Metabolites最新文献

{"title":"Impact of Tributyltin (TBT) on Energy Metabolism and Redox Homeostasis in Blue Crab <i>Callinectes sapidus</i>.","authors":"Leonardo Airton Ressel Simões, Rafaella Sanfelice Normann, Daniela Drosdowski, Bruna Selau, Marjoriane de Amaral, Alex Sander da Rosa Araujo, Anapaula Sommer Vinagre","doi":"10.3390/metabo15040253","DOIUrl":"https://doi.org/10.3390/metabo15040253","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Tributyltin (TBT), a potent biocide used in antifouling paints, is highly toxic to aquatic environments, causing oxidative stress, endocrine dysfunction, and metabolic disorders in aquatic organisms, including crustaceans. The blue crab <i>Callinectes sapidus</i> is an economically and ecologically important species in several countries worldwide and is considered an invasive species in Europe. <b>Methods</b>: This study evaluated the effects of 7 days of exposure to environmentally relevant TBT concentrations (100 and 1000 ng.L^-1) on the intermediary metabolism and oxidative balance of the blue crab <i>Callinectes sapidus</i>. After exposure, hemolymph samples were analyzed to determine glucose, lactate, total protein, and cholesterol levels. In tissue samples, concentrations of triglycerides, glycogen, total glutathione (GSH), reactive oxygen species (ROS), sulfhydryls, lipid peroxidation (LPO), and glutathione S-transferase (GST) activity were assessed. <b>Results</b>: In the hemolymph, glucose and lactate levels increased, while the total cholesterol, triglycerides, and total proteins decreased in all exposed groups. The GST activity increased in exposed tissues, while the total GSH and sulfhydryl content decreased. The ROS concentration increased in response to higher TBT concentrations. <b>Conclusions</b>: These findings highlight the toxicity of TBT and show that 7 days of exposure to environmentally relevant concentrations disrupts the metabolic homeostasis and oxidative balance in <i>C. sapidus</i>. Additionally, this study demonstrates that <i>C. sapidus</i> is sensitive to TBT exposure and has potential as a model species for ecotoxicological studies.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12029525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032278","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":"The Role of the Intrauterine Environment in Shaping Childhood and Adolescence Metabolic Outcomes.","authors":"Asli Derya Kardelen, Feyza Darendeliler","doi":"10.3390/metabo15040252","DOIUrl":"https://doi.org/10.3390/metabo15040252","url":null,"abstract":"<p><p>Emerging research suggests that the intrauterine environment plays a critical role in predisposing individuals to metabolic syndrome (MetS), a constellation of conditions that heightens the risk for heart disease, stroke, and diabetes. Traditionally linked to lifestyle, the risk for MetS is now understood to be also influenced by fetal exposures. The environment in which a child lives offers abundant potential sources that can contribute to an increased risk of developing various diseases, and in some cases, these factors can be avoided. This review integrates findings from both epidemiological and experimental research to underscore the impact of prenatal factors, including maternal nutrition, obesity, gestational diabetes (GDM), and birth size, on the subsequent development of metabolic derangements in offspring, particularly during puberty. The progression of genetic and epigenetic studies has enlightened the pathophysiology of these conditions starting in the intrauterine period and continuing into early life. By examining data and studies, this article elucidates the prenatal influences and underlying mechanisms that contribute to the pathogenesis of MetS. The updated understanding of the link between the intrauterine environment and future health comorbidities will draw attention to intrauterine care and maternal health and contribute to the prevention of serious diseases in adulthood.