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Long non-coding and circular RNAs in osteoporosis: Translation to clinical practice. 骨质疏松症中的长非编码 RNA 和环状 RNA:转化为临床实践。
Pub Date : 2024-01-01 Epub Date: 2024-06-25 DOI: 10.1016/bs.acc.2024.06.007
Martina Faraldi, Paola Maroni, Marta Gomarasca, Veronica Sansoni, Giuseppe Banfi, Giovanni Lombardi

Non-coding RNAs (ncRNAs) belong to a class of untranslated nucleic acids involved in regulation of gene expression. ncRNAs are categorized as small (<200 ribonucleotides in length), i.e., microRNAs (miRNAs), and long ncRNAs (lncRNAs) (200 to thousands of ribonucleotides in length) and circular RNAs (circRNAs). In contrast to miRNAs, the roles of lncRNAs in general and circRNAs in bone metabolism specifically are not well understood. As such, a comprehensive understanding of these RNA species in bone turnover could be of great value in the development of new diagnostic tools and therapeutic targets. Unfortunately, measurement of these unique RNAs lacks standardization, a component critical to clinical translation. This review examines the potential role of lncRNA and circRNA as bone biomarkers, the need for validated and standardized measurement and challenges thereof.

非编码 RNA(ncRNA)属于参与基因表达调控的一类非翻译核酸。
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引用次数: 0
Molecular biology of SARS-CoV-2 and techniques of diagnosis and surveillance. SARS-CoV-2 的分子生物学以及诊断和监测技术。
Pub Date : 2024-01-01 Epub Date: 2023-12-14 DOI: 10.1016/bs.acc.2023.11.003
Takayuki Ishige

The World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19), a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a global pandemic in March 2020. Reverse transcription-polymerase chain reaction (RT-PCR) is the reference technique for molecular diagnosis of SARS-CoV-2 infection. The SARS-CoV-2 virus is constantly mutating, and more transmissible variants have emerged, making genomic surveillance a crucial tool for investigating virus transmission dynamics, detecting novel genetic variants, and assessing mutation impact. The S gene, which encodes the spike protein, is frequently mutated, and it plays an important role in transmissibility. Spike protein mutations affect infectivity and vaccine effectiveness. SARS-CoV-2 variants are tracked using whole genome sequencing (WGS) and S-gene analysis. WGS, Sanger sequencing, and many S-gene-targeted RT-PCR methods have been developed. WGS and Sanger sequencing are standard methods for detecting mutations and can be used to identify known and unknown mutations. Melting curve analysis, endpoint genotyping assay, and S-gene target failure are used in the RT-PCR-based method for the rapid detection of specific mutations in SARS-CoV-2 variants. Therefore, these assays are suitable for high-throughput screening. The combinatorial use of RT-PCR-based assays, Sanger sequencing, and WGS enables rapid and accurate tracking of SARS-CoV-2 variants. In this review, we described RT-PCR-based detection and surveillance techniques for SARS-CoV-2.

世界卫生组织(WHO)于 2020 年 3 月宣布由严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)引起的 2019 年冠状病毒病(COVID-19)为全球大流行病。逆转录聚合酶链反应(RT-PCR)是分子诊断 SARS-CoV-2 感染的参考技术。SARS-CoV-2 病毒不断变异,出现了更多可传播的变种,因此基因组监测成为研究病毒传播动态、检测新型基因变种和评估变异影响的重要工具。编码尖峰蛋白的 S 基因经常发生变异,它在传播性方面发挥着重要作用。尖峰蛋白变异会影响感染性和疫苗效果。利用全基因组测序(WGS)和 S 基因分析追踪 SARS-CoV-2 变异。目前已开发出 WGS、Sanger 测序和许多 S 基因靶向 RT-PCR 方法。WGS 和 Sanger 测序是检测突变的标准方法,可用于识别已知和未知突变。基于 RT-PCR 的方法中使用了熔解曲线分析、终点基因分型检测和 S 基因靶向失败等方法,用于快速检测 SARS-CoV-2 变异株中的特定突变。因此,这些检测方法适用于高通量筛选。将基于 RT-PCR 的检测方法、Sanger 测序和 WGS 结合使用,可以快速准确地追踪 SARS-CoV-2 变体。在这篇综述中,我们介绍了基于 RT-PCR 的 SARS-CoV-2 检测和监控技术。
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引用次数: 0
Advances in familial hypercholesterolemia. 家族性高胆固醇血症的研究进展。
Pub Date : 2024-01-01 Epub Date: 2024-03-06 DOI: 10.1016/bs.acc.2024.02.004
Martine Paquette, Alexis Baass

Familial hypercholesterolemia (FH), a semi-dominant genetic disease affecting more than 25 million people worldwide, is associated with severe hypercholesterolemia and premature atherosclerotic cardiovascular disease. Over the last decade, advances in data analysis, screening, diagnosis and cardiovascular risk stratification has significantly improved our ability to deliver precision medicine for these patients. Furthermore, recent updates on guideline recommendations and new therapeutic approaches have also proven to be highly beneficial. It is anticipated that both ongoing and upcoming clinical trials will offer further insights for the care and treatment of FH patients.

