Alex Castro, Antonio Gilberto Ferreira, Aparecida Maria Catai, Matheus Alejandro Bolina Amaral, Claudia Regina Cavaglieri, Mara Patrícia Traina Chacon-Mikahil
Background/Objectives: Cardiorespiratory fitness (CRF) levels significantly modulate the risk of cardiometabolic diseases, aging, and mortality. Nevertheless, there is a substantial interindividual variability in CRF responsiveness to a given standardized exercise dose despite the type of training. Predicting the responsiveness to regular exercise has the potential to contribute to personalized exercise medicine applications. This study aimed to identify predictive biomarkers for the classification of CRF responsiveness based on serum and intramuscular metabolic levels before continuous endurance training (ET) or high-intensity interval training (HIIT) programs using a randomized controlled trial. Methods: Forty-three serum and seventy intramuscular (vastus lateralis) metabolites were characterized and quantified via proton nuclear magnetic resonance (1H NMR), and CRF levels (expressed in METs) were measured in 70 sedentary young men (age: 23.7 ± 3.0 years; BMI: 24.8 ± 2.5 kg·m-2), at baseline and post 8 weeks of the ET, HIIT, and control (CO) periods. A multivariate binary logistic regression model was used to classify individuals at baseline as Responders or Non-responders to CRF gains after the training programs. Results: CRF responses ranged from 0.9 to 3.9 METs for ET, 1.1 to 4.7 METs for HIIT, and -0.9 to 0.2 METs for CO. The frequency of Responder/Non-responder individuals between ET (76.7%/23.3%) and HIIT (90.0%/10.0%) programs was similar (p = 0.166). The model based on serum O-acetylcarnitine levels [OR (odds ratio) = 4.72, p = 0.012] classified Responder/Non-responders individuals to changes in CRF regardless of the training program with 78.0% accuracy (p = 0.006), while the intramuscular model based on creatinine levels (OR = 4.53, p = 0.0137) presented 72.3% accuracy (p = 0.028). Conclusions: These results highlight the potential value of serum and intramuscular metabolites as biomarkers for the classification of CRF responsiveness previous to different aerobic training programs.
{"title":"Metabolic Predictors of Cardiorespiratory Fitness Responsiveness to Continuous Endurance and High-Intensity Interval Training Programs: The TIMES Study-A Randomized Controlled Trial.","authors":"Alex Castro, Antonio Gilberto Ferreira, Aparecida Maria Catai, Matheus Alejandro Bolina Amaral, Claudia Regina Cavaglieri, Mara Patrícia Traina Chacon-Mikahil","doi":"10.3390/metabo14090512","DOIUrl":"https://doi.org/10.3390/metabo14090512","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Cardiorespiratory fitness (CRF) levels significantly modulate the risk of cardiometabolic diseases, aging, and mortality. Nevertheless, there is a substantial interindividual variability in CRF responsiveness to a given standardized exercise dose despite the type of training. Predicting the responsiveness to regular exercise has the potential to contribute to personalized exercise medicine applications. This study aimed to identify predictive biomarkers for the classification of CRF responsiveness based on serum and intramuscular metabolic levels before continuous endurance training (ET) or high-intensity interval training (HIIT) programs using a randomized controlled trial. <b>Methods:</b> Forty-three serum and seventy intramuscular (vastus lateralis) metabolites were characterized and quantified via proton nuclear magnetic resonance (<sup>1</sup>H NMR), and CRF levels (expressed in METs) were measured in 70 sedentary young men (age: 23.7 ± 3.0 years; BMI: 24.8 ± 2.5 kg·m<sup>-2</sup>), at baseline and post 8 weeks of the ET, HIIT, and control (CO) periods. A multivariate binary logistic regression model was used to classify individuals at baseline as Responders or Non-responders to CRF gains after the training programs. <b>Results:</b> CRF responses ranged from 0.9 to 3.9 METs for ET, 1.1 to 4.7 METs for HIIT, and -0.9 to 0.2 METs for CO. The frequency of Responder/Non-responder individuals between ET (76.7%/23.3%) and HIIT (90.0%/10.0%) programs was similar (<i>p</i> = 0.166). The model based on serum O-acetylcarnitine levels [OR (odds ratio) = 4.72, <i>p</i> = 0.012] classified Responder/Non-responders individuals to changes in CRF regardless of the training program with 78.0% accuracy (<i>p</i> = 0.006), while the intramuscular model based on creatinine levels (OR = 4.53, <i>p</i> = 0.0137) presented 72.3% accuracy (<i>p</i> = 0.028). <b>Conclusions:</b> These results highlight the potential value of serum and intramuscular metabolites as biomarkers for the classification of CRF responsiveness previous to different aerobic training programs.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11433752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349781","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}
