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Myocardial fibrosis in right heart dysfunction. 右心功能不全的心肌纤维化
Pub Date : 2024-01-01 Epub Date: 2024-02-22 DOI: 10.1016/bs.acc.2024.02.005
Lucia Agoston-Coldea, Andra Negru

Cardiac fibrosis, associated with right heart dysfunction, results in significant morbidity and mortality. Stimulated by various cellular and humoral stimuli, cardiac fibroblasts, macrophages, CD4+ and CD8+ T cells, mast and endothelial cells promote fibrogenesis directly and indirectly by synthesizing numerous profibrotic factors. Several systems, including the transforming growth factor-beta and the renin-angiotensin system, produce type I and III collagen, fibronectin and α-smooth muscle actin, thus modifying the extracellular matrix. Although magnetic resonance imaging with gadolinium enhancement remains the gold standard, the use of circulating biomarkers represents an inexpensive and attractive means to facilitate detection and monitor cardiovascular fibrosis. This review explores the use of protein and nucleic acid (miRNAs) markers to better understand underlying pathophysiology as well as their role in the development of therapeutics to inhibit and potentially reverse cardiac fibrosis.

心脏纤维化与右心功能障碍有关,会导致严重的发病率和死亡率。在各种细胞和体液刺激下,心脏成纤维细胞、巨噬细胞、CD4+ 和 CD8+ T 细胞、肥大细胞和内皮细胞通过合成多种促纤维化因子,直接或间接地促进纤维化。包括转化生长因子-β 和肾素-血管紧张素系统在内的多个系统可产生 I 型和 III 型胶原蛋白、纤连蛋白和 α 平滑肌肌动蛋白,从而改变细胞外基质。尽管带钆增强的磁共振成像仍是金标准,但使用循环生物标记物是促进检测和监测心血管纤维化的一种廉价而有吸引力的方法。本综述探讨了如何利用蛋白质和核酸(miRNA)标记物来更好地了解潜在的病理生理学,以及它们在开发抑制和可能逆转心脏纤维化的疗法中的作用。
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引用次数: 0
Advances in periodontal biomarkers. 牙周生物标志物的研究进展。
Pub Date : 2024-01-01 Epub Date: 2024-04-18 DOI: 10.1016/bs.acc.2024.03.003
Ulvi Kahraman Gürsoy, Meltem Özdemir Kabalak, Mervi Gürsoy

Due to technologic advancements, periodontology has witnessed a boost in biomarker research over the past three decades. Indeed, with the aid of omics, our understanding of the healthy periodontium, pathogenesis of periodontal diseases, and healing after periodontal treatment has improved significantly. Yet, the traditional methods, periodontal probing and radiographies, remain the most common methods to diagnose periodontal disease and monitor treatment. Although these approaches can produce reliable diagnostic outcomes, they generally detect disease only after significant tissue degradation thus making treatment outcome highly uncertain. Accordingly, laboratories worldwide have collaborated with clinicians to design accurate, rapid and cost-effective biomarkers for periodontal disease diagnosis. Despite these efforts, biomarkers that can be widely used in early disease diagnosis and for treatment outcome prediction are far from daily use. The aim of this chapter is to give a general overview on periodontal health and diseases, and review recent advancements in periodontal biomarker research. A second aim will discuss the strengths and limitations of translating periodontal biomarker research to clinical practice. Genetic biomarkers of periodontitis are not discussed as the available confirmatory data is scarce.

由于技术的进步,牙周病学在过去三十年里见证了生物标志物研究的发展。事实上,在全息技术的帮助下,我们对健康牙周、牙周疾病的发病机制以及牙周治疗后的愈合情况的了解有了显著提高。然而,牙周探诊和拍片等传统方法仍然是诊断牙周疾病和监测治疗的最常用方法。虽然这些方法可以产生可靠的诊断结果,但它们通常只有在组织严重退化后才会检测到疾病,因此治疗结果具有很大的不确定性。因此,世界各地的实验室与临床医生合作,设计出准确、快速、经济有效的牙周病诊断生物标志物。尽管做出了这些努力,但可广泛用于早期疾病诊断和治疗效果预测的生物标志物还远未被日常使用。本章旨在概述牙周健康和疾病,并回顾牙周生物标志物研究的最新进展。第二个目的是讨论将牙周生物标志物研究转化为临床实践的优势和局限性。由于现有的确证数据很少,因此本章不讨论牙周炎的遗传生物标志物。
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引用次数: 0
Tear biomarkers. 泪液生物标志物
Pub Date : 2024-01-01 Epub Date: 2024-04-11 DOI: 10.1016/bs.acc.2024.03.002
Erika Ponzini

