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A specific diagnostic metabolome signature in adult IgA vasculitis. 成人 IgA 血管炎的特异性诊断代谢组特征。
IF 3.5 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-24 DOI: 10.1007/s11306-024-02107-0
Alexandre Boissais, Hélène Blasco, Patrick Emond, Antoine Lefèvre, Adrien Bigot, Yanis Ramdani, Nicole Ferreira Maldent, Denis Mulleman, Evangéline Pillebout, François Maillot, Alexandra Audemard-Verger

Introduction: IgA vasculitis diagnosis relies primarily on clinical features and is confirmed by pathological findings. To date, there is no reliable noninvasive diagnostic biomarker.

Objective: We aimed to explore the baseline serum metabolome of adult patients with IgA vasculitis to identify potential diagnostic biomarkers.

Methods: We performed a study comparing the serum metabolome of patients with IgA vasculitis to that of patients with inflammatory condition, namely spondyloarthritis. Serum analyses were performed by high-performance liquid chromatography-mass spectrometry.

Results: Fifty-five patients with IgA vasculitis and 77 controls with spondyloarthritis (age- and sex-matched) were included in this study. The median age of IgA vasculitis patients was 53 years. Two-thirds of patients were female (n = 32). At the time of vasculitis diagnosis, 100% of patients had skin involvement and 69% presented with glomerulonephritis (n = 38). Joint and digestive involvement were observed in 56% (n = 31) and 42% (n = 23) of patients. Four discriminative metabolites between the two groups were identified: 1-methyladenosine, L-glutamic acid, serotonin, and thymidine. The multivariate model built from the serum metabolomes of patients with IgA vasculitis and spondyloarthritis revealed an accuracy > 90%. As this model was significant according to the permutation test (p < 0.01), independent validation showed an excellent predictive value of the test set: sensitivity 98%; specificity 98%, positive predictive value 97% and negative predictive value 98%.

Conclusion: To our knowledge, this study is the first to use the metabolomic approach for diagnostic purposes in adult IgA vasculitis, highlighting a specific diagnostic metabolome signature.

导言:IgA 血管炎的诊断主要依赖于临床特征,并通过病理结果加以确认。迄今为止,尚无可靠的非侵入性诊断生物标志物:我们旨在探索成年 IgA 血管炎患者的血清代谢组基线,以确定潜在的诊断生物标志物:我们将 IgA 血管炎患者的血清代谢组与脊柱关节炎患者的血清代谢组进行了比较。血清分析采用高效液相色谱-质谱法进行:本研究共纳入 55 名 IgA 血管炎患者和 77 名脊柱关节炎对照组患者(年龄和性别匹配)。IgA 血管炎患者的中位年龄为 53 岁。三分之二的患者为女性(32 人)。在确诊为血管炎时,100%的患者皮肤受累,69%的患者出现肾小球肾炎(n = 38)。56%(31 人)和 42%(23 人)的患者出现关节和消化系统受累。两组患者的四种代谢物具有鉴别性:1-甲基腺苷、L-谷氨酸、血清素和胸腺嘧啶。根据 IgA 血管炎和脊柱关节炎患者的血清代谢组建立的多变量模型显示,准确率大于 90%。根据置换检验,该模型具有显著性(p 结论:"该模型的准确性高于90%":据我们所知,这项研究首次将代谢组学方法用于成人 IgA 血管炎的诊断,并突出了一个特定的诊断代谢组特征。
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引用次数: 0
Workshop report - interdisciplinary metabolomic epidemiology: the pathway to clinical translation. 研讨会报告--跨学科代谢组流行病学:临床转化之路。
IF 3.5 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-21 DOI: 10.1007/s11306-024-02111-4
Krista A Zanetti, Lining Guo, Deeba Husain, Rachel S Kelly, Jessica Lasky-Su, David Broadhurst, Craig E Wheelock

Metabolomic epidemiology studies are complex and require a broad array of domain expertise. Although many metabolite-phenotype associations have been identified; to date, few findings have been translated to the clinic. Bridging this gap requires understanding of both the underlying biology of these associations and their potential clinical implications, necessitating an interdisciplinary team approach. To address this need in metabolomic epidemiology, a workshop was held at Metabolomics 2023 in Niagara Falls, Ontario, Canada that highlighted the domain expertise needed to effectively conduct these studies -- biochemistry, clinical science, epidemiology, and assay development for biomarker validation -- and emphasized the role of interdisciplinary teams to move findings towards clinical translation.