Minami Yamauchi, Masamitsu Maekawa, Toshihiro Sato, Yu Sato, Masaki Kumondai, Mio Tsuruoka, Jun Inoue, Atsushi Masamune, Nariyasu Mano
Imaging tests, tumor marker (TM) screening, and biochemical tests provide a definitive diagnosis of hepatocellular carcinoma (HCC). However, some patients with HCC may present TM-negative results, warranting a need for developing more sensitive and accurate screening biomarkers. Various diseases exhibit increased blood levels of bile acids, biosynthesized from cholesterol in the liver, and they have been associated with HCC. Herein, we analyzed plasma bile acids using liquid chromatography/tandem mass spectrometry and integrated them with conventional biomarkers to develop a diagnostic screening model for HCC. Plasma samples were obtained from patients diagnosed with chronic hepatitis, hepatic cirrhosis (HC), and HCC. A QTRAP 6500 mass spectrometer and a Nexera liquid chromatograph with a YMC-Triart C18 analytical column were used. The mobile phase A was a 20 mmol/L ammonium formate solution, and mobile phase B was a methanol/acetonitrile mixture (1:1, v/v) with 20 mmol/L ammonium formate. After determining the concentrations of 32 bile acids, statistical analysis and diagnostic screening model development were performed. Plasma concentrations of bile acids differed between sample groups, with significant differences observed between patients with HC and HCC. By integrating bile acid results with conventional biochemical tests, a potential diagnostic screening model for HCC was successfully developed. Future studies should increase the sample size and analyze the data in detail to verify the diagnostic efficacy of the model.
{"title":"Liquid Chromatography/Tandem Mass Spectrometry-Based Simultaneous Analysis of 32 Bile Acids in Plasma and Conventional Biomarker-Integrated Diagnostic Screening Model Development for Hepatocellular Carcinoma.","authors":"Minami Yamauchi, Masamitsu Maekawa, Toshihiro Sato, Yu Sato, Masaki Kumondai, Mio Tsuruoka, Jun Inoue, Atsushi Masamune, Nariyasu Mano","doi":"10.3390/metabo14090513","DOIUrl":"https://doi.org/10.3390/metabo14090513","url":null,"abstract":"<p><p>Imaging tests, tumor marker (TM) screening, and biochemical tests provide a definitive diagnosis of hepatocellular carcinoma (HCC). However, some patients with HCC may present TM-negative results, warranting a need for developing more sensitive and accurate screening biomarkers. Various diseases exhibit increased blood levels of bile acids, biosynthesized from cholesterol in the liver, and they have been associated with HCC. Herein, we analyzed plasma bile acids using liquid chromatography/tandem mass spectrometry and integrated them with conventional biomarkers to develop a diagnostic screening model for HCC. Plasma samples were obtained from patients diagnosed with chronic hepatitis, hepatic cirrhosis (HC), and HCC. A QTRAP 6500 mass spectrometer and a Nexera liquid chromatograph with a YMC-Triart C18 analytical column were used. The mobile phase A was a 20 mmol/L ammonium formate solution, and mobile phase B was a methanol/acetonitrile mixture (1:1, <i>v</i>/<i>v</i>) with 20 mmol/L ammonium formate. After determining the concentrations of 32 bile acids, statistical analysis and diagnostic screening model development were performed. Plasma concentrations of bile acids differed between sample groups, with significant differences observed between patients with HC and HCC. By integrating bile acid results with conventional biochemical tests, a potential diagnostic screening model for HCC was successfully developed. Future studies should increase the sample size and analyze the data in detail to verify the diagnostic efficacy of the model.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11433973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349780","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}
Introduction: Although aging is a natural phenomenon, in recent years it has accelerated. One key factor implicated in the aging process is oxidative stress. Oxidative stress also plays a role in frailty (frail) and metabolic syndrome (MetS).
Methods: A total of 66 elderly persons (65 years old and older) with no acute or severe chronic disorders were assessed for waist circumference (WC), arterial blood pressure, glycemia, glycated hemoglobin (HbA1c), plasma lipids, and activity of erythrocyte superoxide dismutase (SOD-1). Patients were classified as NonMetS-Nonfrail (n = 19), NonMetS-frail (n = 20), MetS-Nonfrail (n = 17), or MetS-frail (n = 10).
Results: There were no significant differences in superoxide dismutase activity among investigated elderly groups. However, the data suggest that MetS individuals, both frail and nonfrail, have higher risk factors for cardiovascular disease compared to NonMetS individuals. The correlations analyses of SOD-1 and other metabolic indices suggest that SOD-1 levels may be influenced by age, total cholesterol, HDL cholesterol, and fasting glucose levels in certain groups of seniors.