An extensive exploration of lacrimal fluid molecular biomarkers in understanding and diagnosing a spectrum of ocular and systemic diseases is presented. The chapter provides an overview of lacrimal fluid composition, elucidating the roles of proteins, lipids, metabolites, and nucleic acids within the tear film. Pooled versus single-tear analysis is discussed to underline the benefits and challenges associated with both approaches, offering insights into optimal strategies for tear sample analysis. Subsequently, an in-depth analysis of tear collection methods is presented, with a focus on Schirmer's test strips and microcapillary tubes methods. Alternative tear collection techniques are also explored, shedding light on their applicability and advantages. Variability factors, including age, sex, and diurnal fluctuations, are examined in the context of their impact on tear biomarker analysis. The main body of the chapter is dedicated to discussing specific biomarkers associated with ocular discomfort and a wide array of ocular diseases. From dry eye disease and thyroid-associated ophthalmopathy to keratoconus, age-related macular degeneration, diabetic retinopathy, and glaucoma, the intricate relationship between molecular biomarkers and these conditions is thoroughly dissected. Expanding beyond ocular pathologies, the chapter explores the applicability of tear biomarkers in diagnosing systemic diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and cancer. This broader perspective underscores the potential of lacrimal fluid analysis in offering non-invasive diagnostic tools for conditions with far-reaching implications.

本章广泛探讨了泪液分子生物标志物在理解和诊断一系列眼部和全身疾病方面的作用。本章概述了泪液的组成,阐明了蛋白质、脂类、代谢物和核酸在泪膜中的作用。本章讨论了集合泪液分析与单泪液分析,强调了这两种方法的优点和挑战,为泪液样本分析的最佳策略提供了见解。随后,深入分析了泪液采集方法,重点介绍了施尔默试纸和微毛细管方法。此外,还探讨了其他泪液采集技术,揭示了它们的适用性和优势。此外,还研究了年龄、性别和昼夜波动等变异因素对泪液生物标记分析的影响。本章的主体部分专门讨论了与眼部不适和各种眼部疾病相关的特定生物标志物。从干眼症和甲状腺相关眼病到角膜炎、老年性黄斑变性、糖尿病视网膜病变和青光眼,本章彻底剖析了分子生物标志物与这些疾病之间错综复杂的关系。除眼部病变外,本章还探讨了泪液生物标志物在诊断多发性硬化症、肌萎缩性脊髓侧索硬化症、阿尔茨海默病、帕金森病和癌症等全身性疾病中的适用性。这一更广阔的视角强调了泪液分析在为具有深远影响的疾病提供非侵入性诊断工具方面的潜力。
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引用次数: 0
Molecular tools to regulate gene expression in Trypanosoma cruzi. 调控克氏锥虫基因表达的分子工具。
Pub Date : 2024-01-01 Epub Date: 2024-05-03 DOI: 10.1016/bs.acc.2024.04.008
Lays Adrianne M Trajano-Silva, Simon Ngao Mule, Giuseppe Palmisano

Developing molecular strategies to manipulate gene expression in trypanosomatids is challenging, particularly with respect to the unique gene expression mechanisms adopted by these unicellular parasites, such as polycistronic mRNA transcription and multi-gene families. In the case of Trypanosoma cruzi (T. cruzi), the causative agent of Chagas Disease, the lack of RNA interference machinery further complicated functional genetic studies important for understanding parasitic biology and developing biomarkers and potential therapeutic targets. Therefore, alternative methods of performing knockout and/or endogenous labelling experiments were developed to identify and understand the function of proteins for survival and interaction with the host. In this review, we present the main tools for the genetic manipulation of T. cruzi, focusing on the Clustered Regularly Interspaced Short Palindromic Repeats Cas9-associated system technique widely used in this organism. Moreover, we highlight the importance of using these tools to elucidate the function of uncharacterized and glycosylated proteins. Further developments of these technologies will allow the identification of new biomarkers, therapeutic targets and potential vaccines against Chagas disease with greater efficiency and speed.

