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Critical reviews in clinical laboratory sciences最新文献

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From population-based to personalized laboratory medicine: continuous monitoring of individual laboratory data with wearable biosensors.
IF 6.6 2区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-02-01 DOI: 10.1080/10408363.2025.2453152
Abdurrahman Coskun, Irem Nur Savas, Ozge Can, Giuseppe Lippi

Monitoring individuals' laboratory data is essential for assessing their health status, evaluating the effectiveness of treatments, predicting disease prognosis and detecting subclinical conditions. Currently, monitoring is performed intermittently, measuring serum, plasma, whole blood, urine and occasionally other body fluids at predefined time intervals. The ideal monitoring approach entails continuous measurement of concentration and activity of biomolecules in all body fluids, including solid tissues. This can be achieved through the use of biosensors strategically placed at various locations on the human body where measurements are required for monitoring. High-tech wearable biosensors provide an ideal, noninvasive, and esthetically pleasing solution for monitoring individuals' laboratory data. However, despite significant advances in wearable biosensor technology, the measurement capacities and the number of different analytes that are continuously monitored in patients are not yet at the desired level. In this review, we conducted a literature search and examined: (i) an overview of the background of monitoring for personalized laboratory medicine, (ii) the body fluids and analytes used for monitoring individuals, (iii) the different types of biosensors and methods used for measuring the concentration and activity of biomolecules, and (iv) the statistical algorithms used for personalized data analysis and interpretation in monitoring and evaluation.

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引用次数: 0
Establishing, evaluating and monitoring analytical quality in the traceability era. 追溯时代分析质量的建立、评价和监控。
IF 6.6 2区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-01-01 DOI: 10.1080/10408363.2024.2434562
Mauro Panteghini, Magdalena Krintus

Poor analytical quality may be the bane of medical use of laboratory tests, and the fight against excessive analytical variability presents a daily struggle. Laboratories should prioritize the perspectives and needs of their customers (the patients and healthcare personnel). Among them, comparability of results from the same patient sample when measured by different laboratories using different in vitro diagnostic (IVD) medical devices is a logical priority to avoid result misinterpretation and potential patient harm. Harmonization (standardization) of laboratory measurements can be achieved by establishing metrological traceability of the results on clinical samples to stated higher-order references and providing an estimate of the uncertainty of measurement (MU). This estimate should be based on an MU budget including all known MU contributions generated by the employed calibration hierarchy, which in turn should be validated against fit-for-purpose maximum allowable MU derived according to internationally recommended models. In this report, we review the available strategies for establishing, evaluating, and monitoring analytical quality, drawing on three decades experience in the field. We discuss the most important aspects that may influence obtaining and maintaining analytical standardization in laboratory medicine, and offer practical solutions aimed at educating all stakeholders for the achievement of harmonized laboratory results. To fully implement the recommended approaches, all involved parties-i.e. reference providers, IVD manufacturers, medical laboratories, and External Quality Assessment organizers-must agree on their importance and enhance their specific knowledge.

较差的分析质量可能是医疗使用实验室测试的祸源,与过度的分析可变性作斗争是每天的斗争。实验室应优先考虑客户(患者和医护人员)的观点和需求。其中,在不同实验室使用不同体外诊断(IVD)医疗器械检测同一患者样本时,结果的可比性是一个逻辑上的优先事项,以避免结果误解和潜在的患者伤害。实验室测量的协调(标准化)可以通过建立临床样品结果的计量可追溯性来实现,以规定高阶参考,并提供测量不确定度(MU)的估计。这一估计应基于包括所采用的校准层次结构产生的所有已知的平均单位贡献的平均单位预算,而这些平均单位又应根据根据国际推荐模型得出的适合目的的最大允许平均单位进行验证。在本报告中,我们回顾了建立、评估和监测分析质量的可用策略,借鉴了该领域三十年的经验。我们讨论可能影响获得和维持检验医学分析标准化的最重要方面,并提供实用的解决方案,旨在教育所有利益相关者实现统一的实验室结果。为全面落实建议的方法,有关各方,即参考提供者、IVD制造商、医学实验室和外部质量评估组织必须就其重要性达成一致,并提高他们的具体知识。
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引用次数: 0
Guidance for securing approvals for new biomarkers: from discovery to clinical implementation. 确保新生物标记物获得批准的指南:从发现到临床应用。
IF 6.6 2区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-01-01 Epub Date: 2024-07-31 DOI: 10.1080/10408363.2024.2379278
Harriet Feilotter, Christine Bruce, Eleftherios P Diamandis, Miyo K Chatanaka, George M Yousef

