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Insights into the sperm chromatin and implications for male infertility from a protein perspective. 从蛋白质的角度深入了解精子染色质及其对男性不育的影响。
IF 3.1 3区 医学 Q2 Medicine Pub Date : 2023-03-01 DOI: 10.1002/wsbm.1588
Alberto de la Iglesia, Meritxell Jodar, Rafael Oliva, Judit Castillo

Male germ cells undergo an extreme but fascinating process of chromatin remodeling that begins in the testis during the last phase of spermatogenesis and continues through epididymal sperm maturation. Most of the histones are replaced by small proteins named protamines, whose high basicity leads to a tight genomic compaction. This process is epigenetically regulated at many levels, not only by posttranslational modifications, but also by readers, writers, and erasers, in a context of a highly coordinated postmeiotic gene expression program. Protamines are key proteins for acquiring this highly specialized chromatin conformation, needed for sperm functionality. Interestingly, and contrary to what could be inferred from its very specific DNA-packaging function across protamine-containing species, human sperm chromatin contains a wide spectrum of protamine proteoforms, including truncated and posttranslationally modified proteoforms. The generation of protamine knock-out models revealed not only chromatin compaction defects, but also collateral sperm alterations contributing to infertile phenotypes, evidencing the importance of sperm chromatin protamination toward the generation of a new individual. The unique features of sperm chromatin have motivated its study, applying from conventional to the most ground-breaking techniques to disentangle its peculiarities and the cellular mechanisms governing its successful conferment, especially relevant from the protein point of view due to the important epigenetic role of sperm nuclear proteins. Gathering and contextualizing the most striking discoveries will provide a global understanding of the importance and complexity of achieving a proper chromatin compaction and exploring its implications on postfertilization events and beyond. This article is categorized under: Reproductive System Diseases > Genetics/Genomics/Epigenetics Reproductive System Diseases > Molecular and Cellular Physiology.

男性生殖细胞经历了一个极端而迷人的染色质重塑过程,这个过程始于精子发生的最后阶段,一直持续到附睾精子成熟。大多数组蛋白被称为精蛋白的小蛋白质所取代,其高碱度导致基因组紧密压实。在减数分裂后基因表达程序高度协调的背景下,这一过程在许多水平上受到表观遗传调控,不仅通过翻译后修饰,还通过读取器、写入器和擦除器。精氨酸是获得这种高度特化的染色质构象的关键蛋白质,是精子功能所必需的。有趣的是,与从含有鱼精蛋白的物种中其非常特殊的dna包装功能推断的相反,人类精子染色质含有广泛的鱼精蛋白蛋白形式,包括截断和翻译后修饰的蛋白质形式。鱼精蛋白敲除模型的产生不仅揭示了染色质压实缺陷,而且还揭示了导致不育表型的附带精子改变,证明了精子染色质蛋白化对新个体产生的重要性。精子染色质的独特特征激发了它的研究,从传统到最具突破性的技术来解开它的特性和控制其成功授予的细胞机制,特别是从蛋白质的角度来看,由于精子核蛋白的重要表观遗传作用。收集和背景下最引人注目的发现将提供实现适当的染色质压实的重要性和复杂性的全球理解,并探索其对受精后事件和超越的影响。本文分类如下:生殖系统疾病>遗传学/基因组学/表观遗传学生殖系统疾病>分子和细胞生理学。
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引用次数: 6
Beyond the classical amyloid hypothesis in Alzheimer's disease: Molecular insights into current concepts of pathogenesis, therapeutic targets, and study models. 超越阿尔茨海默病的经典淀粉样蛋白假说:对当前发病机制、治疗靶点和研究模型概念的分子见解。
IF 3.1 3区 医学 Q2 Medicine Pub Date : 2023-03-01 DOI: 10.1002/wsbm.1591
Atsadang Theerasri, Sakawrat Janpaijit, Tewin Tencomnao, Anchalee Prasansuklab