代谢组流行病学研究非常复杂,需要广泛的领域专业知识。尽管已经确定了许多代谢组-表型关联,但迄今为止,很少有研究结果被应用于临床。要弥合这一差距,需要了解这些关联的基础生物学及其潜在的临床影响,这就需要采用跨学科的团队方法。为了满足代谢组流行病学的这一需求,2023 年在加拿大安大略省尼亚加拉瀑布市举行的代谢组学研讨会强调了有效开展这些研究所需的领域专业知识--生物化学、临床科学、流行病学和生物标记物验证的检测开发--并强调了跨学科团队在将研究结果转化为临床应用方面的作用。
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引用次数: 0
Lipidomics random forest algorithm of seminal plasma is a promising method for enhancing the diagnosis of necrozoospermia. 精浆脂质组学随机森林算法是提高死精症诊断率的有效方法。
IF 3.5 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-21 DOI: 10.1007/s11306-024-02118-x
Tianqin Deng, Wanxue Wang, Zhihong Fu, Yuli Xie, Yonghong Zhou, Jiangbo Pu, Kexin Chen, Bing Yao, Xuemei Li, Jilong Yao

Background: Despite the clear clinical diagnostic criteria for necrozoospermia in andrology, the fundamental mechanisms underlying it remain elusive. This study aims to profile the lipid composition in seminal plasma systematically and to ascertain the potential of lipid biomarkers in the accurate diagnosis of necrozoospermia. It also evaluates the efficacy of a lipidomics-based random forest algorithm model in identifying necrozoospermia.

Methods: Seminal plasma samples were collected from patients diagnosed with necrozoospermia (n = 28) and normozoospermia (n = 28). Liquid chromatography-mass spectrometry (LC-MS) was used to perform lipidomic analysis and identify the underlying biomarkers. A lipid functional enrichment analysis was conducted using the LION lipid ontology database. The top 100 differentially significant lipids were subjected to lipid biomarker examination through random forest machine learning model.

Results: Lipidomic analysis identified 46 lipid classes comprising 1267 lipid metabolites in seminal plasma. The top five enriched lipid functions as follows: fatty acid (FA) with ≤ 18 carbons, FA with 16-18 carbons, monounsaturated FA, FA with 18 carbons, and FA with 16 carbons. The top 100 differentially significant lipids were subjected to machine learning analysis and identified 20 feature lipids. The random forest model identified lipids with an area under the curve > 0.8, including LPE(20:4) and TG(4:0_14:1_16:0).

Conclusions: LPE(20:4) and TG(4:0_14:1_16:0), were identified as differential lipids for necrozoospermia. Seminal plasma lipidomic analysis could provide valuable biochemical information for the diagnosis of necrozoospermia, and its combination with conventional sperm analysis may improve the accuracy and reliability of the diagnosis.

背景:尽管男性学界对死精症有明确的临床诊断标准,但死精症的基本机制仍然难以捉摸。本研究旨在系统分析精浆中的脂质成分,并确定脂质生物标志物在准确诊断死精症方面的潜力。研究还评估了基于脂质组学的随机森林算法模型在识别坏死性精子症方面的功效:方法:收集被诊断为坏死性无精子症(28 人)和正常无精子症(28 人)患者的精浆样本。采用液相色谱-质谱联用技术(LC-MS)进行脂质体分析并确定潜在的生物标志物。利用 LION 脂质本体数据库进行了脂质功能富集分析。通过随机森林机器学习模型,对差异显著的前100种脂质进行脂质生物标志物检测:结果:脂质组分析确定了精浆中的46类脂质,包括1267种脂质代谢物。前五位富集的脂质功能如下:碳原子数≤18的脂肪酸(FA)、碳原子数为16-18的脂肪酸、单不饱和脂肪酸、碳原子数为18的脂肪酸和碳原子数为16的脂肪酸。对差异显著性最高的 100 种脂质进行机器学习分析,确定了 20 种特征脂质。随机森林模型确定了曲线下面积大于 0.8 的脂质,包括 LPE(20:4) 和 TG(4:0_14:1_16:0):结论:LPE(20:4)和TG(4:0_14:1_16:0)被确定为死精症的差异脂质。精浆脂质体分析可为坏死性无精子症的诊断提供有价值的生化信息,与常规精子分析相结合可提高诊断的准确性和可靠性。
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引用次数: 0
NMR and LC-MS-based metabolomics to investigate the efficacy of a commercial bio stimulant for the treatment of wheat (Triticum aestivum). 基于 NMR 和 LC-MS 的代谢组学研究一种商业生物刺激剂对小麦(Triticum aestivum)的功效。
IF 3.5 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-21 DOI: 10.1007/s11306-024-02131-0
Kamar Hamade, Ophelie Fliniaux, Jean-Xavier Fontaine, Roland Molinié, Laurent Petit, David Mathiron, Vivien Sarazin, Francois Mesnard

Introduction: Bio stimulants are substances and/or microorganisms that are used to improve plant growth and crop yields by modulating physiological processes and metabolism of plants. While research has primarily focused on the broad effects of bio stimulants in crops, understanding their cellular and molecular influences in plants, using metabolomic analysis, could elucidate their effectiveness and offer possibilities for fine-tuning their application. One such bio stimulant containing galacturonic acid as elicitor is used in agriculture to improve wheat vigor and strengthen resistance to lodging.

