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Comparative Pathogenesis of Severe Acute Respiratory Syndrome Coronaviruses. 严重急性呼吸系统综合征冠状病毒发病机制的比较。
IF 36.2 1区 医学 Q1 Medicine Pub Date : 2024-01-24 Epub Date: 2023-10-13 DOI: 10.1146/annurev-pathol-052620-121224
Jingshu Zhang, Melanie Rissmann, Thijs Kuiken, Bart L Haagmans

Over the last two decades the world has witnessed the global spread of two genetically related highly pathogenic coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. However, the impact of these outbreaks differed significantly with respect to the hospitalizations and fatalities seen worldwide. While many studies have been performed recently on SARS-CoV-2, a comparative pathogenesis analysis with SARS-CoV may further provide critical insights into the mechanisms of disease that drive coronavirus-induced respiratory disease. In this review, we comprehensively describe clinical and experimental observations related to transmission and pathogenesis of SARS-CoV-2 in comparison with SARS-CoV, focusing on human, animal, and in vitro studies. By deciphering the similarities and disparities of SARS-CoV and SARS-CoV-2, in terms of transmission and pathogenesis mechanisms, we offer insights into the divergent characteristics of these two viruses. This information may also be relevant to assessing potential novel introductions of genetically related highly pathogenic coronaviruses.

在过去的二十年里,世界见证了两种基因相关的高致病性冠状病毒的全球传播,即严重急性呼吸综合征冠状病毒(SARS-CoV)和严重急性呼吸系统综合征冠状病毒2型。然而,这些疫情的影响在全球范围内的住院人数和死亡人数方面存在显著差异。尽管最近对严重急性呼吸系统综合征冠状病毒2型进行了许多研究,但与严重急性呼吸系综合征冠状病毒的比较发病机制分析可能会进一步深入了解导致冠状病毒诱导的呼吸道疾病的疾病机制。在这篇综述中,我们全面描述了与严重急性呼吸系统综合征冠状病毒2型的传播和发病机制相关的临床和实验观察,并将重点放在人类、动物和体外研究上。通过解读SARS冠状病毒和严重急性呼吸系统综合征冠状病毒2型在传播和发病机制方面的相似性和差异,我们可以深入了解这两种病毒的不同特征。这些信息也可能与评估基因相关的高致病性冠状病毒的潜在新引入有关。《病理学年度评论:疾病机制》第19卷预计最终在线出版日期为2024年1月。请参阅http://www.annualreviews.org/page/journal/pubdates用于修订估算。
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引用次数: 0
Haploinsufficient Transcription Factors in Myeloid Neoplasms. 髓系肿瘤中的单倍体转录因子。
IF 36.2 1区 医学 Q1 Medicine Pub Date : 2024-01-24 Epub Date: 2023-10-31 DOI: 10.1146/annurev-pathmechdis-051222-013421
Tanner C Martinez, Megan E McNerney

Many transcription factors (TFs) function as tumor suppressor genes with heterozygous phenotypes, yet haploinsufficiency generally has an underappreciated role in neoplasia. This is no less true in myeloid cells, which are normally regulated by a delicately balanced and interconnected transcriptional network. Detailed understanding of TF dose in this circuitry sheds light on the leukemic transcriptome. In this review, we discuss the emerging features of haploinsufficient transcription factors (HITFs). We posit that: (a) monoallelic and biallelic losses can have distinct cellular outcomes; (b) the activity of a TF exists in a greater range than the traditional Mendelian genetic doses; and (c) how a TF is deleted or mutated impacts the cellular phenotype. The net effect of a HITF is a myeloid differentiation block and increased intercellular heterogeneity in the course of myeloid neoplasia.

