Metabolites最新文献

{"title":"Ceramide in Coronary Artery Disease: Troublesome or Helpful Future Tools in the Assessment of Risk Prediction and Therapy Effectiveness?","authors":"Melania Gaggini, Adrian Florentin Suman, Cristina Vassalle","doi":"10.3390/metabo15030168","DOIUrl":"10.3390/metabo15030168","url":null,"abstract":"<p><p>Lipids are a complex entity of different molecules, among which ceramides (Cers), ubiquitous sphingolipids with remarkable biological activity, can represent a potential additive biomarker that can be used to better understand the underlying mechanisms which drive the onset and development of atherosclerotic damage and plaque vulnerability and facilitate coronary disease management, as possible risk/prognostic biomarkers and targets for therapeutic intervention. Accordingly, this review aims to discuss the available results on the role Cersplay in contributing to atherosclerosis development and acute coronary event precipitation, their impact on complications and adverse prognosis, as well as the impact of treatment options in modulating Cerlevels.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toll-like Receptor Activation Remodels the Polyamine and Tryptophan Metabolism in Porcine Macrophages.","authors":"Meimei Zhang, Lingfei Du, Yinhao Shen, Peng Bin","doi":"10.3390/metabo15030162","DOIUrl":"10.3390/metabo15030162","url":null,"abstract":"<p><p><b>Background:</b> The early nutritional metabolism of piglets is intimately associated with the regulation of immune function, and amino acids play a crucial role in modulating the fate and function of porcine immune cells, especially macrophages. However, the metabolic changes upon macrophage activation remain elusive. <b>Methods:</b> We established an in vitro activation model of porcine macrophages and investigated alterations in metabolites involved in polyamine and tryptophan metabolism upon activation by various toll-like receptor (TLR) activators. <b>Results:</b> TLR activation inhibits the production of spermine and alters the kynurenine pathway of the tryptophan metabolism toward the kynurenic acid biosynthesis. Specifically, TLR9 activation redirects the metabolic pathway of tryptophan toward kynurenic acid synthesis, which subsequently inhibits melatonin production via the protein kinase A (PKA)/cyclic adenosine monophosphate (cAMP)/cAMP-responsive element-binding protein (CREB) signaling pathways. <b>Conclusions:</b> TLR activation reprograms the polyamine and tryptophan metabolism in porcine macrophages. Knowledge of the metabolic alterations in polyamine and tryptophan upon TLR activation in macrophages offers valuable insights and potential strategies for nutritional intervention to enhance piglet immunity.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of L-β-Galactoglucan Supplementation on Growth Performance, Palatability, and Intestinal Microbiota in Adult Beagle Dogs.","authors":"Chenghe Chang, Zifeng Gu, Lingling Du, Jiantao Guo, Ying Yang, Zhenlong Wu","doi":"10.3390/metabo15030160","DOIUrl":"10.3390/metabo15030160","url":null,"abstract":"<p><p><b>Background:</b> This study was conducted to investigate the effects of different levels of L-β-galactoglucan on growth performance, palatability, and health condition of dogs. <b>Methods:</b> A total of 32 healthy beagle dogs (2.0 ± 0.5 yr; 13.2 ± 2.1 kg) were randomly assigned into four treatment groups, with 8 dogs in each group. The dogs were fed basal diets supplemented with 0 (control), 0.25, 0.5, or 1% L-β-galactoglucan. <b>Results:</b> The results showed that the feed intake ratio of the dogs in the Low_Gal (0.25%) group was significantly higher (<i>p</i> < 0.05) as compared with the control (Con) group. The low-density lipoprotein cholesterol (LDL-C) levels of the Mid_Gal (0.5%) group showed a trend toward lower levels as compared with the control (Con) group (<i>p</i> = 0.069). Compared with the control (Con) group, the alpha diversity of the bacterial flora of the Shannon index of the Mid_Gal (0.5%) group was significantly higher (<i>p</i> < 0.05). The Simpson index was significantly reduced (<i>p</i> < 0.05), and a PCoA indicated a significant change in the gut microbiota structure among the four groups (<i>p</i> < 0.05). The relative abundance of <i>Blautia</i> and <i>Peptoclostridium</i> in the Low_Gal (0.25%) group was significantly higher as compared with the control (Con) group (<i>p</i> < 0.05). <b>Conclusions:</b> These results indicated that L-β-galactoglucan exhibited a positive effect on improving the palatability and gut microbiota of dogs.