The journey of translating a molecular discovery into the clinic involves multiple steps and requires planning, time, effort, and money. In this review, we provide a quick guide on the technical and clinical validation parameters that are necessary for successful commercialization of molecular and other markers. We also briefly address the different options for regulatory approvals. Successful clinical implantation depends on rigorous technical and clinical validation, and the ability to develop clear guidelines for the indications for testing (i.e. which patients are eligible to have this test), the frequency of testing, and also a clear interpretation of test results. Successful implementation requires providing evidence that the results of this test can be used to improve patient care. There are currently multiple routes for implementation of clinical molecular tests, which include regulatory agency- approved companion diagnostics, laboratory developed tests, or direct-to-consumer testing. Regulatory approval is considered the gold-standard, but it requires time and resources. There is an ongoing debate about the need for regulatory approval of laboratory developed testing. Ongoing oversight is maintained through lab accreditation and proficiency testing programs, which provide a common approach to ensuring high standards and consistent performance in clinical molecular labs. Before moving into the clinic, confirmation of both the clinical and analytic validity of a new molecular test is essential.

将分子发现转化为临床应用的过程涉及多个步骤,需要规划、时间、精力和金钱。在本综述中,我们将快速介绍分子标记物和其他标记物成功商业化所需的技术和临床验证参数。我们还简要介绍了监管审批的不同选择。成功的临床植入取决于严格的技术和临床验证,以及为检测适应症(即哪些患者有资格接受该检测)、检测频率和检测结果的明确解释制定明确指南的能力。成功实施需要提供证据,证明检测结果可用于改善患者护理。目前,临床分子检验有多种实施途径,包括监管机构批准的辅助诊断、实验室开发的检验或直接面向消费者的检验。监管机构批准被认为是黄金标准,但需要时间和资源。关于实验室开发的检测是否需要监管机构批准的争论一直存在。通过实验室认证和能力验证计划进行持续监督,是确保临床分子实验室高标准和一致性能的通用方法。在进入临床之前,必须确认新分子检测的临床和分析有效性。
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引用次数: 0
Clinical applications of volatilomic assays. 挥发测定的临床应用。
IF 6.6 2区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-01-01 Epub Date: 2024-08-12 DOI: 10.1080/10408363.2024.2387038
Rosamaria Capuano, Marco Ciotti, Alexandro Catini, Sergio Bernardini, Corrado Di Natale

The study of metabolomics is revealing immense potential for diagnosis, therapy monitoring, and understanding of pathogenesis processes. Volatilomics is a subcategory of metabolomics interested in the detection of molecules that are small enough to be released in the gas phase. Volatile compounds produced by cellular processes are released into the blood and lymph, and can reach the external environment through different pathways, such as the blood-air interface in the lung that are detected in breath, or the blood-water interface in the kidney that leads to volatile compounds detected in urine. Besides breath and urine, additional sources of volatile compounds such as saliva, blood, feces, and skin are available. Volatilomics traces its roots back over fifty years to the pioneering investigations in the 1970s. Despite extensive research, the field remains in its infancy, hindered by a lack of standardization despite ample experimental evidence. The proliferation of analytical instrumentations, sample preparations and methods of volatilome sampling still make it difficult to compare results from different studies and to establish a common standard approach to volatilomics. This review aims to provide an overview of volatilomics' diagnostic potential, focusing on two key technical aspects: sampling and analysis. Sampling poses a challenge due to the susceptibility of human samples to contamination and confounding factors from various sources like the environment and lifestyle. The discussion then delves into targeted and untargeted approaches in volatilomics. Some case studies are presented to exemplify the results obtained so far. Finally, the review concludes with a discussion on the necessary steps to fully integrate volatilomics into clinical practice.