Conclusions: Aging is associated with decreased antioxidant enzyme SOD-1 activity with glucose alteration in frailty syndrome as well as with lipids disturbances in metabolic syndrome. These factors provide a nuanced view of how frailty and metabolic syndrome interact with various health parameters, informing both clinical practice and future research directions.
{"title":"Relationship of SOD-1 Activity in Metabolic Syndrome and/or Frailty in Elderly Individuals.","authors":"Sylwia Dzięgielewska-Gęsiak, Ewa Wysocka, Edyta Fatyga, Małgorzata Muc-Wierzgoń","doi":"10.3390/metabo14090514","DOIUrl":"https://doi.org/10.3390/metabo14090514","url":null,"abstract":"<p><strong>Introduction: </strong>Although aging is a natural phenomenon, in recent years it has accelerated. One key factor implicated in the aging process is oxidative stress. Oxidative stress also plays a role in frailty (frail) and metabolic syndrome (MetS).</p><p><strong>Methods: </strong>A total of 66 elderly persons (65 years old and older) with no acute or severe chronic disorders were assessed for waist circumference (WC), arterial blood pressure, glycemia, glycated hemoglobin (HbA1c), plasma lipids, and activity of erythrocyte superoxide dismutase (SOD-1). Patients were classified as NonMetS-Nonfrail (n = 19), NonMetS-frail (n = 20), MetS-Nonfrail (n = 17), or MetS-frail (n = 10).</p><p><strong>Results: </strong>There were no significant differences in superoxide dismutase activity among investigated elderly groups. However, the data suggest that MetS individuals, both frail and nonfrail, have higher risk factors for cardiovascular disease compared to NonMetS individuals. The correlations analyses of SOD-1 and other metabolic indices suggest that SOD-1 levels may be influenced by age, total cholesterol, HDL cholesterol, and fasting glucose levels in certain groups of seniors.</p><p><strong>Conclusions: </strong>Aging is associated with decreased antioxidant enzyme SOD-1 activity with glucose alteration in frailty syndrome as well as with lipids disturbances in metabolic syndrome. These factors provide a nuanced view of how frailty and metabolic syndrome interact with various health parameters, informing both clinical practice and future research directions.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11434245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142336467","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}
Background: Neolamarckia cadamba (Rubiaceae) is a well-recognized medicinal plant with recorded therapeutical attributes. However, a thorough assessment of active compounds in its fruits is lacking, limiting their use and valorization in pharmacological industries.
Methods: Thus, this study investigated variations in the fruits' secondary metabolite (SM) profiles, as well as antioxidant activities in aqueous (WA) and ethanol (ET) extracts.
Results: Liquid chromatography-electrospray ionization tandem mass spectrometry identified 541 SMs, of which 14 and 1 (di-O-glucosylquinic acid) were specifically detected in ET and WA, respectively. Phenolic acids (36.97%), flavonoids (28.10%), terpenoids (12.20%), and alkaloids (9.98%) were the dominant SMs. The SM profiles of the fruits in WA and ET were quite different. We revealed 198 differentially extracted (DE) metabolites between WA and ET, including 62 flavonoids, 57 phenolic acids, 45 terpenoids, 14 alkaloids, etc. Most DE flavones (36 out of 40), terpenoids (45 out of 45), and alkaloids (12 out of 14) had higher content in ET. Catechin and its derivatives, procyanidins, and tannins had higher content in WA. ABTS and DPPH assays showed that the antioxidant activity of ET was significantly higher than that of WA.
Conclusions: Our findings will facilitate the efficient extraction and evaluation of specific active compounds in N. cadamba.