Alzheimer's disease (AD) is one of the progressive neurodegenerative disorders and the most common cause of dementia in the elderly worldwide causing difficulties in the daily life of the patient. AD is characterized by the aberrant accumulation of β-amyloid plaques and tau protein-containing neurofibrillary tangles (NFTs) in the brain giving rise to neuroinflammation, oxidative stress, synaptic failure, and eventual neuronal cell death. The total cost of care in AD treatment and related health care activities is enormous and pharmaceutical drugs approved by Food and Drug Administration have not manifested sufficient efficacy in protection and therapy. In recent years, there are growing studies that contribute a fundamental understanding to AD pathogenesis, AD-associated risk factors, and pharmacological intervention. However, greater molecular process-oriented research in company with suitable experimental models is still of the essence to enhance the prospects for AD therapy and cell lines as a disease model are still the major part of this milestone. In this review, we provide an insight into molecular mechanisms, particularly the recent concept in gut-brain axis, vascular dysfunction and autophagy, and current models used in the study of AD. Here, we emphasized the importance of therapeutic strategy targeting multiple mechanisms together with utilizing appropriate models for the discovery of novel effective AD therapy. This article is categorized under: Neurological Diseases > Molecular and Cellular Physiology.

阿尔茨海默病(Alzheimer's disease, AD)是一种进行性神经退行性疾病,是世界范围内老年人痴呆症的最常见病因,给患者的日常生活带来困难。阿尔茨海默病的特点是大脑中β-淀粉样斑块和含tau蛋白的神经原纤维缠结(nft)的异常积累,导致神经炎症、氧化应激、突触衰竭和最终的神经元细胞死亡。阿尔茨海默病治疗和相关卫生保健活动的总护理费用是巨大的,食品药品监督管理局批准的药物在保护和治疗方面没有显示出足够的功效。近年来,越来越多的研究对阿尔茨海默病的发病机制、阿尔茨海默病相关危险因素和药物干预有了基本的认识。然而,更大的分子过程导向研究和合适的实验模型仍然是增强阿尔茨海默病治疗前景的关键,细胞系作为疾病模型仍然是这一里程碑的主要组成部分。在这篇综述中,我们提供了深入了解的分子机制,特别是最近的概念肠脑轴,血管功能障碍和自噬,以及目前用于研究AD的模型。在这里,我们强调了针对多种机制的治疗策略的重要性,并利用适当的模型来发现新的有效的阿尔茨海默病治疗方法。本文分类为:神经系统疾病>分子与细胞生理学。
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引用次数: 3
Comparing RNA-sequencing datasets from astrocytes, oligodendrocytes, and microglia in multiple sclerosis identifies novel dysregulated genes relevant to inflammation and myelination. 比较多发性硬化症中星形胶质细胞、少突胶质细胞和小胶质细胞的rna测序数据集,发现了与炎症和髓鞘形成相关的新的失调基因。
IF 3.1 3区 医学 Q2 Medicine Pub Date : 2023-03-01 DOI: 10.1002/wsbm.1594
Sienna S Drake, Aliyah Zaman, Tristan Simas, Alyson E Fournier

Central nervous system (CNS) inflammation is a key factor in multiple sclerosis (MS). Invasion of peripheral immune cells into the CNS resulting from an unknown signal or combination of signals results in activation of resident immune cells and the hallmark feature of the disease: demyelinating lesions. These lesion sites are an amalgam of reactive peripheral and central immune cells, astrocytes, damaged and dying oligodendrocytes, and injured neurons and axons. Sustained inflammation affects cells directly located within the lesion site and further abnormalities are apparent diffusely throughout normal-appearing white matter and grey matter. It is only relatively recently, using animal models, new tissue sampling techniques, and next-generation sequencing, that molecular changes occurring in CNS resident cells have been broadly captured. Advances in cell isolation through Fluorescence Activated Cell Sorting (FACS) and laser-capture microdissection together with the emergence of single-cell sequencing have enabled researchers to investigate changes in gene expression in astrocytes, microglia, and oligodendrocytes derived from animal models of MS as well as from primary patient tissue. The contribution of some dysregulated pathways has been followed up in individual studies; however, corroborating results often go unreported between sequencing studies. To this end, we have consolidated results from numerous RNA-sequencing studies to identify and review novel patterns of differentially regulated genes and pathways occurring within CNS glial cells in MS. This article is categorized under: Neurological Diseases > Molecular and Cellular Physiology.

