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In addition to early biomarkers, what else can be done with urine? 除了早期生物标志物,尿液还能做什么?
Pub Date : 2024-01-01 DOI: 10.1016/j.urine.2023.12.001
Yuzhen Chen, Youhe Gao

Biomarkers are measurable changes associated with physiological or pathophysiological processes in the body. Many types of biomarkers can accumulate in urine, which is not strictly subjected to homeostatic control. Therefore, it can reflect changes in the body earlier and more sensitively than other biomarker sources. Promising progress has been made in research on finding early biomarkers of diseases by using urine proteomics. In this review, we summarize our laboratory's research using urine proteomics in areas closely related to human health, with the aim of comprehensively demonstrating the great potential of urine proteomics in other areas in addition to early biomarkers.

生物标志物是与体内生理或病理生理过程相关的可测量变化。许多类型的生物标记物都可以在尿液中积累,而尿液并不受严格的体内平衡控制。因此,与其他生物标志物来源相比,尿液能更早更灵敏地反映体内的变化。利用尿液蛋白质组学寻找疾病早期生物标志物的研究取得了可喜的进展。在这篇综述中,我们总结了本实验室利用尿液蛋白质组学在与人类健康密切相关的领域开展的研究,旨在全面展示尿液蛋白质组学在早期生物标志物之外的其他领域的巨大潜力。
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引用次数: 0
CreCENT: Creatinine and Chloride based Electrochemical Non-faradaic renal health mapping Technology CreCENT:基于肌酐和氯化物的电化学非法拉第肾脏健康绘图技术
Pub Date : 2023-12-04 DOI: 10.1016/j.urine.2023.11.001
Antra Ganguly, Varun Gunda, Shalini Prasad

In this work, we propose a novel biosensing scheme to enable the stratification of kidney diseases based on severity and progression for timely triage and efficient management. Here, using Creatinine and Chloride as target analytes for the biosensor, we have discussed an arbitrary three-class stratification mapping renal health for Chronic Kidney Disease (CKD) management. Our method is fully quantitative, fast (<5 min turn-around time), and can work with any combination of disease biomarkers to categorize diseases by subtypes and severity. At its core, the biosensor relies on electrochemical impedance spectroscopy to transduce subtle changes at the input Creatinine and Chloride levels in a drop of neat, unprocessed urine. It can operate over a wide dynamic range of 0.15-5 mg/mL for Creatinine and 15-105 mM for Chloride. Further, as proof of concept, the biosensing scheme utilizes a simple Support Vector Machine-based supervised machine learning model for 3-state output disease state classification (corresponding to low, medium, and high disease severity) with a 97.96% accuracy. This scheme is versatile and can be extended to more complex scenarios with more biomarker input stimuli for improved diagnostics and precision therapy for other chronic urological diseases.

在这项工作中,我们提出了一种新颖的生物传感方案,可根据肾脏疾病的严重程度和进展情况进行分层,以便及时分流和有效管理。在这里,我们使用肌酐和氯化物作为生物传感器的目标分析物,讨论了一种任意的三类分层方法,用于慢性肾脏病(CKD)的管理。我们的方法完全定量、快速(5 分钟即可完成),可与任何疾病生物标记物组合使用,按亚型和严重程度对疾病进行分类。该生物传感器的核心是依靠电化学阻抗光谱来传递一滴未经处理的纯净尿液中肌酐和氯化物含量的微妙变化。它可以在很宽的动态范围内工作,肌酐为 0.15-5 mg/mL,氯化物为 15-105 mM。此外,作为概念验证,该生物传感方案利用一个简单的基于支持向量机的有监督机器学习模型进行 3 态输出疾病状态分类(对应低、中、高疾病严重程度),准确率高达 97.96%。该方案用途广泛,可扩展到更复杂的场景,使用更多的生物标记输入刺激来改进诊断和其他慢性泌尿系统疾病的精准治疗。
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引用次数: 0
A facile strategy for comprehensive proteome analysis of urine using ultracentrifugation fractionation, solid-phase alkylation based sample preparation and liquid chromatography-mass spectrometry 使用超离心分离、固相烷基化样品制备和液相色谱-质谱法对尿液进行综合蛋白质组分析的简便策略
Pub Date : 2023-01-01 DOI: 10.1016/j.urine.2023.05.002
Xinxin Liu , Mengchun Cheng , Zhigang Sui , Hongli Lin , Nan Wang , Xianan Guo , Huiming Yuan , Lihua Zhang , Yukui Zhang