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12029342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992783","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 Long-Term Airport Noise Exposure on Inflammation and Intestinal Flora and Their Metabolites in Mice.","authors":"Jian Yang, Longwei Wei, Yuan Xia, Junyi Wang, Yan Bai, Yun Xia","doi":"10.3390/metabo15040251","DOIUrl":"https://doi.org/10.3390/metabo15040251","url":null,"abstract":"<p><p><b>Background</b>: The World Health Organization has indicated that airport noise is strongly associated with cardiovascular disease, with vascular inflammation identified as the primary mechanism. Therefore, long-term exposure to airport noise is considered far more harmful than other types of noise. However, there remains a lack of research into the mechanisms underlying long-term exposure to airport noise and harm to the human body. <b>Methods</b>: A mouse model was established and exposed to airport noise at a maximum sound pressure level of 95 dB(A) and an equivalent continuous sound pressure level of 72 dB(A) for 12 h per day over a period of 100 days. Quantitative polymerase chain reaction (qPCR) was used to detect the mRNA expression levels of pro-inflammatory and anti-inflammatory factors. Enzyme-linked immunosorbent assay (ELISA) was used to detect LPS, LTA, TMA, and TMAO levels. Intestinal flora composition was analyzed by 16S rDNA sequencing, and targeted metabolomics was employed to determine the levels of serum short-chain fatty acids. <b>Results</b>: Long-term airport noise exposure significantly increased systolic blood pressure, diastolic blood pressure, and mean blood pressure (<i>p</i> < 0.05); significantly increased the mRNA expression levels of oxidative stress parameters (nuclear matrix protein 2, 3-nitrotyrosine, and monocyte chemoattractant protein-1) (<i>p</i> < 0.05); significantly increased pro-inflammatory factors (interleukin 6 and tumor necrosis factor alpha) (<i>p</i> < 0.05); significantly decreased the mRNA expression level of anti-inflammatory factor interleukin 10 (<i>p</i> < 0.05); and significantly increased the content of LPS and LTA (<i>p</i> < 0.05). The composition of the main flora in the intestinal tract was structurally disordered, and there were significant differences between the noise-exposed and control groups at the levels of the phylum, family, and genus of bacteria. β-diversity of the principal component analysis diagrams was clearly distinguished. Compared with those of the control group, TMA-producing bacteria and levels of TMA and TMAO were significantly reduced, and the serum ethanoic acid and propanoic acid levels of the noise-exposed group were significantly decreased (<i>p</i> < 0.05). <b>Conclusions</b>: Long-term airport noise exposure causes significant elevation of blood pressure and structural disruption in the composition of the intestinal flora in mice, leading to elevated levels of oxidative stress and inflammation, resulting in metabolic disorders that lead to significant changes in the production of metabolites.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12029524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009240","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":"Untargeted Metabolomics Reveals Acylcarnitines as Major Metabolic Targets of Resveratrol in Breast Cancer Cells.","authors":"Isabella G Falcone, Blake R Rushing","doi":"10.3390/metabo15040250","DOIUrl":"https://doi.org/10.3390/metabo15040250","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Millions of new diagnoses of breast cancer are made each year, with many cases having poor prognoses and limited treatment options, particularly for some subtypes such as triple-negative breast cancer. Resveratrol, a naturally occurring polyphenol, has demonstrated many anticancer properties in breast cancer studies. However, the mechanism of action of this compound remains elusive, although prior evidence suggests that this compound may work through altering cancer cell metabolism. Our objective for the current study was to perform untargeted metabolomics analysis on resveratrol-treated breast cancer cells to identify key metabolic targets of this compound. <b>Methods:</b> MCF-7 and MDA-MB-231 breast cancer cells were treated with varying doses of resveratrol and extracted for mass spectrometry-based untargeted metabolomics. Data preprocessing and filtering of metabolomics data from MCF-7 samples yielded 4751 peaks, with 312 peaks matched to an in-house standards library and 3459 peaks matched to public databases. <b>Results:</b> Pathway analysis in MetaboAnalyst identified significant (<i>p</i> < 0.05) metabolic pathways affected by resveratrol treatment, particularly those involving steroid, fatty acid, amino acid, and nucleotide metabolism. Evaluation of standard-matched peaks revealed acylcarnitines as a major target of resveratrol treatment, with long-chain acylcarnitines exhibiting a 2-5-fold increase in MCF-7 cells and a 5-13-fold increase in MDA-MB-231 cells when comparing the 100 µM treated cells to vehicle-treated cells (<i>p</i> < 0.05, VIP > 1). Notably, doses below 10 µM showed an opposite effect, possibly indicating a biphasic effect of resveratrol due to a switch from anti-oxidant to pro-oxidant effects as dose levels increase. <b>Conclusions:</b> These findings suggest that resveratrol induces mitochondrial metabolic reprogramming in breast cancer cells in a dose-dependent manner. The biphasic response indicates a potential optimal dosage for therapeutic effectiveness. Further research is warranted to explore the mechanisms underlying these metabolic alterations and their implications for precision nutrition strategies in cancer treatment.