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling Shared Pathways Linking Metabolic Syndrome, Mild Cognitive Impairment, Dementia, and Sarcopenia.","authors":"Daniela Ceccarelli Ceccarelli, Sebastiano Bruno Solerte","doi":"10.3390/metabo15030159","DOIUrl":"10.3390/metabo15030159","url":null,"abstract":"<p><p><b>Background</b>: Aging is characterized by shared cellular and molecular processes, and aging-related diseases might co-exist in a cluster of comorbidities, particularly in vulnerable individuals whose phenotype meets the criteria for frailty. Whilst the multidimensional definition of frailty is still controversial, there is an increasing understanding of the common pathways linking metabolic syndrome, cognitive decline, and sarcopenia, frequent conditions in frail elderly patients. <b>Methods</b>: We performed a systematic search in the electronic databases Cochrane Library and PubMed and included preclinical studies, cohort and observational studies, and trials. <b>Discussion</b>: Metabolic syndrome markers, such as insulin resistance and the triglyceride/HDL C ratio, correlate with early cognitive impairment. Insulin resistance is a cause of synaptic dysfunction and neurodegeneration. Conversely, fasting and fasting-mimicking agents promote neuronal resilience by enhancing mitochondrial efficiency, autophagy, and neurogenesis. Proteins acting as cellular metabolic sensors, such as SIRT1, play a pivotal role in aging, neuroprotection, and metabolic health. In AD, β-amyloid accumulation and hyperphosphorylated tau in neurofibrillary tangles can cause metabolic reprogramming in brain cells, shifting from oxidative phosphorylation to aerobic glycolysis, similar to the Warburg effect in cancer. The interrelation of metabolic syndrome, sarcopenia, and cognitive decline suggests that targeting these shared metabolic pathways could mitigate all the conditions. Pharmacological interventions, including GLP-1 receptor agonists, metformin, and SIRT 1 inducers, demonstrated neuroprotective effects in animals and some preliminary clinical models. <b>Conclusions</b>: These findings encourage further research on the prevention and treatment of neurodegenerative diseases as well as the drug-repurposing potential of molecules currently approved for diabetes, dyslipidemia, and metabolic syndrome.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic and Lipidomic Characteristics of Subcutaneous Fat Deposition in Small-Sized Meat Ducks.","authors":"Hao Zheng, Cui Wang, Ao Zhou, Xing Chen","doi":"10.3390/metabo15030158","DOIUrl":"10.3390/metabo15030158","url":null,"abstract":"<p><p><b>Background:</b> Subcutaneous fat deposition is associated with ducks' meat quality and the methods used to cook them. However, the reasons underlying the differences in the lipid deposition of small-sized Wuqin10 meat ducks remain unclear. <b>Method:</b> In the present study, to elucidate the metabolic mechanisms of lipid deposition, we comprehensively analyzed the transcriptomics and lipidomics of subcutaneous fat in Wuqin10 meat ducks with different subcutaneous thicknesses with six replicates. <b>Results:</b> A total of 1120 lipids were detected in the lipidomic analysis, and 39 lipids were inexorably regulated in the ducks with the thick subcutaneous layer compared to those with the thin layer; further, the up-regulated lipids were primarily triglycerides (TGs), which may have resulted in adipocyte enlargement. Furthermore, the transcriptomic analysis identified 265 differentially expressed genes (DEGs), including 119 down-regulated and 146 up-regulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the DEGs were significantly enriched in the histidine, arginine, proline metabolism signaling and adipocytokine signaling pathways. The protein-protein interaction (PPI) network in Cytoscape 3.8.2 identified hub genes HSP90AA1, RUNX2, ACTN2, ACTA1, IL10, CXCR4, EGF, SOCS3 and PTK2, which were associated with the JAK-STAT signaling pathway and regulation of adipocyte hypertrophy. <b>Conclusion:</b> Taken together, our findings reveal the patterns of lipids and the gene expression of subcutaneous fat, providing a basis for future studies of subcutaneous fat deposition in small-sized meat ducks.