开发操纵锥虫基因表达的分子策略极具挑战性,尤其是这些单细胞寄生虫所采用的独特基因表达机制,如多核苷酸 mRNA 转录和多基因家族。对于南美锥虫病的病原体--克鲁斯锥虫(T. cruzi)来说,缺乏 RNA 干扰机制使功能基因研究变得更加复杂,而功能基因研究对于了解寄生虫生物学、开发生物标记物和潜在治疗靶点非常重要。因此,人们开发了进行基因敲除和/或内源标记实验的替代方法,以确定和了解蛋白质的生存功能以及与宿主的相互作用。在这篇综述中,我们介绍了对 T. cruzi 进行遗传操作的主要工具,重点介绍了在该生物体中广泛使用的簇状规律性间隔短文句重复序列 Cas9 相关系统技术。此外,我们还强调了利用这些工具阐明未表征和糖基化蛋白质功能的重要性。这些技术的进一步发展将有助于以更高的效率和更快的速度鉴定新的生物标记物、治疗靶点和潜在的南美锥虫病疫苗。
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引用次数: 0
Proteostasis in neurodegenerative diseases. 神经退行性疾病中的蛋白稳态。
Pub Date : 2024-01-01 Epub Date: 2024-04-30 DOI: 10.1016/bs.acc.2024.04.002
Sumit Kinger, Yuvraj Anandrao Jagtap, Prashant Kumar, Akash Choudhary, Amit Prasad, Vijay Kumar Prajapati, Amit Kumar, Gunjan Mehta, Amit Mishra

Proteostasis is essential for normal function of proteins and vital for cellular health and survival. Proteostasis encompasses all stages in the "life" of a protein, that is, from translation to functional performance and, ultimately, to degradation. Proteins need native conformations for function and in the presence of multiple types of stress, their misfolding and aggregation can occur. A coordinated network of proteins is at the core of proteostasis in cells. Among these, chaperones are required for maintaining the integrity of protein conformations by preventing misfolding and aggregation and guide those with abnormal conformation to degradation. The ubiquitin-proteasome system (UPS) and autophagy are major cellular pathways for degrading proteins. Although failure or decreased functioning of components of this network can lead to proteotoxicity and disease, like neuron degenerative diseases, underlying factors are not completely understood. Accumulating misfolded and aggregated proteins are considered major pathomechanisms of neurodegeneration. In this chapter, we have described the components of three major branches required for proteostasis-chaperones, UPS and autophagy, the mechanistic basis of their function, and their potential for protection against various neurodegenerative conditions, like Alzheimer's, Parkinson's, and Huntington's disease. The modulation of various proteostasis network proteins, like chaperones, E3 ubiquitin ligases, proteasome, and autophagy-associated proteins as therapeutic targets by small molecules as well as new and unconventional approaches, shows promise.

蛋白稳态对蛋白质的正常功能至关重要,对细胞的健康和存活也至关重要。蛋白稳态包括蛋白质 "生命 "的所有阶段,即从翻译到发挥功能,最终到降解。蛋白质需要原生构象才能发挥功能,而在多种压力下,它们会发生错误折叠和聚集。一个协调的蛋白质网络是细胞蛋白质稳定的核心。其中,伴侣蛋白需要通过防止错误折叠和聚集来维持蛋白质构象的完整性,并引导那些构象异常的蛋白质降解。泛素-蛋白酶体系统(UPS)和自噬是降解蛋白质的主要细胞途径。虽然这一网络的组成部分失效或功能减弱会导致蛋白质毒性和疾病,如神经元退行性疾病,但其根本原因尚未完全明了。错误折叠和聚集蛋白的累积被认为是神经变性的主要病理机制。在本章中,我们介绍了蛋白稳态所需的三大分支--伴侣蛋白、UPS 和自噬的组成成分、其功能的机理基础,以及它们在预防阿尔茨海默氏症、帕金森氏症和亨廷顿氏症等各种神经退行性疾病方面的潜力。通过小分子以及新的和非常规的方法来调节各种蛋白稳态网络蛋白,如伴侣蛋白、E3 泛素连接酶、蛋白酶体和自噬相关蛋白,并将其作为治疗靶点,显示出了巨大的前景。
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引用次数: 0
Advances in sepsis biomarkers. 败血症生物标志物的研究进展。
Pub Date : 2024-01-01 Epub Date: 2024-02-15 DOI: 10.1016/bs.acc.2024.02.003
Maximo J Marin, Xander M R van Wijk, Allison B Chambliss

