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A matter of perspective—Cutting-edge technology-driven urine proteome in COVID-19 前沿技术驱动的尿蛋白质组学在COVID-19中的应用
Pub Date : 2021-01-01 DOI: 10.1016/j.urine.2021.01.001
Siyuan Wang , Catherine CL. Wong

In a recent issue of Nature Communications, we highlighted in-depth urine proteomic research in which significant immunosuppression was revealed in early SARS-CoV-2- infected patients 1. The application of urine in mapping the landscape of molecular changes closely associated with human diseases has been widely accepted. Herein, we take a systematic review of the published article from the perspective of both methodology and clinical significance.

在最近一期的《自然通讯》中,我们重点介绍了深入的尿液蛋白质组学研究,其中发现早期SARS-CoV-2感染患者存在显著的免疫抑制1。尿液在绘制与人类疾病密切相关的分子变化景观中的应用已被广泛接受。在此,我们从方法学和临床意义的角度对已发表的文章进行系统回顾。
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引用次数: 1
The start of diabetes insipidus? 尿崩症的开始?
Pub Date : 2021-01-01 DOI: 10.1016/j.urine.2021.05.001
Youhe Gao
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引用次数: 0
The potential of spot and overnight urine in the evaluating of proteinuria and electrolyte 斑点尿和夜尿在评价蛋白尿和电解质中的潜力
Pub Date : 2021-01-01 DOI: 10.1016/j.urine.2021.07.001
Chen Yang , Guang-Yan Cai , Zhi-Yu Duan , Shu-Wei Duan , Yong Wang , Zhe Feng , Xiang-Mei Chen

Urine testing has been a primary standard clinical method for assessing proteinuria and electrolyte intake. The traditional 24 ​h urine collection method, despite its high accuracy, has some limitations in practice. To overcome its drawbacks, two alternatives are widely recommended: spot urine collection and overnight urine collection. However, questions about the ability of the two alternatives in replacing the 24 ​h urine collection are still on debate, which requires further investigation. This article makes a systematic review of the two alternatives methods for assessing proteinuria and electrolyte, which may provide a useful insight for using them in actual clinical evaluation and diagnosis.

尿液检测一直是评估蛋白尿和电解质摄入的主要标准临床方法。传统的24小时尿液采集方法虽然准确率高,但在实际应用中存在一定的局限性。为了克服它的缺点,两种替代方法被广泛推荐:就地收集尿液和夜间收集尿液。然而,关于这两种替代方法是否能够替代24小时尿液收集的问题仍存在争议,这需要进一步的研究。本文对蛋白尿和电解质的两种替代方法进行了系统的综述,以期为实际临床评价和诊断提供有益的见解。
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引用次数: 1
Comments on: Saenger T. et al. “Urinary Biomarkers for Orange Juice Consumption.” Molecular Nutrition & Food Research (2021) 评论:senger T.等人的《饮用橙汁的尿液生物标志物》。分子营养与食品研究(2021)
Pub Date : 2021-01-01 DOI: 10.1016/j.urine.2021.05.002
Haibin Zhang, Jianfei Lu, Jie Li

This paper by Saenger T., et al. has suggested the potential biomarkers for orange juice consumption and addressed an approach to distinguish between low, medium, and high orange juice consumption. Although these findings of intake biomarkers are of great significance for single-nutrient-intake assessment, a comprehensive measurement of overall dietary pattern remains elusive due to the complexity of dietary metabolism. In contrast, urinary metabolomics is probably a preferable approach.