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Bioactive Metabolites of <i>Capirona macrophylla</i> by Metabolomic Analysis, Molecular Docking, and In Vitro Antiparasitic Assays.","authors":"Joseph Evaristo, Elise de Laia, Bruna Tavares, Esdras Mendonça, Larissa Grisostenes, Caroline Rodrigues, Welington do Nascimento, Carolina Garcia, Sheila Guterres, Fábio Nogueira, Fernando Zanchi, Geisa Evaristo","doi":"10.3390/metabo15030157","DOIUrl":"10.3390/metabo15030157","url":null,"abstract":"<p><p><i>Capirona macrophylla</i> is a Rubiaceae known as \"mulateiro\". Ethnobotanical extracts have been used for skin treatment and in the management of leishmaniasis and malaria.</p><p><strong>Objectives: </strong>The metabolites in aqueous extracts from wood bark, leaves, and stems were identified, and their in silico docking and in vitro cellular efficacy against <i>Leishmania amazonensis</i> and <i>Plasmodium falciparum</i> were evaluated.</p><p><strong>Methods: </strong>The extracts were analyzed by UHPLC/HRMSⁿ using untargeted metabolomics approach with MSDial, MSFinder, and GNPS software for metabolite identification and spectra clustering. The most abundant metabolites underwent molecular docking using AutoDock via PyRx, targeting the dihydroorotate dehydrogenase from <i>Leishmania</i> and <i>P. falciparum</i>, and evaluated through molecular dynamics simulations using Gromacs. In vitro biological assays were conducted on 60 HPLC-fractions against these parasites.</p><p><strong>Results: </strong>Metabolomics analysis identified 5100 metabolites in ESI+ and 2839 in ESI- spectra among the \"mulateiro\" samples. GNPS clustering highlighted large clusters of quercetin and chlorogenic acid groups. The most abundant metabolites were isofraxidin, scopoletin, 5(S)-5-carboxystrictosidine, loliolide, quercetin, quinic acid, caffeoylquinic acid (and isomers), chlorogenic acid, neochlorogenic acid, tryptophan, N-acetyltryptophan, epicatechin, procyanidin, and kaempferol-3-O-robinoside-7-O-rhamnoside. Molecular docking pointed to 3,4-dicaffeoylquinic acid and kaempferol as promising inhibitors. The in vitro assays yielded four active HPLC-fractions against <i>L. amazonensis</i> with IC50 values ranging from 175.2 μg/mL to 194.8 μg/mL, and fraction G29 showed an IC50 of 119.8 μg/mL against <i>P. falciparum</i>.</p><p><strong>Conclusions: </strong>The ethnobotanical use of \"mulateiro\" wood bark tea as an antimalarial and antileishmanial agent was confirmed through in vitro assays. We speculate that these activities are attributed to linoleic acids and quinic acids.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Multifaceted Computational Approach to Identify PAD4 Inhibitors for the Treatment of Rheumatoid Arthritis (RA).","authors":"Mansour S Alturki, Mohamed S Gomaa, Nada Tawfeeq, Abdulaziz H Al Khzem, Mohsina B Shaik, Murtadha Alshaikh Jafar, Mohammad Alsamen, Hasan Al Nahab, Mohammad Al-Eid, Alhassan Almutawah, Thankhoe A Rants'o, Khaled A G Ayil, Mohammed Almaghrabi","doi":"10.3390/metabo15030156","DOIUrl":"10.3390/metabo15030156","url":null,"abstract":"<p><strong>Background/objectives: </strong>Neutrophil cells' lysis forms the extracellular traps (NETs) to counter the foreign body during insults to the body. Peptidyl arginine deiminase (PAD) participates in this process and is then released into the extracellular fluid with the lysed cell components. In some diseases, patients with abnormal function of PADs, especially PAD 4, tend to form autoantibodies against the abnormal citrullinated proteins that are the result of PAD activity on arginine side chains. Those antibodies, which are highly distinct in RA, are distinctly anti-citrullinated protein antibodies (ACPA). This study used an in-silico drug repurposing approach of FDA-approved medications to identify potential alternative medications that can inhibit this process and address solutions to the current limitations of existing therapies.</p><p><strong>Methods: </strong>We utilized Maestro Schrödinger as a computational tool for preparing and docking simulations on the PAD 4 enzyme crystal structure that is retrieved from RCSB Protein Data Bank (PDB ID: 4X8G) while the docked FDA-approved medications are obtained from the Zinc 15 database. The protein was bound to GSK 199-an investigational compound-as a positive control for the docked molecules. Preparation of the protein was performed by Schrödinger Protein Preparation Wizard tool. Binding pocket determination was performed by Glide software (Schrödinger Release 2021-3:Schrödinger, LLC., New York, NY, USA, 2021). and validation of molecular docking was carried out through the redocking of GSK 199 and superimposition. After that, standard and induced fit docking were performed.