中枢神经系统(CNS)炎症是多发性硬化症(MS)的关键因素。由未知信号或信号组合引起的外周免疫细胞侵入中枢神经系统导致常驻免疫细胞的激活和疾病的标志性特征:脱髓鞘病变。这些病变部位是反应性外周和中枢免疫细胞、星形胶质细胞、受损和死亡的少突胶质细胞以及受损的神经元和轴突的混合体。持续的炎症影响直接位于病变部位的细胞,进一步的异常在正常的白质和灰质中弥漫性表现明显。直到最近,使用动物模型、新的组织取样技术和下一代测序技术,才广泛地捕捉到发生在中枢神经系统驻留细胞中的分子变化。通过荧光活化细胞分选(FACS)和激光捕获显微解剖分离细胞的进展,以及单细胞测序的出现,使研究人员能够研究来自多发性硬化症动物模型和原发患者组织的星形胶质细胞、小胶质细胞和少突胶质细胞基因表达的变化。一些失调通路的贡献在个体研究中得到了跟进;然而,在测序研究之间,证实的结果往往没有报道。为此,我们整合了大量rna测序研究的结果,以鉴定和回顾多发性硬化症中中枢神经胶质细胞内发生的差异调节基因和通路的新模式。
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引用次数: 2
In silico modeling for the hepatic circulation and transport: From the liver organ to lobules. 肝脏循环和运输的计算机模拟:从肝器官到小叶。
IF 3.1 3区 医学 Q2 Medicine Pub Date : 2023-03-01 DOI: 10.1002/wsbm.1586
Harvey Ho, Shawn Means, Soroush Safaei, Peter John Hunter

The function of the liver depends critically on its blood supply. Numerous in silico models have been developed to study various aspects of the hepatic circulation, including not only the macro-hemodynamics at the organ level, but also the microcirculation at the lobular level. In addition, computational models of blood flow and bile flow have been used to study the transport, metabolism, and clearance of drugs in pharmacokinetic studies. These in silico models aim to provide insights into the liver organ function under both healthy and diseased states, and to assist quantitative analysis for surgical planning and postsurgery treatment. The purpose of this review is to provide an update on state-of-the-art in silico models of the hepatic circulation and transport processes. We introduce the numerical methods and the physiological background of these models. We also discuss multiscale frameworks that have been proposed for the liver, and their linkage with the large context of systems biology, systems pharmacology, and the Physiome project. This article is categorized under: Metabolic Diseases > Computational Models Metabolic Diseases > Biomedical Engineering Cardiovascular Diseases > Computational Models.

肝脏的功能主要取决于它的血液供应。许多计算机模型已经被开发出来,用于研究肝循环的各个方面,不仅包括器官水平的宏观血流动力学,还包括小叶水平的微循环。此外,在药代动力学研究中,血流和胆汁流量的计算模型已被用于研究药物的转运、代谢和清除。这些计算机模型旨在深入了解健康和患病状态下的肝脏器官功能,并协助定量分析手术计划和术后治疗。本综述的目的是提供最新的最先进的肝脏循环和运输过程的计算机模型。我们介绍了这些模型的数值方法和生理背景。我们还讨论了为肝脏提出的多尺度框架,以及它们与系统生物学、系统药理学和生理组项目的大背景的联系。本文分类如下:代谢疾病>计算模型代谢疾病>生物医学工程心血管疾病>计算模型。
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引用次数: 1
Organoids of the male reproductive system: Challenges, opportunities, and their potential use in fertility research. 男性生殖系统类器官:挑战、机遇及其在生育研究中的潜在应用。
IF 3.1 3区 医学 Q2 Medicine Pub Date : 2023-03-01 DOI: 10.1002/wsbm.1590
Daniela Patrício, Joana Santiago, João F Mano, Margarida Fardilha

Organoids are units of function of a given organ able to reproduce, in culture, a biological structure similar in architecture and function to its counterpart in vivo. Today, it is possible to develop an organoid from a fragment of tissue, a stem cell located in an adult organ, an embryonic stem cell, or an induced pluripotent stem cell. In the past decade, many organoids have been developed which mimic stomach, pancreas, liver and brain tissues, optic cups, among many others. Additionally, different male reproductive system organs have already been developed as organoids, including the prostate and testis. These 3D cultures may be of great importance for urological cancer research and have the potential to be used in fertility research for the study of spermatozoa production and maturation, germ cells-somatic cells interactions, and mechanisms of disease. They also provide an accurate preclinical pipeline for drug testing and discovery, as well as for the study of drug resistance. In this work, we revise the current knowledge on organoid technology and its use in healthcare and research, describe the male reproductive system organoids and other biomaterials already developed, and discuss their current application. Finally, we highlight the research gaps, challenges, and opportunities in the field and propose strategies to improve the use of organoids for the study of male infertility situations. This article is categorized under: Reproductive System Diseases > Stem Cells and Development Reproductive System Diseases > Biomedical Engineering.