代谢组学研究为诊断、治疗监测和了解发病过程揭示了巨大的潜力。挥发物组学是代谢组学的一个子类别,主要研究如何检测小到可以在气相中释放的分子。细胞过程产生的挥发性化合物会释放到血液和淋巴中,并通过不同的途径到达外部环境,例如通过肺部的血气界面在呼气中检测到挥发性化合物,或通过肾脏的血水界面在尿液中检测到挥发性化合物。除呼气和尿液外,还有唾液、血液、粪便和皮肤等其他挥发性化合物来源。挥发性物质组学的起源可追溯到 20 世纪 70 年代的开创性研究,至今已有 50 多年的历史。尽管进行了广泛的研究,但该领域仍处于起步阶段,尽管有大量的实验证据,但由于缺乏标准化而受到阻碍。分析仪器、样品制备和挥发物取样方法的激增仍然难以比较不同研究的结果,也难以确定挥发物组学的通用标准方法。本综述旨在概述挥发物组学的诊断潜力,重点关注两个关键技术方面:取样和分析。由于人体样本容易受到环境和生活方式等各种来源的污染和混杂因素的影响,取样是一项挑战。讨论随后深入探讨了挥发物组学中的定向和非定向方法。文中还介绍了一些案例研究,以说明迄今为止所取得的成果。最后,本综述还讨论了将挥发物组学全面融入临床实践的必要步骤。
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引用次数: 0
The significance of antigen-antibody-binding avidity in clinical diagnosis. 抗原-抗体结合率在临床诊断中的意义。
IF 6.6 2区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-01-01 Epub Date: 2024-07-23 DOI: 10.1080/10408363.2024.2379286
Yaxin Li, He S Yang, P J Klasse, Zhen Zhao

Immunoglobulin G (IgG) and immunoglobulin M (IgM) testing are commonly used to determine infection status. Typically, the detection of IgM indicates an acute or recent infection, while the presence of IgG alone suggests a chronic or past infection. However, relying solely on IgG and IgM antibody positivity may not be sufficient to differentiate acute from chronic infections. This limitation arises from several factors. The prolonged presence of IgM can complicate diagnostic interpretations, and false positive IgM results often arise from antibody cross-reactivity with various antigens. Additionally, IgM may remain undetectable in prematurely collected samples or in individuals who are immunocompromised, further complicating accurate diagnosis. As a result, additional diagnostic tools are required to confirm infection status. Avidity is a measure of the strength of the binding between an antigen and antibody. Avidity-based assays have been developed for various infectious agents, including toxoplasma, cytomegalovirus (CMV), SARS-CoV-2, and avian influenza, and are promising tools in clinical diagnostics. By measuring the strength of antibody binding, they offer critical insights into the maturity of the immune response. These assays are instrumental in distinguishing between acute and chronic or past infections, monitoring disease progression, and guiding treatment decisions. The development of automated platforms has optimized the testing process by enhancing efficiency and minimizing the risk of manual errors. Additionally, the recent advent of real-time biosensor immunoassays, including the label-free immunoassays (LFIA), has further amplified the capabilities of these assays. These advances have expanded the clinical applications of avidity-based assays, making them useful tools for the diagnosis and management of various infectious diseases. This review is structured around several key aspects of IgG avidity in clinical diagnosis, including: (i) a detailed exposition of the IgG affinity maturation process; (ii) a thorough discussion of the IgG avidity assays, including the recently emerged biosensor-based approaches; and (iii) an examination of the applications of IgG avidity in clinical diagnosis. This review is intended to contribute toward the development of enhanced diagnostic tools through critical assessment of the present landscape of avidity-based testing, which allows us to identify the existing knowledge gaps and highlight areas for future investigation.

