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Tau and Amyloid beta causes microglial activation in Alzheimer's disease. Tau蛋白和β淀粉样蛋白在阿尔茨海默病中引起小胶质细胞激活。
Pub Date : 2025-01-01 Epub Date: 2025-07-11 DOI: 10.1016/bs.acc.2025.06.002
Subashchandrabose Chinnathambi, Anusree Adithyan, Madhura Chandrashekar, Nagaraj Rangappa

Alzheimer's disease is a neurodegenerative condition characterized by the accumulation of hyperphosphorylated Tau in neurofibrillary tangles and amyloid-beta plaques. Tau, a microtubule-associated protein essential for neuronal stability, detaches from microtubules upon hyperphosphorylation, forming aggregates that disrupt neuronal function. Amyloid beta (Aβ) plaques act as upstream triggers, promoting Tau hyperphosphorylation and activating glial cells, particularly microglia and astrocytes. While these glial cells initially serve protective roles, their chronic activation leads to neuroinflammation, oxidative stress, and neuronal damage. Calcium dysregulation further exacerbates AD pathology by contributing to Tau hyperphosphorylation, mitochondrial dysfunction, and Aβ generation. This review highlights the intricate interplay between Tau, Aβ, and glial cells in the progression of AD, emphasizing both their protective and detrimental roles. It also explores the therapeutic implications of targeting these pathways, including modulating Tau phosphorylation, enhancing Aβ clearance, regulating glial activation, restoring calcium homeostasis, and preserving mitochondrial function. By addressing these multifaceted processes, this review underscores the potential for novel therapeutic strategies to slow or manage the progression of AD, ultimately improving patient outcomes.

阿尔茨海默病是一种神经退行性疾病,其特征是神经原纤维缠结和淀粉样斑块中过度磷酸化Tau的积累。Tau是一种对神经元稳定至关重要的微管相关蛋白,在过度磷酸化时从微管分离,形成破坏神经元功能的聚集体。淀粉样蛋白(Aβ)斑块作为上游触发器,促进Tau过度磷酸化并激活胶质细胞,特别是小胶质细胞和星形胶质细胞。虽然这些神经胶质细胞最初起到保护作用,但它们的慢性激活会导致神经炎症、氧化应激和神经元损伤。钙失调通过促进Tau过度磷酸化、线粒体功能障碍和Aβ生成进一步加剧AD病理。这篇综述强调了Tau、Aβ和胶质细胞在AD进展中的复杂相互作用,强调了它们的保护和有害作用。它还探讨了靶向这些途径的治疗意义,包括调节Tau磷酸化,增强Aβ清除,调节胶质细胞激活,恢复钙稳态和保护线粒体功能。通过解决这些多方面的过程,本综述强调了新的治疗策略的潜力,以减缓或控制AD的进展,最终改善患者的预后。
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引用次数: 0
The cancer microbiome. 癌症微生物群。
Pub Date : 2025-01-01 Epub Date: 2025-04-19 DOI: 10.1016/bs.acc.2025.04.001
Huapeng Li, Anne A Leaman, Qingfei Zheng

The cancer microbiome is an emerging concept that is referred to as the microorganism communities associated with cancer. There has been controversy in terms of the bona fide functions of the microbiome in carcinogenesis and cancer development, since the microorganisms were first observed within tumor tissues. Recently, there has been growing evidence showing that the microbiome indeed plays a role in cancer initiation, development, diagnosis, and treatment through diverse mechanisms and interactions between host cells and microbes. Rather than contaminants or artifacts, the cancer microbiome has been proven to be alive in the tumor microenvironment and possess significantly differential physiological and morphological properties compared to the corresponding environmental microorganisms. However, due to the low abundance of microbes within cancer tissues (especially the intratumoral microbiota) and lack of efficient analytical tools (e.g., sensitive antibodies, sensors, and probes), there are still a number of challenges and question marks in this fast-growing field. In this chapter, we made a systematic summary of the cancer microbiome, specifically focusing on its discovery and the recent research advances with respect to the studies on its functions and corresponding technology development.

