multiple sclerosis (MS). We investigated BA acceleration through metabolic profiling in people with MS (PwMS) and its association with SDoH, measured by the area deprivation index. Accelerated BA was observed in PwMS compared to healthy controls in independent adult and pediatric-onset MS cohorts. Greater social deprivation correlated with greater BA acceleration in PwMS. These findings highlight BA as a potential mediator linking SDoH to MS outcomes and a target to reduce health disparities.PMID:39974014 | PMC:PMC11838630 | DOI:10.1101/2025.01.29.25321260

Biostatistics. 2024 Dec 31;26(1):kxaf001. doi: 10.1093/biostatistics/kxaf001.ABSTRACTThere is still more to learn about the pathobiology of coronavirus disease (COVID-19) despite 4 years of the pandemic. A multiomics approach offers a comprehensive view of the disease and has the potential to yield deeper insight into the pathogenesis of the disease. Previous multiomics integrative analysis and prediction studies for COVID-19 severity and status have assumed simple relationships (ie linear relationships) between omics data and between omics and COVID-19 outcomes. However, these linear methods do not account for the inherent underlying nonlinear structure associated with these different types of data. The motivation behind this work is to model nonlinear relationships in multiomics and COVID-19 outcomes, and to determine key multidimensional molecules associated with the disease. Toward this goal, we develop scalable randomized kernel methods for jointly associating data from multiple sources or views and simultaneously predicting an outcome or classifying a unit into one of 2 or more classes. We also determine variables or groups of variables that best contribute to the relationships among the views. We use the idea that random Fourier bases can approximate shift-invariant kernel functions to construct nonlinear mappings of each view and we use these mappings and the outcome variable to learn view-independent low-dimensional representations. We demonstrate the effectiveness of the proposed methods through extensive simulations. When the proposed methods were applied to gene expression, metabolomics, proteomics, and lipidomics data pertaining to COVID-19, we identified several molecular signatures for COVID-19 status and severity. Our results agree with previous findings and suggest potential avenues for future research. Our algorithms are implemented in Pytorch and interfaced in R and available at: https://github.com/lasandrall/RandMVLearn.PMID:39973130 | DOI:10.1093/biostatistics/kxaf001

Brain Behav. 2025 Feb;15(2):e70352. doi: 10.1002/brb3.70352.ABSTRACTOBJECTIVE: This study aimed to explore the causal effects of lipidome on Alzheimer's disease (AD) and the mediated effects of the metabolites using Mendelian randomization (MR).METHODS: Data were obtained in genome-wide association studies, and single-nucleotide polymorphisms were screened according to the underlying assumptions of MR. Subsequently, weighted inverse variance was used to analyze the causality of lipidome with AD as well as the mediated effects of metabolites. Finally, MR-Egger, Cochran's Q, and sensitivity analysis were used to assess horizontal pleiotropy, heterogeneity, and robustness of the results, respectively.RESULTS: The MR analysis showed that phosphatidylcholine (PC) (15:0_18:2) (mediated proportion: 18.30%, p = 0.024) and phosphatidylethanolamine (PE) (18:0_18:2) (mediated proportion: 14.60%, p = 0.028) mediated the reduction of AD risk by lowering betaine levels, which revealed lipidomic susceptibility. The MR-Egger intercept showed no horizontal pleiotropy for all results (p ≥ 0.05). Cochran's Q showed heterogeneity in some of the results. Sensitivity analysis indicated that all results were robust.CONCLUSION: Our findings reveal the pathways through which PC (15:0_18:2) and PE (18:0_18:2) mediated the reduction of AD risk by lowering betaine levels.PMID:39972983 | DOI:10.1002/brb3.70352

Physiol Plant. 2025 Jan-Feb;177(1):e70108. doi: 10.1111/ppl.70108.ABSTRACTBulb physiological dormancy significantly limits the development and utilization of Cardiocrinum giganteum (Wall.) Makino, a valuable medicinal, edible and ornamental plant. In the current study, to break the dormancy and reveal its mechanism, metabolome and transcriptome analyses using bulbs stored at 4°C for 0, 30, and 60 days (d) were conducted. Results revealed that bulb dormancy release and development were linked to hormones such as ABA, IAA, GA and ZR, as well as sucrose and starch. Total soluble sugars initially increased and then decreased within 60 days of low temperature treatment, contrary to the behaviour of starch content. Dormancy release predominantly relied on GA accumulation and ABA degradation. Additionally, genes involved in carbohydrate metabolism, including HK, SPS, BGLU, and SuSy, were up-regulated in the later stage. The energy production during carbohydrate metabolism mainly depended on the tricarboxylic acid cycle and glycolysis pathway. Hormone-mediated regulation and hormone signal transduction metabolism pathways were also obviously changed. Co-expression analysis indicated that key genes, such as NCED, PP2C and DELLA, related to the ABA signal transduction pathway, and GA2ox, ARF and SAUR, related to the IAA and GA signal transduction pathway, played a crucial role in dormancy release. Moreover, ZR signal transduction genes such as CRE, ARR-B, ARR-A and TRIT1 involved in cell division were up-regulated in bulbs treated at 4°C for 30 or 60 d. This study provides evidence for understanding the molecular mechanism underlying bulb dormancy release and is a guide for industry development and utilization of Cardiocrinum giganteum (Wall.) Makino.PMID:39972976 | DOI:10.1111/ppl.70108