Sepsis, a dysregulated host immune response to an infectious agent, significantly increases morbidity and mortality for hospitalized patients worldwide. This chapter reviews (1) the basic principles of infectious diseases, pathophysiology and current definition of sepsis, (2) established sepsis biomarkers such lactate, procalcitonin and C-reactive protein, (3) novel, newly regulatory-cleared/approved biomarkers, such as assays that evaluate white blood cell properties and immune response molecules, and (4) emerging biomarkers and biomarker panels to highlight future directions and opportunities in the diagnosis and management of sepsis.

败血症是宿主对感染性病原体的一种失调免疫反应,它大大增加了全球住院病人的发病率和死亡率。本章回顾了:(1) 感染性疾病的基本原理、病理生理学和脓毒症的当前定义;(2) 已确立的脓毒症生物标志物,如乳酸、降钙素原和 C 反应蛋白;(3) 新近获得监管部门批准/认可的新型生物标志物,如评估白细胞特性和免疫反应分子的检测方法;(4) 新出现的生物标志物和生物标志物面板,以突出脓毒症诊断和管理的未来方向和机遇。
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引用次数: 0
Gastrointestinal hormones: History, biology, and measurement. 胃肠激素:历史、生物学和测量。
Pub Date : 2024-01-01 Epub Date: 2024-01-09 DOI: 10.1016/bs.acc.2023.11.004
Jens F Rehfeld, Jens P Goetze

This chapter attempts to provide an all-round picture of a dynamic and major branch of modern endocrinology, i.e. the gastrointestinal endocrinology. The advances during the last half century in our understanding of the dimensions and diversity of gut hormone biology - inside as well as outside the digestive tract - are astounding. Among major milestones are the dual brain-gut relationship, i.e. the comprehensive expression of gastrointestinal hormones as potent transmitters in central and peripheral neurons; the hormonal signaling from the enteroendocrine cells to the brain and other extraintestinal targets; the role of gut hormones as growth and fertility factors; and the new era of gut hormone-derived drugs. Accordingly, gastrointestinal hormones have pathogenetic roles in major metabolic disorders (diabetes mellitus and obesity); in tumor development (common cancers, sarcomas, and neuroendocrine tumors); and in cerebral diseases (anxiety, panic attacks, and probably eating disorders). Such clinical aspects require accurate pathogenetic and diagnostic measurements of gastrointestinal hormones - an obvious responsibility for clinical chemistry/biochemistry. In order to obtain a necessary insight into today's gastrointestinal endocrinology, the chapter will first describe the advances in gastrointestinal endocrinology in a historical context. The history provides a background for the subsequent description of the present biology of gastrointestinal hormones, and its biomedical consequences - not least for clinical chemistry/biochemistry with its specific responsibility for selection of appropriate assays and reliable measurements.

本章试图全面介绍现代内分泌学中一个充满活力的重要分支,即胃肠道内分泌学。在过去的半个世纪中,我们对消化道内外肠道激素生物学的层面和多样性的认识取得了惊人的进步。其中的主要里程碑包括:大脑与肠道的双重关系,即胃肠激素作为强效递质在中枢和外周神经元中的全面表达;从肠道内分泌细胞到大脑和其他肠道外靶点的激素信号传导;肠道激素作为生长和生育因子的作用;以及肠道激素衍生药物的新时代。因此,肠道激素在主要代谢性疾病(糖尿病和肥胖症)、肿瘤发生(常见癌症、肉瘤和神经内分泌肿瘤)以及脑部疾病(焦虑症、恐慌症和可能的饮食失调症)中具有致病作用。这些临床方面需要对胃肠激素进行准确的病理和诊断测量,这显然是临床化学/生物化学的职责所在。为了对当今的胃肠道内分泌学有一个必要的了解,本章将首先从历史的角度描述胃肠道内分泌学的进展。这段历史为下文描述目前胃肠激素的生物学特性及其生物医学后果提供了背景资料--尤其是对临床化学/生物化学而言,选择适当的检测方法和可靠的测量结果是其特定的责任。
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引用次数: 0
Neurofilaments in neurologic disease. 神经疾病中的神经丝。
Pub Date : 2024-01-01 Epub Date: 2024-07-08 DOI: 10.1016/bs.acc.2024.06.010
Christina Mousele, David Holden, Sharmilee Gnanapavan