Objective: However, whether a metabolic response is evolved by plants treated with this bio stimulant and the manner in which the latter might regulate plant metabolism have not been studied.

Method: Therefore, the present study used 1H-NMR and LC-MS to assess changes in primary and secondary metabolites in the roots, stems, and leaves of wheat (Triticum aestivum) treated with the bio stimulant. Orthogonal partial least squares discriminant analysis effectively distinguished between treated and control samples, confirming a metabolic response to treatment in the roots, stems, and leaves of wheat.

Results: Fold-change analysis indicated that treatment with the bio stimulation solution appeared to increase the levels of hydroxycinnamic acid amides, lignin, and flavonoid metabolism in different plant parts, potentially promoting root growth, implantation, and developmental cell wall maturation and lignification.

Conclusion: These results demonstrate how non-targeted metabolomic approaches can be utilized to investigate and monitor the effects of new agroecological solutions based on systemic responses.

简介:生物刺激剂是通过调节植物的生理过程和新陈代谢来改善植物生长和提高作物产量的物质和/或微生物。虽然研究主要集中在生物刺激剂对作物的广泛影响,但利用代谢组学分析了解其对植物细胞和分子的影响,可以阐明其有效性,并为微调其应用提供可能性。目的:然而,使用这种生物刺激剂的植物是否会产生新陈代谢反应,以及后者可能调节植物新陈代谢的方式尚未得到研究:因此,本研究使用 1H-NMR 和 LC-MS 评估了使用该生物刺激剂的小麦(Triticum aestivum)根、茎和叶中初级和次级代谢物的变化。正交偏最小二乘法判别分析有效区分了处理样本和对照样本,证实了小麦根、茎和叶对处理的代谢反应:结果:折叠变化分析表明,使用生物刺激液处理似乎提高了植物不同部位的羟基肉桂酸酰胺、木质素和类黄酮代谢水平,可能促进了根系生长、植入、发育细胞壁成熟和木质化:这些结果表明,非靶向代谢组学方法可用于研究和监测基于系统反应的新农业生态解决方案的效果。
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引用次数: 0
Identifying potential breath biomarkers for early diagnosis of papillary thyroid cancer based on solid-phase microextraction gas chromatography-high resolution mass spectrometry with metabolomics. 基于固相微萃取气相色谱-高分辨质谱联用代谢组学鉴定用于甲状腺乳头状癌早期诊断的潜在呼气生物标记物
IF 3.5 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-21 DOI: 10.1007/s11306-024-02119-w
Lan Li, Xinxin Wen, Xian Li, Yaqi Yan, Jiayu Wang, Xuyang Zhao, Yonghui Tian, Rui Ling, Yixiang Duan

Introduction: Thyroid cancer incidence rate has increased substantially worldwide in recent years. Fine needle aspiration biopsy (FNAB) is currently the golden standard of thyroid cancer diagnosis, which however, is invasive and costly. In contrast, breath analysis is a non-invasive, safe and simple sampling method combined with a promising metabolomics approach, which is suitable for early cancer diagnosis in high volume population.

Objectives: This study aims to achieve a more comprehensive and definitive exhaled breath metabolism profile in papillary thyroid cancer patients (PTCs).

Methods: We studied both end-tidal and mixed expiratory breath, solid-phase microextraction gas chromatography coupled with high resolution mass spectrometry (SPME-GC-HRMS) was used to analyze the breath samples. Multivariate combined univariate analysis was applied to identify potential breath biomarkers.

Results: The biomarkers identified in end-tidal and mixed expiratory breath mainly included alkanes, olefins, enols, enones, esters, aromatic compounds, and fluorine and chlorine containing organic compounds. The area under the curve (AUC) values of combined biomarkers were 0.974 (sensitivity: 96.1%, specificity: 90.2%) and 0.909 (sensitivity: 98.0%, specificity: 74.5%), respectively, for the end-tidal and mixed expiratory breath, indicating of reliability of the sampling and analysis method CONCLUSION: This work not only successfully established a standard metabolomic approach for early diagnosis of PTC, but also revealed the necessity of using both the two breath types for comprehensive analysis of the biomarkers.