免疫球蛋白 G (IgG) 和免疫球蛋白 M (IgM) 检测通常用于确定感染状态。通常情况下,检测到 IgM 表示急性感染或近期感染,而仅出现 IgG 则表示慢性感染或既往感染。然而,仅仅依靠 IgG 和 IgM 抗体阳性可能不足以区分急性和慢性感染。这种局限性来自几个因素。IgM 的长期存在会使诊断解释复杂化,而 IgM 假阳性结果往往是由于抗体与各种抗原的交叉反应引起的。此外,在过早采集的样本中或在免疫力低下的个体中可能仍然检测不到 IgM,从而使准确诊断更加复杂。因此,需要额外的诊断工具来确认感染状态。效价是衡量抗原与抗体之间结合强度的指标。目前已针对弓形虫、巨细胞病毒 (CMV)、SARS-CoV-2 和禽流感等多种感染性病原体开发出了基于效价的检测方法,是临床诊断中很有前途的工具。通过测量抗体结合的强度,它们可以提供有关免疫反应成熟度的重要信息。这些检测有助于区分急性感染和慢性感染或既往感染、监测疾病进展和指导治疗决策。自动化平台的开发提高了效率,最大程度地降低了人工操作失误的风险,从而优化了检测流程。此外,最近出现的实时生物传感器免疫测定,包括无标记免疫测定(LFIA),进一步提高了这些检测方法的能力。这些进步扩大了基于热敏性检测的临床应用,使其成为诊断和管理各种传染病的有用工具。本综述围绕 IgG 阳性在临床诊断中的几个关键方面展开,包括:(i) IgG 亲和力成熟过程的详细阐述;(ii) IgG 阳性检测方法的深入讨论,包括最近出现的基于生物传感器的方法;以及 (iii) IgG 阳性在临床诊断中的应用研究。本综述旨在通过对目前基于亲和力检测的现状进行批判性评估,找出现有的知识空白并强调未来研究的重点领域,从而为开发更先进的诊断工具做出贡献。
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引用次数: 0
Copeptin as a surrogate marker for arginine vasopressin: analytical insights, current utility, and emerging applications. 作为精氨酸加压素替代标记物的 Copeptin:分析见解、当前用途和新兴应用。
IF 6.6 2区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-01-01 Epub Date: 2024-07-31 DOI: 10.1080/10408363.2024.2383899
Kay Weng Choy, Nilika Wijeratne, Cherie Chiang, Andrew Don-Wauchope
<p><p>Copeptin is a 39-amino-acid long glycosylated peptide with a leucine-rich core segment in the C-terminal part of pre-pro-vasopressin. It exhibits a rapid response comparable to arginine vasopressin (AVP) in response to osmotic, hemodynamic, and nonspecific stress-related stimuli. This similarity can be attributed to equimolar production of copeptin alongside AVP. However, there are markedly different decay kinetics for both peptides, with an estimated initial half-life of copeptin being approximately two times longer than that of AVP. Like AVP, copeptin correlates strongly over a wide osmolality range in healthy individuals, making it a useful alternative to AVP measurement. While copeptin does not appear to be significantly affected by food intake, small amounts of oral fluid intake may result in a significant decrease in copeptin levels. Compared to AVP, copeptin is considerably more stable <i>in vitro</i>. An automated immunofluorescent assay is now available and has been used in recent landmark trials. However, separate validation studies are required before copeptin thresholds from these studies are applied to other assays. The biological variation of copeptin in presumably healthy subjects has been recently reported, which could assist in defining analytical performance specifications for this measurand. An established diagnostic utility of copeptin is in the investigation of polyuria-polydipsia syndrome and copeptin-based testing protocols have been explored in recent years. A single baseline plasma copeptin >21.4 pmol/L differentiates AVP resistance (formerly known as nephrogenic diabetes insipidus) from other causes with 100% sensitivity and specificity, rendering water deprivation testing unnecessary in such cases. In a recent study among adult patients with polyuria-polydipsia syndrome, AVP deficiency (formerly known as central diabetes insipidus) was more accurately diagnosed with hypertonic saline-stimulated copeptin than with arginine-stimulated copeptin. Glucagon-stimulated copeptin has been proposed as a potentially safe and precise test in the investigation of polyuria-polydipsia syndrome. Furthermore, copeptin could reliably identify those with AVP deficiency among patients with severe hypernatremia, though its diagnostic utility is reportedly limited in the differential diagnosis of profound hyponatremia. Copeptin measurement may be a useful tool for early goal-directed management of post-operative AVP deficiency. Additionally, the potential prognostic utility of copeptin has been explored in other diseases. There is an interest in examining the role of the AVP system (with copeptin as a marker) in the pathogenesis of insulin resistance and diabetes mellitus. Copeptin has been found to be independently associated with an increased risk of incident stroke and cardiovascular disease mortality in men with diabetes mellitus. Increased levels of copeptin have been reported to be independently predictive of a decline in estimat
Copeptin 是一种 39 氨基酸的糖基化长肽,在前血管加压素的 C 端部分有一个富含亮氨酸的核心段。在对渗透压、血液动力学和非特异性压力相关刺激的反应中,它表现出与精氨酸血管加压素(AVP)相当的快速反应。这种相似性可归因于 copeptin 与 AVP 的等摩尔生成。然而,这两种肽的衰减动力学明显不同,据估计, copeptin 的初始半衰期约为 AVP 的两倍。与 AVP 一样,在健康人的较大渗透压范围内, copeptin 与 AVP 的相关性很强,因此是 AVP 测量的有效替代品。虽然 copeptin 似乎不会受到食物摄入量的明显影响,但少量口服液摄入可能会导致 copeptin 水平显著下降。与 AVP 相比, copeptin 在体外更为稳定。目前已有一种自动免疫荧光测定法,并已用于近期的标志性试验中。不过,在将这些研究得出的 copeptin 临界值应用于其他检测方法之前,还需要进行单独的验证研究。最近有报道称,假定健康受试者体内的 copeptin 存在生物变异,这有助于确定该测量指标的分析性能指标。多尿多钾综合征的调查和基于 copeptin 的检测方案在近几年得到了探索。单次基线血浆 copeptin >21.4 pmol/L 可以区分 AVP 抵抗(以前称为肾源性糖尿病性尿崩症)和其他原因,敏感性和特异性均为 100%,因此在此类病例中无需进行缺水测试。在最近一项针对多尿多饮综合征成年患者的研究中,用高渗盐水刺激 copeptin 比用精氨酸刺激 copeptin 更能准确诊断 AVP 缺乏症(以前称为中枢性糖尿病)。胰高血糖素刺激的 copeptin 被认为是调查多尿多脂综合征的一种潜在安全而精确的检测方法。此外,胰高血糖素还能可靠地鉴别出严重高钠血症患者中的 AVP 缺乏者,但据报道,它在鉴别诊断深度低钠血症方面的作用有限。Copeptin测量可能是术后AVP缺乏症早期目标导向管理的有用工具。此外,人们还在其他疾病中探讨了谷丙肽的潜在预后作用。人们有兴趣研究 AVP 系统(以 copeptin 为标志物)在胰岛素抵抗和糖尿病发病机制中的作用。研究发现,在男性糖尿病患者中,谷丙肽与中风和心血管疾病死亡风险的增加密切相关。据报道,谷丙肽水平的升高可独立预测估计肾小球滤过率的下降和新发慢性肾病的更大风险。此外,常染色体显性多囊肾患者体内的 copeptin 与疾病的严重程度有关。在老年人群中,谷丙肽可预测冠状动脉疾病的发展和心血管死亡率。此外,研究还发现,对于心力衰竭患者的全因死亡率,谷丙肽的预测价值与 N 末端前脑钠尿肽相当。在这些情况下测量 copeptin 是否会改变临床管理,还有待今后的研究证明。
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引用次数: 0
SGLT2 inhibitors as a potential therapeutic option for pulmonary hypertension: mechanisms and clinical perspectives. 作为肺动脉高压潜在治疗方案的 SGLT2 抑制剂:机制与临床前景。
IF 6.6 2区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-06-07 DOI: 10.1080/10408363.2024.2361012
Jiang-Shan Tan, Yixiao Wei, Lingtao Chong, Yanmin Yang, Song Hu, Yimeng Wang

