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Annual Review of Pathology-Mechanisms of Disease最新文献

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Inherited Predispositions to Myeloid Neoplasms: Pathogenesis and Clinical Implications. 髓样肿瘤的遗传倾向：发病机制和临床意义。
IF 28.4 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-01-01 Epub Date: 2025-01-02 DOI: 10.1146/annurev-pathmechdis-111523-023420
Yen-Chun Liu, Mohammad K Eldomery, Jamie L Maciaszek, Jeffery M Klco
{"title":"Inherited Predispositions to Myeloid Neoplasms: Pathogenesis and Clinical Implications.","authors":"Yen-Chun Liu, Mohammad K Eldomery, Jamie L Maciaszek, Jeffery M Klco","doi":"10.1146/annurev-pathmechdis-111523-023420","DOIUrl":"10.1146/annurev-pathmechdis-111523-023420","url":null,"abstract":"<p><p>Myeloid neoplasms with and without preexisting platelet disorders frequently develop in association with an underlying germline predisposition. Germline alterations affecting <i>ANKRD26</i>, <i>CEBPA</i>, <i>DDX41</i>, <i>ETV6</i>, and <i>RUNX1</i> are associated with nonsyndromic predisposition to the development of myeloid neoplasms including acute myeloid leukemia and myelodysplastic syndrome. However, germline predisposition to myeloid neoplasms is also associated with a wide range of other syndromes, including <i>SAMD9</i>/<i>9L</i> associated predisposition, <i>GATA2</i> deficiency, RASopathies, ribosomopathies, telomere biology disorders, Fanconi anemia, severe congenital neutropenia, Down syndrome, and others. In the fifth edition of the World Health Organization (WHO) series on the classification of tumors of hematopoietic and lymphoid tissues, myeloid neoplasms associated with germline predisposition have been recognized as a separate entity. Here, we review several disorders from this WHO entity as well as other related conditions with an emphasis on the molecular pathogenesis of disease and accompanying somatic alterations. Finally, we provide an overview of establishing the molecular diagnosis of these germline genetic conditions and general recommendations for screening and management of the associated hematologic conditions.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":" ","pages":"87-114"},"PeriodicalIF":28.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Contributions of Inflammation to Cardiometabolic Heart Failure with Preserved Ejection Fraction. 炎症对射血分数保留型心脏代谢性心力衰竭的影响
IF 28.4 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-01-01 Epub Date: 2025-01-02 DOI: 10.1146/annurev-pathmechdis-111523-023405
Edward B Thorp, Mallory Filipp
{"title":"Contributions of Inflammation to Cardiometabolic Heart Failure with Preserved Ejection Fraction.","authors":"Edward B Thorp, Mallory Filipp","doi":"10.1146/annurev-pathmechdis-111523-023405","DOIUrl":"10.1146/annurev-pathmechdis-111523-023405","url":null,"abstract":"<p><p>The most common form of heart failure is heart failure with preserved ejection fraction (HFpEF). While heterogeneous in origin, the most common form of HFpEF is the cardiometabolic manifestation. Obesity and aging promote systemic inflammation that appears integral to cardiometabolic HFpEF pathophysiology. Accumulation of immune cells within the heart, fueled by an altered metabolome, contribute to cardiac inflammation and fibrosis. In spite of this, broad anti-inflammatory therapy has not shown significant benefit in patient outcomes. Thus, understanding of the nuances to metabolic and age-related inflammation during HFpEF is paramount for more targeted interventions. Here, we review clinical evidence of inflammation in the context of HFpEF and summarize our mechanistic understanding of immunometabolic inflammation, highlighting pathways of therapeutic potential along the way.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":" ","pages":"143-167"},"PeriodicalIF":28.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Role of Fungi in Tumorigenesis: Promises and Challenges. 真菌在肿瘤发生中的作用：希望与挑战。
IF 28.4 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-01-01 DOI: 10.1146/annurev-pathmechdis-111523-023524
Silvia Guglietta, Xin Li, Deepak Saxena
