Cold Spring Harbor perspectives in medicine最新文献

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Advances in Islet Transplantation and the Future of Stem Cell-Derived Islets to Treat Diabetes. 胰岛移植的进展和干细胞衍生胰岛治疗糖尿病的未来。
IF 4.9 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-05-05 DOI: 10.1101/cshperspect.a041624
Timothy J Kieffer, Corinne A Hoesli, A M James Shapiro
{"title":"Advances in Islet Transplantation and the Future of Stem Cell-Derived Islets to Treat Diabetes.","authors":"Timothy J Kieffer, Corinne A Hoesli, A M James Shapiro","doi":"10.1101/cshperspect.a041624","DOIUrl":"10.1101/cshperspect.a041624","url":null,"abstract":"<p><p>β-Cell replacement for type 1 diabetes (T1D) can restore normal glucose homeostasis, thereby eliminating the need for exogenous insulin and halting the progression of diabetes complications. Success in achieving insulin independence following transplantation of cadaveric islets fueled academic and industry efforts to develop techniques to mass produce β cells from human pluripotent stem cells, and these have now been clinically validated as an alternative source of regulated insulin production. Various encapsulation strategies are being pursued to contain implanted cells in a retrievable format, and different implant sites are being explored with some strategies reaching clinical studies. Stem cell lines, whether derived from embryonic sources or reprogrammed somatic cells, are being genetically modified for designer features, including immune evasiveness to enable implant without the use of chronic immunosuppression. Although hurdles remain in optimizing large-scale manufacturing, demonstrating efficacy, durability, and safety, products containing stem cell-derived β cells promise to provide a potent treatment for insulin-dependent diabetes.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12047745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792094","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
Historical Perspectives of Parkinson's Disease: Early Clinical Descriptions and Neurological Therapies. 帕金森病的历史展望:早期临床描述和神经疗法。
IF 4.9 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-04-01 DOI: 10.1101/cshperspect.a041642
Christopher G Goetz
{"title":"Historical Perspectives of Parkinson's Disease: Early Clinical Descriptions and Neurological Therapies.","authors":"Christopher G Goetz","doi":"10.1101/cshperspect.a041642","DOIUrl":"10.1101/cshperspect.a041642","url":null,"abstract":"<p><p>Although components of possible Parkinson's disease can be found in earlier documents, the first clear medical description was written in 1817 by James Parkinson. In the mid-1800s, Jean-Martin Charcot was particularly influential in refining and expanding this early description and in disseminating information internationally about Parkinson's disease. He separated the clinical spectrum of Parkinson's disease from multiple sclerosis and other disorders characterized by tremor, and he recognized cases that later would likely be classified among the parkinsonism-plus syndromes. Early treatments of Parkinson's disease were based on empirical observation, and anticholinergic drugs were used as early as the nineteenth century. The discovery of dopaminergic deficits in Parkinson's disease and the synthetic pathway of dopamine led to the first human trials of levodopa. Further historically important anatomical, biochemical, and physiological studies identified additional pharmacological and neurosurgical targets for Parkinson's disease and allow modern clinicians to offer an array of therapies aimed at improving function in this still incurable disease.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300205","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 Chicken or the Egg Dilemma: Understanding the Interplay between the Immune System and the β Cell in Type 1 Diabetes. 鸡还是蛋的两难选择:了解 1 型糖尿病中免疫系统与 β 细胞之间的相互作用。
IF 4.9 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-04-01 DOI: 10.1101/cshperspect.a041591
Maria Skjøtt Hansen, Pravil Pokharel, Jon Piganelli, Lori Sussel