Pulmonary arterial hypertension (PAH), one subtype of pulmonary hypertension (PH), is a life-threatening condition characterized by pulmonary arterial remodeling, elevated pulmonary vascular resistance, and blood pressure in the pulmonary arteries, leading to right heart failure and increased mortality. The disease is marked by endothelial dysfunction, vasoconstriction, and vascular remodeling. The role of Sodium-Glucose Co-Transporter-2 (SGLT2) inhibitors, a class of medications originally developed for diabetes management, is increasingly being explored in the context of cardiovascular diseases, including PAH, due to their potential to modulate these pathophysiological processes. In this review, we systematically examine the burgeoning evidence from both basic and clinical studies that describe the effects of SGLT2 inhibitors on cardiovascular health, with a special emphasis on PAH. By delving into the complex interactions between these drugs and the potential pathobiology that underpins PH, this study seeks to uncover the mechanistic underpinnings that could justify the use of SGLT2 inhibitors as a novel therapeutic approach for PAH. We collate findings that illustrate how SGLT2 inhibitors may influence the normal function of pulmonary arteries, possibly alleviating the pathological hallmarks of PAH such as inflammation, oxidative stress, aberrant cellular proliferation, and so on. Our review thereby outlines a potential paradigm shift in PAH management, suggesting that these inhibitors could play a crucial role in modulating the disease's progression by targeting the potential dysfunctions that drive it. This comprehensive synthesis of existing research underscores the imperative need for further clinical trials to validate the efficacy of SGLT2 inhibitors in PAH and to integrate them into the therapeutic agents used against this challenging disease.