许多转录因子(TF)作为具有杂合表型的肿瘤抑制基因发挥作用,但单倍性不足在肿瘤形成中的作用通常被低估。骨髓细胞也是如此,它们通常由一个微妙平衡和相互连接的转录网络调节。对TF在该回路中的剂量的详细了解为白血病转录组提供了线索。在这篇综述中,我们讨论了单倍充足转录因子(HITF)的新特点。我们假设:(a)单等位基因和双等位基因缺失可能具有不同的细胞结果;(b) TF的活性存在于比传统孟德尔遗传剂量更大的范围内;和(c)TF如何被删除或突变影响细胞表型。HITF的净作用是髓系分化阻滞和髓系肿瘤过程中细胞间异质性增加。《病理学年度评论:疾病机制》第19卷预计最终在线出版日期为2024年1月。请参阅http://www.annualreviews.org/page/journal/pubdates用于修订估算。
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引用次数: 0
Neurodegenerative Disease Tauopathies. 神经退行性疾病Taopathies。
IF 36.2 1区 医学 Q1 Medicine Pub Date : 2024-01-24 Epub Date: 2023-10-13 DOI: 10.1146/annurev-pathmechdis-051222-120750
Benjamin C Creekmore, Ryohei Watanabe, Edward B Lee

Tauopathies are a diverse group of progressive and fatal neurodegenerative diseases characterized by aberrant tau inclusions in the central nervous system. Tau protein forms pathologic fibrillar aggregates that are typically closely associated with neuronal cell death, leading to varied clinical phenotypes including dementia, movement disorders, and motor neuron disease. In this review, we describe the clinicopathologic features of tauopathies and highlight recent advances in understanding the mechanisms that lead to spread of pathologic aggregates through interconnected neuronal pathways. The cell-to-cell propagation of tauopathy is then linked to posttranslational modifications, tau fibril structural variants, and the breakdown of cellular protein quality control.

tau病是一组进行性和致命的神经退行性疾病,其特征是中枢神经系统中异常的tau内含物。Tau蛋白形成病理性原纤维聚集体,通常与神经元细胞死亡密切相关,导致各种临床表型,包括痴呆、运动障碍和运动神经元疾病。在这篇综述中,我们描述了tau病的临床病理特征,并强调了在理解导致病理聚集体通过相互连接的神经元途径传播的机制方面的最新进展。tau病的细胞间繁殖与翻译后修饰、tau原纤维结构变异和细胞蛋白质质量控制的破坏有关。《病理学年度评论:疾病机制》第19卷预计最终在线出版日期为2024年1月。请参阅http://www.annualreviews.org/page/journal/pubdates用于修订估算。
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引用次数: 0
The Immunobiology and Pathogenesis of Celiac Disease. 乳糜泻的免疫生物学及其发病机制。
IF 36.2 1区 医学 Q1 Medicine Pub Date : 2023-01-24 DOI: 10.1146/annurev-pathmechdis-031521-032634
Rasmus Iversen, Ludvig M Sollid

Among human leukocyte antigen (HLA)-associated disorders, celiac disease has an immunopathogenesis that is particularly well understood. The condition is characterized by hypersensitivity to cereal gluten proteins, and the disease lesion is localized in the gut. Still, the diagnosis can be made by detection of highly disease-specific autoantibodies to transglutaminase 2 in the blood. We now have mechanistic insights into how the disease-predisposing HLA-DQ molecules, via presentation of posttranslationally modified gluten peptides, are connected to the generation of these autoantibodies. This review presents our current understanding of the immunobiology of this common disorder that is positioned in the border zone between food hypersensitivity and autoimmunity.

在人类白细胞抗原(HLA)相关疾病中,乳糜泻的免疫发病机制已被充分了解。这种疾病的特点是对谷物麸质蛋白过敏,疾病病变局限于肠道。尽管如此,可以通过检测血液中针对谷氨酰胺转酶2的高度疾病特异性自身抗体来诊断。通过翻译后修饰的谷蛋白肽的呈现,我们现在有了关于疾病易感性HLA-DQ分子如何与这些自身抗体的产生相关联的机制见解。这篇综述介绍了我们目前对这种常见疾病的免疫生物学理解,这种疾病位于食物过敏和自身免疫之间的边界地带。
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引用次数: 15
My Journey. 我的旅程
IF 36.2 1区 医学 Q1 Medicine Pub Date : 2023-01-24 DOI: 10.1146/annurev-pathmechdis-031621-025854
Lucy Balian Rorke-Adams