背景:茜草科(Rubiaceae)茜草属(Neolamarckia cadamba)是一种广受认可的药用植物,其治疗特性已被记录在案。然而,由于缺乏对其果实中活性化合物的全面评估,限制了其在制药业中的应用和价值提升:因此,本研究调查了果实中次生代谢物(SM)的变化,以及水提取物(WA)和乙醇提取物(ET)中的抗氧化活性:液相色谱-电喷雾串联质谱法鉴定出 541 种次生代谢物,其中 14 种(二-O-葡萄糖基奎宁酸)和 1 种(二-O-葡萄糖基奎宁酸)分别在 ET 和 WA 中被特别检测到。酚酸类(36.97%)、黄酮类(28.10%)、萜类(12.20%)和生物碱类(9.98%)是主要的 SMs。西澳和东澳果实的 SM 图谱差异很大。我们发现西澳和东澳的差异提取代谢物有 198 种,包括 62 种黄酮类化合物、57 种酚酸类化合物、45 种萜类化合物和 14 种生物碱类化合物等。大多数 DE 黄酮类化合物(40 种中的 36 种)、萜类化合物(45 种中的 45 种)和生物碱(14 种中的 12 种)在 ET 中含量较高。儿茶素及其衍生物、原花青素和单宁酸在 WA 中含量较高。ABTS 和 DPPH 试验表明,ET 的抗氧化活性明显高于 WA:我们的研究结果将有助于有效提取和评估 N. cadamba 中的特定活性化合物。
{"title":"Comprehensive Secondary Metabolite Profiling and Antioxidant Activity of Aqueous and Ethanol Extracts of <i>Neolamarckia cadamba</i> (Roxb.) Bosser Fruits.","authors":"Lin Yang, Liyan Wu, Yongxin Li, Yuhui Yang, Yuting Gu, Jialin Yang, Luzy Zhang, Fanxin Meng","doi":"10.3390/metabo14090511","DOIUrl":"https://doi.org/10.3390/metabo14090511","url":null,"abstract":"<p><strong>Background: </strong><i>Neolamarckia cadamba</i> (Rubiaceae) is a well-recognized medicinal plant with recorded therapeutical attributes. However, a thorough assessment of active compounds in its fruits is lacking, limiting their use and valorization in pharmacological industries.</p><p><strong>Methods: </strong>Thus, this study investigated variations in the fruits' secondary metabolite (SM) profiles, as well as antioxidant activities in aqueous (WA) and ethanol (ET) extracts.</p><p><strong>Results: </strong>Liquid chromatography-electrospray ionization tandem mass spectrometry identified 541 SMs, of which 14 and 1 (di-<i>O</i>-glucosylquinic acid) were specifically detected in ET and WA, respectively. Phenolic acids (36.97%), flavonoids (28.10%), terpenoids (12.20%), and alkaloids (9.98%) were the dominant SMs. The SM profiles of the fruits in WA and ET were quite different. We revealed 198 differentially extracted (DE) metabolites between WA and ET, including 62 flavonoids, 57 phenolic acids, 45 terpenoids, 14 alkaloids, etc. Most DE flavones (36 out of 40), terpenoids (45 out of 45), and alkaloids (12 out of 14) had higher content in ET. Catechin and its derivatives, procyanidins, and tannins had higher content in WA. ABTS and DPPH assays showed that the antioxidant activity of ET was significantly higher than that of WA.</p><p><strong>Conclusions: </strong>Our findings will facilitate the efficient extraction and evaluation of specific active compounds in <i>N. cadamba</i>.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11434403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142336466","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}
Metabolism is a network of chemical reactions that sustain cellular life. Parts of this metabolic network are defined as metabolic pathways containing specific biochemical reactions. Products and reactants of these reactions are called metabolites, which are associated with certain human-defined metabolic pathways. Metabolic knowledgebases, such as the Kyoto Encyclopedia of Gene and Genomes (KEGG) contain metabolites, reactions, and pathway annotations; however, such resources are incomplete due to current limits of metabolic knowledge. To fill in missing metabolite pathway annotations, past machine learning models showed some success at predicting the KEGG Level 2 pathway category involvement of metabolites based on their chemical structure. Here, we present the first machine learning model to predict metabolite association to more granular KEGG Level 3 metabolic pathways. We used a feature and dataset engineering approach to generate over one million metabolite-pathway entries in the dataset used to train a single binary classifier. This approach produced a mean Matthews correlation coefficient (MCC) of 0.806 ± 0.017 SD across 100 cross-validation iterations. The 172 Level 3 pathways were predicted with an overall MCC of 0.726. Moreover, metabolite association with the 12 Level 2 pathway categories was predicted with an overall MCC of 0.891, representing significant transfer learning from the Level 3 pathway entries. These are the best metabolite pathway prediction results published so far in the field.