</p><p><strong>Results/conclusions: </strong>Among the four obtained hits Pemetrexed, Leucovorin, Chlordiazepoxide, and Ioversol, which showed the highest XP scores providing favorable binding interactions. The induced-fit docking (IFD) results displayed the strong binding affinities of Ioversol, Pemetrexed, Leucovorin, Chlordiazepoxide in the order IFD values -11.617, -10.599, -10.521, -9.988, respectively. This research investigates Pemetrexed, Leucovorin, Chlordiazepoxide, and Ioversol as potential repurposing agents in the treatment of rheumatoid arthritis (RA) as they are identified as PAD4 inhibitors.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Roasting Process on Sensory Qualities, Color, Physicochemical Components, and Identification of Key Aroma Compounds in Hubei Strip-Shaped Green Tea.","authors":"Fei Ye, Anhui Gui, Xiaoyan Qiao, Panpan Liu, Xueping Wang, Shengpeng Wang, Lin Feng, Jin Teng, Jinjin Xue, Xun Chen, Yuanhong Mei, Binghua Zhang, Hanshan Han, Anhua Liao, Pengcheng Zheng, Shiwei Gao","doi":"10.3390/metabo15030155","DOIUrl":"10.3390/metabo15030155","url":null,"abstract":"<p><strong>Background: </strong>Roasting conditions significantly influence the sensory profile of Hubei strip-shaped green tea (HSSGT).</p><p><strong>Methods: </strong>This study examined the effects of roast processing on the sensory attributes, color qualities, physicochemical properties, and key aroma compounds of HSSGT. Sensory evaluation, color qualities determination, principal component analysis of physicochemical components (PCA), HS-SPME (headspace solid-phase microextraction) coupled with GC-MS (gas chromatography-mass spectrometry), relative odor activity value (ROAV), gas chromatography-olfactometry (GC-O), and absolute quantification analysis were employed to identify the critical difference in compounds that influence HSSGT desirability.</p><p><strong>Results: </strong>The results indicated that HSSGT roasted at 110 °C for 14 min achieved the highest sensory scores, superior physicochemical qualities, and an enhanced aroma index, which was attributed to shifting the proportion of chestnut to floral volatile compounds. Additionally, sensory-guided ROAV, GC-O, and absolute quantification revealed that linalool, octanal, nonanal, and hexanal were the most significant volatile compounds. The variations in these four critical compounds throughout the roasting process were further elucidated, showing that the ideal roasting conditions heightened floral aromas while diminishing the presence of less desirable green odors. These findings offer technical guidance and theoretical support for producing HSSGT with a more desirable balance of chestnut and floral aroma characteristics.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Proteomics and Metabolomics of Aromatase Inhibitors-Related Musculoskeletal Syndrome in Early Breast Cancer Patients.","authors":"Feng Jing, Lingyun Jiang, Yuling Cao, Maoting Tian, Jiajia Qiu, Jing Zhang, Lichen Tang, Renquan Lu, Yan Hu","doi":"10.3390/metabo15030153","DOIUrl":"10.3390/metabo15030153","url":null,"abstract":"<p><strong>Background: </strong>Aromatase inhibitors-related musculoskeletal syndrome (AIMSS) is a common side effect experienced by early breast cancer patients undergoing endocrine therapy. This condition can result in medication discontinuation and a diminished quality of life. The objective of this study was to characterize AIMSS, investigate its pathogenesis, and identify potential biomarkers at both the protein and metabolic levels.</p><p><strong>Methods: </strong>We collected peripheral blood samples from 60 women diagnosed with breast cancer undergoing aromatase inhibitor therapy, of whom 30 had AIMSS and 30 did not. The samples were analyzed using four-dimensional data-independent acquisition (DIA)-based proteomics and untargeted metabolomics, employing liquid chromatography-mass spectrometry (LC-MS) on the latest platform.