癌症微生物组是一个新兴的概念,被称为与癌症相关的微生物群落。微生物群在致癌和癌症发展中的真正功能一直存在争议,因为微生物是在肿瘤组织中首次观察到的。近年来,越来越多的证据表明,微生物组确实通过宿主细胞与微生物之间的多种机制和相互作用,在癌症的发生、发展、诊断和治疗中发挥作用。与污染物或人工制品不同,癌症微生物组已被证明在肿瘤微环境中存活,并且与相应的环境微生物相比具有显著不同的生理和形态特性。然而,由于肿瘤组织内的微生物丰度较低(特别是肿瘤内的微生物群),以及缺乏有效的分析工具(如敏感抗体、传感器和探针),在这个快速发展的领域仍然存在许多挑战和问号。在这一章中,我们对癌症微生物组进行了系统的总结,重点介绍了癌症微生物组的发现和最新的研究进展,包括对其功能的研究和相应的技术发展。
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引用次数: 0
Advances in neurofilament light chain analysis. 神经丝蛋白轻链分析的进展。
Pub Date : 2025-01-01 Epub Date: 2025-03-17 DOI: 10.1016/bs.acc.2025.01.006
Arejas J Uzgiris, Lance A Ladic, Sophia X Pfister

This chapter provides a comprehensive summary of clinical laboratory testing for neurofilament light chain (NfL) in neurologic disease. A primer on the NfL structure and function is presented with its potential use as a biomarker. The most widely utilized methods for NfL in biologic samples are highlighted and examined. Limitations of current knowledge are considered, as are outstanding questions related to dissemination and standardization of testing. Herein we focus on methods available today and those in development for clinical use. In the final section, a broad vision is presented of how NfL may be utilized in the future to improve diagnosis and treatment of neurologic diseases as well as for maintaining health.

本章对神经系统疾病中神经丝轻链(NfL)的临床实验室检测进行了综述。介绍了NfL的结构和功能及其作为生物标志物的潜在用途。强调并检查了生物样品中最广泛使用的NfL方法。考虑到现有知识的局限性,以及与传播和标准化测试有关的悬而未决的问题。在这里,我们将重点介绍目前可用的方法和正在开发的临床应用方法。在最后一节,提出了未来如何利用NfL来提高神经系统疾病的诊断和治疗以及维持健康的广阔前景。
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引用次数: 0
Advances in biomimetic sensor technology. 仿生传感器技术的进展。
Pub Date : 2025-01-01 Epub Date: 2025-05-02 DOI: 10.1016/bs.acc.2025.04.003
Merve Asena Özbek, Özge Altıntaş, Fatma Yılmaz, Adil Denizli

Biomimetic sensor technology, inspired by nature's ingenious designs, has garnered significant attention for its potential in revolutionizing various fields, ranging from healthcare to environmental monitoring. Recent advances in biomimetic sensor technology have made it possible to develop unique and extremely sensitive sensors that imitate the capabilities of biological systems. The enhanced detection of different analytes with high specificity and sensitivity is facilitated by these sensors, which draw inspiration from natural organisms and their sensory capacities. New developments in materials science and nanotechnology have further enabled the development of novel biomimetic sensing platforms, such as nanostructured surfaces, membranes, and nanoparticles. This chapter highlights recent advances in biomimetic sensor technology, elucidating the principles, design strategies and applications driving its rapid development. We provide an overview of the most recent advancements in biomimetic sensor technology, which are driving the field forward by exploring the diverse applications of biomimetic sensors across various fields. Challenges and future aspects in biomimetic sensor research are also addressed, such as improving sensor biocompatibility, enhancing sensor stability-reproducibility and scaling up production for commercialization.

