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Fracture Risk in Chronic Kidney Disease: Addressing an Overlooked Complication. 慢性肾脏疾病的骨折风险:解决一个被忽视的并发症。
IF 3.4 3区 生物学
Metabolites Pub Date : 2025-07-07 DOI: 10.3390/metabo15070460
Guido Gembillo, Concetto Sessa, Walter Morale, Luca Zanoli, Antonino Catalano, Salvatore Silipigni, Luca Soraci, Andrea Corsonello, Maria Princiotto, Carlo Lomonte, Domenico Santoro
{"title":"Fracture Risk in Chronic Kidney Disease: Addressing an Overlooked Complication.","authors":"Guido Gembillo, Concetto Sessa, Walter Morale, Luca Zanoli, Antonino Catalano, Salvatore Silipigni, Luca Soraci, Andrea Corsonello, Maria Princiotto, Carlo Lomonte, Domenico Santoro","doi":"10.3390/metabo15070460","DOIUrl":"https://doi.org/10.3390/metabo15070460","url":null,"abstract":"<p><p>Fracture risk is a serious yet underrecognized complication among patients with chronic kidney disease (CKD), especially in those with stages G3-G5D. The overlap between CKD-Mineral and Bone Disorder (CKD-MBD) and osteoporosis leads to complex bone changes that increase the likelihood of fragility fractures. Studies show that 18% to 32% of CKD patients also have osteoporosis, and these individuals are more than 2.5 times as likely to suffer from fractures compared to those without CKD. In the advanced stages of the disease, fracture risk is up to four times higher than in the general population, with the femur, forearm, and humerus being the most commonly affected sites. Hip fractures are of particular concern as they are linked to longer hospital stays and higher rates of morbidity and mortality. Furthermore, dialysis patients who experience hip fractures have a mortality rate 2.4 times higher than those in the general population with similar fractures. This increased risk underscores the need for proactive bone health maintenance in CKD patients to prevent fractures and related complications. This review explores the underlying pathophysiological mechanisms, diagnostic challenges, and treatment options related to bone fragility in CKD. Diagnostic tools, such as bone mineral density (BMD) assessments, the trabecular bone score (TBS), and biochemical markers, remain underused, especially in advanced CKD stages. Recent treatment strategies emphasize a multidisciplinary, stage-specific approach, incorporating calcium and vitamin D supplements, anti-resorptive agents like denosumab, and anabolic therapies such as teriparatide and romosozumab. Effective management needs to be tailored to the patient's bone turnover status and stage of CKD. Despite progress in understanding bone fragility in CKD, significant gaps remain in both diagnosis and treatment. Personalized care, guided by updated KDIGO recommendations and based on an interdisciplinary approach, is essential to reduce fracture risk and improve outcomes in this vulnerable population. Further research is needed to validate risk assessment tools and refine therapeutic protocols.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
ATP Supply from Cytosol to Mitochondria Is an Additional Role of Aerobic Glycolysis to Prevent Programmed Cell Death by Maintenance of Mitochondrial Membrane Potential. ATP从细胞质向线粒体的供应是有氧糖酵解的一个额外作用,通过维持线粒体膜电位来防止程序性细胞死亡。
IF 3.4 3区 生物学
Metabolites Pub Date : 2025-07-07 DOI: 10.3390/metabo15070461
Akane Sawai, Takeo Taniguchi, Kohsuke Noguchi, Taisuke Seike, Nobuyuki Okahashi, Masak Takaine, Fumio Matsuda