{"title":"Predicting the Association of Metabolites with Both Pathway Categories and Individual Pathways.","authors":"Erik D Huckvale, Hunter N B Moseley","doi":"10.3390/metabo14090510","DOIUrl":"https://doi.org/10.3390/metabo14090510","url":null,"abstract":"<p><p>Metabolism is a network of chemical reactions that sustain cellular life. Parts of this metabolic network are defined as metabolic pathways containing specific biochemical reactions. Products and reactants of these reactions are called metabolites, which are associated with certain human-defined metabolic pathways. Metabolic knowledgebases, such as the Kyoto Encyclopedia of Gene and Genomes (KEGG) contain metabolites, reactions, and pathway annotations; however, such resources are incomplete due to current limits of metabolic knowledge. To fill in missing metabolite pathway annotations, past machine learning models showed some success at predicting the KEGG Level 2 pathway category involvement of metabolites based on their chemical structure. Here, we present the first machine learning model to predict metabolite association to more granular KEGG Level 3 metabolic pathways. We used a feature and dataset engineering approach to generate over one million metabolite-pathway entries in the dataset used to train a single binary classifier. This approach produced a mean Matthews correlation coefficient (MCC) of 0.806 ± 0.017 SD across 100 cross-validation iterations. The 172 Level 3 pathways were predicted with an overall MCC of 0.726. Moreover, metabolite association with the 12 Level 2 pathway categories was predicted with an overall MCC of 0.891, representing significant transfer learning from the Level 3 pathway entries. These are the best metabolite pathway prediction results published so far in the field.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11433779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349782","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}
Xiao-Qiao Zhu, Mei Li, Rong-Ping Li, Wen-Qiang Tang, Yun-Yue Wang, Xiao Fei, Ping He, Guang-Yu Han
[Background] Intercropping is considered an effective approach to defending rice disease. [Objectives/Methods] This study aimed to explore the resistance mechanism of rice intraspecific intercropping by investigating soil metabolites and their regulation on the rhizosphere soil microbial community using metabolomic and microbiome analyses. [Results] The results showed that the panicle blast disease occurrence of the resistant variety Shanyou63 (SY63) and the susceptible variety Huangkenuo (HKN) were both decreased in the intercropping compared to monoculture. Notably, HKN in the intercropping system exhibited significantly decreased disease incidence and increased disease resistance-related enzyme protease activity. KEGG annotation from soil metabolomics analysis revealed that phenylalanine metabolic pathway, phenylalanine, tyrosine, and tryptophan biosynthesis pathway, and fructose and mannose metabolic pathway were the key pathways related to rice disease resistance. Soil microbiome analysis indicated that the bacterial genera Nocardioides, Marmoricola, Luedemannella, and Desulfomonile were significantly enriched in HKN after intercropping, while SY63 experienced a substantial accumulation of Ruminiclostridium and Cellulomonas. Omics-based correlation analysis highlighted that the community assembly of Cellulomonas and Desulfomonile significantly affected the content of the metabolites D-sorbitol, D-mannitol, quinic acid, which further proved that quinic acid had a significantly inhibitory effect on the mycelium growth of Magnaporthe oryzae, and these three metabolites had a significant blast control effect. The optimal rice blast-control efficiency on HKN was 51.72%, and Lijiangxintuanheigu (LTH) was 64.57%. [Conclusions] These findings provide a theoretical basis for rice varieties intercropping and sustainable rice production, emphasizing the novelty of the study in elucidating the underlying mechanisms of intercropping-mediated disease resistance.
{"title":"Rice Varieties Intercropping Induced Soil Metabolic and Microbial Recruiting to Enhance the Rice Blast (<i>Magnaporthe Oryzae</i>) Resistance.","authors":"Xiao-Qiao Zhu, Mei Li, Rong-Ping Li, Wen-Qiang Tang, Yun-Yue Wang, Xiao Fei, Ping He, Guang-Yu Han","doi":"10.3390/metabo14090507","DOIUrl":"https://doi.org/10.3390/metabo14090507","url":null,"abstract":"<p><p>[Background] Intercropping is considered an effective approach to defending rice disease. [Objectives/Methods] This study aimed to explore the resistance mechanism of rice intraspecific intercropping by investigating soil metabolites and their regulation on the rhizosphere soil microbial community using metabolomic and microbiome analyses. [Results] The results showed that the panicle blast disease occurrence of the resistant variety Shanyou63 (SY63) and the susceptible variety Huangkenuo (HKN) were both decreased in the intercropping compared to monoculture. Notably, HKN in the intercropping system exhibited significantly decreased disease incidence and increased disease resistance-related enzyme protease activity. KEGG annotation from soil metabolomics analysis revealed that phenylalanine metabolic pathway, phenylalanine, tyrosine, and tryptophan biosynthesis pathway, and fructose and mannose metabolic pathway were the key pathways related to rice disease resistance. Soil microbiome analysis indicated that the bacterial genera <i>Nocardioides</i>, <i>Marmoricola</i>, <i>Luedemannella</i>, and <i>Desulfomonile</i> were significantly enriched in HKN after intercropping, while SY63 experienced a substantial accumulation of <i>Ruminiclostridium</i> and <i>Cellulomonas.</i> Omics-based correlation analysis highlighted that the community assembly of <i>Cellulomonas</i> and <i>Desulfomonile</i> significantly affected the content of the metabolites D-sorbitol, D-mannitol, quinic acid, which further proved that quinic acid had a significantly inhibitory effect on the mycelium growth of <i>Magnaporthe oryzae</i>, and these three metabolites had a significant blast control effect. The optimal rice blast-control efficiency on HKN was 51.72%, and Lijiangxintuanheigu (LTH) was 64.57%. [Conclusions] These findings provide a theoretical basis for rice varieties intercropping and sustainable rice production, emphasizing the novelty of the study in elucidating the underlying mechanisms of intercropping-mediated disease resistance.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11434330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349783","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}