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12029535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144008038","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":"Gut-Microbiota-Driven Lipid Metabolism: Mechanisms and Applications in Swine Production.","authors":"Shuqi Xiong","doi":"10.3390/metabo15040248","DOIUrl":"https://doi.org/10.3390/metabo15040248","url":null,"abstract":"<p><p><b>Background/Objectives:</b> The gut microbiota plays a pivotal role in host physiology through metabolite production, with lipids serving as essential biomolecules for cellular structure, metabolism, and signaling. This review aims to elucidate the interactions between gut microbiota and lipid metabolism and their implications for enhancing swine production. <b>Methods:</b> We systematically analyzed current literature on microbial lipid metabolism, focusing on mechanistic studies on microbiota-lipid interactions, key regulatory pathways in microbial lipid metabolism, and multi-omics evidence (metagenomic/metabolomic) from swine models. <b>Results:</b> This review outlines the structural and functional roles of lipids in bacterial membranes and examines the influence of gut microbiota on the metabolism of key lipid classes, including cholesterol, bile acids, choline, sphingolipids, and fatty acids. Additionally, we explore the potential applications of microbial lipid metabolism in enhancing swine production performance. <b>Conclusions:</b> Our analysis establishes a scientific framework for microbiota-based strategies to optimize lipid metabolism. The findings highlight potential interventions to improve livestock productivity through targeted manipulation of gut microbial communities.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12029090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003877","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":"Towards Optimizing Neural Network-Based Quantification for NMR Metabolomics.","authors":"Hayden Johnson, Aaryani Tipirneni-Sajja","doi":"10.3390/metabo15040249","DOIUrl":"https://doi.org/10.3390/metabo15040249","url":null,"abstract":"<p><p><b>Background:</b> Quantification of metabolites from nuclear magnetic resonance (NMR) spectra in an accurate, high-throughput manner requires effective data processing tools. Neural networks are relatively underexplored in quantitative NMR metabolomics despite impressive speed and throughput compared to more conventional peak-fitting metabolomics software. <b>Methods:</b> This work investigates practices for dataset and model development in the task of metabolite quantification directly from simulated NMR spectra for three neural network models: the multi-layered perceptron, the convolutional neural network, and the transformer. Model architectures, training parameters, and training datasets are optimized before comparing each model on simulated 400-MHz ¹H-NMR spectra of complex mixtures with 8, 44, or 86 metabolites to quantify in spectra ranging from simple to highly complex and overlapping peaks. The optimized models were further validated on spectra at 100- and 800-MHz. <b>Results:</b> The transformer was the most effective network for NMR metabolite quantification, especially as the number of metabolites per spectra increased or target concentrations were low or had a large dynamic range. Further, the transformer was able to accurately quantify metabolites in simulated spectra from 100-MHz up to 800-MHz. <b>Conclusions:</b> The methods developed in this work reveal that transformers have the potential to accurately perform fully automated metabolite quantification in real-time and, with further development with experimental data, could be the basis for automated quantitative NMR metabolomics software.