家族性高胆固醇血症(FH)是一种半显性遗传疾病,影响着全球超过 2500 万人,与严重的高胆固醇血症和过早的动脉粥样硬化性心血管疾病相关。过去十年间,数据分析、筛查、诊断和心血管风险分层方面的进步大大提高了我们为这些患者提供精准医疗的能力。此外,最近更新的指南建议和新的治疗方法也被证明是非常有益的。预计正在进行和即将进行的临床试验将为 FH 患者的护理和治疗提供更多启示。
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引用次数: 0
Biomarkers of minimal residual disease and treatment. 极小残留病和治疗的生物标志物。
Pub Date : 2024-01-01 Epub Date: 2024-02-24 DOI: 10.1016/bs.acc.2024.02.002
Nigel P Murray

Minimal residual disease (MRD) has been defined as a very small numbers of cancer cells that remain in the body after curative treatment. Its presence or absence will ultimately determine prognosis. With the introduction of new technologies the presence of MRD in patients with solid tumours can be detected and characterized. As MRD predicts future relapse, be it early or late treatment failure, in an otherwise asymptomatic patient its treatment and when to start treatment remains to be determined. Thus the concepts of personalized medicine using different biomarkers to classify the biological properties of MRD maybe come possible. Based on this determinations it may be possible to use targeted therapies rather than all patients with the same type of cancer receiving a standard treatment. However, it is important to understand the limitations of the different technologies, what these techniques are detecting and how they may help in the treatment of patients with cancer. The majority of published studies are in patients with metastatic cancer and there are few reports in patients with MRD. In this chapter the concept of MRD, the methods used to detect it and what treatments may be effective based on the biological characteristics of the tumour cells as determined by different biomarkers is reviewed. MRD depends on the phenotypic properties of the tumour cells to survive in their new environment and the anti-tumour immune response. This is a dynamic process and changes with time in the wake of immunosuppression caused by the tumour cells and/or the effects of treatment to select resistant tumour cells. With the use of biomarkers to typify the characteristics of MRD and the development of new drugs a personalized treatment can be designed rather than all patients given the same treatment. Patients who are initially negative for MRD may not require further treatment with liquid biopsies used to monitor the patients during follow-up in order to detect those patients who may become MRD positive. The liquid biopsy used during the follow up of MRD positive patients can be used to detect changes in the biological properties of the tumour cells and thus may need treatment changes to overcome tumour cell resistance.

最小残留病(MRD)被定义为治愈性治疗后仍留在体内的极少量癌细胞。它的存在与否将最终决定预后。随着新技术的引入,实体瘤患者体内是否存在 MRD 可以被检测出来并加以定性。由于 MRD 可以预测未来的复发(无论是早期还是晚期治疗失败),因此对于无症状的患者,其治疗方法和何时开始治疗仍有待确定。因此,利用不同的生物标志物对 MRD 的生物特性进行分类,或许可以实现个性化医疗的概念。在此基础上,就有可能使用靶向疗法,而不是让所有同类癌症患者都接受标准疗法。不过,重要的是要了解不同技术的局限性、这些技术能检测出什么以及它们如何帮助治疗癌症患者。已发表的研究大多针对转移性癌症患者,而针对 MRD 患者的报告却很少。本章将回顾 MRD 的概念、用于检测 MRD 的方法以及根据不同生物标记物确定的肿瘤细胞生物学特征可能有效的治疗方法。MRD取决于肿瘤细胞在新环境中生存的表型特性和抗肿瘤免疫反应。这是一个动态过程,会随着肿瘤细胞造成的免疫抑制和/或选择抗性肿瘤细胞的治疗效果而发生变化。通过使用生物标志物对 MRD 的特征进行分型,并开发新的药物,可以设计出个性化的治疗方法,而不是对所有患者进行相同的治疗。最初MRD呈阴性的患者可能不需要进一步治疗,但在随访过程中需要使用液体活检对患者进行监测,以发现那些MRD可能呈阳性的患者。MRD 阳性患者随访期间使用的液体活检可用于检测肿瘤细胞生物特性的变化,因此可能需要改变治疗方法以克服肿瘤细胞的抗药性。
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引用次数: 0
suPAR in cardiovascular disease. 心血管疾病中的 suPAR。
Pub Date : 2024-01-01 Epub Date: 2024-04-25 DOI: 10.1016/bs.acc.2024.04.005
Jaya Montecillo, Thomas Pirker, Christopher Pemberton, Janice Chew-Harris