仿生传感器技术受到大自然巧妙设计的启发,因其在从医疗保健到环境监测等各个领域的革命性潜力而受到广泛关注。仿生传感器技术的最新进展使得开发独特和极其敏感的传感器成为可能,这些传感器可以模仿生物系统的能力。这些传感器的灵感来自于自然生物及其感官能力,有助于提高对不同分析物的高特异性和高灵敏度的检测。材料科学和纳米技术的新发展进一步推动了新型仿生传感平台的发展,如纳米结构表面、膜和纳米颗粒。本章重点介绍了仿生传感器技术的最新进展,阐述了推动其快速发展的原理、设计策略和应用。我们概述了仿生传感器技术的最新进展,通过探索仿生传感器在各个领域的不同应用,这些技术正在推动该领域的发展。本文还讨论了仿生传感器研究的挑战和未来发展方向,如提高传感器的生物相容性、增强传感器的稳定性和可重复性以及扩大商业化生产。
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引用次数: 0
Tumor-associated carbohydrate antigens: Biomarker discovery and clinical application. 肿瘤相关碳水化合物抗原:生物标志物的发现和临床应用。
Pub Date : 2025-01-01 Epub Date: 2025-07-20 DOI: 10.1016/bs.acc.2025.06.006
Teresa Freire, Valeria da Costa

Tumor-Associated Carbohydrate Antigens (TACAs) are carbohydrate structures uniquely expressed on the surface of tumor cells while being absent or minimally present in normal tissues. These molecular signatures play crucial roles in tumor progression, contributing to essential processes such as cell adhesion, motility, invasion, immune evasion, angiogenesis, metastasis, and proliferation. TACAs arise due to aberrant glycosylation, a hallmark of cancer cells, leading to their overexpression in various malignancies. Notably, elevated levels of certain TACAs have been associated with poor clinical outcomes in cancer patients. Because of their selective expression, TACAs serve as important biomarkers for cancer detection, prognosis, and disease monitoring. Their presence in the bloodstream of patients with epithelial carcinomas, neuroblastomas, and melanomas has led to the development of assays capable of quantifying these antigens in sera, providing valuable tools for clinical applications. The ability to measure TACAs in biological fluids enables early diagnosis and improved patient management, making them attractive targets for liquid biopsy strategies. Beyond their diagnostic utility, TACAs hold great promise for therapeutic applications, particularly in cancer immunotherapy. Their restricted expression on cancer cells makes them ideal targets for vaccine development, monoclonal antibody therapy, and chimeric antigen receptor (CAR) T-cell approaches. By exploiting the immune system's ability to recognize and target these antigens, novel treatment strategies are being explored to enhance anti-tumor immunity. Continued research into TACAs may lead to innovative diagnostic and therapeutic advancements, improving cancer patient outcomes and broadening the scope of precision medicine.

肿瘤相关碳水化合物抗原(TACAs)是肿瘤细胞表面唯一表达的碳水化合物结构,而在正常组织中不存在或极少存在。这些分子特征在肿瘤进展中起着至关重要的作用,促进了细胞粘附、运动、侵袭、免疫逃避、血管生成、转移和增殖等基本过程。TACAs的产生是由于异常的糖基化,这是癌细胞的一个标志,导致它们在各种恶性肿瘤中过度表达。值得注意的是,某些特定的taca水平升高与癌症患者的不良临床结果有关。由于它们的选择性表达,TACAs作为癌症检测、预后和疾病监测的重要生物标志物。它们存在于上皮癌、神经母细胞瘤和黑色素瘤患者的血液中,导致了能够在血清中量化这些抗原的检测方法的发展,为临床应用提供了有价值的工具。测量生物体液中taca的能力可以实现早期诊断和改善患者管理,使其成为液体活检策略的有吸引力的目标。除了诊断之外,TACAs在治疗方面也有很大的应用前景,特别是在癌症免疫治疗方面。它们在癌细胞上的有限表达使它们成为疫苗开发、单克隆抗体治疗和嵌合抗原受体(CAR) t细胞方法的理想靶点。通过利用免疫系统识别和靶向这些抗原的能力,人们正在探索新的治疗策略来增强抗肿瘤免疫。对taca的持续研究可能会带来创新的诊断和治疗进步,改善癌症患者的治疗效果,拓宽精准医疗的范围。
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引用次数: 0
Brain white matter damage biomarkers. 脑白质损伤生物标志物。
Pub Date : 2025-01-01 Epub Date: 2024-12-10 DOI: 10.1016/bs.acc.2024.11.005
Fardin Nabizadeh