肺动脉高压(PAH)是肺动脉高压(PH)的一种亚型,是一种危及生命的疾病,其特点是肺动脉重塑、肺血管阻力和肺动脉血压升高,导致右心衰竭和死亡率升高。这种疾病以内皮功能障碍、血管收缩和血管重塑为特征。钠-葡萄糖共转运体-2(SGLT2)抑制剂是一类最初为治疗糖尿病而开发的药物,由于其具有调节这些病理生理过程的潜力,在包括 PAH 在内的心血管疾病中的作用正日益受到关注。在这篇综述中,我们系统地研究了来自基础和临床研究的大量证据,这些证据描述了 SGLT2 抑制剂对心血管健康的影响,并特别强调了 PAH。通过深入探讨这些药物与 PH 潜在病理生物学之间复杂的相互作用,本研究试图揭示 SGLT2 抑制剂作为 PAH 新型治疗方法的机理基础。我们整理的研究结果说明了 SGLT2 抑制剂如何影响肺动脉的正常功能,并可能减轻 PAH 的病理特征,如炎症、氧化应激、细胞异常增殖等。我们的综述由此勾勒出 PAH 治疗的潜在范式转变,表明这些抑制剂可以通过针对驱动疾病的潜在功能障碍,在调节疾病进展方面发挥关键作用。对现有研究的全面综述强调了进一步临床试验的迫切需要,以验证 SGLT2 抑制剂在 PAH 中的疗效,并将其纳入针对这种挑战性疾病的治疗药物中。
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引用次数: 0
G protein-coupled receptor (GPCR) pharmacogenomics. G 蛋白偶联受体 (GPCR) 药物基因组学。
IF 6.6 2区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-08-09 DOI: 10.1080/10408363.2024.2358304
Miles D Thompson, David Reiner-Link, Alessandro Berghella, Brinda K Rana, G Enrico Rovati, Valerie Capra, Caroline M Gorvin, Alexander S Hauser