This is the life story of Dr. Lucy B. Rorke-Adams, who was raised in the rural Midwest of the United States by Armenian immigrant parents during the Depression. The youngest in a family of five girls, she was lovingly nurtured by her parents and sisters. She was encouraged to become educated in order to lead a worthwhile life and contribute to society. She chose medicine, specifically the specialty of pediatric neuropathology, and over her long career succeeded in advancing the field. In particular, she made major contributions to understanding childhood brain tumors, central nervous system (CNS) malformations, and pathophysiology of abusive CNS injury in infants and children.

这是露西-B-罗克-亚当斯博士的生平故事,大萧条时期,她的父母是亚美尼亚移民,在美国中西部农村长大。她是家中五个女孩中最小的一个,受到父母和姐妹们的悉心养育。他们鼓励她接受教育,以便过上有价值的生活,为社会做出贡献。她选择了医学,特别是小儿神经病理学专业,并在漫长的职业生涯中成功地推动了这一领域的发展。特别是,她在了解儿童脑肿瘤、中枢神经系统(CNS)畸形以及婴幼儿中枢神经系统虐待性损伤的病理生理学方面做出了重大贡献。
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引用次数: 0
New Insights into the Pathogenesis of Mastocytosis: Emerging Concepts in Diagnosis and Therapy. 肥大细胞增多症发病机制的新认识:诊断和治疗的新概念。
IF 36.2 1区 医学 Q1 Medicine Pub Date : 2023-01-24 DOI: 10.1146/annurev-pathmechdis-031521-042618
Peter Valent, Cem Akin, Wolfgang R Sperr, Hans-Peter Horny, Michel Arock, Dean D Metcalfe, Stephen J Galli

Mastocytosis is a heterogeneous group of neoplasms defined by a numerical increase and accumulation of clonal mast cells (MCs) in various organ systems. The disease may present as cutaneous mastocytosis or systemic mastocytosis (SM). On the basis of histopathological and molecular features, clinical variables, and organ involvement, SM is divided into indolent SM, smoldering SM, SM with an associated hematologic neoplasm, aggressive SM, and MC leukemia. Each variant is defined by unique diagnostic criteria and a unique spectrum of clinical presentations. A key driver of MC expansion and disease evolution is the oncogenic machinery triggered by mutant forms of KIT. The genetic background, additional somatic mutations, and comorbidities also contribute to the course and prognosis. Patients with SM may also suffer from mediator-related symptoms or even an MC activation syndrome. This article provides an update of concepts on the genetics, etiology, and pathology of mastocytosis, with emphasis on diagnostic criteria and new treatment concepts.

肥大细胞增多症是一种异质性肿瘤,其特征是克隆肥大细胞(MCs)在各器官系统中的数量增加和积累。该病可表现为皮肤肥大细胞增多症或全身肥大细胞增多症。根据组织病理学和分子特征、临床变量和器官受累情况,SM分为惰性SM、阴燃SM、伴血液学肿瘤SM、侵袭性SM和MC白血病。每种变异都有独特的诊断标准和独特的临床表现。MC扩增和疾病进化的关键驱动因素是KIT突变形式触发的致癌机制。遗传背景、额外的体细胞突变和合并症也影响病程和预后。SM患者还可能出现与介质相关的症状,甚至是MC激活综合征。本文介绍了肥大细胞增多症的遗传学、病因学和病理学的最新概念,重点介绍了肥大细胞增多症的诊断标准和新的治疗概念。
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引用次数: 12
Tumor-Derived Extracellular Vesicles: Multifunctional Entities in the Tumor Microenvironment. 肿瘤来源的细胞外囊泡:肿瘤微环境中的多功能实体。
IF 36.2 1区 医学 Q1 Medicine Pub Date : 2023-01-24 DOI: 10.1146/annurev-pathmechdis-031521-022116
James W Clancy, Crislyn D'Souza-Schorey