Soluble urokinase plasminogen activator receptor (suPAR), the soluble counterpart of urokinase plasminogen activator receptor, is found in the circulation at various levels. suPAR and its parent molecule, cell surface uPAR, exhibit similar structure and extracellular functional roles facilitating fibrinolysis, cellular adhesion, and migration. Studies have assessed the correlation between suPAR in cardiovascular disease (CVD). It is postulated that suPAR may serve as an indicator of inflammatory activation and burden during CVD progression. Increased suPAR independently predicts poorer outcomes in acute coronary syndromes, in heart failure, as well as in coronary artery disease and atherosclerosis. To guide translation into clinical utization, suPAR has been assessed in numerous CVD settings for improved risk discrimination independently or in association with established traditional risk factors. Whilst the involvement of suPAR has been explored in other diseases such as kidney diseases and cancer, there is only emerging evidence of suPAR's mechanistic involvement in cardiovascular disease. In this review, we provide a background into suPAR and its potential role as a biomarker in CVD.

可溶性尿激酶纤溶酶原激活物受体(suPAR)是尿激酶纤溶酶原激活物受体的可溶性对应物,存在于血液循环的各个层面。suPAR与其母体分子--细胞表面uPAR--具有相似的结构和细胞外功能作用,可促进纤维蛋白溶解、细胞粘附和迁移。研究评估了 suPAR 与心血管疾病(CVD)之间的相关性。据推测,suPAR 可作为心血管疾病进展过程中炎症激活和负担的指标。suPAR 的增加可独立预测急性冠状动脉综合征、心力衰竭以及冠状动脉疾病和动脉粥样硬化的不良预后。为了指导临床应用,已在许多心血管疾病环境中对 suPAR 进行了评估,以提高其独立或与既定传统风险因素相关的风险识别能力。虽然 suPAR 参与肾脏疾病和癌症等其他疾病的研究,但目前只有新的证据表明 suPAR 参与心血管疾病的机理。在这篇综述中,我们将介绍 suPAR 的背景及其作为心血管疾病生物标志物的潜在作用。
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引用次数: 0
Osteopontin in cancer. 癌症中的骨蛋白
Pub Date : 2024-01-01 Epub Date: 2024-01-06 DOI: 10.1016/bs.acc.2023.11.002
Alpana Kumari, Dharambir Kashyap, Vivek Kumar Garg

Osteopontin (OPN) is a heavily post-translationally modified protein with a molecular weight of 44-70 kDa, depending on the degree of glycosylation. OPN is involved in various biological processes, including bone remodeling, immune response, cell adhesion, migration, and survival. It is essential for controlling osteoclast and osteoblast activity for maintaining bone mass and bone strength. Additionally, OPN has been linked to cardiovascular, inflammatory illnesses, as well as the onset and progression of cancer. OPN is a multifunctional protein that can interact with a variety of cell surface receptors, such as integrins, CD44, the urokinase-type plasminogen activator receptor (uPAR), as well as extracellular matrix (ECM) components (e.g. collagen and hydroxyapatite). These interactions contribute to its wide range of biological functions in general and has significant implications for bone biology, immunology and cancer, specifically. In this chapter, we summarize the structure of OPN with a focus on its molecular mechanisms of action in various cancers.

骨化蛋白(OPN)是一种经过大量翻译后修饰的蛋白质,分子量为 44-70 kDa,具体取决于糖基化程度。OPN 参与各种生物过程,包括骨重塑、免疫反应、细胞粘附、迁移和存活。它对控制破骨细胞和成骨细胞的活动以保持骨量和骨强度至关重要。此外,OPN 还与心血管疾病、炎症以及癌症的发生和发展有关。OPN 是一种多功能蛋白质,可与多种细胞表面受体相互作用,如整合素、CD44、尿激酶型纤溶酶原激活剂受体(uPAR)以及细胞外基质(ECM)成分(如胶原蛋白和羟基磷灰石)。这些相互作用有助于其广泛的生物功能,特别是对骨生物学、免疫学和癌症具有重要影响。在本章中,我们将总结 OPN 的结构,重点介绍其在各种癌症中的分子作用机制。
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引用次数: 0
New markers in chronic obstructive pulmonary disease. 慢性阻塞性肺病的新指标。
Pub Date : 2024-01-01 Epub Date: 2024-07-03 DOI: 10.1016/bs.acc.2024.06.001
Yonca Senem Akdeniz, Seda Özkan