White matter (WM), constituting nearly half of the human brain's mass, is pivotal for the rapid transmission of neural signals across different brain regions, significantly influencing cognitive processes like learning, memory, and problem-solving. The integrity of WM is essential for brain function, and its damage, which can occur due to conditions such as multiple sclerosis (MS), stroke, and traumatic brain injury, results in severe neurological deficits and cognitive decline. The primary objective of this book chapter is to discuss the clinical significance of fluid biomarkers in assessing WM damage within the central nervous system (CNS). It explores the biological underpinnings and pathological changes in WM due to various neurological conditions and details how alterations can be detected and quantified through fluid biomarkers. By examining biomarkers like Myelin Basic Protein (MBP), Neurofilament light chain (NFL), and others, the chapter highlights their role in enhancing diagnostic precision, monitoring disease progression, and guiding therapeutic interventions, thus providing crucial insights into maintaining WM integrity and preventing cognitive and physical disabilities.

白质(WM)占人类大脑质量的近一半,是神经信号在不同大脑区域快速传递的关键,对学习、记忆和解决问题等认知过程产生重大影响。WM的完整性对脑功能至关重要,多发性硬化症(MS)、中风和创伤性脑损伤等疾病可能导致WM损伤,导致严重的神经功能缺损和认知能力下降。本章的主要目的是讨论液体生物标志物在评估中枢神经系统(CNS)内WM损伤中的临床意义。它探讨了由各种神经系统疾病引起的WM的生物学基础和病理变化,并详细介绍了如何通过液体生物标志物检测和量化这些变化。通过检查髓鞘碱性蛋白(MBP)、神经丝轻链(NFL)等生物标志物,本章强调了它们在提高诊断精度、监测疾病进展和指导治疗干预方面的作用,从而为维持WM完整性和预防认知和身体残疾提供了重要见解。
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引用次数: 0
Visceral fat distribution: Interracial studies. 内脏脂肪分布:跨种族研究。
Pub Date : 2025-01-01 Epub Date: 2024-11-05 DOI: 10.1016/bs.acc.2024.10.001
Santasree Banerjee, Jiayin Lv, Chang He, Baiyu Qi, Weijie Ding, Kongrong Long, Junrong Chen, Jianping Wen, Peng Chen

Visceral adipose tissue, a type of abdominal adipose tissue, is highly involved in lipolysis. Because increased visceral adiposity is strongly associated with the metabolic complications related with obesity, such as type 2 diabetes and cardiovascular disease, there is a need for precise, targeted, personalized and site-specific measures clinically. Existing studies showed that ectopic fat accumulation may be characterized differently among different populations due to complex genetic architecture and non-genetic or epigenetic components, ie, Asians have more and Africans have less visceral fat vs Europeans. In this review, we summarize the effects of multiple non-genetic and genetic factors on visceral fat distribution across races. Non-genetic factors include diet, socioeconomic status, sex hormones and psychological factors, etc. We examine genetic factors of racial differences in visceral fat content as well as possible regulatory pathways associated with interracial visceral fat distribution. A comprehensive understanding of both genetic and non-genetic factors that influence the distribution of visceral fat among races, leads us to predict risk of abdominal obesity and metabolic diseases in ethnic groups that enables targeted interventions through accurate diagnosis and treatment as well as reduced risk of obesity-associated complications.

