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Urinary biomarkers of preeclampsia: An update. 子痫前期的尿液生物标志物:最新进展。
Pub Date : 2025-01-01 Epub Date: 2024-11-22 DOI: 10.1016/bs.acc.2024.11.002
Caio Ribeiro Vieira Leal, Heloisa Botezelli, Júlia Fernandes do Carmo Las Casas, Ana Cristina Simões E Silva, Fernando M Reis

Preeclampsia (PE), a pregnancy-related syndrome, has motivated extensive research to understand its pathophysiology and develop early diagnostic methods. 'Omic' technologies, focusing on genes, mRNA, proteins, and metabolites, have revolutionized biological system studies. Urine emerges as an ideal non-invasive specimen for omics analysis, offering accessibility, easy collection, and stability, making it valuable for identifying biomarkers. A comprehensive exploration of urinary omics in preeclampsia is discussed in this review. Proteomic studies identified biomarkers such as SERPINA-1 and uromodulin, showing promise for early diagnosis and severity assessment. Metabolomic analyses revealed alterations in metabolites like glycine and hippurate, providing insights into molecular mechanisms underlying PE. Challenges include methodological inconsistencies and the need for standardized protocols. Urinary omics technologies have significantly advanced our understanding of PE pathophysiology and hold promise for improved diagnosis and management. Biomarkers identified through these approaches offer potential for early detection, severity stratification, and elucidation of underlying mechanisms.

先兆子痫(PE)是一种妊娠相关综合征,已引起广泛的研究,以了解其病理生理和开发早期诊断方法。“组学”技术,专注于基因,mRNA,蛋白质和代谢物,已经彻底改变了生物系统的研究。尿液作为组学分析的理想非侵入性标本,具有可访问性、易于收集和稳定性,使其对识别生物标志物有价值。本文综述了泌尿组学在子痫前期的研究进展。蛋白质组学研究确定了SERPINA-1和尿调蛋白等生物标志物,显示了早期诊断和严重程度评估的希望。代谢组学分析揭示了代谢物如甘氨酸和hippurate的变化,为PE的分子机制提供了见解。挑战包括方法的不一致性和对标准化协议的需求。泌尿组学技术显著提高了我们对PE病理生理学的理解,并有望改善诊断和管理。通过这些方法确定的生物标志物为早期检测、严重程度分层和阐明潜在机制提供了潜力。
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引用次数: 0
Advances in periodontal healing biomarkers. 牙周愈合生物标志物研究进展。
Pub Date : 2025-01-01 Epub Date: 2025-01-30 DOI: 10.1016/bs.acc.2024.11.007
Ulvi Kahraman Gürsoy, Ilias Oikonomou, Mustafa Yilmaz, Mervi Gürsoy

Periodontitis is the infectious-inflammatory disease of tooth-supporting tissues. Periodontal treatment, either non-surgical or surgical, aims to remove infection, reduce inflammation, eliminate tissue loss, and gain clinical attachment. Clinical and radiographic recordings are widely used and accepted as gold-standard methods in periodontal diagnostics. While these traditional methods allow clinicians to monitor and diagnose periodontitis, they cannot be used to estimate the course of periodontal healing, or predict the disease recurrence or estimate the treatment outcome. Early prediction of the long-term consequences of periodontal treatment would be a crucial and valuable information not only for the clinicians, but also for the patients. Rapid advancements during past few decades boosted the periodontal biomarker studies and various microbe- or host-derived biochemical markers have been suggested as diagnostic biomarkers of periodontitis. Yet, there is no consensus regarding the accuracy of diagnostic biomarkers to monitor treatment response or to predict prognosis. The aim of this chapter will be to describe the healing patterns of periodontal tissues after treatment and present the available evidence on biomarkers that can indicate or predict successful treatment outcomes.