</p><p><strong>Results: </strong>The mean age of participants was 49.2 (11.3) years in the AIMSS group and 50.1 (11.5) years in the non-AIMSS group. There were no statistically significant differences between the two groups in terms of age, BMI, education level, clinical stage, and treatment. In total, we identified 3473 proteins and 1247 metabolites in the samples. The chemokine signaling pathway (<i>p</i> = 0.015), cytokine-cytokine receptor interaction (<i>p</i> = 0.015), complement and coagulation cascades (<i>p</i> = 0.004), neuroactive ligand-receptor interaction (<i>p</i> = 0.004), and the estrogen signaling pathway (<i>p</i> = 0.004) were significant enriched in differentially expressed proteins (DEPs). GnRH secretion (<i>p</i> < 0.001), sphingolipid signaling pathways (<i>p</i> < 0.001), endocrine resistance (<i>p</i> < 0.001), the estrogen signaling pathway (<i>p</i> = 0.001), endocrine and other factor-regulated calcium reabsorption (<i>p</i> = 0.001), dopaminergic synapse (<i>p</i> = 0.003), regulation of lipolysis in adipocytes (<i>p</i> = 0.004), biosynthesis of cofactors (<i>p</i> = 0.004), thyroid hormone synthesis (<i>p</i> = 0.008), aldosterone synthesis and secretion (<i>p</i> = 0.001), taurine and hypotaurine metabolism (<i>p</i> = 0.011), ovarian steroidogenesis (<i>p</i> = 0.011), and the cAMP signaling pathway (<i>p</i> = 0.011) were significantly enriched in differentially expressed metabolites (DEMs). Complement C3 (<i>p</i> = 0.004), platelet factor 4 (<i>p</i> = 0.015), KRT10 (<i>p</i> = 0.004), KRT14 (<i>p</i> = 0.004), beta-estradiol (<i>p</i> = 0.019), testosterone (<i>p</i> = 0.023), sphingosine (<i>p</i> < 0.001), and 1-stearoyl-2-arachidonoyl-sn-glycerol (<i>p</i> = 0.039) could be the monitoring and therapeutic targets for AIMSS.</p><p><strong>Conclusions: </strong>This study offered new insights into the mechanisms underlying musculoskeletal symptoms associated with aromatase inhibitors. It also highlighted potential biomarkers for predicting and addressing these symptoms in breast cancer patients, paving the way for improved intervention strategies.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polar Metabolite Profiles Distinguish Between Early and Severe Sub-Maintenance Nutritional States of Wild Bighorn Sheep.","authors":"Galen O'Shea-Stone, Brian Tripet, Jennifer Thomson, Robert Garrott, Valérie Copié","doi":"10.3390/metabo15030154","DOIUrl":"10.3390/metabo15030154","url":null,"abstract":"<p><p><b>Background:</b> Understanding the metabolic adaptations of wild bighorn sheep (<i>Ovis c. canadensis</i>) to nutritional stress is crucial for their conservation. <b>Methods:</b> This study employed ¹H nuclear magnetic resonance (NMR) metabolomics to investigate the biochemical responses of these animals to varying sub-maintenance nutritional states. Serum samples from 388 wild bighorn sheep collected between 2014 and 2017 from December (early sub-maintenance) through March (severe sub-maintenance) across Wyoming and Montana were analyzed. Multivariate statistics and machine learning analyses were employed to identify characteristic metabolic patterns and metabolic interactions between early and severe sub-maintenance nutritional states. <b>Results:</b> Significant differences were observed in the levels of 15 of the 49 quantified metabolites, including formate, thymine, glucose, choline, and others, pointing to disruptions in one-carbon, amino acid, and central carbon metabolic pathways. These metabolites may serve as indicators of critical physiological processes such as nutritional intake, immune function, energy metabolism, and protein catabolism, which are essential for understanding how wild bighorn sheep adapt to nutritional stress. <b>Conclusions:</b> This study has generated valuable insights into molecular networks underlying the metabolic resilience of wild bighorn sheep, highlighting the potential for using specific biochemical markers to evaluate nutritional and energetic states in free-ranging ungulates. These insights may help wildlife managers and ecologists compare populations across different times in seasonal cycles, providing information to assess the adequacy of seasonal ranges and support conservation efforts. This research strengthens our understanding of metabolic adaptations to environmental stressors in wild ruminants, offering a foundation for improving management practices to maintain healthy bighorn sheep populations.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}