内脏脂肪组织,腹部脂肪组织的一种,高度参与脂肪分解。由于内脏脂肪增加与肥胖相关的代谢并发症(如2型糖尿病和心血管疾病)密切相关,因此临床上需要精确、有针对性、个性化和部位特异性的措施。现有研究表明,由于复杂的遗传结构和非遗传或表观遗传成分,不同人群的异位脂肪积累可能具有不同的特征,即与欧洲人相比,亚洲人的内脏脂肪较多,非洲人的内脏脂肪较少。在这篇综述中,我们总结了多种非遗传和遗传因素对不同种族内脏脂肪分布的影响。非遗传因素包括饮食、社会经济地位、性激素和心理因素等。我们研究了种族间内脏脂肪含量差异的遗传因素,以及与种族间内脏脂肪分布相关的可能的调节途径。全面了解影响种族间内脏脂肪分布的遗传和非遗传因素,使我们能够预测种族中腹部肥胖和代谢性疾病的风险,从而通过准确的诊断和治疗进行有针对性的干预,并降低肥胖相关并发症的风险。
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引用次数: 0
Emerging biomarkers in Gaucher disease. 戈谢病新出现的生物标志物。
Pub Date : 2025-01-01 Epub Date: 2025-01-07 DOI: 10.1016/bs.acc.2024.11.001
Danielle M Luettel, Marcia R Terluk, Jaehyeok Roh, Neal J Weinreb, Reena V Kartha

Gaucher disease (GD) is a rare lysosomal disorder characterized by the accumulation of glycosphingolipids in macrophages resulting from glucocerebrosidase (GCase) deficiency. The accumulation of toxic substrates, which causes the hallmark symptoms of GD, is dependent on the extent of enzyme dysfunction. Accordingly, three distinct subtypes have been recognized, with type 1 GD (GD1) as the common and milder form, while types 2 (GD2) and 3 (GD3) are categorized as neuronopathic and severe. Manifestations variably include hepatosplenomegaly, anemia, thrombocytopenia, easy bruising, inflammation, bone pain and other skeletal pathologies, abnormal eye movements and neuropathy. Although the molecular basis of GD is relatively well understood, currently used biomarkers are nonspecific and inadequate for making finer distinctions between subtypes and in evaluating changes in disease status and guiding therapy. Thus, there is continued effort to investigate and identify potential biomarkers to improve GD diagnosis, monitoring and potential identification of novel therapeutic targets. Here, we provide a comprehensive review of emerging biomarkers in GD that can enhance current understanding and improve quality of life through better testing, disease management and treatment.

戈谢病(GD)是一种罕见的溶酶体疾病,其特征是糖脑苷酶(GCase)缺乏导致巨噬细胞中鞘糖脂积累。引起GD标志性症状的有毒底物的积累取决于酶功能障碍的程度。因此,已经识别出三种不同的亚型,1型GD (GD1)是常见的和较轻的形式,而2型(GD2)和3型(GD3)被归类为神经病变和严重。表现多样,包括肝脾肿大、贫血、血小板减少、易瘀伤、炎症、骨痛等骨骼病变、眼动异常和神经病变。虽然GD的分子基础已经被很好地理解,但目前使用的生物标志物是非特异性的,不足以对亚型进行更精细的区分,也不足以评估疾病状态的变化和指导治疗。因此,需要继续努力研究和鉴定潜在的生物标志物,以改善GD的诊断、监测和潜在的新治疗靶点的鉴定。在这里,我们全面回顾了GD中新兴的生物标志物,这些标志物可以通过更好的检测、疾病管理和治疗来增强当前的认识并改善生活质量。
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引用次数: 0
Cell-cell junctional proteins in cancer. 癌细胞中的细胞连接蛋白。
Pub Date : 2025-01-01 Epub Date: 2024-12-14 DOI: 10.1016/bs.acc.2024.11.006
Aparajita Das, Sarbani Giri, Pubali Dey

A hallmark change during carcinogenesis is disruption or dysregulation of cell-cell junctions. It enables a transformed cell to adopt mesenchymal phenotype and acquire higher potential to migrate and invade. This ultimately leads to cancer metastasis. During this process, junctional proteins undergo remarkable changes in terms of their expressional pattern, localization, and activity. De-localized junctional proteins may adopt atypical roles which might act to either suppress tumorigenesis or facilitate cancer development, depending on several factors. In this chapter, the authors attempt to know the expression pattern of junctional proteins in different types of cancer, understand its significance, and gather knowledge about the mechanisms by which they regulate tumorigenesis and cancer development.