In this work, a facile strategy with combination of ultracentrifugation fraction, solid-phase alkylation sample preparation and liquid chromatography-mass spectrometry (LC-MS) was developed to achieve comprehensive proteome profiling of urine (CPU). By this strategy, a total of 1659 proteins could be identified using a short LC gradient of 1h, 2.3 times more than those (730) obtained from raw urine without fractionation. Compared to the current existing methods for urine sample preparation, not only the analysis time could be greatly shortened by 3–4 times, but also the identification coverage of urine proteome was increased by 130%–160%. Such a method was further combined with label-free quantification for the comparative proteome analysis of urine from IgA nephropathy (IgAN) patients and healthy donors, 227 differentially expressed proteins were identified. In addition to 90 proteins that were reported to be closely related to IgAN, we found that multiple members of solute carrier family 22 (SLC22) were up-regulated in IgAN, which might be related to the disturbance of renal metabolic function in patients. All these results demonstrated that our developed method would provide a promising tool for discovering disease related biomarkers in urine.

在这项工作中,建立了一种简单的策略,结合超离心馏分,固相烷基化样品制备和液相色谱-质谱(LC-MS)来实现尿液(CPU)的全面蛋白质组分析。通过这种策略,使用短的LC梯度(~ 1h)可以鉴定出总共1659种蛋白质,比未经分离的原始尿液(730种)多2.3倍。与现有的尿液样品制备方法相比,不仅分析时间可大大缩短3-4倍,而且尿液蛋白质组的鉴定覆盖率提高了130%-160%。进一步将该方法与无标记定量相结合,对IgA肾病(IgAN)患者与健康供者尿液进行蛋白质组比较分析,鉴定出227种差异表达蛋白。除了已报道的与IgAN密切相关的90个蛋白外,我们还发现在IgAN中有多个溶质载体家族22 (SLC22)成员上调,这可能与患者肾代谢功能紊乱有关。所有这些结果表明,我们开发的方法将为发现尿液中与疾病相关的生物标志物提供一个有前途的工具。
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引用次数: 0
Urine; a new promising biological fluid to act as a non-invasive biomarker for different human diseases 尿;一种新的有前途的生物液体,可作为不同人类疾病的非侵入性生物标志物
Pub Date : 2023-01-01 DOI: 10.1016/j.urine.2023.06.001
Namrata Balhara , Mamta Devi , Ajay Balda , Manisha Phour , Arup Giri
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引用次数: 1
Changes in the urine proteome in patients with advanced lung cancer after different drug treatments 不同药物治疗后晚期肺癌患者尿蛋白质组的变化
Pub Date : 2023-01-01 DOI: 10.1016/j.urine.2023.02.001
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 and the changes in the biological processes 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.

肺癌因其高致死率而成为危害人类生命健康的主要疾病之一。如何为晚期肺癌患者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敏感地反映机体的病理或生理变化,因此具有反映机体药物治疗后动态变化的潜力。为探讨不同药物治疗后晚期肺癌患者尿液蛋白质组的变化,收集不同时间点的尿液样本进行分析。预处理状态下尿蛋白质组的变化在每个患者中是不同的,生物学过程的变化与患者临床表现的变化是一致的。本研究表明,不同药物治疗后晚期肺癌患者的病理生理变化可以通过尿蛋白的变化来反映。此外,尿蛋白的变化可以反映相同药物治疗后患者不同的生物学过程,患者的临床病情评估结果与这些变化相一致。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: 0
Urine biomarkers can outperform serum biomarkers in certain diseases 在某些疾病中,尿液生物标志物的表现优于血清生物标志物
Pub Date : 2023-01-01 DOI: 10.1016/j.urine.2023.10.001
Cheng Xue , Bo Yang , Lili Fu , Huihui Hou , Jihua Qiang , Chenchen Zhou , Youhe Gao , Zhiguo Mao

Urinary biomarkers offer a non-invasive and easily accessible means of assessing an individual's health and susceptibility to various diseases. Urine biomarkers have advantages in no need or mechanism for stability, specific biomarkers produced by tubules, and non-invasive nature compared with serum biomarkers. Urine biomarkers can provide critical insights into an individual's predisposition to certain conditions, disease progression, and therapeutic response. In this review, we summarized the currently reported urinary biomarkers that outperformed serum biomarkers, including urinary protein biomarkers, gene biomarkers, urinary metabolites, electrolytes, and urinary extracellular vesicles. Combining urinary and serum biomarkers can offer a more comprehensive approach to disease diagnosis, monitoring, and personalized medicine. Despite some challenges in standardization and expanding the repertoire of diseases that can be diagnosed using urinary biomarkers, urinary biomarkers hold immense promise in improving patient outcomes and transforming healthcare.