{"title":"ATP Supply from Cytosol to Mitochondria Is an Additional Role of Aerobic Glycolysis to Prevent Programmed Cell Death by Maintenance of Mitochondrial Membrane Potential.","authors":"Akane Sawai, Takeo Taniguchi, Kohsuke Noguchi, Taisuke Seike, Nobuyuki Okahashi, Masak Takaine, Fumio Matsuda","doi":"10.3390/metabo15070461","DOIUrl":"https://doi.org/10.3390/metabo15070461","url":null,"abstract":"<p><p>Eukaryotic cells generate ATP primarily via oxidative and substrate-level phosphorylation. Despite the superior efficiency of oxidative phosphorylation, eukaryotic cells often use both pathways as aerobic glycolysis, even in the presence of oxygen. However, its role in cell survival remains poorly understood. <b>Objectives:</b> In this study, aerobic glycolysis was compared between the Warburg effect in breast cancer cells (MCF7) and the Crabtree effect in a laboratory strain of <i>Saccharomyces cerevisiae</i> (S288C). <b>Methods:</b> The metabolic adaptations of MCF7 and S288C cells were compared following treatment with electron transport chain inhibitors, including FCCP, antimycin A, and oligomycin. <b>Results:</b> MCF7 and S288C cells exhibited strikingly similar metabolic rewiring toward substrate-level phosphorylation upon inhibitor treatment, suggesting that mitochondrial oxidative phosphorylation and cytosolic substrate-level phosphorylation communicate through a common mechanism. Measurement of mitochondrial membrane potential (MMP) and ATP concentrations further indicated that cytosolic ATP was transported into the mitochondria under conditions of reduced electron transport chain activity. This ATP was likely utilized in the reverse mode of H<sup>+</sup>/ATPase to maintain MMP, which contributed to the avoidance of programmed cell death. <b>Conclusions</b>: These results suggest that the ATP supply to mitochondria plays a conserved role in aerobic glycolysis in yeast and mammalian cancer cells. This mechanism likely contributes to cell survival under conditions of fluctuating oxygen availability.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Serum Osteopontin and Procollagen Type 1 N-Terminal Propeptide Concentrations: Links to Liver Function, Muscle Mass, and Bone Mineral Density in MASLD and Hypertension. 血清骨桥蛋白和1型前胶原n端前肽浓度:与MASLD和高血压患者肝功能、肌肉质量和骨密度的关系
IF 3.4 3区 生物学
Metabolites Pub Date : 2025-07-06 DOI: 10.3390/metabo15070459
Anna F Sheptulina, Anastasia Yu Elkina, Elvira M Mamutova, Yuriy S Timofeev, Victoria A Metelskaya, Oxana M Drapkina
{"title":"Serum Osteopontin and Procollagen Type 1 N-Terminal Propeptide Concentrations: Links to Liver Function, Muscle Mass, and Bone Mineral Density in MASLD and Hypertension.","authors":"Anna F Sheptulina, Anastasia Yu Elkina, Elvira M Mamutova, Yuriy S Timofeev, Victoria A Metelskaya, Oxana M Drapkina","doi":"10.3390/metabo15070459","DOIUrl":"https://doi.org/10.3390/metabo15070459","url":null,"abstract":"<p><strong>Background/objectives: </strong>Increasing evidence suggests that metabolic dysfunction-associated steatotic liver disease (MASLD) and hypertension (HTN), a well-established cardiometabolic risk factor, both negatively impact bone metabolism. This study aimed to investigate the associations between bone turnover markers (BTMs)-namely, osteopontin (OPN) and procollagen type 1 N-terminal propeptide (P1NP)-and metabolic health indicators, non-invasive measures of liver disease severity, as well as skeletal muscle mass (SMM), muscle strength, and bone mineral density (BMD) in patients with MASLD and HTN.</p><p><strong>Methods: </strong>We enrolled 117 patients diagnosed with MASLD and HTN and conducted anthropometric measurements, laboratory analyses, abdominal ultrasound, and point shear-wave elastography. Muscle strength was evaluated using grip strength measurements and the Five Times Sit-to-Stand Test (FTSST). SMM and BMD were quantified using dual-energy X-ray absorptiometry (DEXA). Serum OPN and P1NP concentrations were quantified using enzyme-linked immunosorbent assays (ELISAs).</p><p><strong>Results: </strong>Serum OPN concentrations below 2.89 ng/mL were associated with significantly elevated levels of AST (<i>p</i> = 0.001), ALT (<i>p</i> = 0.006), and GGT (<i>p</i> = 0.025), while serum P1NP concentrations above 47.5 pg/mL were associated only with significantly elevated GGT levels (<i>p</i> = 0.024). In addition, patients with MASLD and HTN with lower serum OPN levels had higher liver stiffness values (<i>p</i> = 0.003). Serum OPN concentrations were inversely associated with the following metabolic health indicators: waist circumference (WC, <i>p</i> < 0.001) and epicardial fat thickness (EFT, <i>p</i> = 0.001). In addition, they were significantly elevated in patients with MASLD and HTN who had decreased spinal BMD (<i>p</i> = 0.017). In turn, serum P1NP levels were reduced in patients with decreased SMM (<i>p</i> = 0.023).