导言近年来,甲状腺癌的发病率在全球范围内大幅上升。细针穿刺活检(FNAB)是目前诊断甲状腺癌的黄金标准,但其具有创伤性且成本高昂。相比之下,呼气分析是一种无创、安全、简便的采样方法,并结合了前景广阔的代谢组学方法,适用于大样本人群的早期癌症诊断:本研究旨在对甲状腺乳头状癌(PTC)患者的呼气代谢情况进行更全面、更明确的分析:我们研究了潮气末呼气和混合呼气,采用固相微萃取气相色谱-高分辨质谱联用技术(SPME-GC-HRMS)分析呼气样本。采用多变量联合单变量分析来确定潜在的呼气生物标志物:结果:在潮气末和混合呼气中发现的生物标记物主要包括烷烃、烯烃、烯醇、烯酮、酯、芳香族化合物以及含氟和氯的有机化合物。潮气末呼气和混合呼气的综合生物标志物曲线下面积(AUC)值分别为0.974(灵敏度:96.1%,特异性:90.2%)和0.909(灵敏度:98.0%,特异性:74.5%),表明采样和分析方法可靠。 结论:该研究不仅成功建立了用于PTC早期诊断的标准代谢组学方法,而且揭示了使用两种呼气类型对生物标志物进行综合分析的必要性。
{"title":"Identifying potential breath biomarkers for early diagnosis of papillary thyroid cancer based on solid-phase microextraction gas chromatography-high resolution mass spectrometry with metabolomics.","authors":"Lan Li, Xinxin Wen, Xian Li, Yaqi Yan, Jiayu Wang, Xuyang Zhao, Yonghui Tian, Rui Ling, Yixiang Duan","doi":"10.1007/s11306-024-02119-w","DOIUrl":"10.1007/s11306-024-02119-w","url":null,"abstract":"<p><strong>Introduction: </strong>Thyroid cancer incidence rate has increased substantially worldwide in recent years. Fine needle aspiration biopsy (FNAB) is currently the golden standard of thyroid cancer diagnosis, which however, is invasive and costly. In contrast, breath analysis is a non-invasive, safe and simple sampling method combined with a promising metabolomics approach, which is suitable for early cancer diagnosis in high volume population.</p><p><strong>Objectives: </strong>This study aims to achieve a more comprehensive and definitive exhaled breath metabolism profile in papillary thyroid cancer patients (PTCs).</p><p><strong>Methods: </strong>We studied both end-tidal and mixed expiratory breath, solid-phase microextraction gas chromatography coupled with high resolution mass spectrometry (SPME-GC-HRMS) was used to analyze the breath samples. Multivariate combined univariate analysis was applied to identify potential breath biomarkers.</p><p><strong>Results: </strong>The biomarkers identified in end-tidal and mixed expiratory breath mainly included alkanes, olefins, enols, enones, esters, aromatic compounds, and fluorine and chlorine containing organic compounds. The area under the curve (AUC) values of combined biomarkers were 0.974 (sensitivity: 96.1%, specificity: 90.2%) and 0.909 (sensitivity: 98.0%, specificity: 74.5%), respectively, for the end-tidal and mixed expiratory breath, indicating of reliability of the sampling and analysis method CONCLUSION: This work not only successfully established a standard metabolomic approach for early diagnosis of PTC, but also revealed the necessity of using both the two breath types for comprehensive analysis of the biomarkers.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"20 3","pages":"59"},"PeriodicalIF":3.5,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Analysis of the metabolic profile of humans naturally exposed to RF-EM radiation. 分析自然暴露于射频-电磁辐射的人体的代谢概况。
IF 3.5 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-18 DOI: 10.1007/s11306-024-02121-2
Neel Mani Rangesh, Arun Kumar Malaisamy, Nitesh Kumar, Sanjay Kumar

Introduction: The world is experiencing exponential growth in communication, especially wireless communication. Wireless connectivity has recently become a part of everyone's daily life. Recent developments in low-cost, low-power, and miniature devices contribute to a significant rise in radiofrequency-electromagnetic field (RF-EM) radiation exposure in our environment, raising concern over its effect on biological systems. The inconsistent and conflicting research results make it difficult to draw definite conclusions about how RF-EM radiation affects living things.

Objectives: This study identified two micro-environments based on their level of exposure to cellular RF-EM radiation, one with significantly less exposure and another with very high exposure to RF-EM radiation. Emphasis is given to studying the metabolites in the urine samples of humans naturally exposed to these two different microenvironments to understand short-term metabolic dysregulations.