Tumor cells release extracellular vesicles (EVs) that can function as mediators of intercellular communication in the tumor microenvironment. EVs contain a host of bioactive cargo, including membrane, cytosolic, and nuclear proteins, in addition to noncoding RNAs, other RNA types, and double-stranded DNA fragments. These shed vesicles may deposit paracrine information and can also be taken up by stromal cells, causing the recipient cells to undergo phenotypic changes that profoundly impact diverse facets of cancer progression. For example, this unique form of cellular cross talk helps condition the premetastatic niche, facilitates evasion of the immune response, and promotes invasive and metastatic activity. These findings, coupled with those demonstrating that the number and content of EVs produced by tumors can vary depending on their tumor of origin, disease stage, or response to therapy, have raised the exciting possibility that EVs can be used for risk stratification, diagnostic, and even prognostic purposes. We summarize recent developments and the current knowledge of EV cargoes, their impact on disease progression, and implementation of EV-based liquid biopsies as tumor biomarkers.

肿瘤细胞释放的细胞外囊泡(EVs)可以作为肿瘤微环境中细胞间通讯的介质。除了非编码RNA、其他RNA类型和双链DNA片段外,电动汽车还含有大量生物活性货物,包括膜蛋白、细胞质蛋白和核蛋白。这些脱落囊泡可以储存旁分泌信息,也可以被基质细胞吸收,导致受体细胞经历表型变化,深刻影响癌症进展的各个方面。例如,这种独特形式的细胞串扰有助于调节转移前生态位,促进免疫反应的逃避,并促进侵袭和转移活性。这些发现,再加上肿瘤产生的EVs的数量和含量可以根据其肿瘤起源、疾病分期或对治疗的反应而变化,提出了EVs可用于风险分层、诊断甚至预后的令人兴奋的可能性。我们总结了最近的发展和目前对EV货物的了解,它们对疾病进展的影响,以及基于EV的液体活检作为肿瘤生物标志物的实施。
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引用次数: 14
Metabolism and Colorectal Cancer. 代谢与结直肠癌。
IF 36.2 1区 医学 Q1 Medicine Pub Date : 2023-01-24 Epub Date: 2022-11-02 DOI: 10.1146/annurev-pathmechdis-031521-041113
Joseph C Sedlak, Ömer H Yilmaz, Jatin Roper

Reprogrammed metabolism is a hallmark of colorectal cancer (CRC). CRC cells are geared toward rapid proliferation, requiring nutrients and the removal of cellular waste in nutrient-poor environments. Intestinal stem cells (ISCs), the primary cell of origin for CRCs, must adapt their metabolism along the adenoma-carcinoma sequence to the unique features of their complex microenvironment that include interactions with intestinal epithelial cells, immune cells, stromal cells, commensal microbes, and dietary components. Emerging evidence implicates modifiable risk factors related to the environment, such as diet, as important in CRC pathogenesis. Here, we focus on describing the metabolism of ISCs, diets that influence CRC initiation, CRC genetics and metabolism, and the tumor microenvironment. The mechanistic links between environmental factors, metabolic adaptations, and the tumor microenvironment in enhancing or supporting CRC tumorigenesis are becoming better understood. Thus, greater knowledge of CRC metabolism holds promise for improved prevention and treatment.

新陈代谢重编程是结直肠癌(CRC)的一大特征。结直肠癌细胞需要快速增殖,在缺乏营养的环境中需要营养和清除细胞废物。肠干细胞(ISCs)是 CRC 的主要起源细胞,它们的新陈代谢必须沿着腺瘤-癌的顺序进行调整,以适应其复杂微环境的独特特征,包括与肠上皮细胞、免疫细胞、基质细胞、共生微生物和饮食成分的相互作用。新的证据表明,与饮食等环境相关的可改变风险因素在 CRC 发病机制中起着重要作用。在此,我们重点介绍 ISC 的新陈代谢、影响 CRC 发病的饮食、CRC 遗传学和新陈代谢以及肿瘤微环境。人们对环境因素、代谢适应和肿瘤微环境之间在增强或支持 CRC 肿瘤发生方面的机理联系有了更深入的了解。因此,加深对 CRC 代谢的了解有望改善预防和治疗。
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引用次数: 11
Adipose Tissue Remodeling in Pathophysiology. 病理生理学中的脂肪组织重塑。
IF 36.2 1区 医学 Q1 Medicine Pub Date : 2023-01-24 DOI: 10.1146/annurev-pathol-042220-023633
Christopher Auger, Shingo Kajimura