尿液生物标志物提供了一种非侵入性和易于获取的方法来评估个人健康和对各种疾病的易感性。与血清生物标志物相比,尿液生物标志物具有不需要或机制稳定、由小管产生特异性生物标志物、无创性等优点。尿液生物标志物可以为个体对某些疾病的易感性、疾病进展和治疗反应提供关键的见解。在这篇综述中,我们总结了目前报道的优于血清生物标志物的尿液生物标志物,包括尿蛋白生物标志物、基因生物标志物、尿代谢物、电解质和尿细胞外囊泡。结合尿液和血清生物标志物可以为疾病诊断、监测和个性化医疗提供更全面的方法。尽管在标准化和扩大可使用尿液生物标志物诊断的疾病库方面存在一些挑战,但尿液生物标志物在改善患者预后和改变医疗保健方面具有巨大的希望。
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引用次数: 0
Induced crystal formation in urine as an easily accessible indicator of tumor stage? – A translational explorative study 尿中诱导晶体形成作为肿瘤分期的一个容易接近的指标?-翻译探索性研究
Pub Date : 2023-01-01 DOI: 10.1016/j.urine.2023.05.001
Norbert Laube , Florian Klein , Christian Fisang

Urinary concentrations of metabolic products associated with neoplasms can change the supersaturation and thus alter the potential of crystal formation in urine. This study examines the ability of the BONN-Risk-Index (BRI)-method of induced crystallization of Ca-oxalate in urine for monitoring the progression of (uro-)oncological diseases.

BRI was compared to tumor marker concentrations and imaging in patients with prostate cancer (PC) and patients with neuroendocrine tumors (NET). In NET, a correlation between BRI and the amount of bone metastases emerges. In PC, log2(BRI) and bone-specific alkaline-phosphatase inversely correlate with r ​= ​0.71.

It was shown that BRI and the clinical picture promisingly correlate.

与肿瘤相关的代谢产物的尿浓度可以改变过饱和,从而改变尿中晶体形成的潜力。本研究检验了波恩风险指数(BRI)——尿液中诱导草酸钙结晶的方法——监测(非)肿瘤疾病进展的能力。将BRI与前列腺癌(PC)和神经内分泌肿瘤(NET)患者的肿瘤标志物浓度和影像学进行比较。在NET中,BRI与骨转移量之间存在相关性。在PC中,log2(BRI)和骨特异性碱性磷酸酶呈负相关,r = 0.71。结果表明,BRI与临床表现有良好的相关性。
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引用次数: 0
A review on traditional natural compounds and conventional methods for the treatment of UTI 传统天然化合物和治疗尿路感染的传统方法综述
Pub Date : 2023-01-01 DOI: 10.1016/j.urine.2023.04.001
Tannupriya, Vivek Kumar Garg

The intensity of the urinary tract infection (UTI), a recurrent infection that is common in coastal locations and that affects people of different ages, varies. One of the main bacteria that causes UTI is Escherichia coli. The objective of the present study is to regulate the prevalence of UTI and to evaluate the effectiveness of recent developments in alternative medicine. Quinolones and cephalosporin are well-known treatments for UTIs. The only costly, non-Indian plant source medicine is cranberry extract. The growth of opportunistic Uropathogens is facilitated by pH change in urethra that occur throughout puberty and menopause in females. Additionally adding to the defence is innate immunity. Although innate immunity can support the body's resistance, a recent study found that infection rates differ among people depending on their age, immunity, and lifestyle. The microorganisms that cause UTI are becoming more and more medication resistant. Understanding the value of enhancing innate immunity and being aware of the most effective UTI treatment plan are both necessary. Alternative, innovative methods to treatment have so raised some hope. Homeopathic, Ayurvedic, Unani, and other herbal-based medications were among the therapeutic options. Nanoparticles may play new, unproven roles in the fight against UTIs in the future. Nanotechnology techniques based on medicinal plants have produced encouraging results. Therefore, there needs to be ongoing study into herbal treatments for UTIs, like Ayurvedic Biology.

尿路感染(UTI)是一种反复感染,在沿海地区很常见,影响不同年龄的人,其强度各不相同。引起尿路感染的主要细菌之一是大肠杆菌。本研究的目的是调节尿路感染的流行,并评估替代医学的最新发展的有效性。喹诺酮类药物和头孢菌素是众所周知的治疗尿路感染的药物。唯一昂贵的非印度植物源药物是蔓越莓提取物。机会性尿路病原体的生长是由发生在女性青春期和更年期尿道的pH值变化促进的。此外,增强防御的是先天免疫。虽然先天免疫可以支持身体的抵抗力,但最近的一项研究发现,感染率因年龄、免疫力和生活方式的不同而不同。引起尿路感染的微生物变得越来越耐药。了解增强先天免疫的价值和了解最有效的尿路感染治疗方案都是必要的。替代的、创新的治疗方法带来了一些希望。顺势疗法、阿育吠陀疗法、乌纳尼疗法和其他以草药为基础的药物都是治疗选择。纳米颗粒可能会在未来与尿路感染的斗争中发挥新的、未经证实的作用。基于药用植物的纳米技术已经产生了令人鼓舞的结果。因此,需要对尿路感染的草药治疗进行持续的研究,比如阿育吠陀生物学。
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引用次数: 1
A new HPLC-MS/MS method for urinary creatinine determination: Comparison study with Jaffè’s method HPLC-MS/MS测定尿肌酐的新方法:与Jaffè方法的比较研究
Pub Date : 2023-01-01 DOI: 10.1016/j.urine.2023.04.002
Lidia Caporossi, Enrico Paci, Silvia Capanna, Bruno Papaleo, Giovanna Tranfo, Daniela Pigini