Saenger T.等人的论文提出了橙汁消费的潜在生物标志物,并提出了一种区分低、中、高橙汁消费的方法。尽管这些摄入生物标志物的发现对单一营养素摄入评估具有重要意义,但由于饮食代谢的复杂性,对整体饮食模式的全面测量仍然难以实现。相比之下,尿代谢组学可能是一种更好的方法。
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引用次数: 0
Changes in the Urine Proteome in Patients With Advanced Lung Cancer After Different Drug Treatments 晚期癌症患者不同药物治疗后尿蛋白组的变化
Pub Date : 2020-11-30 DOI: 10.21203/rs.3.rs-109321/v1
Yameng Zhang, Ziqi Heng, Jing Wei, Yingyi Wang, Youhe Gao
Lung cancer is one of the most threatening diseases to human life and health because of its mortality. How to choose more efficient drugs and the appropriate timing of treatment for patients with advanced lung cancer is still a problem. As the urine proteome can sensitively reflect the pathological or physiological changes of the body, it has the potential to reflect the dynamic changes of the body after drug treatment. To investigate the changes in the urine proteome of patients with advanced lung cancer after different drug treatments, urine samples were collected and analyzed at different time points. The changes in the urine proteome from the pretreatment state were different in each patient, although some of them were treated with the same drugs. The changes in the biological processes reflected by the differential urinary proteins were consistent with the changes in the clinical manifestations of the patients. This study demonstrates that the pathophysiological changes of patients with advanced lung cancer can be reflected by changes in urinary protein after different drug treatments. In addition, the changes in urinary proteins can reflect the different biological processes in patients after the same drug treatment, and the patients’ clinical condition assessment results are consistent with these changes. These findings may provide additional information for clinical treatment.
癌症是威胁人类生命和健康的最严重疾病之一。对于晚期癌症患者,如何选择更有效的药物和合适的治疗时机仍然是一个问题。由于尿液蛋白质组能够灵敏地反映身体的病理或生理变化,因此有可能反映药物治疗后身体的动态变化。为了研究晚期癌症患者在不同药物治疗后尿液蛋白质组的变化,采集不同时间点的尿液样本进行分析。每个患者的尿液蛋白质组从预处理状态的变化是不同的,尽管其中一些患者使用了相同的药物。差异尿蛋白所反映的生物学过程的变化与患者临床表现的变化一致。这项研究表明,晚期癌症患者的病理生理变化可以通过不同药物治疗后尿蛋白的变化来反映。此外,尿蛋白的变化可以反映患者在接受相同药物治疗后的不同生物学过程,患者的临床状况评估结果与这些变化一致。这些发现可能为临床治疗提供额外的信息。
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引用次数: 1
Urine proteome of COVID-19 patients COVID-19患者尿蛋白质组学分析
Pub Date : 2020-01-01 DOI: 10.1016/j.urine.2021.02.001
Yanchang Li , Yihao Wang , Huiying Liu , Wei Sun , Baoqing Ding , Yinghua Zhao , Peiru Chen , Li Zhu , Zhaodi Li , Naikang Li , Lei Chang , Hengliang Wang , Changqing Bai , Ping Xu

The atypical pneumonia (COVID-19) caused by SARS-CoV-2 is a serious threat to global public health. However, early detection and effective prediction of patients with mild to severe symptoms remain challenging. The proteomic profiling of urine samples from healthy individuals, mild and severe COVID-19 positive patients with comorbidities can be clearly differentiated. Multiple pathways have been compromised after the COVID-19 infection, including the dysregulation of complement activation, platelet degranulation, lipoprotein metabolic process and response to hypoxia. This study demonstrates the COVID-19 pathophysiology related molecular alterations could be detected in the urine and the potential application in auxiliary diagnosis of COVID-19.

由SARS-CoV-2引起的非典型肺炎(COVID-19)是对全球公共卫生的严重威胁。然而,早期发现和有效预测轻度至重度症状患者仍然具有挑战性。健康人、轻、重度COVID-19阳性合并合并症患者尿液样本的蛋白质组学分析可以明确区分。COVID-19感染后,补体激活、血小板脱颗粒、脂蛋白代谢过程和缺氧反应等多种途径被破坏。本研究表明,尿中可以检测到COVID-19病理生理相关的分子改变,以及在COVID-19辅助诊断中的潜在应用。
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引用次数: 52
Effect of vancomycin, teicoplanin, and linezolid on renal function of critically ill patients with sepsis 万古霉素、替柯planin和利奈唑胺对危重脓毒症患者肾功能的影响
Pub Date : 2019-06-01 DOI: 10.1016/j.urine.2020.05.003
Sara Šundalić , Ela Ćurčić , Željko Pavić , Ivan Gornik , Ana Vujaklija Brajković
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引用次数: 1
Urinary metabolomic and proteomic analyses in a mouse model of prostatic inflammation 前列腺炎小鼠模型的尿代谢组学和蛋白质组学分析
Pub Date : 2019-06-01 DOI: 10.1016/j.urine.2020.05.002
Pingli Wei , Ling Hao , Fengfei Ma , Qing Yu , Amanda Rae Buchberger , Sanghee Lee , Wade Bushman , Lingjun Li

