Metabolites最新文献

{"title":"Development of Sucrose-Utilizing <i>Escherichia coli</i> Nissle 1917 for Efficient Heparosan Biosynthesis.","authors":"Yaozong Chen, Zihua Wan, Zheng-Jun Li","doi":"10.3390/metabo15060410","DOIUrl":"10.3390/metabo15060410","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Heparosan is a component of the capsular polysaccharide in <i>Escherichia coli</i> K5 and <i>Pasteurella multocida</i> Type D. It shares a similar glycan structure with heparin and can be enzymatically modified to produce bioactive heparin. <b>Methods</b>: In this study, the probiotic strain <i>E. coli</i> Nissle 1917 (EcN), which naturally produces heparosan, was genetically engineered to utilize sucrose as a carbon source for growth while achieving high-yield heparosan biosynthesis. <b>Results</b>: By expressing the sucrose hydrolase genes <i>sacA</i> (from <i>Bacillus subtilis</i>) or <i>spI</i> (from <i>Bifidobacterium adolescentis</i>), EcN was enabled to utilize sucrose, achieving heparosan titers of 131 mg/L and 179 mg/L, respectively. Further metabolic engineering was performed to block the glycolytic and pentose phosphate pathways, thereby redirecting sucrose-derived glucose-6-phosphate and fructose-6-phosphate toward heparosan biosynthesis, while glycerol was supplemented as an auxiliary carbon source to support cell growth. Finally, the key biosynthesis genes <i>galU</i>, <i>kfiD</i>, and <i>glmM</i> were overexpressed, resulting in an engineered strain with a heparosan titer of 622 mg/L. <b>Conclusions</b>: This study represents the first successful engineering of EcN to utilize sucrose as the carbon source for growth, while achieving enhanced heparosan production through synergistic carbon source utilization. These findings establish a foundational strategy for employing this strain in the sucrose-based biosynthesis of other glycosaminoglycans.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12194944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485009","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-Microbiome Signatures Predicting Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer: A Systematic Review.","authors":"Ielmina Domilescu, Bogdan Miutescu, Florin George Horhat, Alina Popescu, Camelia Nica, Ana Maria Ghiuchici, Eyad Gadour, Ioan Sîrbu, Delia Hutanu","doi":"10.3390/metabo15060412","DOIUrl":"10.3390/metabo15060412","url":null,"abstract":"<p><strong>Background and objectives: </strong>Rectal cancer management increasingly relies on watch-and-wait strategies after neoadjuvant chemoradiotherapy (nCRT). Accurate, non-invasive prediction of pathological complete response (pCR) remains elusive. Emerging evidence suggests that gut-microbiome composition modulates radio-chemosensitivity. We systematically reviewed primary studies that correlated baseline or on-treatment gut-microbiome features with nCRT response in locally advanced rectal cancer (LARC).</p><p><strong>Methods: </strong>MEDLINE, Embase and PubMed were searched from inception to 30 April 2025. Eligibility required (i) prospective or retrospective human studies of LARC, (ii) faecal or mucosal microbiome profiling by 16S, metagenomics, or metatranscriptomics, and (iii) response assessment using tumour-regression grade or pCR. Narrative synthesis and random-effects proportion meta-analysis were performed where data were homogeneous.</p><p><strong>Results: </strong>Twelve studies (n = 1354 unique patients, median sample = 73, range 22-735) met inclusion. Four independent machine-learning models achieved an Area Under the Receiver Operating Characteristic curve AUROC ≥ 0.85 for pCR prediction. Consistently enriched taxa in responders included <i>Lachnospiraceae bacterium</i>, <i>Blautia wexlerae</i>, <i>Roseburia</i> spp., and <i>Intestinimonas butyriciproducens</i>. Non-responders showed over-representation of <i>Fusobacterium nucleatum</i>, <i>Bacteroides fragilis</i>, and <i>Prevotella</i> spp. Two studies linked butyrate-producing modules to radiosensitivity, whereas nucleotide-biosynthesis pathways conferred resistance. Pooled pCR rate in patients with a \"butyrate-rich\" baseline profile was 44% (95% CI 35-54) versus 21% (95% CI 15-29) in controls (I² = 18%).</p><p><strong>Conclusions: </strong>Despite heterogeneity, convergent functional and taxonomic signals underpin a microbiome-based radiosensitivity axis in LARC. Multi-centre validation cohorts and intervention trials manipulating these taxa, such as prebiotics or live-biotherapeutics, are warranted before clinical deployment.