Neurofilaments (NFs), major cytoskeletal constituents of neurons, have emerged as universal biomarkers of neuronal injury. Neuroaxonal damage underlies permanent disability in various neurological conditions. It is crucial to accurately quantify and longitudinally monitor this damage to evaluate disease progression, evaluate treatment effectiveness, contribute to novel treatment development, and offer prognostic insights. Neurofilaments show promise for this purpose, as their levels increase with neuroaxonal damage in both cerebrospinal fluid and blood, independent of specific causal pathways. New assays with high sensitivity allow reliable measurement of neurofilaments in body fluids and open avenues to investigate their role in neurological disorders. This book chapter will delve into the evolving landscape of neurofilaments, starting with their structure and cellular functions within neurons. It will then provide a comprehensive overview of their broad clinical value as biomarkers in diseases affecting the central or peripheral nervous system.

神经丝(NFs)是神经元的主要细胞骨架成分,已成为神经元损伤的通用生物标志物。神经轴突损伤是各种神经疾病导致永久性残疾的原因。准确量化和纵向监测这种损伤对于评估疾病进展、评价治疗效果、促进新疗法开发和提供预后见解至关重要。神经丝蛋白在这方面大有可为,因为神经丝蛋白水平会随着脑脊液和血液中神经轴受损程度的增加而增加,与特定的致病途径无关。新的高灵敏度检测方法可以可靠地测量体液中的神经丝,为研究神经丝在神经系统疾病中的作用开辟了道路。本书的这一章将从神经丝的结构和在神经元中的细胞功能入手,深入探讨神经丝的演变过程。然后,它将全面概述神经丝作为生物标记物在影响中枢或周围神经系统疾病中的广泛临床价值。
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引用次数: 0
Natriuretic peptide testing strategies in heart failure: A 2023 update. 心力衰竭钠尿肽检测策略:2023 年更新。
Pub Date : 2024-01-01 Epub Date: 2023-11-21 DOI: 10.1016/bs.acc.2023.11.005
Thanat Chaikijurajai, Hernan Rincon-Choles, W H Wilson Tang

Natriuretic peptides (NPs), including B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP), have been recommended as standard biomarkers for diagnosing heart failure (HF), and one of the strongest risk predictors for mortality and HF hospitalization regardless of ejection fraction (EF) and etiology of HF. BNP is an active neurohormone opposing renin-angiotensin-aldosterone and sympathetic nervous system overactivated in HF, whereas NT-proBNP is an inactive prohormone released from cardiomyocytes in response to wall stress. Despite substantial advances in the development of guideline-directed medical therapy (GDMT) for HF with reduced EF, studies demonstrating direct benefits of NP-guided chronic HF therapy on mortality, HF hospitalization, and GDMT optimization have yielded conflicting results. However, accumulating evidence shows that achieving prespecified BNP or NT-proBNP target over time is significantly associated with favorable outcomes, suggesting that benefits of serially measured NPs may be limited to particular groups of HF patients, such as those with extreme levels of baseline BNP or NT-proBNP, which could represent severe phenotypes of HF associated with natriuretic peptide resistance or cardiorenal syndrome. Over the past decade, clinical utilization of BNP and NT-proBNP has been expanded, especially using serial NP measurements for guiding HF therapy, optimizing GDMT and identifying at-risk patients with HF phenotypes who may be minimally symptomatic or asymptomatic.

