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Cold Spring Harbor perspectives in medicine最新文献

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Type 1 Diabetes: Advances in Understanding and Treatment 100 Years after the Discovery of Insulin. 1型糖尿病：胰岛素发现100年后的认识和治疗进展。
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-02-10 DOI: 10.1101/cshperspect.a041843
Jeffrey A Bluestone, Kevan C Herold, Lori Sussel
{"title":"Type 1 Diabetes: Advances in Understanding and Treatment 100 Years after the Discovery of Insulin.","authors":"Jeffrey A Bluestone, Kevan C Herold, Lori Sussel","doi":"10.1101/cshperspect.a041843","DOIUrl":"https://doi.org/10.1101/cshperspect.a041843","url":null,"abstract":"<p><p>Type 1 diabetes is an autoimmune condition in which the pancreatic β cells that produce insulin are destroyed by the body's immune system. For 100 years, diet and insulin injections have been the only effective treatment. Recent advances have led to significant progress in our understanding of the pathogenesis of the disease and the interplay between the environment, components of the immune system, and the β cells that are targeted. This has led to new therapies that rebalance the immune system and finally offer the promise of a cure.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Clinical Immunologic Interventions for the Treatment of Type 1 Diabetes: Challenges, Choice, and Timing of Immunomodulators. 治疗1型糖尿病的临床免疫干预：免疫调节剂的挑战、选择和时机。
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-02-10 DOI: 10.1101/cshperspect.a041597
Danijela Tatovic, Colin Dayan
{"title":"Clinical Immunologic Interventions for the Treatment of Type 1 Diabetes: Challenges, Choice, and Timing of Immunomodulators.","authors":"Danijela Tatovic, Colin Dayan","doi":"10.1101/cshperspect.a041597","DOIUrl":"https://doi.org/10.1101/cshperspect.a041597","url":null,"abstract":"<p><p>Replacement insulin therapy has been the mainstay of type 1 diabetes mellitus (T1D) treatment ever since its introduction into clinical care more than 100 years ago. Despite advances in delivery methods, insulin remains a challenging medication. It is, therefore, not surprising that most people with T1D do not achieve optimal glycemic control and remain at risk of complications. The recent introduction of teplizumab as the first immunotherapy for T1D has ushered in an exciting era where the focus is shifted from metabolic replacement therapy with insulin to proactive disease-modifying treatments that prevent the loss of insulin secretory capacity. At least nine other clinical immunologic interventions have shown phase 2 trial efficacy in preserving β-cell function in T1D. To translate these findings to patient benefit, many changes are required. These include improvements in end points and trial design to accelerate drug development, changing the attitude of healthcare professionals toward novel strategies, and the development of effective screening programs to identify affected individuals in early-stage disease. This will enable a broad portfolio of β-cell preserving therapies to be approved, in turn allowing appropriate selection of immunomodulators tailored to an individual's response with an ultimate goal of \"insulin-free T1D.\"</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
A History of Cancer Research: The P53 Pathway. 癌症研究的历史：P53通路。
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-02-03 DOI: 10.1101/cshperspect.a035931
Joseph Lipsick
{"title":"A History of Cancer Research: The P53 Pathway.","authors":"Joseph Lipsick","doi":"10.1101/cshperspect.a035931","DOIUrl":"10.1101/cshperspect.a035931","url":null,"abstract":"<p><p>The p53 tumor suppressor was first identified as a cellular protein that bound to the large T antigen in SV40-transformed cells. Initially thought to be the product of an oncogene, p53 turned out to be an anticancer protein whose loss or mutation could promote tumorigenesis. Subsequent work revealed it functions as a DNA-binding transcription factor central to the DNA damage response and cell cycle control. In this excerpt from his forthcoming book on the history of cancer research, Joe Lipsick looks back at the discovery of p53 and the groundbreaking work that revealed its role as \"guardian of the genome.\"</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"15 2","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Corrigendum: Modeling Parkinson's Disease in Primates. 更正：模拟灵长类动物的帕金森病。