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485029","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":"Impact of Dietary Carbohydrate Levels on Growth Performance, Feed Efficiency, and Immune Response in <i>Litopenaeus vannamei</i> Cultured in Biofloc Systems.","authors":"Yulong Sun, Shuailiang Zhang, Wenping Feng, Yunqi Zhang, Tao Han, Jiteng Wang","doi":"10.3390/metabo15060409","DOIUrl":"10.3390/metabo15060409","url":null,"abstract":"<p><p><b>Background/Objective:</b> Over an eight-week period, this study assessed the influence of dietary carbohydrate levels on growth, metabolism, and immunity in Pacific white shrimp (<i>Litopenaeus vannamei</i>) raised within a biofloc technology (BFT) system. <b>Methods:</b> Five isonitrogenous and isolipidic diets, spanning carbohydrate levels from 11% to 47%, were evaluated. <b>Results:</b> The results showed that dietary carbohydrate significantly impacted both growth performance and feed utilization. The diet containing 38% carbohydrate yielded the best outcomes, resulting in the highest weight gain, specific growth rate, and an optimal feed conversion ratio in the shrimp. Hepatopancreatic metabolic analysis revealed that the shrimp adapted to diets high in carbohydrates through the upregulation of glycolytic enzymes (PK, PFK) and downregulation of gluconeogenic enzymes (PEPCK, G6Pase). By optimizing the water quality and supplementing microbial nutrition, <i>L. vannamei</i> in the BFT system exhibited enhanced dietary carbohydrate utilization and strengthened innate immunity. Specifically, SOD and CAT activities remained largely unaffected by varying carbohydrate levels. However, excessive carbohydrate intake still induced oxidative stress. The high-sugar group (47%) exhibited a significant increase in hemolymph MDA content (<i>p</i> < 0.05), with corresponding metabolic alterations observed in glucose, triglyceride, and total protein levels. On the basis of the results of this study, the BFT system may mitigate the adverse effects of a high-carbohydrate diet by enhancing lysosomal enzyme activity (e.g., ACP) and increasing total protein levels. <b>Conclusions:</b> These findings suggest that the BFT system enhances shrimp immunity and mitigates the potential adverse effects of imbalanced dietary components. Piecewise regression analysis determined the optimal dietary carbohydrate level for shrimp within the BFT system to be 31.44-31.77%.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485043","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":"Metabolomics Signatures of a Respiratory Tract Infection During an Altitude Training Camp in Elite Rowers.","authors":"Félix Boudry, Fabienne Durand, Corentine Goossens","doi":"10.3390/metabo15060408","DOIUrl":"10.3390/metabo15060408","url":null,"abstract":"<p><p><b>Background</b>: Respiratory pathologies, such as COVID-19 and bronchitis, pose significant challenges for high-level athletes, particularly during demanding altitude training camps. Metabolomics offers a promising approach for early detection of such pathologies, potentially minimizing their impact on performance. This study investigates the metabolic differences between athletes with and without respiratory illnesses during an altitude training camp using urine samples and multivariate analysis. <b>Methods</b>: Twenty-seven elite rowers (15 males, 12 females) participated in a 12-day altitude training camp at 1850 m. Urine samples were collected daily, with nine athletes developing respiratory pathologies (8 COVID-19, 1 bronchitis). Nuclear Magnetic Resonance spectroscopy was used to analyze the samples, followed by data processing with Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA), allowing to use Variable Importance in Projection (VIP) scores to identify key metabolites contributing to group separation. <b>Results</b>: The PLS-DA model for respiratory illness showed good performance (R² = 0.89, Q² = 0.35, <i>p</i> < 0.05). Models for altitude training achieved higher predictive power (Q² = 0.51 and 0.72, respectively). Metabolites kynurenine, <i>N</i>-methylnicotinamide, pyroglutamate, propionate, <i>N</i>-formyltryptophan, tryptophan and glucose were significantly highlighted in case of respiratory illness while trigonelline, 3-hydroxyphenylacetate, glutamate, creatine, citrate, urea, o-hydroxyhippurate, creatinine, hippurate and alanine were correlated to effort in altitude. This distinction confirms that respiratory illness induces a unique metabolic profile, clearly separable from hypoxia and training-induced adaptations. <b>Conclusions</b>: This study highlights the utility of metabolomics in identifying biomarkers of respiratory pathologies in athletes during altitude training, offering the potential for improved monitoring and intervention strategies. These findings could enhance athlete health management, reducing the impact of illness on performance during critical training periods. Further research with larger cohorts is warranted to confirm these results and explore targeted interventions.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485062","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":"An LC-MS Method to Quantify Rhein and Its Metabolites in Plasma: Application to a Pharmacokinetic Study in Rats.","authors":"Nyma Siddiqui, Yuan Chen, Ting Du, Yang Wang, Charmeyce Buck, Song Gao","doi":"10.3390/metabo15060407","DOIUrl":"10.3390/metabo15060407","url":null,"abstract":"<p><p><b>Background:</b> Diacerein, a prodrug of Rhein, is commonly prescribed for the management of joint disorders, specifically osteoarthritis. This study aimed to develop and validate an LC-MS/MS method to quantify Rhein and its major metabolites, Rhein-G1 and Rhein-G2, in plasma samples. <b>Method:</b> An ACE C18 column was used for chromatographic separation with a mobile phase comprising ammonium acetate at a concentration of 1.0 mM and acetonitrile. Detection was achieved