</p><p><strong>Conclusions: </strong>These findings in patients with MASLD and HTN suggest an association between serum P1NP levels and SMM, and between OPN levels and spinal BMD, indicating a potential interplay among liver function, muscle mass, and bone health. Furthermore, OPN appeared to be strongly associated with overall metabolic health indicators, such as WC and EFT, whereas P1NP exhibited a stronger association with muscle mass.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nutraceutical Potential of Havardia pallens and Vachellia rigidula in the Diet Formulation for Male Goat. 淡色哈瓦氏菌和刚硬Vachellia在公山羊日粮配方中的营养潜力。
IF 3.4 3区 生物学
Metabolites Pub Date : 2025-07-05 DOI: 10.3390/metabo15070457
Jesús Humberto Reyna-Fuentes, Cecilia Carmela Zapata-Campos, Jorge Ariel Torres-Castillo, Daniel López-Aguirre, Juan Antonio Núñez-Colima, Luis Eliezer Cruz-Bacab, Fabián Eliseo Olazarán-Santibáñez, Fernando Sánchez-Dávila, Aida Isabel Leal-Robles, Juan Antonio Granados-Montelongo
{"title":"Nutraceutical Potential of <i>Havardia pallens</i> and <i>Vachellia rigidula</i> in the Diet Formulation for Male Goat.","authors":"Jesús Humberto Reyna-Fuentes, Cecilia Carmela Zapata-Campos, Jorge Ariel Torres-Castillo, Daniel López-Aguirre, Juan Antonio Núñez-Colima, Luis Eliezer Cruz-Bacab, Fabián Eliseo Olazarán-Santibáñez, Fernando Sánchez-Dávila, Aida Isabel Leal-Robles, Juan Antonio Granados-Montelongo","doi":"10.3390/metabo15070457","DOIUrl":"https://doi.org/10.3390/metabo15070457","url":null,"abstract":"<p><p><b>Background</b>: Xerophilous scrubland is a semi-desert ecosystem characterized by a wide diversity of shrubs, which have secondary compounds with nutraceutical potential that could be used as feed for livestock, specifically by goats, since this species has developed behavioral and physiological adaptations that allow it to take advantage of the plant resources of said scrubland. <b>Objective</b>: To evaluate the nutraceutical potential of <i>Havardia pallens</i> and <i>Vachellia rigidula</i>, native species of the xerophilous scrubland, when incorporated as ingredients in goat diets. <b>Methods:</b> Integral diets for male goats were prepared, formulated with 35% inclusion of <i>Havardia pallens</i>, <i>Vachellia rigidula</i>, and <i>Medicago sativa</i>, the latter used as a plant control species. The content of flavonoids and total phenols was compared using colorimetric methods, and the antioxidant capacity was measured using the FRAP method. RP-HPLC-ESI-MS characterized the bioactive compounds in the different extracts. Statistical analysis was performed by ANOVA. <b>Results</b>: The aqueous extraction of <i>Vachellia rigidula</i> showed the highest concentration of total phenols (x¯ = 18.22 mg GAE/g<sup>-1</sup>), followed by the ethanolic extract in the same species (x¯ = 17.045 mg GAE/g<sup>-1</sup>). Similarly, <i>Vachellia rigidula</i> presented the highest antioxidant capacity (x¯ = 144,711.53 µmol TE/g<sup>-1</sup>), while <i>Medicago sativa</i> presented the lowest (x¯ = 11,701.92 µmol TE/g). The RP-HPLC-ESI-MS analysis revealed that <i>Vachellia rigidula</i> presented a higher abundance of flavones, catechins, flavonols, methoxyflavones, and tyrosols. However, <i>Harvardia pallens</i> presented higher levels of methoxycinnamic and hydroxycinnamic acids. One-way ANOVA results showed that diets containing 35% <i>Vachellia rigidula</i> and <i>Havardia pallens</i> significantly contrasted (<i>p</i> < 0.05), increased the content of secondary compounds and antioxidant capacity compared to the control species. Furthermore, including <i>Vachellia rigidula</i> led to a significantly higher antioxidant capacity (<i>p</i> < 0.05) than diets with <i>Havardia pallens</i> or <i>Medicago sativa</i>. <b>Conclusions</b>: Incorporating the leguminous shrubs <i>Vachellia rigidula</i> and <i>Havardia pallens</i> into the formulation of comprehensive diets for buck goats improves the content and availability of phenols, flavonoids, and antioxidants. However, in vivo evaluation of these diets is important to determine their physiological and productive effects on the animals.