Equine Vet J. 2025 Feb 19. doi: 10.1111/evj.14490. Online ahead of print.ABSTRACTBACKGROUND: Equine osteoarthritis (OA) is predominantly diagnosed through clinical examination and radiography, leading to detection only after significant joint pathology. The pathogenesis of OA remains unclear and while many medications modify the disease's inflammatory components, no curative or reversal treatments exist. Identifying differentially abundant metabolites and proteins correlated with osteoarthritis severity could improve early diagnosis, track disease progression, and evaluate responses to interventions.OBJECTIVES: To identify molecular markers of osteoarthritis severity based on histological and macroscopic grading.STUDY DESIGN: Cross-sectional study.METHODS: Post-mortem synovial fluid was collected from 58 Thoroughbred racehorse joints and 83 joints from mixed breeds. Joints were histologically and macroscopically scored and categorised by OA and synovitis grade. Synovial fluid nuclear magnetic resonance metabolomic and mass spectrometry proteomic analyses were performed, individually and combined.RESULTS: In Thoroughbreds, synovial fluid concentrations of metabolites 2-aminobutyrate, alanine and creatine were elevated for higher OA grades, while glutamate was reduced for both Thoroughbreds and mixed breeds. In mixed breeds, concentrations of three uncharacterised proteins, lipopolysaccharide binding protein and immunoglobulin kappa constant were lower for higher OA grades; concentrations of an uncharacterised protein were higher for OA grade 1 only, and apolipoprotein A1 concentrations were higher for OA grades 1 and 2 compared with lower grades. For Thoroughbreds, gelsolin concentrations were lower for higher OA grades, and afamin was lower at a higher synovitis grade. Correlation analyses of combined metabolomics and proteomics datasets revealed 58 and 32 significant variables for Thoroughbreds and mixed breeds, respectively, with correlations from -0.48 to 0.42 and -0.44 to 0.49.MAIN LIMITATIONS: The study's reliance on post-mortem assessments limits correlation with clinical osteoarthritis severity.CONCLUSIONS: Following stratification of equine OA severity through histological and macroscopic grading, synovial fluid metabolomic and proteomic profiling identified markers that may support earlier diagnosis and progression tracking. Further research is needed to correlate these markers with clinical osteoarthritis severity.PMID:39972657 | DOI:10.1111/evj.14490

Arthritis Res Ther. 2025 Feb 19;27(1):35. doi: 10.1186/s13075-025-03500-3.ABSTRACTBACKGROUND: Plasmacytoid dendritic cells (pDCs) play a key role in systemic sclerosis (SSc) pathophysiology. However, despite the recognised importance of metabolic reprogramming for pDC function, their metabolic profile in SSc remains to be elucidated. Thus, our study aimed to explore the metabolic profile of pDCs in SSc and their potential contribution to the disease.METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from the blood of healthy donors and SSc patients. SCENITH™, a single-cell flow cytometry-based method, was applied to infer the metabolic profile of circulating pDCs from patients with SSc. pDCs (CD304+ Lin-) at steady-state or stimulated with CpG A were analysed. Toll-like receptor (TLR)9 activation was confirmed by ribosomal protein S6 phosphorylation.RESULTS: Circulating pDCs from ten healthy donors and fourteen SSc patients were analysed. pDCs from anti-centromere antibody-positive (ACA+) patients displayed higher mitochondrial dependence and lower glycolytic capacity than those from anti-topoisomerase I antibody-positive (ATA+) patients. Furthermore, cells from both ACA+ patients and limited cutaneous SSc (lcSSc) patients showed a stronger response towards TLR9 activation than cells from ATA+, anti-RNA polymerase III antibody-positive (ARA+) or diffuse cutaneous SSc (dcSSc) patients.CONCLUSIONS: An innovative single cell flow cytometry-based methodology was applied to analyse the metabolic profile of pDCs from SSc patients. Our results suggest that pDCs from ACA+ patients rely more on oxidative phosphorylation (OXPHOS) and are more responsive to external stimuli, whereas pDCs from ATA+ patients may exhibit a more activated or exhausted profile.PMID:39972361 | DOI:10.1186/s13075-025-03500-3

Mol Plant Pathol. 2025 Feb;26(2):e70066. doi: 10.1111/mpp.70066.ABSTRACTPlant viruses pose a significant threat to global agriculture, leading to substantial crop losses that jeopardise food security and disrupt ecosystem stability. These viral infections often reprogramme plant metabolism, compromising key pathways critical for growth and defence. For instance, infections by cucumber mosaic virus alter amino acid and secondary metabolite biosynthesis, including flavonoid and phenylpropanoid pathways, thereby weakening plant defences. Similarly, tomato bushy stunt virus disrupts lipid metabolism by altering the synthesis and accumulation of sterols and phospholipids, which are essential for viral replication and compromise membrane integrity. Recent advancements in gene-editing technologies, such as CRISPR/Cas9, and metabolomics offer innovative strategies to mitigate these impacts. Precise genetic modifications can restore or optimise disrupted metabolic pathways, enhancing crop resilience to viral infections. Metabolomics further aids in identifying metabolic biomarkers linked to viral resistance, guiding breeding programmes aimed at developing virus-resistant plants. By reducing the susceptibility of crops to viral infections, these approaches hold significant potential to reduce dependence on chemical pesticides, increase crop yields and promote sustainable agricultural practices. Future research should focus on expanding our understanding of virus-host interactions at the molecular level while exploring the long-term ecological impacts of viral infections. Interdisciplinary approaches integrating multi-omics technologies and sustainable management strategies will be critical in addressing the challenges posed by plant viruses and ensuring global agricultural stability.PMID:39972520 | DOI:10.1111/mpp.70066