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12029129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031603","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":"Uncovering Non-Invasive Biomarkers in Paediatric Severe Acute Asthma Using Targeted Exhaled Breath Analysis.","authors":"Sarah van den Berg, Annabel S Zaat, Isabel F van der Poel, Yoni E van Dijk, Simone Hashimoto, Niels W P Rutjes, Suzanne W J Terheggen-Largo, Bart E van Ewijk, Claudia Gagliani, Fleur L Sondaal, Job B M van Woensel, Anke-Hilse Maitland-van der Zee, Paul Brinkman, Susanne J H Vijverberg, Berber Kapitein","doi":"10.3390/metabo15040247","DOIUrl":"https://doi.org/10.3390/metabo15040247","url":null,"abstract":"<p><strong>Background: </strong>Severe acute asthma (SAA) in children can be life-threatening. There has been a significant rise in paediatric intensive care unit (PICU) admissions due to SAA over the past two decades. While asthma is a heterogeneous disease, its underlying pathophysiological pathways remain underexplored. This study aimed to assess the value of non-invasive targeted exhaled breath metabolomics analysis to better characterise SAA.</p><p><strong>Methods: </strong>Breath samples from 17 children admitted to the PICU with SAA (cases) and 27 children with controlled severe asthma (controls) were analysed using thermal desorption gas chromatography-mass spectrometry (TD-GC-MS).</p><p><strong>Results: </strong>A targeted volatile organic compound (VOC) analysis identified 25 compounds, of which 16 were shared between groups. Four VOCs were significantly more often present in SAA, and nine VOCs exhibited higher concentrations in SAA. Longitudinal analysis of VOCs from follow-up samples of 10 cases showed no significant temporal differences, reinforcing the reproducibility of identified biomarkers.</p><p><strong>Conclusions: </strong>This study exemplifies the potential of exhaled breath analysis to provide insights into the molecular background of SAA. Breath metabolomics may enable early recognition of severe asthma attacks and preventive therapeutic interventions in children with severe asthma.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12029713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031501","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":"Purine Metabolism Pathway Influence on Running Capacity in Rats.","authors":"Dengbo Chen, Christian Noble Biney, Qian Wang, Mingzheng Cai, Shi Cheng, Wentao Chen, Jinrui Zhang, Junran Zhao, Yuhan Zhang, Wenzhong Zhang","doi":"10.3390/metabo15040241","DOIUrl":"https://doi.org/10.3390/metabo15040241","url":null,"abstract":"<p><p><b>Background</b>: The natural differences in running capacities among rats remain poorly understood, and the mechanisms driving these differences need further investigation. <b>Methods</b>: Twenty male Sprague-Dawley (SD) rats were selected. High and low running capacity rats were identified using Treadmill Exhaustion Tests. Peripheral blood was collected for serum isolation, followed by a metabolomics analysis using LC-MS/MS. Data were preprocessed, and a principal component analysis (PCA) and a partial least squares-discriminant analysis (PLS-DA) were applied to identify metabolic profile differences. Significant metabolites were screened, and a pathway enrichment analysis was conducted using the KEGG database to determine key metabolic pathways. Forty SD rats (equal male and female) were randomly divided into an inosine triphosphate (ITP) group (24.29 mg/kg.bw daily) and a control group. Running capacity was assessed after one week of continuous treatment. <b>Results</b>: Three independent measurements showed consistent differences in running capacity. A total of 519 differential metabolites were identified, with 255 up-regulated and 264 down-regulated. The KEGG pathway analysis revealed a significant enrichment of the Purine Metabolism pathway (ITP-ATP) in the high running capacity group (<i>p</i> < 0.05). The ITP-treated group exhibited a significantly higher running capacity than the controls (<i>p</i> < 0.05), confirming the efficacy of dietary ITP supplementation. <b>Conclusions</b>: The running capacity of rats is influenced by the ITP-ATP pathway, and exogenous ITP administration through dietary intervention significantly improves running ability.