Methods: Untargeted 1H NMR spectroscopy was employed for metabolomics analyses to identify dysregulated metabolites. A total of 60 subjects were recruited with 5 ml urine samples each. These subjects were divided into two groups: one highly exposed to RF-EM (n = 30) and the other consisting of low-exposure populations (n = 30).

Results: The study found that the twenty-nine metabolites were dysregulated. Among them, 19 were downregulated, and 10 were upregulated. In particular, Glyoxylate and dicarboxylate and the TCA cycle metabolism pathway have been perturbed. The dysregulated metabolites were validated using the ROC curve analysis.

Conclusion: Untargeted urine metabolomics was conducted to identify dysregulated metabolites linked to RF-EM radiation exposure. Preliminary findings suggest a connection between oxidative stress and gut microbiota imbalance. However, further research is needed to validate these biomarkers and understand the effects of RF-EM radiation on human health. Further research is needed with a diverse population.

引言全球通信,尤其是无线通信正经历着指数级增长。无线连接最近已成为每个人日常生活的一部分。近来,低成本、低功耗和微型设备的发展导致我们环境中的射频电磁场(RF-EM)辐射显著增加,引起了人们对其对生物系统影响的关注。由于研究结果不一致且相互矛盾,因此很难就射频电磁场辐射如何影响生物得出明确的结论:本研究根据细胞射频-电磁辐射的暴露程度确定了两种微环境,一种暴露程度明显较低,另一种暴露程度非常高。重点研究自然暴露在这两种不同微环境中的人体尿液样本中的代谢物,以了解短期代谢失调情况:方法:采用非靶向 1H NMR 光谱进行代谢组学分析,以确定失调的代谢物。共招募了 60 名受试者,每人采集 5 毫升尿样。这些受试者被分为两组:一组高度暴露于射频-电磁场(n = 30),另一组为低暴露人群(n = 30):研究发现,29 种代谢物出现了失调。结果:研究发现,29 种代谢物出现失调,其中 19 种下调,10 种上调。其中,乙醛酸和二羧酸以及 TCA 循环代谢途径受到了干扰。采用 ROC 曲线分析法对失调代谢物进行了验证:结论:通过非靶向尿液代谢组学研究,确定了与射频-电磁辐射照射有关的失调代谢物。初步研究结果表明,氧化应激与肠道微生物群失衡之间存在联系。然而,要验证这些生物标记物并了解射频-电磁辐射对人体健康的影响,还需要进一步的研究。还需要对不同人群进行进一步研究。
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引用次数: 0
Metabolomic prediction of severe maternal and newborn complications in preeclampsia. 子痫前期产妇和新生儿严重并发症的代谢组学预测。
IF 3.5 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-18 DOI: 10.1007/s11306-024-02123-0
Jay Idler, Onur Turkoglu, Ali Yilmaz, Nadia Ashrafi, Marta Szymanska, Ilyas Ustun, Kara Patek, Amy Whitten, Stewart F Graham, Ray O Bahado-Singh

Introduction: Preeclampsia (PreE) remains a major source of maternal and newborn complications. Prenatal prediction of these complications could significantly improve pregnancy management.

Objectives: Using metabolomic analysis we investigated the prenatal prediction of maternal and newborn complications in early and late PreE and investigated the pathogenesis of such complications.

Methods: Serum samples from 76 cases of PreE (36 early-onset and 40 late-onset), and 40 unaffected controls were collected. Direct Injection Liquid Chromatography-Mass Spectrometry combined with Nuclear Magnetic Resonance (NMR) spectroscopy was performed. Logistic regression analysis was used to generate models for prediction of adverse maternal and neonatal outcomes in patients with PreE. Metabolite set enrichment analysis (MSEA) was used to identify the most dysregulated metabolites and pathways in PreE.

Results: Forty-three metabolites were significantly altered (p < 0.05) in PreE cases with maternal complications and 162 metabolites were altered in PreE cases with newborn adverse outcomes. The top metabolite prediction model achieved an area under the receiver operating characteristic curve (AUC) = 0.806 (0.660-0.952) for predicting adverse maternal outcomes in early-onset PreE, while the AUC for late-onset PreE was 0.843 (0.712-0.974). For the prediction of adverse newborn outcomes, regression models achieved an AUC = 0.828 (0.674-0.982) in early-onset PreE and 0.911 (0.828-0.994) in late-onset PreE. Profound alterations of lipid metabolism were associated with adverse outcomes.