牙周炎是牙齿支撑组织的感染性炎症性疾病。牙周治疗,无论是非手术还是手术,目的是消除感染,减少炎症,消除组织损失,并获得临床依附。临床和放射学记录作为牙周诊断的金标准方法被广泛使用和接受。虽然这些传统方法允许临床医生监测和诊断牙周炎,但它们不能用于估计牙周愈合过程,或预测疾病复发或估计治疗结果。早期预测牙周治疗的长期后果不仅对临床医生,而且对患者都是至关重要和有价值的信息。在过去的几十年里,牙周生物标志物的研究进展迅速,各种微生物或宿主来源的生物化学标志物被认为是牙周炎的诊断生物标志物。然而,关于诊断性生物标志物监测治疗反应或预测预后的准确性尚无共识。本章的目的是描述治疗后牙周组织的愈合模式,并提出可以指示或预测成功治疗结果的生物标志物的现有证据。
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引用次数: 0
Multiomics in cancer biomarker discovery and cancer subtyping. 多组学在癌症生物标志物发现和癌症分型中的应用。
Pub Date : 2025-01-01 Epub Date: 2024-10-29 DOI: 10.1016/bs.acc.2024.10.004
Seunghwan Choi, Joon-Yong An

The advent of multiomics has ushered in a new era of cancer research characterized by integrated genomic, transcriptomic and proteomic analysis to unravel the complexities of cancer biology and facilitate the discovery of novel biomarkers. This chapter provides a comprehensive overview of the concept of multiomics, detailing the significant advances in the underlying technologies and their contributions to our understanding of cancer. It delves into the evolution of genomics and transcriptomics, breakthroughs in proteomics, and overarching progress in multiomic methodologies, highlighting their collective impact on cancer biomarker discovery. Furthermore, this chapter explores the computational methods essential for multiomic studies, including clustering techniques for delineating cancer subtypes, strategies for estimating molecular features and activities, and utility of pathway enrichment analyses for interpreting multiomic datasets. Particular focus has been placed on the application of these methods for identifying distinct cancer subtypes, thereby enabling a more personalized approach to cancer treatment. Through a detailed discussion of the scientific principles, technological advancements, and practical applications of multiomics, this chapter aims to underscore the pivotal role of multiomics in advancing cancer research and paving the way for personalized medicine. The insights provided herein not only illuminate the current landscape of cancer biomarker discovery, but also forecast future directions of multiomics research in oncology, advocating for a more integrated and nuanced approach to understanding and combating cancer.

多组学的出现开创了癌症研究的新时代,其特点是整合基因组学、转录组学和蛋白质组学分析,以揭示癌症生物学的复杂性,并促进新的生物标志物的发现。本章提供了多组学概念的全面概述,详细介绍了基础技术的重大进展及其对我们理解癌症的贡献。它深入研究了基因组学和转录组学的发展,蛋白质组学的突破,以及多组学方法的总体进展,突出了它们对癌症生物标志物发现的集体影响。此外,本章探讨了多组学研究必不可少的计算方法,包括描述癌症亚型的聚类技术,估计分子特征和活动的策略,以及解释多组学数据集的途径富集分析的效用。特别关注的是这些方法的应用,以识别不同的癌症亚型,从而使癌症治疗更加个性化。通过对多组学的科学原理、技术进步和实际应用的详细讨论,本章旨在强调多组学在推进癌症研究和为个性化医疗铺平道路方面的关键作用。本文提供的见解不仅阐明了癌症生物标志物发现的现状,而且预测了肿瘤学多组学研究的未来方向,倡导一种更综合、更细致的方法来理解和对抗癌症。
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引用次数: 0
Preface. 前言。
Pub Date : 2025-01-01 DOI: 10.1016/S0065-2423(25)00063-0
Gregory S Makowski
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引用次数: 0
Internalization of extracellular Tau oligomers in Alzheimer's disease. 阿尔茨海默病细胞外 Tau 寡聚体的内化。
Pub Date : 2025-01-01 Epub Date: 2025-02-12 DOI: 10.1016/bs.acc.2025.01.005
Subashchandrabose Chinnathambi, Nagaraj Rangappa, Madhura Chandrashekar