using a Sciex 4000 Q-Trap LC-MS/MS, operated in negative ion mode with multiple reaction monitoring (MRM). <b>Results:</b> The analytical results indicated that the lower limit of quantification (LLOQ) for Rhein and its glucuronides was 7.81 nM. Precision was consistently below 9.14%, while accuracy remained within the acceptable range of 80.1-104.2%. We also verified the method's matrix effect recovery and stability variance, which were less than 12.60% and 10.37%, respectively. The pharmacokinetic study demonstrated that diacerein is swiftly metabolized into Rhein, and then Rhein subsequently undergoes glucuronidation, forming detectable concentrations of Rhein-G1 and Rhein-G2 in plasma. <b>Conclusions:</b> This new LC-MS/MS method proved to be both sensitive and selective, allowing for pharmacokinetic studies in rats.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484993","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":"Salivary Metabolite Variation After High-Intensity Rowing Training and Potential Biomarker Screening for Exercise-Induced Muscle Damage.","authors":"Yue Yi, Junjie Ding, Baoguo Wang, Yuxian Li, Liming Wang, Shumin Bo, Qiongqiong Ren, Aiqin Luo","doi":"10.3390/metabo15060405","DOIUrl":"10.3390/metabo15060405","url":null,"abstract":"<p><strong>Background: </strong>Exercise-induced muscle damage (EIMD) is the most common health risk in training. So far, EIMD diagnosis predominantly relies on blood biochemical analysis or medical imaging. EIMD prediction by using saliva shows great prospects in public fitness.</p><p><strong>Methods: </strong>A total of 18 participants performed high-intensity rowing training. Blood biochemical indicator and pain analyses indicated EIMD occurrence. Pseudo-targeted metabolomics techniques were utilized to analyze changes in salivary metabolites after exercise.</p><p><strong>Results: </strong>A total of 43 salivary metabolites significantly increased while 31 salivary metabolites significantly decreased after exercise. The upregulated metabolites were related to hormone secretion, antioxidation, and muscle repair. A partial least squares discriminant analysis model was established, and three potential salivary biomarkers for EIMD prediction were screened. The sensitivity and specificity of single biomarkers achieved more than 88.9% and 94.4% in classification of EIMD occurrence, respectively. The accuracy of classification increased to ~100% with multiple metabolites.</p><p><strong>Conclusion: </strong>Salivary metabolites significantly changed after high-intensity rowing training and EIMD occurrence. Some salivary metabolites exhibited similar trends with blood biochemical indicators. Salivary biomarkers have great prospects in EIMD prediction, and better performance was achieved with multiple salivary metabolites.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485078","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":"SARS-CoV-2 in Asthmatic Children: Same Consequences in Different Endotypes?","authors":"Alice Bosco, Vassilios Fanos, Serena Bosone, Valeria Incandela, Federica La Ciacera, Angelica Dessì","doi":"10.3390/metabo15060406","DOIUrl":"10.3390/metabo15060406","url":null,"abstract":"<p><p>During the early stages of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, concerns arose regarding the susceptibility of asthmatic children, one of the most common chronic conditions in childhood and a major cause of hospitalization in pediatric settings. Unexpectedly, evidences showed milder clinical courses and fewer asthma exacerbations in these patients, even if cases of critical and fatal infection, often related to specific clinical features of the patient, are not negligible. In this regard, obesity is considered not only an important comorbidity in patients with difficult-to-treat asthma but also a risk factor for more severe forms of COVID-19. These observations are of even greater concern in the context of an increase in childhood obesity that began even before the SARS-CoV-2 pandemic and has continued also as a consequence of it. Given asthma's heterogeneity, especially in children, an endotype-based approach is crucial. This is possible through a detailed analysis of the complex metabolic pathways that correlate asthma, COVID-19 infection and obesity thanks to new high-through-put technologies, especially metabolomics, which with minimally invasive sampling, including on exhaled breath condensate (EBC), can provide precise and unbiased evidence in support of existing endotypes, making it possible to identify not only the most vulnerable individuals and thus risk stratification through specific biomarkers, but also new molecular and therapeutic targets. This review explores asthma endotypes by highlighting their shared immunometabolic pathways with COVID-19. Findings suggest that metabolomics could enable more accurate risk stratification and guide personalized interventions during viral pandemics, especially in the presence of relevant comorbidities such as obesity.