{"title":"The Chicken or the Egg Dilemma: Understanding the Interplay between the Immune System and the β Cell in Type 1 Diabetes.","authors":"Maria Skjøtt Hansen, Pravil Pokharel, Jon Piganelli, Lori Sussel","doi":"10.1101/cshperspect.a041591","DOIUrl":"10.1101/cshperspect.a041591","url":null,"abstract":"<p><p>In this review, we explore the complex interplay between the immune system and pancreatic β cells in the context of type 1 diabetes (T1D). While T1D is predominantly considered a T-cell-mediated autoimmune disease, the inability of human leukocyte antigen (HLA)-risk alleles alone to explain disease development suggests a role for β cells in initiating and/or propagating disease. This review delves into the vulnerability of β cells, emphasizing their susceptibility to endoplasmic reticulum (ER) stress and protein modifications, which may give rise to neoantigens. Additionally, we discuss the role of viral infections as contributors to T1D onset, and of genetic factors with dual impacts on the immune system and β cells. A greater understanding of the interplay between environmental triggers, autoimmunity, and the β cell will not only lead to insight as to why the islet β cells are specifically targeted by the immune system in T1D but may also reveal potential novel therapeutic interventions.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476107","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
Lineage-Selective Dependencies in Pediatric Cancers. 小儿癌症的系谱选择依赖性
IF 4.9 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-04-01 DOI: 10.1101/cshperspect.a041573
K Elaine Ritter, Adam D Durbin
{"title":"Lineage-Selective Dependencies in Pediatric Cancers.","authors":"K Elaine Ritter, Adam D Durbin","doi":"10.1101/cshperspect.a041573","DOIUrl":"10.1101/cshperspect.a041573","url":null,"abstract":"<p><p>The quest for effective cancer therapeutics has traditionally centered on targeting mutated or overexpressed oncogenic proteins. However, challenges arise in cancers with low mutational burden or when the mutated oncogene is not conventionally targetable, which are common situations in childhood cancers. This obstacle has sparked large-scale unbiased screens to identify collateral genetic dependencies crucial for cancer cell growth. These screens have revealed promising targets for therapeutic intervention in the form of lineage-selective dependency genes, which may have an expanded therapeutic window compared to pan-lethal dependencies. Many lineage-selective dependencies regulate gene expression and are closely tied to the developmental origins of pediatric tumors. Placing lineage-selective dependencies in a transcriptional network model is helpful for understanding their roles in driving malignant cell behaviors. Here, we discuss the identification of lineage-selective dependencies and how two transcriptional models, core regulatory circuits and gene regulatory networks, can serve as frameworks for understanding their individual and collective actions, particularly in cancers affecting children and young adults.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161168","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
Advances in Studying Cancer Immunology in Mice. 研究小鼠癌症免疫学的进展。
IF 4.9 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-03-03 DOI: 10.1101/cshperspect.a041682
Marcus Bosenberg
{"title":"Advances in Studying Cancer Immunology in Mice.","authors":"Marcus Bosenberg","doi":"10.1101/cshperspect.a041682","DOIUrl":"10.1101/cshperspect.a041682","url":null,"abstract":"<p><p>The recent rise in effective immuno-oncology therapies has increased demand for experimental approaches to model anticancer immunity. A variety of mouse models have been developed and used to study cancer immunology. These include mutagen-induced, genetically engineered, syngeneic, and other models of cancer immunology. These models each have the potential to define mechanistic aspects of anticancer immune responses, identify potential therapeutic targets, and serve as preclinical models for further therapeutic development. Specific benefits and liabilities are characteristic of particular cancer immunology modeling approaches. The optimal choice and utilization of models depends on the cancer immunology scientific question being addressed and can serve to increase mechanistic understanding and development of human immuno-oncology therapies.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075768","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
Toxin-Induced Animal Models of Parkinson's Disease. 毒素诱导的帕金森病动物模型。
IF 4.9 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-03-03 DOI: 10.1101/cshperspect.a041643
Kim Tieu, Said S Salehe, Harry J Brown
{"title":"Toxin-Induced Animal Models of Parkinson's Disease.","authors":"Kim Tieu, Said S Salehe, Harry J Brown","doi":"10.1101/cshperspect.a041643","DOIUrl":"10.1101/cshperspect.a041643","url":null,"abstract":"<p><p>The debilitating motor symptoms of Parkinson's disease (PD) result primarily from the degenerative nigrostriatal dopaminergic pathway. To elucidate pathogenic mechanisms and evaluate therapeutic strategies for PD, numerous animal models have been developed. Understanding the strengths and limitations of these models can significantly impact the choice of model, experimental design, and data interpretation. Herein, we systematically review the literature over the past decade. Some models no longer serve the purpose of PD models. The primary objectives of this review are: First, to assist new investigators in navigating through available animal models and making appropriate selections based on the objective of the study. Emphasis will be placed on common toxin-induced murine models. And second, to provide an overview of basic technical requirements for assessing the nigrostriatal pathway's pathology, structure, and function.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476108","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