A key factor in the progression of Alzheimer's disease (AD) is internalization of extracellular Tau oligomers (ecTauOs) by neuroglial cells. Aberrant hyperphosphorylation of Tau results in their dissociation from microtubules and formation of toxic intracellular Tau oligomers (icTauOs). These are subsequently released to the extracellular space following neuronal dysfunction and death. Although receptor mediated internalization of these ecTauOs by other neurons, microglia and astrocytes can facilitate elimination, incomplete degradation thereof promotes inflammation, exacerbates pathologic spread and accelerates neurodegeneration. Targeting Tau oligomer degradation pathways, blocking internalization receptors, and mitigating neuroinflammation are proposed as therapeutic strategies to control Tau propagation and toxicity. This review highlights the urgent need for innovative approaches to prevent the spread of Tau pathology, emphasizing its implications for AD and related neurodegenerative diseases.

阿尔茨海默病(AD)进展的一个关键因素是神经胶质细胞内化细胞外Tau寡聚物(ectaos)。Tau的异常过度磷酸化导致它们与微管分离并形成有毒的细胞内Tau寡聚物(icTauOs)。这些物质随后在神经元功能障碍和死亡后释放到细胞外空间。虽然受体介导的ectaos内化是由其他神经元、小胶质细胞和星形胶质细胞介导的,但其不完全降解可促进炎症,加剧病理扩散,加速神经退行性变。针对Tau寡聚物降解途径,阻断内化受体,减轻神经炎症被提出作为控制Tau增殖和毒性的治疗策略。这篇综述强调了迫切需要创新的方法来防止Tau病理的传播,强调了它在AD和相关神经退行性疾病中的意义。
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引用次数: 0
Proteomic profiling of the extracellular matrix in skeletal muscle. 骨骼肌细胞外基质的蛋白质组学分析。
Pub Date : 2025-01-01 Epub Date: 2025-07-23 DOI: 10.1016/bs.acc.2025.06.008
Dieter Swandulla, Kay Ohlendieck

A dynamic extracellular matrix (ECM) surrounds individual cellular units and fills the intercellular space to provide physical support, structural organization and a medium for signaling mechanisms. This article focuses on the ECM in skeletal muscles, which exhibits a diverse and dynamic protein composition in the endomysium, perimysium and epimysium. The muscle matrisome plays a key role in providing tissue integrity during embryonic myogenesis, muscle repair and myofiber regeneration. Mass spectrometry-based proteomics has been instrumental in the systematic cataloguing of the muscle ECM, including collagens, glycoproteins, proteoglycans, matricellular proteins and adhesion complexes, and the elucidation of their pathophysiological role in neuromuscular disorders.

一个动态的细胞外基质(ECM)包围着单个细胞单元并填充细胞间空间,提供物理支持、结构组织和信号机制的介质。骨骼肌肌外基质在肌内膜、肌周和肌外膜中表现出多样化和动态的蛋白质组成。在胚胎肌发生、肌肉修复和肌纤维再生过程中,肌基质体在提供组织完整性方面起着关键作用。基于质谱的蛋白质组学在肌肉ECM的系统编目中发挥了重要作用,包括胶原、糖蛋白、蛋白聚糖、基质细胞蛋白和粘附复合物,并阐明了它们在神经肌肉疾病中的病理生理作用。
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引用次数: 0
RNA biomarkers in cancer therapeutics: The promise of personalized oncology. 癌症治疗中的 RNA 生物标记物:个性化肿瘤学的前景。
Pub Date : 2024-01-01 Epub Date: 2024-06-21 DOI: 10.1016/bs.acc.2024.06.003
Hector Katifelis, Maria Gazouli

Cancer therapy is a rapidly evolving and constantly expanding field. Current approaches include surgery, conventional chemotherapy and novel biologic agents as in immunotherapy, that together compose a wide armamentarium. The plethora of choices can, however, be clinically challenging in prescribing the most suitable treatment for any given patient. Fortunately, biomarkers can greatly facilitate the most appropriate selection. In recent years, RNA-based biomarkers have proven most promising. These molecules that range from small noncoding RNAs to protein coding gene transcripts can be valuable in cancer management and especially in cancer therapeutics. Compared to their DNA counterparts which are stable throughout treatment, RNA-biomarkers are dynamic. This allows prediction of success prior to treatment start and can identify alterations in expression that could reflect response. Moreover, improved nucleic acid technology allows RNA to be extracted from practically every biofluid/matrix and evaluated with exceedingly high analytic sensitivity. In addition, samples are largely obtained by minimally invasive procedures and as such can be used serially to assess treatment response real-time. This chapter provides the reader insight on currently known RNA biomarkers, the latest research employing Artificial Intelligence in the identification of such molecules and in clinical decisions driving forward the era of personalized oncology.