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tissue-Based Metabolomic Profiling of Endometrial Cancer and Hyperplasia. 子宫内膜癌和增生的组织代谢组学分析。
IF 3.4 3区 生物学
Metabolites Pub Date : 2025-07-05 DOI: 10.3390/metabo15070458
Khalid Akkour, Afshan Masood, Maha Al Mogren, Reem H AlMalki, Assim A Alfadda, Salini Scaria Joy, Ali Bassi, Hani Alhalal, Maria Arafah, Othman Mahmoud Othman, Hadeel Mohammad Awwad, Anas M Abdel Rahman, Hicham Benabdelkamel
{"title":"Tissue-Based Metabolomic Profiling of Endometrial Cancer and Hyperplasia.","authors":"Khalid Akkour, Afshan Masood, Maha Al Mogren, Reem H AlMalki, Assim A Alfadda, Salini Scaria Joy, Ali Bassi, Hani Alhalal, Maria Arafah, Othman Mahmoud Othman, Hadeel Mohammad Awwad, Anas M Abdel Rahman, Hicham Benabdelkamel","doi":"10.3390/metabo15070458","DOIUrl":"https://doi.org/10.3390/metabo15070458","url":null,"abstract":"<p><p><b>Background</b>: Endometrial cancer (EC) is the sixth most common cancer among women globally, with an estimated 420,000 new cases diagnosed annually. <b>Methods</b>: This study comprised patients with endometrial cancer (EC) (n = 17), hyperplasia (HY) (n = 17), and controls (CO) (n = 20). Tissue was collected from the endometrium of all 54 patients, including patients with HY, EC, and CO, who underwent total hysterectomy. EC and HY diagnoses were confirmed based on histological examination. Untargeted metabolomics profiling was conducted using LC-HRMS. The partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models were used for univariate and multivariate statistical analysis. The fitness of the model (R2Y) and predictive ability (Q2) were used to create OPLS-DA models. ROC analysis was carried out, followed by network analysis using Ingenuity Pathway Analysis. <b>Results</b>: The top metabolites that can discriminate EC and HY from CO were identified. This revealed a decrease in the levels of the lipid species, specifically phosphatidic acid (PA) (PA (14:1/14:0), PA(10:0/17:0), PA(18:1-O(12,13)/12:0)), PG(a-13:0/a-13:0), ganglioside GA1 (d18:1/18:1), PS(14:1/14:0), TG(20:0/18:4/14:1), and CDP-DG(PGF2alpha/18:2), while the levels of 3-Dehydro-L-gulonate, Uridine diphosphate-N-acetylglucosamine, ganglioside GT2 (d18:1/14:0), gamma-glutamyl glutamic acid and oxidized glutathione were increased in cases of EC and HY as compared to CO. Bioinformatics analysis, specifically using Ingenuity Pathway Analysis (IPA), revealed distinct pathway enrichments for EC and HY. For EC, the most highly scored pathways were associated with cell-to-cell signaling and interaction, skeletal and muscular system development and function, and small-molecule biochemistry. In contrast, HY cases showed the highest scoring pathways related to inflammatory disease, inflammatory response, and organismal injury and abnormalities. <b>Conclusions</b>: Developing sensitive biomarkers could improve diagnosis and guide treatment decisions, particularly in identifying which patients with HY may safely avoid hysterectomy and be managed with hormonal therapy.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of Eight Weeks of Aerobic Training Combined with Carbohydrate Mouth Rinse on Body Composition and Exercise Performance in Adult Men with Obesity: Evidence from Korea. 8周有氧训练结合碳水化合物漱口水对成年肥胖男性身体成分和运动表现的影响:来自韩国的证据
IF 3.4 3区 生物学
Metabolites Pub Date : 2025-07-05 DOI: 10.3390/metabo15070455
Jae-Myun Ko, Wi-Young So, Sung-Eun Park