Yuanfeng Huang, Mingjie Liang, Yiwen Liao, Zirui Ji, Wanfen Lin, Xiangjin Pu, Lexun Wang, Weixuan Wang
This study focused on exploring the effects of SW033291, an inhibitor of 15-hydroxyprostaglandin dehydrogenase, on type 2 diabetes mellitus (T2DM) mice from a comprehensive perspective. Studies have demonstrated that SW033291 benefits tissue repair, organ function, and muscle mass in elderly mice. Our recent investigation initially reported the beneficial effect of SW033291 on T2DM progression. Herein, we used a T2DM mouse model induced by a high-fat diet and streptozotocin injection. Then, serum and liver metabolomics, as well as liver transcriptomic analyses, were performed to provide a systematic perspective of the SW033291-ameliorated T2DM. The results indicate SW033291 improved T2DM by regulating steroid hormone biosynthesis and linoleic/arachidonic acid metabolism. Furthermore, integrated transcriptomic and metabolomic analyses suggested that key genes and metabolites such as Cyp2c55, Cyp3a11, Cyp21a1, Myc, Gstm1, Gstm3, 9,10-dihydroxyoctadecenoic acid, 11-dehydrocorticosterone, and 12,13-dihydroxy-9Z-octadecenoic acid played crucial roles in these pathways. qPCR analysis validated the significant decreases in the hepatic gene expressions of Cyp2c55, Cyp3a11, Myc, Gstm1, and Gstm3 in the T2DM mice, which were reversed following SW033291 treatment. Meanwhile, the elevated mRNA level of Cyp21a1 in T2DM mice was decreased after SW033291 administration. Taken together, our findings suggest that SW033291 has promising potential in alleviating T2DM and could be a novel therapeutic candidate.
{"title":"Investigating the Mechanisms of 15-PGDH Inhibitor SW033291 in Improving Type 2 Diabetes Mellitus: Insights from Metabolomics and Transcriptomics.","authors":"Yuanfeng Huang, Mingjie Liang, Yiwen Liao, Zirui Ji, Wanfen Lin, Xiangjin Pu, Lexun Wang, Weixuan Wang","doi":"10.3390/metabo14090509","DOIUrl":"https://doi.org/10.3390/metabo14090509","url":null,"abstract":"<p><p>This study focused on exploring the effects of SW033291, an inhibitor of 15-hydroxyprostaglandin dehydrogenase, on type 2 diabetes mellitus (T2DM) mice from a comprehensive perspective. Studies have demonstrated that SW033291 benefits tissue repair, organ function, and muscle mass in elderly mice. Our recent investigation initially reported the beneficial effect of SW033291 on T2DM progression. Herein, we used a T2DM mouse model induced by a high-fat diet and streptozotocin injection. Then, serum and liver metabolomics, as well as liver transcriptomic analyses, were performed to provide a systematic perspective of the SW033291-ameliorated T2DM. The results indicate SW033291 improved T2DM by regulating steroid hormone biosynthesis and linoleic/arachidonic acid metabolism. Furthermore, integrated transcriptomic and metabolomic analyses suggested that key genes and metabolites such as <i>Cyp2c55</i>, <i>Cyp3a11</i>, <i>Cyp21a1</i>, <i>Myc</i>, <i>Gstm1</i>, <i>Gstm3</i>, 9,10-dihydroxyoctadecenoic acid, 11-dehydrocorticosterone, and 12,13-dihydroxy-9Z-octadecenoic acid played crucial roles in these pathways. qPCR analysis validated the significant decreases in the hepatic gene expressions of <i>Cyp2c55</i>, <i>Cyp3a11</i>, <i>Myc</i>, <i>Gstm1</i>, and <i>Gstm3</i> in the T2DM mice, which were reversed following SW033291 treatment. Meanwhile, the elevated mRNA level of <i>Cyp21a1</i> in T2DM mice was decreased after SW033291 administration. Taken together, our findings suggest that SW033291 has promising potential in alleviating T2DM and could be a novel therapeutic candidate.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11434390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349779","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}
Caroline Brito Nunes, Maria Carolina Borges, Rachel M Freathy, Deborah A Lawlor, Elisabeth Qvigstad, David M Evans, Gunn-Helen Moen
Background/Objectives: During pregnancy, physiological changes in maternal circulating glucose levels and its metabolism are essential to meet maternal and fetal energy demands. Major changes in glucose metabolism occur throughout pregnancy and consist of higher insulin resistance and a compensatory increase in insulin secretion to maintain glucose homeostasis. For some women, this change is insufficient to maintain normoglycemia, leading to gestational diabetes mellitus (GDM), a condition characterized by maternal glucose intolerance and hyperglycaemia first diagnosed during the second or third trimester of pregnancy. GDM is diagnosed in approximately 14.0% of pregnancies globally, and it is often associated with short- and long-term adverse health outcomes in both mothers and offspring. Although recent studies have highlighted the role of genetic determinants in the development of GDM, research in this area is still lacking, hindering the development of prevention and treatment strategies. Methods: In this paper, we review recent advances in the understanding of genetic determinants of GDM and glycaemic traits during pregnancy. Results/Conclusions: Our review highlights the need for further collaborative efforts as well as larger and more diverse genotyped pregnancy cohorts to deepen our understanding of the genetic aetiology of GDM, address research gaps, and further improve diagnostic and treatment strategies.