类器官是特定器官的功能单位,能够在培养中复制与其体内对应器官在结构和功能上相似的生物结构。如今,从组织碎片、成人器官中的干细胞、胚胎干细胞或诱导多能干细胞中培育出类器官是可能的。在过去的十年里,许多类器官已经被开发出来,它们模仿了胃、胰腺、肝脏和脑组织、视杯等许多其他组织。此外,不同的男性生殖系统器官已经发展成为类器官,包括前列腺和睾丸。这些3D培养物可能对泌尿系统癌症的研究具有重要意义,并有可能用于生殖研究,研究精子的产生和成熟、生殖细胞-体细胞的相互作用以及疾病的机制。它们还为药物测试和发现以及耐药性研究提供了准确的临床前管道。在这项工作中,我们修订了目前关于类器官技术及其在医疗保健和研究中的应用的知识,描述了已经开发的男性生殖系统类器官和其他生物材料,并讨论了它们目前的应用。最后,我们强调了该领域的研究差距、挑战和机遇,并提出了改善类器官在男性不育症研究中的应用的策略。本文分类如下:生殖系统疾病>干细胞与发育生殖系统疾病>生物医学工程。
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引用次数: 5
Determination of the Salmonella intracellular lifestyle by the diversified interaction of Type III secretion system effectors and host GTPases. III型分泌系统效应物与宿主gtpase多种相互作用对沙门氏菌胞内生活方式的影响。
IF 3.1 3区 医学 Q2 Medicine Pub Date : 2023-03-01 DOI: 10.1002/wsbm.1587
Kun Meng, Ping Zhu, Liuliu Shi, Shan Li

Intracellular bacteria have developed sophisticated strategies to subvert the host endomembrane system to establish a stable replication niche. Small GTPases are critical players in regulating each step of membrane trafficking events, such as vesicle biogenesis, cargo transport, tethering, and fusion events. Salmonella is a widely studied facultative intracellular bacteria. Salmonella delivers several virulence proteins, termed effectors, to regulate GTPase dynamics and subvert host trafficking for their benefit. In this review, we summarize an updated and systematic understanding of the interactions between bacterial effectors and host GTPases in determining the intracellular lifestyle of Salmonella. This article is categorized under: Infectious Diseases > Molecular and Cellular Physiology.

胞内细菌已经发展出复杂的策略来破坏宿主的膜系统,以建立一个稳定的复制生态位。小gtpase在调节膜运输事件的每个步骤中都起着关键作用,例如囊泡生物发生、货物运输、系结和融合事件。沙门氏菌是一种被广泛研究的兼性细胞内细菌。沙门氏菌提供了几种毒力蛋白,称为效应物,以调节GTPase动力学和破坏宿主运输为他们的利益。在这篇综述中,我们总结了细菌效应物和宿主gtpase在决定沙门氏菌细胞内生活方式中的相互作用的最新和系统的理解。本文分类为:感染性疾病>分子与细胞生理学。
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引用次数: 0
Neurodegeneration in multiple sclerosis. 多发性硬化症的神经变性。
IF 4.6 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 Epub Date: 2022-08-10 DOI: 10.1002/wsbm.1583
Gabrielle M Mey, Kedar R Mahajan, Tara M DeSilva

Axonal loss in multiple sclerosis (MS) is a key component of disease progression and permanent neurologic disability. MS is a heterogeneous demyelinating and neurodegenerative disease of the central nervous system (CNS) with varying presentation, disease courses, and prognosis. Immunomodulatory therapies reduce the frequency and severity of inflammatory demyelinating events that are a hallmark of MS, but there is minimal therapy to treat progressive disease and there is no cure. Data from patients with MS, post-mortem histological analysis, and animal models of demyelinating disease have elucidated patterns of MS pathogenesis and underlying mechanisms of neurodegeneration. MRI and molecular biomarkers have been proposed to identify predictors of neurodegeneration and risk factors for disease progression. Early signs of axonal dysfunction have come to light including impaired mitochondrial trafficking, structural axonal changes, and synaptic alterations. With sustained inflammation as well as impaired remyelination, axons succumb to degeneration contributing to CNS atrophy and worsening of disease. These studies highlight the role of chronic demyelination in the CNS in perpetuating axonal loss, and the difficulty in promoting remyelination and repair amidst persistent inflammatory insult. Regenerative and neuroprotective strategies are essential to overcome this barrier, with early intervention being critical to rescue axonal integrity and function. The clinical and basic research studies discussed in this review have set the stage for identifying key propagators of neurodegeneration in MS, leading the way for neuroprotective therapeutic development. This article is categorized under: Immune System Diseases > Molecular and Cellular Physiology Neurological Diseases > Molecular and Cellular Physiology.