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12194914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485079","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":"Development and Validation of a New LC-MS/MS Method for the Assay of Plasmatic Peripheral Short- and Medium-Chain Fatty Acids for Metabolomics Applications.","authors":"Lenard Farczadi, Laura Barcutean, Smaranda Maier, Rodica Balasa, Silvia Imre","doi":"10.3390/metabo15060403","DOIUrl":"10.3390/metabo15060403","url":null,"abstract":"<p><p><i>Background:</i> Short-chain fatty acids (SCFAs) and medium-chain fatty acids (MCFAs) are human metabolites which are involved in various biochemical processes and can offer valuable insights and information on various pathological and metabolic issues of patients. Accurate, precise, high-performance bioanalytical methods are important tools in both research and diagnostics of many pathologies, with LC-MS being the most frequently used methodology in modern metabolomics studies. <i>Methods:</i> The current paper describes a complete LC-MS/MS methodology for the accurate quantification of total plasmatic SCFA concentrations in humans using high-resolution QTOF mass spectrometric detection, including sample cleanup, preparation, and derivatization. <i>Results and Conclusions:</i> The method was validated with regard to all relevant parameters (selectivity, sensitivity, accuracy, precision, linearity, recovery, carryover, and reproducibility of sample preparation) according to the current applicable guidelines and tested in an in vivo study to quantify peripheral SCFAs in human patients as biomarkers for gut-brain axis disruption.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12194892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485008","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":"Biomolecular Basis of Life.","authors":"Janusz Wiesław Błaszczyk","doi":"10.3390/metabo15060404","DOIUrl":"10.3390/metabo15060404","url":null,"abstract":"<p><p>Life is defined descriptively by the capacity for metabolism, homeostasis, self-organization, growth, adaptation, information metabolism, and reproduction. All these are achieved by a set of self-organizing and self-sustaining processes, among which energy and information metabolism play a dominant role. The energy metabolism of the human body is based on glucose and lipid metabolism. All energy-dependent life processes are controlled by phosphate and calcium signaling. To maintain the optimal levels of energy metabolism, cells, tissues, and the nervous system communicate mutually, and as a result of this signaling, metabolism emerges with self-awareness, which allows for conscience social interactions, which are the most significant determinants of human life. Consequently, the brain representation of our body and the egocentric representation of the environment are built. The last determinant of life optimization is the limited life/death cycle, which exhibits the same pattern at cellular and social levels. This narrative review is my first attempt to systematize our knowledge of life phenomena. Due to the extreme magnitude of this challenge, in the current article, I tried to summarize the current knowledge about fundamental life processes, i.e., energy and information metabolism, and, thus, initiate a broader discussion about the life and future of our species.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484997","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":"Uric Acid Promotes Human Umbilical Vein Endothelial Cell Senescence In Vitro.","authors":"Katarzyna Lewandowska, Justyna Mikuła-Pietrasik, Krzysztof Książek, Andrzej Tykarski, Paweł Uruski","doi":"10.3390/metabo15060402","DOIUrl":"10.3390/metabo15060402","url":null,"abstract":"<p><strong>Background/objectives: </strong>Uric acid can act as a prooxidant or an antioxidant; therefore, its effects on human umbilical vein endothelial cells (HUVECs) were investigated to better understand its role in promoting cellular senescence and vascular dysfunction.</p><p><strong>Methods: </strong>HUVECs were exposed to different concentrations of exogenous uric acid levels typically found in patients with cardiovascular conditions (5 mg/dL, 7.5 mg/dL, and 10 mg/dL) to assess cell viability, proliferation, and senescence markers including SA-β-Gal activity, γ-H2A.X and 53BP1 expression, as well as mitochondrial dysfunction parameters such as reactive oxygen species (ROS) production, mitochondrial mass, and mitochondrial membrane potential (ΔΨm). Additionally, the secretion of factors related to the senescence-associated secretory phenotype (SASP) was quantified.</p><p><strong>Results: </strong>Uric acid concentrations of 7.5 mg/dL and above significantly reduced HUVEC viability, enhanced proliferation, and increased markers of cellular senescence, including SA-β-Gal activity and γ-H2A.X/53BP1 expression. Higher uric acid levels also led to increased ROS production, increased mitochondrial mass, and reduced membrane potential. Uric acid also dose-dependently increased IL-6, IL-8, HGF, GRO-1, and TGF-β1 levels.</p><p><strong>Conclusions: </strong>High uric acid concentrations (≥7.5 mg/dL) promote HUVEC senescence, possibly due to ROS-induced DNA damage. In addition, uric acid triggers the production of pro-inflammatory cytokines and growth factors.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485034","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}