{"title":"Effects of Eight Weeks of Aerobic Training Combined with Carbohydrate Mouth Rinse on Body Composition and Exercise Performance in Adult Men with Obesity: Evidence from Korea.","authors":"Jae-Myun Ko, Wi-Young So, Sung-Eun Park","doi":"10.3390/metabo15070455","DOIUrl":"https://doi.org/10.3390/metabo15070455","url":null,"abstract":"<p><p><b>Background:</b> Considering that the prevalence of obesity has risen rapidly in recent decades, the aim of this study was to investigate the effects of a carbohydrate mouth rinse (CMR) on the outcomes of aerobic training among adult men with obesity, focusing particularly on the effects of repeated use on body composition and exercise performance. <b>Methods:</b> The intervention targeted 20 men with obesity in their 20s and 30s randomly assigned to either a CMR group (n = 10) or a placebo mouth rinse (PMR) group (n = 10). Both groups completed treadmill-based aerobic training three times per week for eight weeks. Prior to each session, participants used a mouth rinse at 60, 40, and 20 s before the start of each exercise, holding either a 6% maltodextrin solution (CMR) or purified water (PMR) in their mouths for 5 to 10 s before expectorating. Pre- and post-intervention assessments included body composition (body weight and body fat percentage), resting metabolic rate (RMR), maximal oxygen uptake (VO<sub>2</sub>max), and exercise performance (rate of perceived exertion [RPE], exercise distance, speed, and time). Data were analyzed using 2 × 2 repeated measures analysis of variance. <b>Results:</b> Following the intervention, the CMR group showed significantly greater improvements than the PMR group did in body fat percentage, RMR, VO<sub>2</sub>max, exercise distance, speed, and time (<i>p</i> < 0.01). However, the interaction effect for RPE was not statistically significant between the groups (<i>p</i> = 0.175). Overall, the repeated use of the CMR during aerobic training contributed to enhanced exercise performance and favorable physiological changes without additional caloric intake. <b>Conclusions:</b> A CMR may be a practical and non-caloric ergogenic aid to support exercise performance and metabolic function in individuals with obesity. Its repeated use during aerobic training appears to be effective and safe, especially when fasting while exercising, when improving endurance without compromising fat loss is essential.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Integrative Modeling of Urinary Metabolomics and Metal Exposure Reveals Systemic Impacts of Electronic Waste in Exposed Populations. 尿代谢组学和金属暴露的综合建模揭示了暴露人群中电子废物的系统性影响。
IF 3.4 3区 生物学
Metabolites Pub Date : 2025-07-05 DOI: 10.3390/metabo15070456
Fiona Hui, Zhiqiang Pang, Charles Viau, Gerd U Balcke, Julius N Fobil, Niladri Basu, Jianguo Xia
{"title":"Integrative Modeling of Urinary Metabolomics and Metal Exposure Reveals Systemic Impacts of Electronic Waste in Exposed Populations.","authors":"Fiona Hui, Zhiqiang Pang, Charles Viau, Gerd U Balcke, Julius N Fobil, Niladri Basu, Jianguo Xia","doi":"10.3390/metabo15070456","DOIUrl":"https://doi.org/10.3390/metabo15070456","url":null,"abstract":"<p><p><b>Background</b>: Informal electronic waste (e-waste) recycling practices release a complex mixture of pollutants, particularly heavy metals, into the environment. Chronic exposure to these contaminants has been linked to a range of health risks, but the molecular underpinnings remain poorly understood. In this study, we investigated the alterations in metabolic profiles due to e-waste exposure and linked these metabolites to systemic biological effects. <b>Methods</b>: We applied untargeted high-resolution metabolomics using dual-column LC-MS/MS and a multi-step analysis workflow combining MS1 feature detection, MS2 annotation, and chemical ontology classification, to characterize urinary metabolic alterations in 91 e-waste workers and 51 community controls associated with the Agbogbloshie site (Accra, Ghana). The impacts of heavy metal exposure in e-waste workers were assessed by