{"title":"Understanding the Genetic Landscape of Gestational Diabetes: Insights into the Causes and Consequences of Elevated Glucose Levels in Pregnancy.","authors":"Caroline Brito Nunes, Maria Carolina Borges, Rachel M Freathy, Deborah A Lawlor, Elisabeth Qvigstad, David M Evans, Gunn-Helen Moen","doi":"10.3390/metabo14090508","DOIUrl":"https://doi.org/10.3390/metabo14090508","url":null,"abstract":"<p><p><b>Background/Objectives:</b> During pregnancy, physiological changes in maternal circulating glucose levels and its metabolism are essential to meet maternal and fetal energy demands. Major changes in glucose metabolism occur throughout pregnancy and consist of higher insulin resistance and a compensatory increase in insulin secretion to maintain glucose homeostasis. For some women, this change is insufficient to maintain normoglycemia, leading to gestational diabetes mellitus (GDM), a condition characterized by maternal glucose intolerance and hyperglycaemia first diagnosed during the second or third trimester of pregnancy. GDM is diagnosed in approximately 14.0% of pregnancies globally, and it is often associated with short- and long-term adverse health outcomes in both mothers and offspring. Although recent studies have highlighted the role of genetic determinants in the development of GDM, research in this area is still lacking, hindering the development of prevention and treatment strategies. <b>Methods:</b> In this paper, we review recent advances in the understanding of genetic determinants of GDM and glycaemic traits during pregnancy. <b>Results/Conclusions:</b> Our review highlights the need for further collaborative efforts as well as larger and more diverse genotyped pregnancy cohorts to deepen our understanding of the genetic aetiology of GDM, address research gaps, and further improve diagnostic and treatment strategies.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11434570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349785","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}
Prince Sellase Gameli, Johannes Kutzler, Diletta Berardinelli, Jeremy Carlier, Volker Auwärter, Francesco Paolo Busardò
Background: The abuse of psychoactive substances presents challenges in clinical and forensic toxicology. The emergence of novel and potent drugs that pose significant health risks, in particular towards frequent abusers and users unaware of the ingredients, further complicates the situation. Designer benzodiazepines have become a fast-growing subgroup of these new psychoactive substances (NPSs), and their overdose may potentially turn fatal, especially when combined with other central nervous system depressants. In 2021, flubrotizolam, a potent thieno-triazolo designer benzodiazepine, emerged on the illicit market, available online as a "research chemical". The identification of markers of consumption for this designer benzodiazepine is essential in analytical toxicology, especially in clinical and forensic cases.
Methods: We therefore aimed to identify biomarkers of flubrotizolam uptake in ten-donor-pooled human hepatocytes, applying liquid chromatography high-resolution mass spectrometry and software-aided data mining supported by in silico prediction tools.
Results: Prediction studies resulted in 10 and 13 first- and second-generation metabolites, respectively, mainly transformed through hydroxylation and sulfation, methylation, and glucuronidation reactions. We identified six metabolites after 3 h human hepatocyte incubation: two hydroxylated metabolites (α- and 6-hydroxy-flubrotizolam), two 6-hydroxy-glucuronides, a reduced-hydroxy-N-glucuronide, and an N-glucuronide.
Conclusions: We suggest detecting flubrotizolam and its hydroxylated metabolites as markers of consumption after the glucuronide hydrolysis of biological samples. The results are consistent with the in vivo metabolism of brotizolam, a medically used benzodiazepine and a chloro-phenyl analog of flubrotizolam.