Lower urinary tract symptoms (LUTS) are common among aging men. Since prostatic inflammation is one of its etiologies, it is plausible that urinary metabolite and protein biomarkers could be identified and used to diagnose inflammation-induced LUTS. We characterized the urine metabolome and proteome in a mouse model of bacterial-induced prostatic inflammation. Mass spectrometry (MS)-based multi-omics analysis was employed to discover urinary protein and metabolite-based biomarkers. The investigation of isobaric dimethylated leucine (DiLeu) labeling on metabolites allowed metabolomics and proteomics analysis on the same liquid chromatography (LC)-MS platform. In total, 143 amine-containing metabolites and 1058 urinary proteins were identified and quantified (data are available via ProteomeXchange with identifier PXD018023); among them, 14 metabolites and 168 proteins were significantly changed by prostatic inflammation. Five metabolic pathways and four inflammation-related biological processes were potentially disrupted. By comparing our findings with urinary biomarkers identified in a mouse model of genetic-induced prostate inflammation and with those previously found to be associated with LUTS in older men, we identified creatine, haptoglobin, immunoglobulin kappa constant and polymeric Ig receptor as conserved biomarkers for prostatic inflammation associated with LUTS. These data suggest that these putative biomarkers could be used to identify men in which prostate inflammation is present and contributing to LUTS.

下尿路症状(LUTS)在老年男性中很常见。由于前列腺炎症是其病因之一,因此尿液代谢物和蛋白质生物标志物可能被识别并用于诊断炎症诱导的LUTS。我们在细菌诱导的前列腺炎症小鼠模型中对尿液代谢组和蛋白质组进行了表征。采用基于质谱(MS)的多组学分析发现尿蛋白和基于代谢产物的生物标志物。等重二甲基化亮氨酸(DiLeu)标记代谢物的研究允许在相同的液相色谱(LC)-MS平台上进行代谢组学和蛋白质组学分析。总共鉴定和定量了143种含胺代谢物和1058种尿蛋白(数据可通过ProteomeXchange获得,标识号为PXD018023);其中有14种代谢物和168种蛋白因前列腺炎症而发生显著改变。五种代谢途径和四种炎症相关的生物过程可能被破坏。通过将我们的研究结果与遗传诱导前列腺炎症小鼠模型中发现的尿液生物标志物以及先前发现的与老年男性LUTS相关的尿液生物标志物进行比较,我们发现肌酸、接触球蛋白、免疫球蛋白kappa常数和聚合Ig受体是与LUTS相关的前列腺炎症的保守生物标志物。这些数据表明,这些假定的生物标志物可用于识别存在前列腺炎症并导致LUTS的男性。
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引用次数: 5
Identification of potential urinary exposure markers for the toxicant diisononyl phthalate in rubber worker urine specimens by high-resolution mass spectrometry-based metabolomics 基于高分辨率质谱的代谢组学方法鉴定橡胶工人尿液标本中有毒物质邻苯二甲酸二异壬酯的潜在尿暴露标记物
Pub Date : 2019-06-01 DOI: 10.1016/j.urine.2020.05.001
Yu-Ting Wang , Jing-Fang Hsu , Yi-Sheng Hsu , Pao-Chi Liao

Diisononyl phthalate (DiNP) is commonly used as a plasticizer in polyvinyl chloride (PVC) products. However, DiNP can interfere with the human endocrine system and is listed as a chemical with reproductive toxicity. It has a short half-life and can be metabolized into water-soluble substances that are excreted in the urine, and thus, DiNP exposure markers can be identified in urine, a noninvasive and easily accessible specimen. In a previous study, we established an isotope tracing strategy involving an in-house computational signal mining algorithm with isotope tracing (SMAIT) to filter probable metabolite signals from complex LC-MS data. In this study, we used SMAIT to filter the probable metabolite signals, which were verified as potential DiNP exposure markers by analyzing human urine specimens from rubber workers who had occupational exposure to DiNP. We filtered 16 probable metabolite signals out of approximately 1400 signals by SMAIT. Fourteen of the 16 probable metabolite signals were confirmed as DiNP structure-related metabolites according to the fragment ion at m/z 121.029, which is a benzoate ion (C6H5CO2), identified in D0-MMOP mass spectra by ultra-high-performance liquid chromatography-high-resolution tandem mass spectrometry (UHPLC-HRMS/MS) in the full-scan mode. The 14 structure-related metabolite signals were further verified as potential DiNP exposure markers by analyzing rubber worker urine specimens. Three DiNP structure-related metabolite signals at m/z 305.139 (MOINP), 307.155 (MHINP), and 375.142 (derivatives of MHINP) were identified as potential exposure markers of DiNP. We need more research to validate whether these metabolites could be used as specific biomarkers for human exposure to DiNP. The 3 structure-related metabolite signals could provide the basis for future exposure and risk assessment for DiNP.