Rather than serving as a mere onlooker, adipose tissue is a complex endocrine organ and active participant in disease initiation and progression. Disruptions of biological processes operating within adipose can disturb healthy systemic physiology, the sequelae of which include metabolic disorders such as obesity and type 2 diabetes. A burgeoning interest in the field of adipose research has allowed for the elucidation of regulatory networks underlying both adipose tissue function and dysfunction. Despite this progress, few diseases are treated by targeting maladaptation in the adipose, an oft-overlooked organ. In this review, we elaborate on the distinct subtypes of adipocytes, their developmental origins and secretory roles, and the dynamic interplay at work within the tissue itself. Central to this discussion is the relationship between adipose and disease states, including obesity, cachexia, and infectious diseases, as we aim to leverage our wealth of knowledge for the development of novel and targeted therapeutics.

脂肪组织不仅仅是一个旁观者,而是一个复杂的内分泌器官,是疾病发生和发展的积极参与者。在脂肪中运作的生物过程的中断会扰乱健康的全身生理,其后遗症包括代谢紊乱,如肥胖和2型糖尿病。在脂肪研究领域蓬勃发展的兴趣已经允许阐明脂肪组织功能和功能障碍背后的调节网络。尽管取得了这些进展,但很少有疾病是通过针对脂肪的不适应来治疗的,脂肪是一个经常被忽视的器官。在这篇综述中,我们详细介绍了脂肪细胞的不同亚型,它们的发育起源和分泌作用,以及在组织内部工作的动态相互作用。讨论的核心是脂肪和疾病状态之间的关系,包括肥胖、恶病质和传染病,因为我们的目标是利用我们丰富的知识来开发新的靶向治疗方法。
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引用次数: 16
Osteoclasts, Master Sculptors of Bone. 破骨细胞,骨骼雕刻大师。
IF 36.2 1区 医学 Q1 Medicine Pub Date : 2023-01-24 DOI: 10.1146/annurev-pathmechdis-031521-040919
Deborah J Veis, Charles A O'Brien

Osteoclasts are multinucleated cells with the unique ability to resorb bone matrix. Excessive production or activation of osteoclasts leads to skeletal pathologies that affect a significant portion of the population. Although therapies that effectively target osteoclasts have been developed, they are associated with sometimes severe side effects, and a fuller understanding of osteoclast biology may lead to more specific treatments. Along those lines, a rich body of work has defined essential signaling pathways required for osteoclast formation, function, and survival. Nonetheless, recent studies have cast new light on long-held views regarding the origin of these cells during development and homeostasis, their life span, and the cellular sources of factors that drive their production and activity during homeostasis and disease. In this review, we discuss these new findings in the context of existing work and highlight areas of ongoing and future investigation.

破骨细胞是一种多核细胞,具有吸收骨基质的独特能力。过度生产或激活破骨细胞导致骨骼病变,影响很大一部分人口。虽然已经开发出有效靶向破骨细胞的治疗方法,但它们有时会产生严重的副作用,对破骨细胞生物学的更全面了解可能会导致更具体的治疗方法。沿着这些思路,大量的工作已经定义了破骨细胞形成、功能和存活所需的基本信号通路。尽管如此,最近的研究对这些细胞在发育和体内平衡期间的起源、它们的寿命以及在体内平衡和疾病期间驱动它们产生和活动的因素的细胞来源等长期持有的观点有了新的认识。在这篇综述中,我们在现有工作的背景下讨论了这些新发现,并强调了正在进行和未来研究的领域。
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引用次数: 13
期刊
Annual Review of Pathology-Mechanisms of Disease
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