{"title":"Exploring the Metabolism of Flubrotizolam, a Potent Thieno-Triazolo Diazepine, Using Human Hepatocytes and High-Resolution Mass Spectrometry.","authors":"Prince Sellase Gameli, Johannes Kutzler, Diletta Berardinelli, Jeremy Carlier, Volker Auwärter, Francesco Paolo Busardò","doi":"10.3390/metabo14090506","DOIUrl":"https://doi.org/10.3390/metabo14090506","url":null,"abstract":"<p><strong>Background: </strong>The abuse of psychoactive substances presents challenges in clinical and forensic toxicology. The emergence of novel and potent drugs that pose significant health risks, in particular towards frequent abusers and users unaware of the ingredients, further complicates the situation. Designer benzodiazepines have become a fast-growing subgroup of these new psychoactive substances (NPSs), and their overdose may potentially turn fatal, especially when combined with other central nervous system depressants. In 2021, flubrotizolam, a potent thieno-triazolo designer benzodiazepine, emerged on the illicit market, available online as a \"research chemical\". The identification of markers of consumption for this designer benzodiazepine is essential in analytical toxicology, especially in clinical and forensic cases.</p><p><strong>Methods: </strong>We therefore aimed to identify biomarkers of flubrotizolam uptake in ten-donor-pooled human hepatocytes, applying liquid chromatography high-resolution mass spectrometry and software-aided data mining supported by in silico prediction tools.</p><p><strong>Results: </strong>Prediction studies resulted in 10 and 13 first- and second-generation metabolites, respectively, mainly transformed through hydroxylation and sulfation, methylation, and glucuronidation reactions. We identified six metabolites after 3 h human hepatocyte incubation: two hydroxylated metabolites (α- and 6-hydroxy-flubrotizolam), two 6-hydroxy-glucuronides, a reduced-hydroxy-<i>N</i>-glucuronide, and an <i>N</i>-glucuronide.</p><p><strong>Conclusions: </strong>We suggest detecting flubrotizolam and its hydroxylated metabolites as markers of consumption after the glucuronide hydrolysis of biological samples. The results are consistent with the in vivo metabolism of brotizolam, a medically used benzodiazepine and a chloro-phenyl analog of flubrotizolam.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11433749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349778","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}
Ya Gao, Rebecca Finlay, Xiaofei Yin, Lorraine Brennan
Introduction There is increasing interest in food biomarkers to address the shortcomings of self-reported dietary assessments. Berries are regarded as important fruits worldwide; however, there are no well-validated biomarkers of berry intake. Thus, the objective of this study is to identify urinary biomarkers of berry intake. Methods For the discovery study, participants consumed 192 g strawberries with 150 g blueberries, and urine samples were collected at 2, 4, 6, and 24 h post-consumption. A dose–response study was performed, whereby participants consumed three portions (78 g, 278 g, and 428 g) of mixed strawberries and blueberries. The urine samples were profiled by an untargeted LC-MS metabolomics approach in the positive and negative modes. Results Statistical analysis of the data revealed that 39 features in the negative mode and 15 in the positive mode significantly increased between fasting and 4 h following mixed berry intake. Following the analysis of the dose–response data, 21 biomarkers showed overall significance across the portions of berry intake. Identification of the biomarkers was performed using fragmentation matches in the METLIN, HMDB, and MoNA databases and in published papers, confirmed where possible with authentic standards. Conclusions The ability of the panel of biomarkers to assess intake was examined, and the predictability was good, laying the foundations for the development of biomarker panels.
{"title":"Urinary Biomarkers of Strawberry and Blueberry Intake","authors":"Ya Gao, Rebecca Finlay, Xiaofei Yin, Lorraine Brennan","doi":"10.3390/metabo14090505","DOIUrl":"https://doi.org/10.3390/metabo14090505","url":null,"abstract":"Introduction There is increasing interest in food biomarkers to address the shortcomings of self-reported dietary assessments. Berries are regarded as important fruits worldwide; however, there are no well-validated biomarkers of berry intake. Thus, the objective of this study is to identify urinary biomarkers of berry intake. Methods For the discovery study, participants consumed 192 g strawberries with 150 g blueberries, and urine samples were collected at 2, 4, 6, and 24 h post-consumption. A dose–response study was performed, whereby participants consumed three portions (78 g, 278 g, and 428 g) of mixed strawberries and blueberries. The urine samples were profiled by an untargeted LC-MS metabolomics approach in the positive and negative modes. Results Statistical analysis of the data revealed that 39 features in the negative mode and 15 in the positive mode significantly increased between fasting and 4 h following mixed berry intake. Following the analysis of the dose–response data, 21 biomarkers showed overall significance across the portions of berry intake. Identification of the biomarkers was performed using fragmentation matches in the METLIN, HMDB, and MoNA databases and in published papers, confirmed where possible with authentic standards. Conclusions The ability of the panel of biomarkers to assess intake was examined, and the predictability was good, laying the foundations for the development of biomarker panels.","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269721","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}