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-02-03 DOI: 10.1101/cshperspect.a041802
Erwan Bezard, Margaux Teil, Marie-Laure Arotcarena, Gregory Porras, Qin Li, Benjamin Dehay
{"title":"Corrigendum: Modeling Parkinson's Disease in Primates.","authors":"Erwan Bezard, Margaux Teil, Marie-Laure Arotcarena, Gregory Porras, Qin Li, Benjamin Dehay","doi":"10.1101/cshperspect.a041802","DOIUrl":"10.1101/cshperspect.a041802","url":null,"abstract":"","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Modeling Parkinson's Disease in Primates. 灵长类动物的帕金森病模型
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-02-03 DOI: 10.1101/cshperspect.a041612
Erwan Bezard, Margaux Teil, Marie-Laure Arotcarena, Gregory Porras, Qin Li, Benjamin Dehay
{"title":"Modeling Parkinson's Disease in Primates.","authors":"Erwan Bezard, Margaux Teil, Marie-Laure Arotcarena, Gregory Porras, Qin Li, Benjamin Dehay","doi":"10.1101/cshperspect.a041612","DOIUrl":"10.1101/cshperspect.a041612","url":null,"abstract":"<p><p>Decades of research have identified the pathological and pathophysiological hallmarks of Parkinson's disease (PD): profound deficit in brain dopamine and other monoamines, pathological α-synuclein aggregation, synaptic and neuronal network dysfunction, aberrant proteostasis, altered energy homeostasis, inflammation, and neuronal cell death. The purpose of this contribution is to present the phenocopy aspect, pathogenic, and etiologic nonhuman primate (NHP) models of PD to readers with limited prior knowledge of PD so that they are ready to start working on PD. How NHPs, the closest species to man on which we can model diseases, contribute to the knowledge progress and how these models represent an invaluable translational step in therapeutic development are highlighted.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Metabolic Signaling in Cancer. 癌症中的代谢信号
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-02-03 DOI: 10.1101/cshperspect.a041544
Laura V Pinheiro, Pedro Costa-Pinheiro, Kathryn E Wellen
{"title":"Metabolic Signaling in Cancer.","authors":"Laura V Pinheiro, Pedro Costa-Pinheiro, Kathryn E Wellen","doi":"10.1101/cshperspect.a041544","DOIUrl":"10.1101/cshperspect.a041544","url":null,"abstract":"<p><p>Metabolic reprogramming in cancer allows cells to survive in harsh environments and sustain macromolecular biosynthesis to support proliferation. In addition, metabolites play crucial roles as signaling molecules. Metabolite fluctuations are detected by various sensors in the cell to regulate gene expression, metabolism, and signal transduction. Metabolic signaling mechanisms contribute to tumorigenesis by altering the physiology of cancer cells themselves, as well as that of neighboring cells in the tumor microenvironment. In this review, we discuss principles of metabolic signaling and provide examples of how cancer cells take advantage of metabolic signals to promote cell proliferation and evade the immune system, thereby contributing to tumor growth and progression.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
The Gut-Brain Axis in Parkinson's Disease. 帕金森病的肠脑轴。
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-01-07 DOI: 10.1101/cshperspect.a041618
Virginia Gao, Carl V Crawford, Jacqueline Burré
{"title":"The Gut-Brain Axis in Parkinson's Disease.","authors":"Virginia Gao, Carl V Crawford, Jacqueline Burré","doi":"10.1101/cshperspect.a041618","DOIUrl":"10.1101/cshperspect.a041618","url":null,"abstract":"<p><p>Parkinson's disease (PD) involves both the central nervous system (CNS) and enteric nervous system (ENS), and their interaction is important for understanding both the clinical manifestations of the disease and the underlying disease pathophysiology. Although the neuroanatomical distribution of pathology strongly suggests that the ENS is involved in disease pathophysiology, there are significant gaps in knowledge about the underlying mechanisms. In this article, we review the clinical presentation and management of gastrointestinal dysfunction in PD. In addition, we discuss the current understanding of disease pathophysiology in the gut, including controversies about early involvement of the gut in disease pathogenesis. We also review current knowledge about gut α-synuclein and the microbiome, discuss experimental models of PD-linked gastrointestinal pathophysiology, and highlight areas for further research. Finally, we discuss opportunities to use the gut-brain axis for the development of biomarkers and disease-modifying treatments.