癌症治疗是一个快速发展和不断扩展的领域。目前的治疗方法包括手术、传统化疗和免疫疗法中的新型生物制剂,它们共同组成了一个庞大的治疗体系。然而,过多的选择可能会给临床带来挑战,难以为特定患者开出最合适的治疗处方。幸运的是,生物标志物可以极大地帮助人们做出最合适的选择。近年来,基于 RNA 的生物标志物被证明是最有前途的。从小型非编码 RNA 到蛋白编码基因转录本,这些分子在癌症管理,特别是癌症治疗中都很有价值。与在整个治疗过程中保持稳定的 DNA 类似物相比,RNA 生物标记物是动态的。这样就可以在治疗开始前预测治疗的成功与否,并能识别反映反应的表达变化。此外,经过改进的核酸技术可以从几乎所有生物流体/基质中提取 RNA,并以极高的分析灵敏度进行评估。此外,大部分样本都是通过微创手术获得的,因此可连续用于实时评估治疗反应。本章将向读者深入介绍目前已知的 RNA 生物标记物、采用人工智能识别此类分子的最新研究以及推动个性化肿瘤学时代到来的临床决策。
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引用次数: 0
Preface. 序言
Pub Date : 2024-01-01 DOI: 10.1016/S0065-2423(24)00077-5
Gregory S Makowski
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引用次数: 0
Adipokines in pregnancy. 孕期脂肪因子
Pub Date : 2024-01-01 Epub Date: 2024-05-15 DOI: 10.1016/bs.acc.2024.04.006
Monika Dawid, Karolina Pich, Ewa Mlyczyńska, Natalia Respekta-Długosz, Dominka Wachowska, Aleksandra Greggio, Oliwia Szkraba, Patrycja Kurowska, Agnieszka Rak

Reproductive success consists of a sequential events chronology, starting with the ovum fertilization, implantation of the embryo, placentation, and cellular processes like proliferation, apoptosis, angiogenesis, endocrinology, or metabolic changes, which taken together finally conduct the birth of healthy offspring. Currently, many factors are known that affect the regulation and proper maintenance of pregnancy in humans, domestic animals, or rodents. Among the determinants of reproductive success should be distinguished: the maternal microenvironment, genes, and proteins as well as numerous pregnancy hormones that regulate the most important processes and ensure organism homeostasis. It is well known that white adipose tissue, as the largest endocrine gland in our body, participates in the synthesis and secretion of numerous hormones belonging to the adipokine family, which also may regulate the course of pregnancy. Unfortunately, overweight and obesity lead to the expansion of adipose tissue in the body, and its excess in both women and animals contributes to changes in the synthesis and release of adipokines, which in turn translates into dramatic changes during pregnancy, including those taking place in the organ that is crucial for the proper progress of pregnancy, i.e. the placenta. In this chapter, we are summarizing the current knowledge about levels of adipokines and their role in the placenta, taking into account the physiological and pathological conditions of pregnancy, e.g. gestational diabetes mellitus, preeclampsia, or intrauterine growth restriction in humans, domestic animals, and rodents.