Chronic obstructive pulmonary disease (COPD), a global healthcare and socioeconomic burden, is a multifaceted respiratory disorder that results in substantial decline in health status and life quality. Acute exacerbations of the disease contribute significantly to increased morbidity and mortality. Consequently, the identification of reliable and effective biomarkers for rapid diagnosis, prediction, and prognosis of exacerbations is imperative. In addition, biomarkers play a crucial role in monitoring responses to therapeutic interventions and exploring innovative treatment strategies. Although established markers such as CRP, fibrinogen and neutrophil count are routinely used, a universal marker is lacking. Fortunately, an increasing number of studies based on next generation analytics have explored potential biomarkers in COPD. Here we review those advances and the need for standardized validation studies in the appropriate clinical setting.

慢性阻塞性肺疾病(COPD)是一种多发性呼吸系统疾病,会导致健康状况和生活质量大幅下降,是全球医疗保健和社会经济的负担。疾病的急性加重会大大增加发病率和死亡率。因此,为快速诊断、预测和预后病情加重而鉴定可靠有效的生物标志物势在必行。此外,生物标志物在监测治疗干预反应和探索创新治疗策略方面也发挥着至关重要的作用。虽然 CRP、纤维蛋白原和中性粒细胞计数等已确立的标志物已被常规使用,但仍缺乏通用的标志物。幸运的是,越来越多基于新一代分析技术的研究探索了慢性阻塞性肺病的潜在生物标志物。在此,我们回顾了这些进展以及在适当的临床环境中进行标准化验证研究的必要性。
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引用次数: 0
A spotlight on the aged pulmonary artery. 聚焦老年肺动脉。
Pub Date : 2024-01-01 Epub Date: 2024-06-20 DOI: 10.1016/bs.acc.2024.06.006
Dalma Horvat, Lucia Agoston-Coldea

The ever-increasing life expectancy of the global population introduces a critical perspective on the impact of aging as an immutable cardiovascular risk factor, particularly manifesting in the alterations observed in the pulmonary artery (PA). Mechanisms contributing to aging-induced changes in PA include endothelial dysfunction, chronic inflammation, and structural changes in the arterial wall over time. These alterations extend beyond mere elasticity, exerting profound effects on pulmonary hemodynamics. The propensity of PAs to develop atherosclerotic plaques underscores an intriguing facet of vascular aging, although the available literature is currently insufficient to comprehensively assess their true incidence. While recognizing the inherent risk of periprocedural complications, right heart catheterization (RHC) stands out as the gold standard for precise hemodynamic evaluation. Echocardiography, a widely employed method, proves valuable for screening pulmonary hypertension (PH), yet falls short of diagnostic capability. Technological advancements usher in a new era with non-invasive modalities such as cardiac magnetic resonance (CMR) imaging emerging as promising tools. These innovations demonstrate their prowess in providing accurate assessments of PA stiffness and hemodynamics, offering a glimpse into the future landscape of diagnostic methodologies. As we navigate the intersection of aging and pulmonary vascular health, this review aims to address mechanisms and techniques for assessing PA aging, highlighting the need for comprehensive assessments to guide clinical decision making in an increasingly aging population.

随着全球人口预期寿命的不断延长,老龄化作为一种不可改变的心血管风险因素,其影响尤其体现在肺动脉(PA)的变化上,这为我们提供了一个重要的视角。导致肺动脉老化引起变化的机制包括内皮功能障碍、慢性炎症和动脉壁结构的长期变化。这些变化不仅仅是弹性的变化,还会对肺血流动力学产生深远影响。肺动脉瓣有形成动脉粥样硬化斑块的倾向,这凸显了血管老化的一个耐人寻味的方面,尽管目前现有的文献还不足以全面评估其真实发生率。右心导管检查(RHC)固然存在围手术期并发症的固有风险,但却是精确评估血液动力学的黄金标准。超声心动图作为一种广泛使用的方法,被证明对肺动脉高压(PH)的筛查很有价值,但在诊断能力方面仍有不足。技术进步开创了一个新时代,心脏磁共振(CMR)成像等无创模式成为前景广阔的工具。这些创新技术在提供 PA 硬度和血流动力学的准确评估方面表现出了卓越的能力,让我们看到了诊断方法的未来前景。在我们探索老龄化与肺血管健康的交叉点时,本综述旨在探讨评估 PA 老化的机制和技术,强调在人口日益老龄化的情况下,需要进行全面评估以指导临床决策。
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引用次数: 0
Uric acid en route to gout. 尿酸导致痛风。
Pub Date : 2023-01-01 Epub Date: 2023-06-07 DOI: 10.1016/bs.acc.2023.05.003
Wei-Zheng Zhang