{"title":"Role of Fungi in Tumorigenesis: Promises and Challenges.","authors":"Silvia Guglietta, Xin Li, Deepak Saxena","doi":"10.1146/annurev-pathmechdis-111523-023524","DOIUrl":"10.1146/annurev-pathmechdis-111523-023524","url":null,"abstract":"<p><p>The mycobiome plays a key role in the host immune responses in homeostasis and inflammation. Recent studies suggest that an imbalance in the gut's fungi contributes to chronic, noninfectious diseases such as obesity, metabolic disorders, and cancers. Pathogenic fungi can colonize specific organs, and the gut mycobiome has been linked to the development and progression of various cancers, including colorectal, breast, head and neck, and pancreatic cancers. Some fungal species can promote tumorigenesis by triggering the complement system. However, in immunocompromised patients, fungi can also inhibit this activation and establish life-threatening infections. Interestingly, the interaction of the fungi and bacteria can also induce unique host immune responses. Recent breakthroughs and advancements in high-throughput sequencing of the gut and tumor mycobiomes are highlighting novel diagnostic and therapeutic opportunities for cancer. We discuss the latest developments in the field of cancer and the mycobiome and the potential benefits and challenges of antifungal therapies.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"20 1","pages":"459-482"},"PeriodicalIF":28.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pathogenesis of Focal Segmental Glomerulosclerosis and Related Disorders. 局灶节段性肾小球硬化及相关疾病的发病机制。
IF 28.4 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-01-01 DOI: 10.1146/annurev-pathol-051220-092001
Mehmet M Altintas, Shivangi Agarwal, Yashwanth Sudhini, Ke Zhu, Changli Wei, Jochen Reiser
{"title":"Pathogenesis of Focal Segmental Glomerulosclerosis and Related Disorders.","authors":"Mehmet M Altintas, Shivangi Agarwal, Yashwanth Sudhini, Ke Zhu, Changli Wei, Jochen Reiser","doi":"10.1146/annurev-pathol-051220-092001","DOIUrl":"10.1146/annurev-pathol-051220-092001","url":null,"abstract":"<p><p>Focal segmental glomerulosclerosis (FSGS) is the morphologic manifestation of a spectrum of kidney diseases that primarily impact podocytes, cells that create the filtration barrier of the glomerulus. As its name implies, only parts of the kidney and glomeruli are affected, and only a portion of the affected glomerulus may be sclerosed. Although the diagnosis is based primarily on microscopic features, patient stratification relies on clinical data such as proteinuria and etiological criteria. FSGS affects both children and adults and has an elevated risk of progression to end-stage renal disease. The prevalence of FSGS is rising among various populations, and the efficacy of various therapies is limited. Therefore, understanding the pathophysiology of FSGS and developing targeted therapies to address the complex needs of FSGS patients are topics of great interest that are currently being studied across various clinical trials. We discuss the etiology of FSGS, describe the major contributing pathophysiological pathways, and outline emerging therapeutic strategies along with their pitfalls.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"20 1","pages":"329-353"},"PeriodicalIF":28.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Challenges and Opportunities in the Clinical Translation of High-Resolution Spatial Transcriptomics. 高分辨率空间转录组学临床转化的挑战与机遇。
IF 28.4 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-01-01 Epub Date: 2025-01-02 DOI: 10.1146/annurev-pathmechdis-111523-023417
Tancredi Massimo Pentimalli, Nikos Karaiskos, Nikolaus Rajewsky
{"title":"Challenges and Opportunities in the Clinical Translation of High-Resolution Spatial Transcriptomics.","authors":"Tancredi Massimo Pentimalli, Nikos Karaiskos, Nikolaus Rajewsky","doi":"10.1146/annurev-pathmechdis-111523-023417","DOIUrl":"10.1146/annurev-pathmechdis-111523-023417","url":null,"abstract":"<p><p>Pathology has always been fueled by technological advances. Histology powered the study of tissue architecture at single-cell resolution and remains a cornerstone of clinical pathology today. In the last decade, next-generation sequencing has become informative for the targeted treatment of many diseases, demonstrating the importance of genome-scale molecular information for personalized medicine. Today, revolutionary developments in spatial transcriptomics technologies digitalize gene expression at subcellular resolution in intact tissue sections, enabling the computational analysis of cell types, cellular phenotypes, and cell-cell communication in routinely collected and archival clinical samples. Here we review how such molecular microscopes work, highlight their potential to identify disease mechanisms and guide personalized therapies, and provide guidance for clinical study design. Finally, we discuss remaining challenges to the swift translation of high-resolution spatial transcriptomics technologies and how integration of multimodal readouts and deep learning approaches is bringing us closer to a holistic understanding of tissue biology and pathology.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":" ","pages":"405-432"},"PeriodicalIF":28.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Apoptosis in Cancer Biology and Therapy. 细胞凋亡在肿瘤生物学和治疗中的作用。