establishing linear regression and four-parameter logistic (4PL) models between heavy metal levels and metabolite concentrations. <b>Results</b>: Significant metal-associated metabolomic changes were identified. Both linear and nonlinear models revealed distinct sets of exposure-responsive compounds, highlighting diverse biological responses. Ontology-informed annotation revealed systemic effects on lipid metabolism, oxidative stress pathways, and xenobiotic biotransformation. This study demonstrates how integrating chemical ontology and nonlinear modeling facilitates exposome interpretation in complex environments and provides a scalable template for environmental biomarker discovery. <b>Conclusions</b>: Integrating dose-response modeling and chemical ontology analysis enables robust interpretation of exposomics datasets when direct compound identification is limited. Our findings indicate that e-waste exposure induces systemic metabolic alterations that can underlie health risks and diseases.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In Vitro Metabolism of Doping Agents (Stanozolol, LGD-4033, Anastrozole, GW1516, Trimetazidine) by Human Seminal Vesicle and Liver Fractions. 兴奋剂(司他唑尔、LGD-4033、阿那曲唑、GW1516、曲美他嗪)在人精囊和肝脏中的体外代谢
IF 3.4 3区 生物学
Metabolites Pub Date : 2025-07-04 DOI: 10.3390/metabo15070452
Johanna Sternberg, Insa Peters, Nana Naumann, Andreas Thomas, Mario Thevis
{"title":"In Vitro Metabolism of Doping Agents (Stanozolol, LGD-4033, Anastrozole, GW1516, Trimetazidine) by Human Seminal Vesicle and Liver Fractions.","authors":"Johanna Sternberg, Insa Peters, Nana Naumann, Andreas Thomas, Mario Thevis","doi":"10.3390/metabo15070452","DOIUrl":"https://doi.org/10.3390/metabo15070452","url":null,"abstract":"<p><p><b>Background:</b> In order to address complex scenarios in anti-doping science, especially in cases where an unintentional exposure of athletes to prohibited substances and a corresponding contamination of doping control samples at the collection event are argued, an understanding of tissue-specific drug metabolism is essential. Hence, in this study, the metabolic capacity of the seminal vesicle using in vitro assays was investigated. <b>Methods:</b> The aim was to assess whether selected doping-relevant substances-stanozolol, LGD-4033, GW1516, trimetazidine, and anastrozole-are metabolised in seminal vesicle cellular fractions (SV-S9) and how that metabolism compares to biotransformations induced by human liver S9 fractions (HL-S9). Liquid chromatography coupled to high-resolution/accurate mass spectrometry (LC HRAM MS) enabled the sensitive detection and identification of metabolites, revealing a limited metabolic activity of SV-S9. <b>Results</b>: For LGD-4033, GW1516, and trimetazidine, minor metabolic transformations were observed, whereas no metabolites of stanozolol or anastrozole were detected. Gene expression analysis using digital polymerase chain reaction (dPCR) confirmed transcripts of CYP2D6, CYP2E1, and CYP2C9 in SV-S9, though no enzymatic activity was detected. Gene expression and enzymatic activity in CYP3A4 and CYP1A2-major hepatic enzymes-were absent in SV-S9. <b>Conclusions:</b> Overall, these pilot study results suggest that the seminal vesicle has only a low capacity for xenobiotic metabolism, which translates into a limited role in the biotransformation of drugs and, hence, the metabolic pattern.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Extracellular Vesicle Metabolomics Holds Promise for Adult Axon Regeneration. 细胞外囊泡代谢组学为成人轴突再生带来希望。
IF 3.4 3区 生物学
Metabolites Pub Date : 2025-07-04 DOI: 10.3390/metabo15070454
Maria D Cabrera Gonzalez, Jackson Watson, Laura Leal, Isabella Moceri, Camille Plummer, Biraj Mahato, Abdelrahman Y Fouda, Sanjoy K Bhattacharya