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12029474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992768","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":"Fibroblast Activation Protein Compared with Other Markers of Activated Smooth Muscle Cells, Extracellular Matrix Turnover and Inflammation in a Mouse Model of Atherosclerosis.","authors":"Adam Mohmand-Borkowski, Dareus O Conover, Tomasz Rozmyslowicz","doi":"10.3390/metabo15040243","DOIUrl":"https://doi.org/10.3390/metabo15040243","url":null,"abstract":"<p><p><b>Background:</b> Fibroblast activation protein (FAP) is a cell surface glycoprotein expressed by myofibroblastic cells in areas of active tissue remodeling, such as wound healing, fibrosis, and certain chronic inflammatory lesions. As FAP is uniquely present in chronic inflammatory lesions and has an important role in extracellular matrix (ECM) turnover, it appears to have all the characteristics necessary for involvement in atherosclerosis and atherosclerotic plaque rupture and has become a potential target in the treatment of myocardial infarction. <b>Methods:</b> To further understand the role of FAP, its expression in atherosclerotic plaques was examined in a genetically modified mouse model of accelerated atherosclerosis (<i>Apobec1</i> -/- <i>Ldlr</i> -/- double-knockout mice). The immunohistochemical Fap staining of atherosclerotic plaques in a mouse model of atherosclerosis was correlated with quantification of <i>Fap</i> mRNA obtained from the atherosclerotic plaques of the aortic arch. Fap distribution was characterized in mouse atherosclerotic plaques relative to other markers of activated smooth muscle cells, such as alpha smooth muscle actin and myosin heavy chain (Acta2 and Myh2), ECM turnover (Ki-67, procollagen III and Mmp-9), and inflammation in atherosclerosis (Cd-44, Il-12 and Tgf beta) using immunohistochemistry (IH) and RT-PCR analysis. <b>Results:</b> The mouse model of accelerated atherosclerosis showed an increasing presence of Fap with the progression of atherosclerosis and a high expression level in advanced atherosclerotic lesions compared with other markers of ECM turnover and inflammation in atherosclerosis. <b>Conclusions:</b> FAP exhibits a distinct pattern of expression in a mouse model of atherosclerosis as compared to other markers of activated vascular smooth muscle cells, ECM degeneration, and inflammatory cytokines.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12029363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970430","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":"Cell-Free DNA (cfDNA) Regulates Metabolic Remodeling in the ES-2 Ovarian Carcinoma Cell Line, Influencing Cell Proliferation, Quiescence, and Chemoresistance in a Cell-of-Origin-Specific Manner.","authors":"Isabel Lemos, Catarina Freitas-Dias, Ana Hipólito, José Ramalho, Fabrizio Carteni, Luís G Gonçalves, Stefano Mazzoleni, Jacinta Serpa","doi":"10.3390/metabo15040244","DOIUrl":"https://doi.org/10.3390/metabo15040244","url":null,"abstract":"<p><p><b>Background:</b> The cell-free DNA (cfDNA) is an extracellular fragmented DNA found in body fluids in physiological and pathophysiological contexts. In cancer, cfDNA has been pointed out as a marker for disease diagnosis, staging, and prognosis; however, little is known about its biological role. <b>Methods:</b> The role of cfDNA released by ES-2 ovarian cancer cells was investigated, along with the impact of glucose bioavailability and culture duration in the cfDNA-induced phenotype. The effect of cfDNA on ES-2 cell proliferation was evaluated by proliferation curves, and cell migration was assessed through wound healing. We explored the impact of different cfDNA variants on ES-2 cells' metabolic profile using nuclear magnetic resonance (NMR) spectroscopy and cisplatin resistance through flow cytometry. Moreover, we assessed the protein levels of DNA-sensitive Toll-like receptor 9 (TLR9) by immunofluorescence and its colocalization with lysosome-associated membrane protein 1 (LAMP1). <b>Results:</b> This study demonstrated that despite inducing similar effects, different variants of cfDNA promote different effects on cells derived from the ES-2 cell line. We observed instant reactions of adopting the metabolic profile that brings back the cell functioning of more favorable culture conditions supporting proliferation and resembling the cell of origin of the cfDNA variant, as observed in unselected ES-2 cells. However, as a long-term selective factor, certain cfDNA variants induced quiescence that favors the chemoresistance of a subset of cancer cells. <b>Conclusions:</b> Therefore, different tumoral microenvironments may generate cfDNA variants that will impact cancer cells differently, orchestrating the disease fate.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12029194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025784","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}