从卵子受精、胚胎植入、胎盘形成到细胞增殖、凋亡、血管生成、内分泌或新陈代谢变化等过程,这些过程共同作用,最终孕育出健康的后代。目前,已知有许多因素会影响人类、家畜或啮齿动物妊娠的调节和正常维持。生殖成功的决定因素包括:母体微环境、基因、蛋白质以及多种妊娠激素,它们能调节最重要的过程并确保机体平衡。众所周知,白色脂肪组织是人体最大的内分泌腺,参与合成和分泌属于脂肪因子家族的多种激素,这些激素也可能调节妊娠过程。不幸的是,超重和肥胖会导致体内脂肪组织的扩张,而妇女和动物体内脂肪组织的过剩又会导致脂肪因子的合成和释放发生变化,进而转化为妊娠期间的剧烈变化,包括对妊娠正常进行至关重要的器官(即胎盘)中发生的变化。在本章中,我们将结合人类、家畜和啮齿类动物妊娠期的生理和病理状况,如妊娠糖尿病、子痫前期或宫内生长受限等,总结目前有关脂肪因子水平及其在胎盘中作用的知识。
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引用次数: 0
Pleiotropic functions and clinical importance of circulating HDL-PON1 complex. 循环 HDL-PON1 复合物的多效应功能和临床重要性。
Pub Date : 2024-01-01 Epub Date: 2024-05-14 DOI: 10.1016/bs.acc.2024.04.003
Abdolkarim Mahrooz

High density lipoprotein (HDL) functions are mostly mediated through a complex proteome, particularly its enzymes. HDL can provide a scaffold for the assembly of several proteins that affect each other's function. HDL particles, particularly small, dense HDL3, are rich in paraoxonase 1 (PON1), which is an important enzyme in the functionality of HDL, so the antioxidant and antiatherogenic properties of HDL are largely attributed to this enzyme. There is an increasing need to represent a valid, reproducible, and reliable method to assay HDL function in routine clinical laboratories. In this context, HDL-associated proteins may be key players; notably PON1 activity (its arylesterase activity) may be a proper candidate because its decreased activity can be considered an important risk factor for HDL dysfunctionality. Of note, automated methods have been developed for the measurement of serum PON1 activity that facilitates its assay in large sample numbers. Arylesterase activity is proposed as a preferred activity among the different activities of PON1 for its assay in epidemiological studies. The binding of PON1 to HDL is critical for the maintenance of its activity and it appears apolipoprotein A-I plays an important role in HDL-PON1 interaction as well as in the biochemical and enzymatic properties of PON1. The interrelationships between HDL, PON1, and HDL's other components are complex and incompletely understood. The purpose of this review is to discuss biochemical and clinical evidence considering the interactions of PON1 with HDL and the role of this enzyme as an appropriate biomarker for HDL function as well as a potential therapeutic target.

高密度脂蛋白(HDL)的功能主要通过复杂的蛋白质组,特别是其酶来介导。高密度脂蛋白可为多种蛋白质的组装提供支架,而这些蛋白质之间的功能又会相互影响。高密度脂蛋白颗粒,尤其是小而致密的高密度脂蛋白3,富含对氧合酶1(PON1),这是高密度脂蛋白功能中的一种重要酶,因此高密度脂蛋白的抗氧化和抗动脉粥样硬化特性主要归功于这种酶。常规临床实验室越来越需要一种有效、可重复、可靠的方法来检测高密度脂蛋白的功能。在这种情况下,高密度脂蛋白相关蛋白可能是关键因素;特别是 PON1 活性(其芳酯酶活性)可能是一个合适的候选指标,因为其活性降低可被视为高密度脂蛋白功能障碍的一个重要风险因素。值得注意的是,目前已开发出自动测量血清 PON1 活性的方法,这有助于对大量样本进行检测。在流行病学研究中,PON1 的不同活性中,芳基酯酶活性是首选的检测活性。PON1 与高密度脂蛋白的结合对维持其活性至关重要,看来脂蛋白 A-I 在高密度脂蛋白与 PON1 的相互作用以及 PON1 的生化和酶特性中发挥着重要作用。高密度脂蛋白、PON1 和高密度脂蛋白其他成分之间的相互关系十分复杂,人们对它们的了解也不全面。本综述旨在讨论考虑 PON1 与 HDL 相互作用的生化和临床证据,以及该酶作为 HDL 功能的适当生物标志物和潜在治疗目标的作用。
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引用次数: 0
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Advances in clinical chemistry
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