Interactions of Fatty Acid and Cholesterol Metabolism with Cellular Stress Response Pathways in Cancer. 癌症中脂肪酸和胆固醇代谢与细胞应激反应途径的相互作用
IF 4.9 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-03-03 DOI: 10.1101/cshperspect.a041548
Alina M Winkelkotte, Kamal Al-Shami, Adriano B Chaves-Filho, Felix C E Vogel, Almut Schulze
{"title":"Interactions of Fatty Acid and Cholesterol Metabolism with Cellular Stress Response Pathways in Cancer.","authors":"Alina M Winkelkotte, Kamal Al-Shami, Adriano B Chaves-Filho, Felix C E Vogel, Almut Schulze","doi":"10.1101/cshperspect.a041548","DOIUrl":"10.1101/cshperspect.a041548","url":null,"abstract":"<p><p>Lipids have essential functions as structural components of cellular membranes, as efficient energy storage molecules, and as precursors of signaling mediators. While deregulated glucose and amino acid metabolism in cancer have received substantial attention, the roles of lipids in the metabolic reprogramming of cancer cells are less well understood. However, since the first description of de novo fatty acid biosynthesis in cancer tissues almost 70 years ago, numerous studies have investigated the complex functions of altered lipid metabolism in cancer. Here, we will summarize the mechanisms by which oncogenic signaling pathways regulate fatty acid and cholesterol metabolism to drive rapid proliferation and protect cancer cells from environmental stress. The review also discusses the role of fatty acid metabolism in metabolic plasticity required for the adaptation to changing microenvironments during cancer progression and the connections between fatty acid and cholesterol metabolism and ferroptosis.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476106","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
Angiogenesis: Biology and Pathology, Second Edition. 血管生成:血管生成:生物学与病理学》,第二版。
IF 4.9 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-03-03 DOI: 10.1101/cshperspect.a041779
Diane R Bielenberg, Patricia A D'Amore
{"title":"Angiogenesis: Biology and Pathology, Second Edition.","authors":"Diane R Bielenberg, Patricia A D'Amore","doi":"10.1101/cshperspect.a041779","DOIUrl":"10.1101/cshperspect.a041779","url":null,"abstract":"<p><p>During development, the first blood vessels are formed by the de novo assembly of angioblasts, endothelial cell precursors, in a process called vasculogenesis. All subsequent sprouting of blood vessels from pre-existing vessels is termed angiogenesis and is a process that continues throughout our lifespan during physiological processes such as wound healing as well as in number of pathological conditions, such as tumor growth and age-related macular degeneration. The circulatory system pumps blood from the heart out to the organs through arteries and deliveries oxygen and nutrients via capillaries to tissues and cells and returns carbon dioxide and waste products back through veins. Each organ varies in its blood vessel patterning, reflecting specialization to accomplish diverse functions including vascular permeability, filtration, immune trafficking, and hormone regulation. Approximately 90% of the fluid extravasated into the interstitium is recycled back to the circulatory system via the unidirectional lymphatic system. Lymphatic capillaries drain fluid, proteins, and cells from tissues and transport this lymph fluid through collecting lymphatic ducts toward lymph nodes. Eventually lymphatic fluid from the right and left lymphatic ducts joins the subclavian veins and recirculates throughout the circulatory system. These two intricate vascular systems, working in cooperation, help to maintain essential bodily functions such as fluid dynamics, tissue homeostasis, blood pressure, metabolism, and immunity. However, dysfunction of these systems is associated with a host of pathological conditions, including cardiovascular diseases, obesity, retinopathy, hypoxia, necrosis, and vascular malformations.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792095","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
A History of Cancer Research: The P53 Pathway. 癌症研究的历史:P53通路。
IF 4.9 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":4.9,"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
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