多发性硬化症(MS)的轴突丢失是疾病进展和永久性神经残疾的关键因素。多发性硬化症是中枢神经系统(CNS)的一种异质性脱髓鞘和神经退行性疾病,表现、病程和预后各不相同。免疫调节疗法可降低作为多发性硬化症标志的炎症性脱髓鞘事件的频率和严重程度,但治疗进展性疾病的疗法很少,而且无法治愈。来自多发性硬化症患者、死后组织学分析和脱髓鞘疾病动物模型的数据阐明了多发性硬化症的发病模式和神经变性的潜在机制。核磁共振成像和分子生物标志物已被提出用于确定神经变性的预测因子和疾病进展的风险因素。轴突功能障碍的早期迹象已经显现,包括线粒体贩运受损、轴突结构变化和突触改变。随着炎症的持续以及再髓鞘化受损,轴突会发生退化,导致中枢神经系统萎缩和疾病恶化。这些研究凸显了中枢神经系统慢性脱髓鞘在轴突缺失中的作用,以及在持续的炎症损伤中促进再髓鞘化和修复的困难。再生和神经保护策略对于克服这一障碍至关重要,早期干预对于挽救轴突的完整性和功能至关重要。本综述中讨论的临床和基础研究为确定多发性硬化症神经退行性变的关键传播因素奠定了基础,为神经保护疗法的开发指明了方向。本文归类于免疫系统疾病 > 分子和细胞生理学 神经系统疾病 > 分子和细胞生理学。
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引用次数: 0
Evolution of precision oncology-guided treatment paradigms. 精准肿瘤指导治疗模式的演变。
IF 3.1 3区 医学 Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1002/wsbm.1585
Ramanuj DasGupta, Aixin Yap, Elena Yong Yaqing, Shumei Chia

Cancer treatment is gradually evolving from the classical use of nonspecific cytotoxic drugs targeting generic mechanisms of cell growth and proliferation. Instead, new "patient-specific treatment paradigms" that are based on an individual patient's tumor-specific molecular features are emerging, and these include "druggable" genomic alterations such as oncogenic driver mutations, downstream activities of cancer-signaling pathways, and the expression of specific genes involved in tumorigenesis and cancer progression. This evolving landscape of making evidence-based treatment decisions forms the foundation of precision oncology, which aims to deliver "the right drug, to the right patient and at the right time". The long-term vision for this approach is to maximize the treatment efficacy while minimizing exposure to ineffective therapy and reducing co-morbidity-related side effects. Successful clinical translation and implementation of this vision have the potential to revolutionize treatment paradigms from predominantly reactive, to more evidence-based, proactive and predictive care. In this article, we review the past and current approaches in precision oncology, and describe their remarkable power and limitations. We also speculate on the evolution of newly emerging methodologies of the future that can be used to address some of the key challenges associated with the existing paradigms. This article is categorized under: Cancer > Genetics/Genomics/Epigenetics Cancer > Molecular and Cellular Physiology Cancer > Computational Models.

癌症治疗正逐渐从传统的使用非特异性细胞毒性药物来靶向一般的细胞生长和增殖机制演变而来。相反,基于个体患者肿瘤特异性分子特征的新的“患者特异性治疗范式”正在出现,其中包括“可药物”的基因组改变,如致癌驱动突变,癌症信号通路的下游活动,以及参与肿瘤发生和癌症进展的特定基因的表达。这种不断发展的以证据为基础的治疗决策构成了精确肿瘤学的基础,其目标是“在正确的时间给正确的病人提供正确的药物”。这种方法的长期目标是最大限度地提高治疗效果,同时最大限度地减少无效治疗的暴露,并减少与合并症相关的副作用。成功的临床翻译和实施这一愿景有可能彻底改变治疗模式,从主要的被动治疗,到更多的循证、主动和预测性护理。在这篇文章中,我们回顾了过去和现在的精确肿瘤学方法,并描述了它们显著的力量和局限性。我们还推测了未来新出现的方法的演变,这些方法可用于解决与现有范式相关的一些关键挑战。本文分类如下:癌症>遗传学/基因组学/表观遗传学癌症>分子和细胞生理学癌症>计算模型。
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引用次数: 3
Computational models for generating microvascular structures: Investigations beyond medical imaging resolution. 生成微血管结构的计算模型:超越医学成像分辨率的研究。
IF 3.1 3区 医学 Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1002/wsbm.1579
Cameron Apeldoorn, Soroush Safaei, Julian Paton, Gonzalo D Maso Talou