Conclusion: Prenatal metabolomic markers achieved robust prediction, superior to conventional markers for the prediction of adverse maternal and newborn outcomes in patients with PreE. We report for the first-time the prediction and metabolomic basis of adverse maternal and newborn outcomes in patients with PreE.

导言子痫前期(Preeclampsia,PRE)仍然是孕产妇和新生儿并发症的主要来源。对这些并发症进行产前预测可大大改善妊娠管理:通过代谢组学分析,我们对早期和晚期子痫前期的孕产妇和新生儿并发症进行了产前预测,并研究了这些并发症的发病机制:方法:收集了 76 例早产儿(36 例早产儿和 40 例晚期早产儿)和 40 例未受影响的对照组的血清样本。进行了直接注射液相色谱-质谱联用和核磁共振(NMR)光谱分析。采用逻辑回归分析法生成预测 PreE 患者不良孕产妇和新生儿结局的模型。代谢物集富集分析(MSEA)用于确定PreE中最失调的代谢物和通路:结果:43 种代谢物发生了显著变化(P产前代谢组标记物在预测PreE患者的不良孕产妇和新生儿结局方面具有强健的预测能力,优于传统标记物。我们首次报道了预测先兆流产患者的不良孕产妇和新生儿结局及其代谢组学基础。
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引用次数: 0
Characterizing poorly controlled type 2 diabetes using 1H-NMR metabolomics. 利用 1H-NMR 代谢组学鉴定控制不佳的 2 型糖尿病。
IF 3.5 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-11 DOI: 10.1007/s11306-024-02127-w
Isabella J Theron, Shayne Mason, Mari van Reenen, Zinandré Stander, Léanie Kleynhans, Katharina Ronacher, Du Toit Loots

Introduction: The prevalence of type 2 diabetes has surged to epidemic proportions and despite treatment administration/adherence, some individuals experience poorly controlled diabetes. While existing literature explores metabolic changes in type 2 diabetes, understanding metabolic derangement in poorly controlled cases remains limited.

Objective: This investigation aimed to characterize the urine metabolome of poorly controlled type 2 diabetes in a South African cohort.

Method: Using an untargeted proton nuclear magnetic resonance metabolomics approach, urine samples from 15 poorly controlled type 2 diabetes patients and 25 healthy controls were analyzed and statistically compared to identify differentiating metabolites.

Results: The poorly controlled type 2 diabetes patients were characterized by elevated concentrations of various metabolites associated with changes to the macro-fuel pathways (including carbohydrate metabolism, ketogenesis, proteolysis, and the tricarboxylic acid cycle), autophagy and/or apoptosis, an uncontrolled diet, and kidney and liver damage.

Conclusion: These results indicate that inhibited cellular glucose uptake in poorly controlled type 2 diabetes significantly affects energy-producing pathways, leading to apoptosis and/or autophagy, ultimately contributing to kidney and mild liver damage. The study also suggests poor dietary compliance as a cause of the patient's uncontrolled glycemic state. Collectively these findings offer a first-time comprehensive overview of urine metabolic changes in poorly controlled type 2 diabetes and its association with secondary diseases, offering potential insights for more targeted treatment strategies to prevent disease progression, treatment efficacy, and diet/treatment compliance.