{"title":"Extracellular Vesicle Metabolomics Holds Promise for Adult Axon Regeneration.","authors":"Maria D Cabrera Gonzalez, Jackson Watson, Laura Leal, Isabella Moceri, Camille Plummer, Biraj Mahato, Abdelrahman Y Fouda, Sanjoy K Bhattacharya","doi":"10.3390/metabo15070454","DOIUrl":"https://doi.org/10.3390/metabo15070454","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are bilayer lipid membrane particles that are released by every cell type. These secretions are further classified as exosomes, ectosomes, and microvesicles. They contain biomolecules (RNAs, proteins, metabolites, and lipids) with the ability to modulate various biological processes and have been shown to play a role in intercellular communication and cellular rejuvenation. Various studies suggest exosomes and/or microvesicles as a potential platform for drug delivery. EVs may deliver lipids and nucleotides directly to an injury site in an axon, promoting growth cone stabilization and membrane expansion as well as repair, thus positively modulating adult axon regeneration. In this review, we will provide a perspective on the metabolite composition of EVs in adult axonal regeneration relevant to the central nervous system (CNS), specifically that pertaining to the optic nerve. We will present an overview of the methods for isolation, enrichment, omics data analysis and quantification of extracellular vesicles with the goal of providing direction for future studies relevant to axon regeneration. We will also include current resources for multi-omics data integration relevant to extracellular vesicles from diverse cell types.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Metabolic Changes in Zebrafish Larvae Infected with Mycobacterium marinum: A Widely Targeted Metabolomic Analysis. 斑马鱼感染海洋分枝杆菌后的代谢变化:一项广泛靶向的代谢组学分析
IF 3.4 3区 生物学
Metabolites Pub Date : 2025-07-04 DOI: 10.3390/metabo15070449
Chongyuan Sima, Qifan Zhang, Xiaoli Yu, Bo Yan, Shulin Zhang
{"title":"Metabolic Changes in Zebrafish Larvae Infected with <i>Mycobacterium marinum</i>: A Widely Targeted Metabolomic Analysis.","authors":"Chongyuan Sima, Qifan Zhang, Xiaoli Yu, Bo Yan, Shulin Zhang","doi":"10.3390/metabo15070449","DOIUrl":"https://doi.org/10.3390/metabo15070449","url":null,"abstract":"<p><strong>Objectives: </strong>To explore the metabolic changes in zebrafish larvae after infection with <i>Mycobacterium marinum</i>, this study adopted a widely targeted metabolomic approach to analyze the changes in the overall metabolic profiles of zebrafish larvae infected for 5 days.</p><p><strong>Methods: </strong>Data were collected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Mass spectrometry data were processed using Analyst 1.6.3 and MultiQuant 3.0.3 software, and multivariate statistical analysis was carried out. The KEGG database, HMDB database, and CHEBI database were used to screen and identify differential metabolites, and metabolic pathway enrichment analysis was performed through KEGG pathways.</p><p><strong>Results: </strong>A total of 329 metabolites were detected, among which 61 differential metabolites were screened. Specifically, 41 metabolites, such as kynurenine, isoallolithocholic acid, 2'-deoxyguanosine, indole-3-carboxaldehyde, and L-lactic acid, were downregulated, while 20 metabolites, such as L-palmitoylcarnitine, myristoyl-L-carnitine, dodecanoylcarnitine, 2-isopropyl-malic acid, and 2-methylsuccinic acid, were upregulated. KEGG metabolic pathway enrichment analysis indicated that these differential metabolites were mainly involved in metabolic pathways such as pyrimidine metabolism, nucleotide metabolism, the pentose phosphate pathway, and purine metabolism.</p><p><strong>Conclusions: </strong>This study demonstrated that significant changes occurred in multiple metabolites and metabolic pathways in zebrafish larvae after infection with <i>M. marinum</i>. The research results have improved the understanding of zebrafish as a model organism in the field of <i>Mycobacterium</i> research and laid a solid foundation for subsequent metabolomic-related research using zebrafish.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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