Angiogenesis, arteriogenesis, and pruning are revascularization processes essential to our natural vascular development and adaptation, as well as central players in the onset and development of pathologies such as tumoral growth and stroke recovery. Computational modeling allows for repeatable experimentation and exploration of these complex biological processes. In this review, we provide an introduction to the biological understanding of the vascular adaptation processes of sprouting angiogenesis, intussusceptive angiogenesis, anastomosis, pruning, and arteriogenesis, discussing some of the more significant contributions made to the computational modeling of these processes. Each computational model represents a theoretical framework for how biology functions, and with rises in computing power and study of the problem these frameworks become more accurate and complete. We highlight physiological, pathological, and technological applications that can be benefit from the advances performed by these models, and we also identify which elements of the biology are underexplored in the current state-of-the-art computational models. This article is categorized under: Cancer > Computational Models Cardiovascular Diseases > Computational Models.

血管生成、动脉生成和剪枝是血管再生过程中必不可少的自然血管发育和适应过程,也是肿瘤生长和中风恢复等病理发生和发展的核心参与者。计算建模允许对这些复杂的生物过程进行可重复的实验和探索。在这篇综述中,我们介绍了对发芽血管生成、肠套管血管生成、吻合、修剪和动脉生成等血管适应过程的生物学理解,并讨论了对这些过程的计算建模做出的一些更重要的贡献。每个计算模型都代表了生物学如何运作的理论框架,随着计算能力的提高和对问题的研究,这些框架变得更加准确和完整。我们强调了可以从这些模型的进步中受益的生理、病理和技术应用,并且我们还确定了当前最先进的计算模型中未充分探索的生物学要素。本文分类如下:癌症>计算模型心血管疾病>计算模型。
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引用次数: 3
Models of the cardiac L-type calcium current: A quantitative review. 心脏 L 型钙电流模型:定量综述。
IF 4.6 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 Epub Date: 2022-08-26 DOI: 10.1002/wsbm.1581
Aditi Agrawal, Ken Wang, Liudmila Polonchuk, Jonathan Cooper, Maurice Hendrix, David J Gavaghan, Gary R Mirams, Michael Clerx

The L-type calcium current ( I CaL ) plays a critical role in cardiac electrophysiology, and models of I CaL are vital tools to predict arrhythmogenicity of drugs and mutations. Five decades of measuring and modeling I CaL have resulted in several competing theories (encoded in mathematical equations). However, the introduction of new models has not typically been accompanied by a data-driven critical comparison with previous work, so that it is unclear which model is best suited for any particular application. In this review, we describe and compare 73 published mammalian I CaL models and use simulated experiments to show that there is a large variability in their predictions, which is not substantially diminished when grouping by species or other categories. We provide model code for 60 models, list major data sources, and discuss experimental and modeling work that will be required to reduce this huge list of competing theories and ultimately develop a community consensus model of I CaL . This article is categorized under: Cardiovascular Diseases > Computational Models Cardiovascular Diseases > Molecular and Cellular Physiology.

L 型钙电流(I CaL)在心脏电生理学中起着至关重要的作用,I CaL 模型是预测药物和突变致心律失常性的重要工具。五十年来,对 I CaL 的测量和建模产生了多种相互竞争的理论(以数学公式编码)。然而,在引入新模型的同时,通常并没有与之前的工作进行数据驱动的批判性比较,因此目前还不清楚哪种模型最适合任何特定应用。在这篇综述中,我们描述并比较了已发表的 73 个哺乳动物 I CaL 模型,并通过模拟实验表明,这些模型的预测结果存在很大的变异性,按物种或其他类别分组后,这种变异性并没有明显减弱。我们提供了 60 个模型的模型代码,列出了主要的数据来源,并讨论了为减少这一庞大的相互竞争的理论清单并最终开发出一个群体共识的 I CaL 模型所需的实验和建模工作。本文归类为心血管疾病 > 计算模型 心血管疾病 > 分子和细胞生理学。
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引用次数: 0
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