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Lessons Learned from Cancer Metabolism for Physiology and Disease. 从癌症代谢中汲取生理和疾病方面的经验教训。
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-01-07 DOI: 10.1101/cshperspect.a041554
Sydney L Campbell, Heather R Christofk
{"title":"Lessons Learned from Cancer Metabolism for Physiology and Disease.","authors":"Sydney L Campbell, Heather R Christofk","doi":"10.1101/cshperspect.a041554","DOIUrl":"10.1101/cshperspect.a041554","url":null,"abstract":"<p><p>Tumor cells divide rapidly and dramatically alter their metabolism to meet biosynthetic and bioenergetic needs. Through studying the aberrant metabolism of cancer cells, other contexts in which metabolism drives cell state transitions become apparent. In this work, we will discuss how principles established by the field of cancer metabolism have led to discoveries in the contexts of physiology and tissue injury, mammalian embryonic development, and virus infection. We present specific examples of findings from each of these fields that have been shaped by the study of cancer metabolism. We also discuss the next important scientific questions facing these subject areas collectively. Altogether, these examples demonstrate that the study of \"cancer metabolism\" is indeed the study of cell metabolism in the context of a tumor, and undoubtedly discoveries from each of the fields discussed here will continue to build on each other in the future.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Developmental Heterogeneity of Rhabdomyosarcoma. 横纹肌肉瘤的发育异质性
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-01-07 DOI: 10.1101/cshperspect.a041583
Bradley T Stevens, Mark E Hatley
{"title":"Developmental Heterogeneity of Rhabdomyosarcoma.","authors":"Bradley T Stevens, Mark E Hatley","doi":"10.1101/cshperspect.a041583","DOIUrl":"10.1101/cshperspect.a041583","url":null,"abstract":"<p><p>Rhabdomyosarcoma (RMS) is a pediatric embryonal solid tumor and the most common pediatric soft tissue sarcoma. The histology and transcriptome of RMS resemble skeletal muscle progenitor cells that have failed to terminally differentiate. Thus, RMS is typically thought to arise from corrupted skeletal muscle progenitor cells during development. However, RMS can occur in body regions devoid of skeletal muscle, suggesting the potential for nonmyogenic cells of origin. Here, we discuss the interplay between RMS driver mutations and cell(s) of origin with an emphasis on driving location specificity. Additionally, we discuss the mechanisms governing RMS transformation events and tumor heterogeneity through the lens of transcriptional networks and epigenetic control. Finally, we reimagine Waddington's developmental landscape to include a plane of transformation connecting distinct lineage landscapes to more accurately reflect the phenomena observed in pediatric cancers.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Corrigendum: Preclinical Modeling of Pathway-Targeted Therapy of Human Lung Cancer in the Mouse. 更正：小鼠肺癌通路靶向治疗的临床前建模。
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-01-07 DOI: 10.1101/cshperspect.a041815
Aria Vaishnavi, Conan G Kinsey, Martin McMahon
{"title":"Corrigendum: Preclinical Modeling of Pathway-Targeted Therapy of Human Lung Cancer in the Mouse.","authors":"Aria Vaishnavi, Conan G Kinsey, Martin McMahon","doi":"10.1101/cshperspect.a041815","DOIUrl":"10.1101/cshperspect.a041815","url":null,"abstract":"","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
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