IF 28.4 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-01-01 DOI: 10.1146/annurev-pathmechdis-051222-115023
Allison Moyer, Kosuke Tanaka, Emily H Cheng
{"title":"Apoptosis in Cancer Biology and Therapy.","authors":"Allison Moyer, Kosuke Tanaka, Emily H Cheng","doi":"10.1146/annurev-pathmechdis-051222-115023","DOIUrl":"10.1146/annurev-pathmechdis-051222-115023","url":null,"abstract":"<p><p>Since its inception, the study of apoptosis has been intricately linked to the field of cancer. The term apoptosis was coined more than five decades ago following its identification in both healthy tissues and malignant neoplasms. The subsequent elucidation of its molecular mechanisms has significantly enhanced our understanding of how cancer cells hijack physiological processes to evade cell death. Moreover, it has shed light on the pathways through which most anticancer therapeutics induce tumor cell death, including targeted therapy and immunotherapy. These mechanistic studies have paved the way for the development of therapeutics directly targeting either pro- or antiapoptotic proteins. Notably, the US Food and Drug Administration (FDA) approved the BCL-2 inhibitor venetoclax in 2016, with additional agents currently undergoing clinical trials. Recent research has brought to the forefront both the anti- and proinflammatory effects of individual apoptotic pathways. This underscores the ongoing imperative to deepen our comprehension of apoptosis, particularly as we navigate the evolving landscape of immunotherapy.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"20 1","pages":"303-328"},"PeriodicalIF":28.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
RNA Damage Responses in Cellular Homeostasis, Genome Stability, and Disease. 细胞稳态、基因组稳定性和疾病中的 RNA 损伤反应
IF 28.4 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-01-01 Epub Date: 2025-01-02 DOI: 10.1146/annurev-pathmechdis-111523-023516
Hani S Zaher, Nima Mosammaparast
{"title":"RNA Damage Responses in Cellular Homeostasis, Genome Stability, and Disease.","authors":"Hani S Zaher, Nima Mosammaparast","doi":"10.1146/annurev-pathmechdis-111523-023516","DOIUrl":"10.1146/annurev-pathmechdis-111523-023516","url":null,"abstract":"<p><p>All cells are exposed to chemicals that can damage their nucleic acids. Cells must protect these polymers because they code for key factors or complexes essential for life. Much of the work on nucleic acid damage has naturally focused on DNA, partly due to the connection between mutagenesis and human disease, especially cancer. Recent work has shed light on the importance of RNA damage, which triggers a host of conserved RNA quality control mechanisms. Because many RNA species are transient, and because of their ability to be retranscribed, RNA damage has largely been ignored. Yet, because of the connection between damaged RNA and DNA during transcription, and the association between essential complexes that process or decode RNAs, notably spliceosomes and ribosomes, the appropriate handling of damaged RNAs is critical for maintaining cellular homeostasis. This notion is bolstered by disease states, including neurodevelopmental and neurodegenerative diseases, that may arise upon loss or misregulation of RNA quality control mechanisms.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":" ","pages":"433-457"},"PeriodicalIF":28.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Circadian Clocks, Daily Stress, and Neurodegenerative Disease 昼夜节律、日常压力与神经退行性疾病
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2024-10-18 DOI: 10.1146/annurev-pathmechdis-031521-033828
Eugene Nyamugenda, Clark Rosensweig, Ravi Allada