导言:2 型糖尿病的发病率已飙升至流行病的程度,尽管进行了治疗/坚持了治疗,但仍有一些人的糖尿病控制不佳。虽然现有文献探讨了 2 型糖尿病的代谢变化,但对控制不佳病例代谢紊乱的了解仍然有限:本研究旨在分析南非队列中控制不佳的 2 型糖尿病患者的尿液代谢组特征:方法:采用非靶向质子核磁共振代谢组学方法,对 15 名控制不佳的 2 型糖尿病患者和 25 名健康对照者的尿液样本进行分析和统计比较,以确定不同的代谢物:结果:控制不佳的 2 型糖尿病患者的特征是各种代谢物浓度升高,这些代谢物与大燃料途径(包括碳水化合物代谢、酮体生成、蛋白质分解和三羧酸循环)的变化、自噬和/或细胞凋亡、饮食失控以及肝肾损伤有关:这些结果表明,控制不佳的 2 型糖尿病患者的细胞葡萄糖摄取受抑制,会严重影响能量生成途径,导致细胞凋亡和/或自噬,最终造成肾脏和肝脏轻度损伤。研究还表明,饮食依从性差是导致患者血糖失控的原因之一。这些研究结果首次全面概述了控制不佳的2型糖尿病患者的尿液代谢变化及其与继发性疾病的关联,为更有针对性的治疗策略提供了潜在的见解,以防止疾病恶化、提高治疗效果和饮食/治疗依从性。
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引用次数: 0
Data-dependent and -independent acquisition lipidomics analysis reveals the tissue-dependent effect of metformin on lipid metabolism. 数据依赖性和非依赖性采集脂质组学分析揭示了二甲双胍对脂质代谢的组织依赖性影响。
IF 3.5 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-09 DOI: 10.1007/s11306-024-02113-2
Grace Scheidemantle, Likun Duan, Mareca Lodge, Magdalina J Cummings, Dalton Hilovsky, Eva Pham, Xiaoqiu Wang, Arion Kennedy, Xiaojing Liu
<p><strong>Introduction: </strong>Despite the well-recognized health benefits, the mechanisms and site of action of metformin remains elusive. Metformin-induced global lipidomic changes in plasma of animal models and human subjects have been reported. However, there is a lack of systemic evaluation of metformin-induced lipidomic changes in different tissues. Metformin uptake requires active transporters such as organic cation transporters (OCTs), and hence, it is anticipated that metformin actions are tissue-dependent. In this study, we aim to characterize metformin effects in non-diabetic male mice with a special focus on lipidomics analysis. The findings from this study will help us to better understand the cell-autonomous (direct actions in target cells) or non-cell-autonomous (indirect actions in target cells) mechanisms of metformin and provide insights into the development of more potent yet safe drugs targeting a particular organ instead of systemic metabolism for metabolic regulations without major side effects.</p><p><strong>Objectives: </strong>To characterize metformin-induced lipidomic alterations in different tissues of non-diabetic male mice and further identify lipids affected by metformin through cell-autonomous or systemic mechanisms based on the correlation between lipid alterations in tissues and the corresponding in-tissue metformin concentrations.</p><p><strong>Methods: </strong>A dual extraction method involving 80% methanol followed by MTBE (methyl tert-butyl ether) extraction enables the analysis of free fatty acids, polar metabolites, and lipids. Extracts from tissues and plasma of male mice treated with or without metformin in drinking water for 12 days were analyzed using HILIC chromatography coupled to Q Exactive Plus mass spectrometer or reversed-phase liquid chromatography coupled to MS/MS scan workflow (hybrid mode) on LC-Orbitrap Exploris 480 mass spectrometer using biologically relevant lipids-containing inclusion list for data-independent acquisition (DIA), named as BRI-DIA workflow followed by data-dependent acquisition (DDA), to maximum the coverage of lipids and minimize the negative effect of stochasticity of precursor selection on experimental consistency and reproducibility.</p><p><strong>Results: </strong>Lipidomics analysis of 6 mouse tissues and plasma allowed a systemic evaluation of lipidomic changes induced by metformin in different tissues. We observed that (1) the degrees of lipidomic changes induced by metformin treatment overly correlated with tissue concentrations of metformin; (2) the impact on lysophosphatidylcholine (lysoPC) and cardiolipins was positively correlated with tissue concentrations of metformin, while neutral lipids such as triglycerides did not correlate with the corresponding tissue metformin concentrations; (3) increase of intestinal tricarboxylic acid (TCA) cycle intermediates after metformin treatment.</p><p><strong>Conclusion: </strong>The data collected in this study from no
简介:尽管二甲双胍对健康的益处已得到广泛认可,但其作用机制和作用部位仍难以捉摸。二甲双胍诱导动物模型和人体血浆中脂质组的整体变化已有报道。然而,目前还缺乏对二甲双胍诱导的不同组织脂质体变化的系统评估。二甲双胍的吸收需要有机阳离子转运体(OCTs)等活性转运体的参与,因此,预计二甲双胍的作用与组织有关。在本研究中,我们旨在描述二甲双胍对非糖尿病雄性小鼠的影响,重点是脂质组学分析。这项研究的结果将有助于我们更好地理解二甲双胍的细胞自主(直接作用于靶细胞)或非细胞自主(间接作用于靶细胞)机制,并为开发针对特定器官而非全身代谢的更强效、更安全的药物提供见解,从而实现无重大副作用的代谢调节:表征二甲双胍诱导的非糖尿病雄性小鼠不同组织的脂质体改变,并根据组织中脂质改变与相应组织内二甲双胍浓度之间的相关性,进一步确定二甲双胍通过细胞自主或全身机制影响脂质体:方法:采用80%甲醇和MTBE(甲基叔丁基醚)双重萃取法对游离脂肪酸、极性代谢物和脂质进行分析。采用HILIC色谱-Q Exactive Plus质谱仪或反相液相色谱-MS/MS扫描工作流程(混合模式),在LC-Orbitrap Exploris 480质谱仪上使用与生物相关的脂质包含列表进行数据独立采集(DIA),分析了在饮用水中添加或不添加二甲双胍12天的雄性小鼠的组织和血浆提取物、该工作流程被命名为 "BRI-DIA 工作流程",然后再进行 "数据依赖性采集(DDA)",以最大限度地扩大脂质的覆盖范围,并将前体选择的随机性对实验一致性和重现性的负面影响降至最低。结果通过对 6 种小鼠组织和血浆进行脂质组学分析,可以系统评估二甲双胍在不同组织中引起的脂质组学变化。我们观察到:(1)二甲双胍治疗诱导的脂质体变化程度与组织中二甲双胍的浓度过度相关;(2)溶血磷脂酰胆碱(lysoPC)和心磷脂的影响与组织中二甲双胍的浓度呈正相关,而甘油三酯等中性脂质与相应组织中二甲双胍的浓度无关;(3)二甲双胍治疗后肠道三羧酸(TCA)循环中间产物增加:本研究从非糖尿病小鼠身上收集的 12 天二甲双胍治疗数据表明,二甲双胍的整体代谢效应与组织浓度呈正相关,对单个脂质亚类的影响是通过细胞自主机制(心磷脂和溶血磷脂)和非细胞自主机制(甘油三酯)产生的。
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引用次数: 0
Metabolomic signatures for blood pressure from early to late adolescence: findings from a U.S. cohort. 从青春期早期到晚期的血压代谢特征:美国队列的研究结果。
IF 3.5 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-09 DOI: 10.1007/s11306-024-02110-5
Mingyu Zhang, Wei Perng, Sheryl L Rifas-Shiman, Izzuddin M Aris, Emily Oken, Marie-France Hivert