The field of pharmacogenetics, the investigation of the influence of one or more sequence variants on drug response phenotypes, is a special case of pharmacogenomics, a discipline that takes a genome-wide approach. Massively parallel, next generation sequencing (NGS), has allowed pharmacogenetics to be subsumed by pharmacogenomics with respect to the identification of variants associated with responders and non-responders, optimal drug response, and adverse drug reactions. A plethora of rare and common naturally-occurring GPCR variants must be considered in the context of signals from across the genome. Many fundamentals of pharmacogenetics were established for G protein-coupled receptor (GPCR) genes because they are primary targets for a large number of therapeutic drugs. Functional studies, demonstrating likely-pathogenic and pathogenic GPCR variants, have been integral to establishing models used for in silico analysis. Variants in GPCR genes include both coding and non-coding single nucleotide variants and insertion or deletions (indels) that affect cell surface expression (trafficking, dimerization, and desensitization/downregulation), ligand binding and G protein coupling, and variants that result in alternate splicing encoding isoforms/variable expression. As the breadth of data on the GPCR genome increases, we may expect an increase in the use of drug labels that note variants that significantly impact the clinical use of GPCR-targeting agents. We discuss the implications of GPCR pharmacogenomic data derived from the genomes available from individuals who have been well-phenotyped for receptor structure and function and receptor-ligand interactions, and the potential benefits to patients of optimized drug selection. Examples discussed include the renin-angiotensin system in SARS-CoV-2 (COVID-19) infection, the probable role of chemokine receptors in the cytokine storm, and potential protease activating receptor (PAR) interventions. Resources dedicated to GPCRs, including publicly available computational tools, are also discussed.

药物遗传学是研究一种或多种序列变异对药物反应表型影响的领域,是药物基因组学的一个特例,而药物基因组学是一门采用全基因组方法的学科。大规模并行的下一代测序(NGS)技术使药物遗传学在确定与应答者和非应答者、最佳药物应答和药物不良反应相关的变异方面被药物基因组学所取代。大量罕见和常见的天然 GPCR 变异必须结合来自整个基因组的信号加以考虑。药物遗传学的许多基本原理都是针对 G 蛋白偶联受体(GPCR)基因建立的,因为它们是大量治疗药物的主要靶点。功能研究显示了可能致病和致病的 GPCR 变异,这些研究对于建立用于硅分析的模型不可或缺。GPCR 基因变异包括编码和非编码单核苷酸变异、插入或缺失(indels),这些变异会影响细胞表面表达(贩运、二聚化和脱敏/下调)、配体结合和 G 蛋白耦合,以及导致编码异构体/变异表达的交替剪接的变异。随着 GPCR 基因组数据广度的增加,我们可能会期待更多药物标签的使用,这些标签会注明对 GPCR 靶向药物的临床使用有重大影响的变异。我们讨论了 GPCR 药物基因组学数据的意义,这些数据来源于已对受体结构和功能以及受体-配体相互作用进行了良好表型的个体的基因组,以及优化药物选择给患者带来的潜在益处。讨论的例子包括 SARS-CoV-2 (COVID-19) 感染中的肾素-血管紧张素系统、趋化因子受体在细胞因子风暴中的可能作用以及潜在的蛋白酶激活受体 (PAR) 干预。此外,还讨论了专门用于 GPCR 的资源,包括可公开获得的计算工具。
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引用次数: 0
Regulatory roles of RNA methylation in vascular lesions in ocular and cardiopulmonary diseases. RNA 甲基化在眼部和心肺疾病血管病变中的调节作用。
IF 6.6 2区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-07-03 DOI: 10.1080/10408363.2024.2370267
Siyi Liu, Yunshan Cao, Yan Zhang

RNA methylation is a widespread regulatory mechanism that controls gene expression in physiological processes. In recent years, the mechanisms and functions of RNA methylation under diseased conditions have been increasingly unveiled by RNA sequencing technologies with large scale and high resolution. In this review, the fundamental concept of RNA methylation is introduced, and the common types of transcript methylation and their machineries are described. Then, the regulatory roles of RNA methylation, particularly N6-methyladenosine and 5-methylcytosine, in the vascular lesions of ocular and cardiopulmonary diseases are discussed and compared. The ocular diseases include corneal neovascularization, retinopathy of prematurity, diabetic retinopathy, and pathologic myopia; whereas the cardiopulmonary ailments involve atherosclerosis and pulmonary hypertension. This review hopes to shed light on the common regulatory mechanisms underlying the vascular lesions in these ocular and cardiopulmonary diseases, which may be conducive to developing therapeutic strategies in clinical practice.

