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Excessive Alcohol Use as a Risk Factor for Alzheimer's Disease: Epidemiological and Preclinical Evidence.
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-81908-7_10
Paige E Anton, Nicole M Maphis, David N Linsenbardt, Leon G Coleman
{"title":"Excessive Alcohol Use as a Risk Factor for Alzheimer's Disease: Epidemiological and Preclinical Evidence.","authors":"Paige E Anton, Nicole M Maphis, David N Linsenbardt, Leon G Coleman","doi":"10.1007/978-3-031-81908-7_10","DOIUrl":"https://doi.org/10.1007/978-3-031-81908-7_10","url":null,"abstract":"<p><p>Alcohol use has recently emerged as a modifiable risk factor for Alzheimer's disease (AD). However, the neurobiological mechanisms by which alcohol interacts with AD pathogenesis remain poorly understood. In this chapter, we review the epidemiological and preclinical support for the interaction between alcohol use and AD. We hypothesize that alcohol use increases the rate of accumulation of specific AD-relevant pathologies during the prodromal phase and exacerbates dementia onset and progression. We find that alcohol consumption rates are increasing in adolescence, middle age, and aging populations. In tandem, rates of AD are also on the rise, potentially as a result of this increased alcohol use throughout the lifespan. We then review the biological processes in common between alcohol use disorder and AD as a means to uncover potential mechanisms by which they interact; these include oxidative stress, neuroimmune function, metabolism, pathogenic tauopathy development and spread, and neuronal excitatory/inhibitory balance (EIB). Finally, we provide some forward-thinking suggestions we believe this field should consider. In particular, the inclusion of alcohol use assessments in longitudinal studies of AD and more preclinical studies on alcohol's impacts using better animal models of late-onset Alzheimer's disease (LOAD).</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1473 ","pages":"211-242"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Classification of Breast Cancer Through the Perspective of Cell Identity Models. 从细胞识别模型的角度对乳腺癌进行分类。
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-70875-6_11
Richard Iggo, Gaetan MacGrogan
{"title":"Classification of Breast Cancer Through the Perspective of Cell Identity Models.","authors":"Richard Iggo, Gaetan MacGrogan","doi":"10.1007/978-3-031-70875-6_11","DOIUrl":"https://doi.org/10.1007/978-3-031-70875-6_11","url":null,"abstract":"<p><p>The mammary epithelium has an inner luminal layer that contains estrogen receptor (ER)-positive hormone-sensing cells and ER-negative alveolar/secretory cells, and an outer basal layer that contains myoepithelial/stem cells. Most human tumours resemble either hormone-sensing cells or alveolar/secretory cells. The most widely used molecular classification, the Intrinsic classification, assigns hormone-sensing tumours to Luminal A/B and human epidermal growth factor 2-enriched (HER2E)/molecular apocrine (MA)/luminal androgen receptor (LAR)-positive classes, and alveolar/secretory tumours to the Basal-like class. Molecular classification is most useful when tumours have classic invasive carcinoma of no special type (NST) histology. It is less useful for special histological types of breast cancer, such as metaplastic breast cancer and adenoid cystic cancer, which are better described with standard pathology terms. Compared to mice, humans show a strong bias towards making tumours that resemble mammary hormone-sensing cells. This could be caused by the formation in adolescence of der(1;16), a translocation through the centromeres of chromosomes 1 and 16, which only occurs in humans and could trap the cells in the hormone-sensing state.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1464 ","pages":"185-207"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Models for Studying Ductal Carcinoma In Situ Progression. 研究导管原位癌进展的模型。
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-70875-6_6
Isabella Nair, Fariba Behbod
{"title":"Models for Studying Ductal Carcinoma In Situ Progression.","authors":"Isabella Nair, Fariba Behbod","doi":"10.1007/978-3-031-70875-6_6","DOIUrl":"https://doi.org/10.1007/978-3-031-70875-6_6","url":null,"abstract":"<p><p>An estimated 55,720 new cases of ductal carcinoma in situ (DCIS) will be diagnosed in 2023 in the USA alone because of the increased use of screening mammography. The treatment goal in DCIS is early detection and treatment with the hope of preventing progression into invasive disease. Previous studies show progression into invasive cancer as well as reduction in mortality from treatment is not as high as previously thought. So, are we overdiagnosing and over-treating DCIS? An understanding of the natural progression of DCIS is paramount to address this. The purpose of this chapter is to describe various models that have been developed to simulate the processes involved in DCIS to invasive ductal carcinoma (IDC) transition. While each model possesses a unique set of strengths and weaknesses, they have collectively contributed to the current understanding of the molecular and cellular mechanisms underlying this transition. Even though much has been learned, continued advancement of the current models to best match the composition of DCIS epithelial and stromal microenvironment including the extracellular matrix (ECM), stromal cell types, and immune microenvironment will be essential. These advances will undoubtedly pave the way toward a full understanding of mechanisms associated with progression and in predicting when a DCIS lesion remains indolent and when triggers tip in the balance toward progression to malignancy.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1464 ","pages":"95-108"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Molecular Basis of Breast Tumor Heterogeneity. 乳腺肿瘤异质性的分子基础。