邻苯二甲酸二异壬酯(DiNP)是聚氯乙烯(PVC)产品中常用的增塑剂。然而,DiNP会干扰人体内分泌系统,被列为具有生殖毒性的化学物质。它的半衰期短,可以代谢成水溶性物质,并随尿液排出,因此,尿中可以识别出DiNP暴露标记物,这是一种无创且易于获取的标本。在之前的研究中,我们建立了一种同位素示踪策略,该策略涉及内部计算信号挖掘算法与同位素示踪(SMAIT),以从复杂的LC-MS数据中过滤可能的代谢物信号。在这项研究中,我们使用SMAIT来过滤可能的代谢物信号,通过分析职业暴露于DiNP的橡胶工人的人类尿液样本,这些信号被证实是潜在的DiNP暴露标志物。我们通过SMAIT从大约1400个信号中过滤出16个可能的代谢物信号。利用超高效液相色谱-高分辨率串联质谱(UHPLC-HRMS/MS)全扫描模式在D0-MMOP质谱中鉴定出的m/z 121.029处的片段离子(苯甲酸盐离子(C6H5CO2)), 16个可能代谢物信号中有14个被确认为DiNP结构相关代谢物。通过对橡胶工人尿液样本的分析,进一步验证了14种结构相关代谢物信号是潜在的DiNP暴露标志物。在m/z 305.139 (MOINP), 307.155 (MHINP)和375.142 (MHINP衍生物)三个与DiNP结构相关的代谢物信号被确定为DiNP的潜在暴露标记。我们需要更多的研究来验证这些代谢物是否可以作为人类暴露于DiNP的特异性生物标志物。这3种结构相关的代谢物信号可以为DiNP的未来暴露和风险评估提供依据。
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引用次数: 0
NF-κB gene expression in peripheral blood and urine in early diagnosis of diabetic nephropathy – A liquid biopsy approach 外周血和尿液中NF-κ b基因表达在糖尿病肾病早期诊断中的应用——液体活检方法
Pub Date : 2019-06-01 DOI: 10.1016/j.urine.2020.05.005
Glaucia Luciano da Veiga , Matheus Gonçalves Della Nina Raffo , Beatriz da Costa Aguiar Alves , Marcelo Rodrigues Bacci , Fernando Luiz Affonso Fonseca

Diabetic nephropathy (DN) is a pathological condition that affects diabetic patients around the world, and it is the main cause of chronic kidney diseases. It is known that the inflammatory pathway is activated in diabetic patients. Thus, the aims of this study were to evaluate the gene expression of Nuclear factor-κappa B (NF-κB) in liquid samples (urine and blood), then to evaluate the correlation between NF-κB gene expression with classical biochemical markers of kidney disease to investigate if the gene expression of this molecule can be used as a biomarker of loss of kidney function in diabetic patients. We recruited 35 patients with type 2 diabetes mellitus for at least 5 years and 29 healthy donors and collected samples of urine and blood to quantify the NF-κB expression. It was found higher expression of NF-κB in both samples in diabetes patients. We verified elevated levels of microalbuminuria, serum creatinine, urea and BMI in diabetic patients, as well as a fall in GFR, without alteration in serum creatinine and proteinuria levels. Our data suggest that overexpression of NF-κB participates in the onset of diabetic nephropathy and that it is possible to quantify these changes in liquid biopsy (blood and urine) through gene expression of this molecule. The NF-κB expression is correlated with increased BMI data.

糖尿病肾病(Diabetic nephropathy, DN)是困扰全世界糖尿病患者的一种病理状态,是慢性肾脏疾病的主要原因。众所周知,炎症通路在糖尿病患者中被激活。因此,本研究的目的是评估核因子-κ κB (Nuclear factor-κappa B, NF-κB)在液体样本(尿液和血液)中的基因表达,进而评估NF-κB基因表达与肾脏疾病经典生化指标的相关性,以探讨该分子的基因表达是否可以作为糖尿病患者肾功能丧失的生物标志物。我们招募了35例2型糖尿病患者和29例健康供体,收集了尿液和血液样本来量化NF-κB的表达。在糖尿病患者两组样本中均发现NF-κB表达较高。我们证实了糖尿病患者微量白蛋白尿、血清肌酐、尿素和BMI水平升高,以及GFR下降,而血清肌酐和蛋白尿水平没有改变。我们的数据表明,NF-κB的过度表达参与了糖尿病肾病的发病,并且可以通过该分子的基因表达来量化液体活检(血液和尿液)中的这些变化。NF-κB表达与BMI升高相关。
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引用次数: 4
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Urine (Amsterdam, Netherlands)
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