RNA 甲基化是控制生理过程中基因表达的一种广泛调控机制。近年来,大规模、高分辨率的 RNA 测序技术越来越多地揭示了 RNA 甲基化在疾病条件下的机制和功能。本综述介绍了 RNA 甲基化的基本概念,描述了常见的转录本甲基化类型及其机制。然后,讨论并比较了 RNA 甲基化,尤其是 N6-甲基腺苷和 5-甲基胞嘧啶,在眼部和心肺疾病血管病变中的调控作用。眼部疾病包括角膜新生血管、早产儿视网膜病变、糖尿病视网膜病变和病理性近视;而心肺疾病则包括动脉粥样硬化和肺动脉高压。本综述希望阐明这些眼科和心肺疾病血管病变的共同调控机制,从而有助于在临床实践中制定治疗策略。
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引用次数: 0
Methods applied to neonatal dried blood spot samples for secondary research purposes: a scoping review. 用于新生儿干血斑样本二次研究的方法:范围界定综述。
IF 6.6 2区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-06-10 DOI: 10.1080/10408363.2024.2360996
Jordan Canning, Rona J Strawbridge, Zosia Miedzybrodzka, Riccardo E Marioni, Mads Melbye, David J Porteous, Matthew E Hurles, Naveed Sattar, Cathie L M Sudlow, Rory Collins, Sandosh Padmanabhan, Jill P Pell

This scoping review aimed to synthesize the analytical techniques used and methodological limitations encountered when undertaking secondary research using residual neonatal dried blood spot (DBS) samples. Studies that used residual neonatal DBS samples for secondary research (i.e. research not related to newborn screening for inherited genetic and metabolic disorders) were identified from six electronic databases: Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Medline, PubMed and Scopus. Inclusion was restricted to studies published from 1973 and written in or translated into English that reported the storage, extraction and testing of neonatal DBS samples. Sixty-seven studies were eligible for inclusion. Included studies were predominantly methodological in nature and measured various analytes, including nucleic acids, proteins, metabolites, environmental pollutants, markers of prenatal substance use and medications. Neonatal DBS samples were stored over a range of temperatures (ambient temperature, cold storage or frozen) and durations (two weeks to 40.5 years), both of which impacted the recovery of some analytes, particularly amino acids, antibodies and environmental pollutants. The size of DBS sample used and potential contamination were also cited as methodological limitations. Residual neonatal DBS samples retained by newborn screening programs are a promising resource for secondary research purposes, with many studies reporting the successful measurement of analytes even from neonatal DBS samples stored for long periods of time in suboptimal temperatures and conditions.

本范围综述旨在总结利用残留新生儿干血斑(DBS)样本进行二次研究时所使用的分析技术和遇到的方法限制。从六个电子数据库中找出了使用新生儿残留干血斑样本进行二次研究(即与新生儿遗传和代谢疾病筛查无关的研究)的研究:Cochrane Library、Cumulative Index to Nursing and Allied Health Literature (CINAHL)、Embase、Medline、PubMed 和 Scopus。纳入的研究仅限于 1973 年以来发表的、用英语撰写或翻译成英语的、报告新生儿 DBS 样本的储存、提取和测试的研究。共有 67 项研究符合纳入条件。所纳入的研究主要是方法学性质的,测量了各种分析物,包括核酸、蛋白质、代谢物、环境污染物、产前药物使用标记物和药物。新生儿 DBS 样本的保存温度(环境温度、冷藏或冷冻)和保存时间(两周到 40.5 年)各不相同,这都会影响某些分析物的回收率,尤其是氨基酸、抗体和环境污染物。使用的 DBS 样本的大小和潜在的污染也被认为是方法学上的局限性。新生儿筛查项目保留的残留新生儿 DBS 样本是一种很有希望用于二次研究的资源,许多研究报告称,即使是在不理想的温度和条件下长期储存的新生儿 DBS 样本也能成功测量出分析物。
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Critical reviews in clinical laboratory sciences
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