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-70875-6_13
Esra Dikoglu, Fresia Pareja
{"title":"Molecular Basis of Breast Tumor Heterogeneity.","authors":"Esra Dikoglu, Fresia Pareja","doi":"10.1007/978-3-031-70875-6_13","DOIUrl":"https://doi.org/10.1007/978-3-031-70875-6_13","url":null,"abstract":"<p><p>Breast cancer (BC) is a profoundly heterogenous disease, with diverse molecular, histological, and clinical variations. The intricate molecular landscape of BC is evident even at early stages, illustrated by the complexity of the evolution from precursor lesions to invasive carcinoma. The key for therapeutic decision-making is the dynamic assessment of BC receptor status and clinical subtyping. Hereditary BC adds an additional layer of complexity to the disease, given that different cancer susceptibility genes contribute to distinct phenotypes and genomic features. Furthermore, the various BC subtypes display distinct metabolic demands and immune microenvironments. Finally, genotypic-phenotypic correlations in special histologic subtypes of BC inform diagnostic and therapeutic approaches, highlighting the significance of thoroughly comprehending BC heterogeneity.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1464 ","pages":"237-257"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Wnt/β-catenin Signaling in Central Nervous System Regeneration. Wnt/β-catenin 信号在中枢神经系统再生中的作用
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/5584_2024_830
Dilek Nazli, Ugur Bora, Gunes Ozhan
{"title":"Wnt/β-catenin Signaling in Central Nervous System Regeneration.","authors":"Dilek Nazli, Ugur Bora, Gunes Ozhan","doi":"10.1007/5584_2024_830","DOIUrl":"10.1007/5584_2024_830","url":null,"abstract":"<p><p>The Wnt/β-catenin signaling pathway plays a pivotal role in the development, maintenance, and repair of the central nervous system (CNS). This chapter explores the diverse functions of Wnt/β-catenin signaling, from its critical involvement in embryonic CNS development to its reparative and plasticity-inducing roles in response to CNS injury. We discuss how Wnt/β-catenin signaling influences various CNS cell types-astrocytes, microglia, neurons, and oligodendrocytes-each contributing to repair and plasticity after injury. The chapter also addresses the pathway's involvement in CNS disorders such as Alzheimer's and Parkinson's diseases, psychiatric disorders, and traumatic brain injury (TBI), highlighting potential Wnt-based therapeutic approaches. Lastly, zebrafish are presented as a promising model organism for studying CNS regeneration and neurodegenerative diseases, offering insights into future research and therapeutic development.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":" ","pages":"13-33"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Influence of RNA Methylation on Cancerous Cells: A Prospective Approach for Alteration of In Vivo Cellular Composition. RNA 甲基化对癌细胞的影响:改变体内细胞组成的前瞻性方法
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/5584_2024_820
Manali Rupareliya, Pravin Shende
{"title":"Influence of RNA Methylation on Cancerous Cells: A Prospective Approach for Alteration of In Vivo Cellular Composition.","authors":"Manali Rupareliya, Pravin Shende","doi":"10.1007/5584_2024_820","DOIUrl":"10.1007/5584_2024_820","url":null,"abstract":"<p><p>RNA methylation is a dynamic and ubiquitous post-transcriptional modification that plays a pivotal role in regulating gene expression in various conditions like cancer, neurological disorders, cardiovascular diseases, viral infections, metabolic disorders, and autoimmune diseases. RNA methylation manifests across diverse RNA species including messenger RNA (mRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA), exerting pivotal roles in gene expression regulation and various biological phenomena. Aberrant activity of writer, eraser, and reader proteins enables dysregulated methylation landscape across diverse malignancy transcriptomes, frequently promoting cancer pathogenesis. Numerous oncogenic drivers, tumour suppressors, invasion/metastasis factors, and signalling cascade components undergo methylation changes that modulate respective mRNA stability, translation, splicing, transport, and protein-RNA interactions accordingly. Functional studies confirm methylation-dependent alterations drive proliferation, survival, motility, angiogenesis, stemness, metabolism, and therapeutic evasion programs systemically. Methyltransferase overexpression typifies certain breast, liver, gastric, and other carcinomas correlating with adverse clinical outcomes like diminished overall survival. Mapping efforts uncover nodal transcripts for targeted drug development against hyperactivated regulators including METTL3. Some erasers and readers also suitable lead candidates based on apparent synthetic lethality. Proteomic screens additionally highlight relevant methylation-sensitive effector pathways amenable to combinatorial blockade, reversing compensatory signalling mechanisms that facilitate solid tumour progression. Quantifying global methylation burdens and responsible enzymes clinically predicts patient prognosis, risk stratification for adjuvant therapy, and overall therapeutic responsiveness.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":" ","pages":"79-103"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Muscle Organoid and Assembloid Systems. 肌肉类器官和类器官系统
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/5584_2024_816
Hazar Eren Soydan, Ayşegül Doğan