钠尿肽(NPs),包括 B 型钠尿肽(BNP)和 N 端原-BNP(NT-proBNP),已被推荐为诊断心力衰竭(HF)的标准生物标志物,也是预测死亡率和 HF 住院治疗的最可靠风险指标之一,与射血分数(EF)和 HF 病因无关。BNP 是一种活性神经激素,在 HF 中与肾素-血管紧张素-醛固酮和交感神经系统的过度激活相对应,而 NT-proBNP 则是心肌细胞在壁应力作用下释放的一种非活性原激素。尽管针对 EF 值降低的心房颤动的指导性医疗疗法(GDMT)的发展取得了重大进展,但证明 NP 指导的慢性心房颤动治疗对死亡率、心房颤动住院率和 GDMT 优化有直接益处的研究结果却相互矛盾。然而,不断积累的证据表明,随着时间的推移,达到预先指定的 BNP 或 NT-proBNP 目标与良好的预后显著相关,这表明连续测量 NP 的益处可能仅限于特定的 HF 患者群体,例如基线 BNP 或 NT-proBNP 水平极高的患者,这些患者可能代表与钠尿肽抵抗或心肾综合征相关的严重 HF 表型。在过去的十年中,BNP 和 NT-proBNP 的临床应用范围不断扩大,尤其是利用连续 NP 测量来指导 HF 治疗、优化 GDMT 和识别具有 HF 表型的高危患者,这些患者可能症状轻微或无症状。
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引用次数: 0
Advances in endotoxin analysis. 内毒素分析的进展。
Pub Date : 2024-01-01 Epub Date: 2024-01-15 DOI: 10.1016/bs.acc.2023.11.001
Palak Sondhi, Taiwo Adeniji, Dhanbir Lingden, Keith J Stine

The outer membrane of gram-negative bacteria is primarily composed of lipopolysaccharide (LPS). In addition to protection, LPS defines the distinct serogroups used to identify bacteria specifically. Furthermore, LPS also act as highly potent stimulators of innate immune cells, a phenomenon essential to understanding pathogen invasion in the body. The complex multi-step process of LPS binding to cells involves several binding partners, including LPS binding protein (LBP), CD14 in both membrane-bound and soluble forms, membrane protein MD-2, and toll-like receptor 4 (TLR4). Once these pathways are activated, pro-inflammatory cytokines are eventually expressed. These binding events are also affected by the presence of monomeric or aggregated LPS. Traditional techniques to detect LPS include the rabbit pyrogen test, the monocyte activation test and Limulus-based tests. Modern approaches are based on protein, antibodies or aptamer binding. Recently, novel techniques including electrochemical methods, HPLC, quartz crystal microbalance (QCM), and molecular imprinting have been developed. These approaches often use nanomaterials such as gold nanoparticles, quantum dots, nanotubes, and magnetic nanoparticles. This chapter reviews current developments in endotoxin detection with a focus on modern novel techniques that use various sensing components, ranging from natural biomolecules to synthetic materials. Highly integrated and miniaturized commercial endotoxin detection devices offer a variety of options as the scientific and technologic revolution proceeds.

革兰氏阴性细菌的外膜主要由脂多糖(LPS)构成。除了保护作用外,LPS 还能确定不同的血清群,用于专门识别细菌。此外,LPS 还是先天性免疫细胞的强效刺激物,这一现象对了解病原体入侵人体至关重要。LPS 与细胞结合的复杂多步骤过程涉及多个结合伙伴,包括 LPS 结合蛋白(LBP)、膜结合型和可溶型 CD14、膜蛋白 MD-2 和收费样受体 4(TLR4)。一旦这些途径被激活,促炎细胞因子最终就会表达出来。这些结合事件也会受到单体或聚集 LPS 的影响。检测 LPS 的传统技术包括家兔热原试验、单核细胞活化试验和基于 Limulus 的试验。现代方法基于蛋白质、抗体或适配体结合。最近,又开发出了包括电化学方法、高效液相色谱法、石英晶体微天平(QCM)和分子印迹法在内的新技术。这些方法通常使用金纳米粒子、量子点、纳米管和磁性纳米粒子等纳米材料。本章回顾了内毒素检测领域的最新发展,重点介绍使用各种传感元件(从天然生物分子到合成材料)的现代新型技术。随着科技革命的发展,高度集成和微型化的商用内毒素检测设备提供了多种选择。
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引用次数: 0
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Advances in clinical chemistry
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