Urinary biomarkers are usually reported as a normalized ratio to creatinuria, a lack of correct creatinine determination lead to wrong final data. This study aimed to evaluate the Jaffè method accuracy, proposing a new HPLC-MS/MS method. The validation parameters were: run time of 4 ​min, LOD of 0.02 ​mg/L, CV% lower than 4%, recovery >96.1%, no matrix effect.

The comparison between HPLC-MS/MS and Jaffè method showed an average bias, variable from high (1.5–3.00 ​g/L) to low concentrations (below than 0.7 ​g/L) of creatinine, ranging from +31% to −25%. The critical issue for the normalization of biomonitoring data was highlighted.

尿液生物标志物通常报告为与肌酐的标准化比率,缺乏正确的肌酐测定导致错误的最终数据。本研究旨在评价Jaffè方法的准确性,提出一种新的HPLC-MS/MS方法。验证参数为:运行时间4 min,检出限0.02 mg/L, CV% < 4%,回收率96.1%,无基质效应。HPLC-MS/MS和Jaffè方法的比较显示平均偏差,从高(1.5-3.00 g/L)到低(低于0.7 g/L)的肌酐浓度变化,范围为+31%到- 25%。强调了生物监测数据规范化的关键问题。
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引用次数: 1
Commentary: Why have different key biomarkers been reported in the same types of samples from patients with identical diseases? 评论:为什么在患有相同疾病的患者的相同类型样本中报告了不同的关键生物标志物?
Pub Date : 2023-01-01 DOI: 10.1016/j.urine.2023.09.001
Takaaki Sato , Yasuhiko Takahashi , Yoichi Mizutani

Accurate biomarkers are crucial for early disease detection and improved prognosis. However, the inconsistent reporting of different key biomarkers in the same types of samples from patients with identical diseases in biomarker discovery studies is often questioned. In contrast to such instrumental analyses, the murine olfactory system consistently distinguishes subtle variations in genetically determined individual-unique body odors in urine samples and more pronounced differences in diet-modulated and fluctuating body odors. Interestingly, sniffer mouse behavioral assays revealed that prostate and bladder cancers alter olfactory cues in urine samples to be more intense compared with diet-modulated or genetically determined individual-specific body odors. The causes of inconsistent key biomarkers include high inter-individual and inter-sample variability due to diet-induced metabolites and cosmetic or environmental contaminations. Previously, we proposed experimental procedures tolerant to such noise-like variability or fluctuation, leading to the identification of ten urinary volatile biomarkers for prostate cancer, including 2,6-di(propan-2-yl)phenol as a unique biomarker for bladder cancer. This commentary discusses the theoretical basis of urinary volatile biomarkers and future directions for complementary biomarker development for diagnosis.

准确的生物标志物对于早期疾病检测和改善预后至关重要。然而,在生物标志物发现研究中,来自相同疾病患者的相同类型样本中不同关键生物标志物的报告不一致,这经常受到质疑。与这种仪器分析相比,小鼠嗅觉系统一致地区分了尿液样本中遗传决定的个体独特体味的细微变化,以及饮食调节和波动体味的更明显差异。有趣的是,嗅探小鼠行为分析显示,与饮食调节或基因确定的个体特定体味相比,前列腺癌和膀胱癌会改变尿液样本中的嗅觉线索,使其更加强烈。关键生物标志物不一致的原因包括由于饮食诱导的代谢产物和化妆品或环境污染导致的个体间和样本间的高度变异。此前,我们提出了耐受此类噪声样变化或波动的实验程序,从而鉴定了10种前列腺癌症的尿液挥发性生物标志物,包括2,6-二(丙-2-基)苯酚作为癌症膀胱的独特生物标志物。这篇评论讨论了尿液挥发性生物标志物的理论基础和诊断用补充生物标志物开发的未来方向。
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引用次数: 0
期刊
Urine (Amsterdam, Netherlands)
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