癌变过程中的一个标志性变化是细胞-细胞连接的破坏或失调。它使转化细胞采用间充质表型,并获得更高的迁移和侵袭潜力。这最终导致癌症转移。在这一过程中,连接蛋白的表达模式、定位和活性都会发生显著变化。由于多种因素的影响,去定位的连接蛋白可能会发挥非典型作用,从而抑制肿瘤发生或促进癌症发展。在本章中,作者试图了解连接蛋白在不同类型癌症中的表达模式,理解其意义,并收集有关它们调控肿瘤发生和癌症发展的机制的知识。
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引用次数: 0
Advances in optical biosensors: Technologies and trends in point of care applications. 光学生物传感器的进展:护理点应用的技术和趋势。
Pub Date : 2025-01-01 Epub Date: 2025-07-23 DOI: 10.1016/bs.acc.2025.07.001
Alper Baran Sözmen, Ayşe Ezgi Bayraktar, Özgür Ülker, Ahu Arslan-Yildiz

A sensor detects changes in its environment and converts them into readable data using three key components: a receptor to sense changes, a transducer to generate a signal, and a detection system to output the signal. Optical sensors are devices that use a receptor and optical transducer to produce signals corresponding to an analyte, and optical biosensors combine a biological sensing element with an optical transducer to detect and quantify specific analytes. They offer easy-to-read, real-time signals, such as color changes or light emission, sometimes even detectable by the naked eye, reducing the need for external devices and providing versatile Point-of-Care (PoC) applicability. Their portability and rapid response time enable remote testing and monitoring, further improving accessibility. They allow sensitive and selective detection of various analytes, making them utile in areas like glucose monitoring, drug testing, and pathogen detection. Many of these sensors provide label-free and non-invasive detection, further enhancing patient comfort and safety. This chapter provides an overview of optical biosensors; it starts with categorizing them by biorecognition elements, transducers, and detection modes. It investigates biosensors that utilize nanomaterials, polymers, and engineered biorecognition elements are discussed, with examples from literature. Technologies such as miniaturization, multiplexing, and wearable designs, which enhance PoC feasibility, are also examined. Lastly, challenges in development and operation are addressed, and future research directions for advancing optical biosensors in PoC diagnostics are discussed.

传感器检测环境的变化,并通过三个关键组件将其转换为可读数据:感知变化的受体、产生信号的传感器和输出信号的检测系统。光学传感器是使用受体和光换能器来产生与分析物相对应的信号的装置,光学生物传感器将生物传感元件与光换能器结合起来,以检测和量化特定的分析物。它们提供易于读取的实时信号,例如颜色变化或发光,有时甚至可以通过肉眼检测到,从而减少了对外部设备的需求,并提供了多功能的护理点(PoC)适用性。它们的可移植性和快速响应时间支持远程测试和监控,进一步提高了可访问性。它们允许对各种分析物进行敏感和选择性检测,使其在葡萄糖监测,药物测试和病原体检测等领域非常有用。许多这些传感器提供无标签和非侵入性检测,进一步提高患者的舒适度和安全性。本章概述了光学生物传感器;它首先通过生物识别元件,传感器和检测模式对它们进行分类。它研究了利用纳米材料、聚合物和工程生物识别元件的生物传感器,并从文献中举例进行了讨论。还研究了诸如小型化、多路复用和可穿戴设计等增强PoC可行性的技术。最后,对光学生物传感器在PoC诊断中的应用前景进行了展望。
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引用次数: 0
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Advances in clinical chemistry
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