{"title":"Circadian Clocks, Daily Stress, and Neurodegenerative Disease","authors":"Eugene Nyamugenda, Clark Rosensweig, Ravi Allada","doi":"10.1146/annurev-pathmechdis-031521-033828","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-031521-033828","url":null,"abstract":"Disrupted circadian or 24-h rhythms are among the most common early findings in a wide range of neurodegenerative disorders. Once thought to be a mere consequence of the disease process, increasing evidence points toward a causal or contributory role of the circadian clock in neurodegenerative disease. Circadian clocks control many aspects of cellular biochemistry, including stress pathways implicated in neuronal survival and death. Given the dearth of disease-modifying therapies for these increasingly prevalent disorders, this understanding may lead to breakthroughs in the development of new treatments. In this review, we provide a background on circadian clocks and focus on some potential mechanisms that may be pivotal in neurodegeneration.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"109 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multiple System Atrophy: Pathology, Pathogenesis, and Path Forward 多系统萎缩：病理学、发病机制和前进之路
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2024-10-15 DOI: 10.1146/annurev-pathmechdis-051122-104528
Alain Ndayisaba, Glenda M. Halliday, Vikram Khurana
{"title":"Multiple System Atrophy: Pathology, Pathogenesis, and Path Forward","authors":"Alain Ndayisaba, Glenda M. Halliday, Vikram Khurana","doi":"10.1146/annurev-pathmechdis-051122-104528","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-051122-104528","url":null,"abstract":"Multiple system atrophy (MSA) is a fatal neurodegenerative disease characterized by autonomic failure and motor impairment. The hallmark pathologic finding in MSA is widespread oligodendroglial cytoplasmic inclusions rich in aggregated α-synuclein (αSyn). MSA is widely held to be an oligodendroglial synucleinopathy, and we outline lines of evidence to support this assertion, including the presence of early myelin loss. We consider emerging data that support the possibility of neuronal or immune dysfunction as primary drivers of MSA. These hypotheses are placed in the context of a major recent discovery that αSyn is conformationally distinct in MSA versus other synucleinopathies such as Parkinson's disease. We outline emerging techniques in epidemiology, genetics, and molecular pathology that will shed more light on this mysterious disease. We anticipate a future in which cutting-edge developments in personalized disease modeling, including with pluripotent stem cells, bridge mechanistic developments at the bench and real benefits at the bedside.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"103 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pathogenesis of Germinal Matrix Hemorrhage: Insights from Single-Cell Transcriptomics. 胚芽基质出血的发病机制：单细胞转录组学的启示。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2024-10-14 DOI: 10.1146/annurev-pathmechdis-111523-023446
Jiapei Chen,Jennifer Ja-Yoon Choi,Pin-Yeh Lin,Eric J Huang
{"title":"Pathogenesis of Germinal Matrix Hemorrhage: Insights from Single-Cell Transcriptomics.","authors":"Jiapei Chen,Jennifer Ja-Yoon Choi,Pin-Yeh Lin,Eric J Huang","doi":"10.1146/annurev-pathmechdis-111523-023446","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-111523-023446","url":null,"abstract":"The germinal matrix harbors neurogenic niches in the subpallium of the prenatal human brain that produce abundant GABAergic neurons. In preterm infants, the germinal matrix is particularly vulnerable to developing hemorrhage, which disrupts neurogenesis and causes severe neurodevelopmental sequelae. However, the disease mechanisms that promote germinal matrix hemorrhage remain unclear. Here, we review recent advances using single-cell transcriptomics to uncover novel mechanisms that govern neurogenesis and angiogenesis in the germinal matrix of the prenatal human brain. These approaches also reveal the critical role of immune-vascular interaction that promotes vascular morphogenesis in the germinal matrix and how proinflammatory factors from activated neutrophils and monocytes can disrupt this process, leading to hemorrhage. Collectively, these results reveal fundamental disease mechanisms and therapeutic interventions for germinal matrix hemorrhage.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"1 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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