Gout and hyperuricemia (HU) have generated immense attention due to increased prevalence. Gout is a multifactorial metabolic and inflammatory disease that occurs when increased uric acid (UA) induce HU resulting in monosodium urate (MSU) crystal deposition in joints. However, gout pathogenesis does not always involve these events and HU does not always cause a gout flare. Treatment with UA-lowering therapeutics may not prevent or reduce the incidence of gout flare or gout-associated comorbidities. UA exhibits both pro- and anti-inflammation functions in gout pathogenesis. HU and gout share mechanistic and metabolic connections at a systematic level, as shown by studies on associated comorbidities. Recent studies on the interplay between UA, HU, MSU and gout as well as the development of HU and gout in association with metabolic syndromes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular, renal and cerebrovascular diseases are discussed. This review examines current and potential therapeutic regimens and illuminates the journey from disrupted UA to gout.

痛风和高尿酸血症(HU)由于患病率的增加而引起了极大的关注。痛风是一种多因素代谢和炎症性疾病,当尿酸(UA)升高诱导HU导致关节中单钠尿酸盐(MSU)晶体沉积时就会发生。然而,痛风的发病机制并不总是涉及这些事件,HU也不总是导致痛风发作。降低UA治疗可能无法预防或降低痛风发作或痛风相关合并症的发生率。UA在痛风发病机制中表现出促炎和抗炎功能。如相关合并症的研究所示,HU和痛风在系统水平上有着共同的机制和代谢联系。讨论了UA、HU、MSU与痛风之间的相互作用,以及HU和痛风与代谢综合征、非酒精性脂肪肝(NAFLD)以及心血管、肾脏和脑血管疾病的发展。这篇综述考察了目前和潜在的治疗方案,并阐明了从UA紊乱到痛风的过程。
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引用次数: 0
Advances in clinical chemistry patient-based real-time quality control (PBRTQC). 基于患者的临床化学实时质量控制(PBRTQC)研究进展
Pub Date : 2023-01-01 Epub Date: 2023-11-01 DOI: 10.1016/bs.acc.2023.08.003
Mark A Cervinski, Andreas Bietenbeck, Alex Katayev, Tze Ping Loh, Huub H van Rossum, Tony Badrick

Patient-Based Real-Time Quality Control involves monitoring an assay using patient samples rather than external material. If the patient population does not change, then a shift in the long-term assay population results represents the introduction of a change in the assay. The advantages of this approach are that the sample(s) are commutable, it is inexpensive, the rules are simple to interpret and there is virtually continuous monitoring of the assay. The disadvantages are that the laboratory needs to understand their patient population and how they may change during the day, week or year and the initial change of mindset required to adopt the system. The concept is not new, having been used since the 1960s and widely adopted on hematology analyzers in the mid-1970s. It was not widely used in clinical chemistry as there were other stable quality control materials available. However, the limitations of conventional quality control approaches have become more evident. There is a greater understanding of how to collect and use patient data in real time and a range of powerful algorithms which can identify changes in assays. There are more assays on more samples being run. There is also a greater interest in providing a theoretical basis for the validation and integration of these techniques into routine practice.

基于患者的实时质量控制包括使用患者样本而不是外部材料来监测检测。如果患者群体没有变化,那么长期测定人群结果的变化代表了测定方法的变化。这种方法的优点是样品是可交换的,价格低廉,规则易于解释,并且几乎可以连续监测分析。缺点是,实验室需要了解他们的患者群体,以及他们在一天、一周或一年中可能发生的变化,以及采用该系统所需的心态的初步变化。这个概念并不新鲜,自20世纪60年代以来一直在使用,并在20世纪70年代中期广泛应用于血液分析仪。由于没有其他稳定的质量控制材料,在临床化学中没有广泛应用。然而,传统的质量控制方法的局限性已经变得更加明显。人们对如何实时收集和使用患者数据有了更深入的了解,并有一系列强大的算法可以识别分析中的变化。对更多的样本进行更多的分析。还有一个更大的兴趣是为这些技术的验证和集成到日常实践中提供理论基础。
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引用次数: 0
期刊
Advances in clinical chemistry
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