Introduction: Metabolite signatures for blood pressure (BP) may reveal biomarkers, elucidate pathogenesis, and provide prevention targets for high BP. Knowledge regarding metabolites associated with BP in adolescence remains limited.

Objectives: Investigate the associations between metabolites and adolescent BP, both cross-sectionally (in early and late adolescence) and prospectively (from early to late adolescence).

Methods: Participants are from the Project Viva prospective cohort. During the early (median: 12.8 years; N = 556) and late (median: 17.4 years; N = 501) adolescence visits, we conducted untargeted plasma metabolomic profiling and measured systolic (SBP) and diastolic BP (DBP). We used linear regression to identify metabolites cross-sectionally associated with BP at each time point, and to assess prospective associations of changes in metabolite levels from early to late adolescence with late adolescence BP. We used Weighted Gene Correlation Network Analysis and Spearman's partial correlation to identify metabolite clusters associated with BP at each time point.

Results: In the linear models, higher androgenic steroid levels were consistently associated with higher SBP and DBP in early and late adolescence. A cluster of 59 metabolites, mainly composed of androgenic steroids, correlated with higher SBP and DBP in early adolescence. A cluster primarily composed of fatty acid lipids was marginally associated with higher SBP in females in late adolescence. Multiple metabolites, including those in the creatine and purine metabolism sub-pathways, were associated with higher SBP and DBP both cross-sectionally and prospectively.

Conclusion: Our results shed light on the potential metabolic processes and pathophysiology underlying high BP in adolescents.

导言:血压(BP)的代谢物特征可揭示生物标志物、阐明发病机制并提供高血压的预防目标。有关青少年血压代谢物的知识仍然有限:研究代谢物与青少年血压之间的关系,包括横断面研究(青春期早期和晚期)和前瞻性研究(青春期早期到晚期):方法:参与者来自 "Project Viva "前瞻性队列。在青春期早期(中位数:12.8 岁;N = 556)和晚期(中位数:17.4 岁;N = 501),我们进行了非靶向血浆代谢组学分析,并测量了收缩压(SBP)和舒张压(DBP)。我们使用线性回归法来确定每个时间点与血压相关的横断面代谢物,并评估代谢物水平从青春期早期到晚期的变化与青春期晚期血压的前瞻性关联。我们使用加权基因相关网络分析和斯皮尔曼偏相关性来确定每个时间点与血压相关的代谢物群:结果:在线性模型中,较高的雄激素类固醇水平始终与青春期早期和晚期较高的 SBP 和 DBP 相关。主要由雄激素类固醇组成的 59 个代谢物群与青春期早期较高的 SBP 和 DBP 相关。一个主要由脂肪酸脂组成的代谢物群与青春期后期女性较高的 SBP 稍有关联。多种代谢物,包括肌酸和嘌呤代谢子途径中的代谢物,在横断面和前瞻性研究中均与较高的 SBP 和 DBP 相关:我们的研究结果揭示了青少年高血压的潜在代谢过程和病理生理学基础。
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