{"title":"Muscle Organoid and Assembloid Systems.","authors":"Hazar Eren Soydan, Ayşegül Doğan","doi":"10.1007/5584_2024_816","DOIUrl":"10.1007/5584_2024_816","url":null,"abstract":"<p><p>Skeletal muscle is one of the most complex and largest tissues that perform important processes in the body, including performing voluntary movements and maintaining body temperature. Disruption of muscle homeostasis results in the development of several disorders, including diabetes and sarcopenia. To study the developmental and regenerative dynamics of skeletal muscle and the mechanism behind muscle diseases, it is important to model skeletal muscle and diseases in vitro. Since skeletal muscle has a complex structure and interaction with other tissues and cells that are required to perform their function, conventional 2D cultures are not sufficient to model the skeletal muscle with their interactions. Advances in the field of organoids and assembloids will enable the establishment of more complex and realistic tissue or disease models which cannot be fully recapitulated in conventional 2D culture systems for use in several areas, including disease research, regenerative, and tissue biology. To overcome these limitations, 3D organoid systems and assembloid systems are promising because of their success in recapitulating the complex structural organization, function, and cellular interactions of skeletal muscle.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":" ","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Recording Lineage History with Cellular Barcodes in the Mammary Epithelium and in Breast Cancer. 用细胞条形码记录乳腺上皮和乳腺癌的谱系史。
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-70875-6_5
Candice Merle, Silvia Fre
{"title":"Recording Lineage History with Cellular Barcodes in the Mammary Epithelium and in Breast Cancer.","authors":"Candice Merle, Silvia Fre","doi":"10.1007/978-3-031-70875-6_5","DOIUrl":"https://doi.org/10.1007/978-3-031-70875-6_5","url":null,"abstract":"<p><p>Lineage tracing methods have extensively advanced our understanding of physiological cell behaviour in vivo and in situ and have vastly contributed to decipher the phylogeny and cellular hierarchies during normal and tumour development. In recent years, increasingly complex systems have been developed to track thousands of cells within a given tissue or even entire organisms. Cellular barcoding comprises all techniques designed to genetically label single cells with unique DNA sequences or with a combination of fluorescent proteins, in order to trace their history and lineage production in space and time. We distinguish these two types of cellular barcoding as genetic or optical barcodes. Furthermore, transcribed cellular barcodes can integrate the lineage information with single-cell profiling of each barcoded cell. This enables the potential identification of specific markers or signalling pathways defining distinct stem cell states during development, but also signals promoting tumour growth and metastasis or conferring therapy resistance.In this chapter, we describe recent advances in cellular barcoding technologies and outline experimental and computational challenges. We discuss the biological questions that can be addressed using single-cell dynamic lineage tracing, with a focus on the study of cellular hierarchies in the mammary epithelium and in breast cancer.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1464 ","pages":"77-94"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Light as a Mediator of Acute and Chronic Retina Degeneration.
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_41
Rosellina Guarascio, Michael E Cheetham
{"title":"Light as a Mediator of Acute and Chronic Retina Degeneration.","authors":"Rosellina Guarascio, Michael E Cheetham","doi":"10.1007/978-3-031-76550-6_41","DOIUrl":"https://doi.org/10.1007/978-3-031-76550-6_41","url":null,"abstract":"<p><p>In age-related macula dystrophy (AMD) and some forms of inherited retinal dystrophies (IRDs), blindness is caused by the loss of photoreceptors and retinal pigment epithelium (RPE) cells. This process can be exacerbated by genetic and environmental risk factors, including exposure of the retina to bright light. Several light damage models have been developed and have proved to be powerful tools to study retinal degeneration. These models have enabled the investigation of common mechanisms of cell death and inflammation, as well as the identification of therapeutic targets and the assessment of potential new therapies against retinal degeneration. Here, we discuss the principal mechanisms of light-induced toxicity and highlight how this has been used in the development of therapeutic approaches to treat AMD and IRDs.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"247-251"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Oxidative Stress and Energetic Failure: Common Features and Dissimilarities in 3 Different Mouse Models of Retinal Pigment Epithelium Phagocytosis Defects.
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_43
Elora M Vanoni, Julie Enderlin, Quentin Rieu, Florian Hamieh, Salomé Réty, Emeline F Nandrot
{"title":"Oxidative Stress and Energetic Failure: Common Features and Dissimilarities in 3 Different Mouse Models of Retinal Pigment Epithelium Phagocytosis Defects.","authors":"Elora M Vanoni, Julie Enderlin, Quentin Rieu, Florian Hamieh, Salomé Réty, Emeline F Nandrot","doi":"10.1007/978-3-031-76550-6_43","DOIUrl":"https://doi.org/10.1007/978-3-031-76550-6_43","url":null,"abstract":"<p><p>Amidst the various crucial functions ensured by retinal pigment epithelial (RPE) cells is the circadian phagocytosis of oxidized photoreceptor outer segments (POS) extremities. We have been exploring three mouse models with defective RPE phagocytosis: β5<sup>-/-</sup> mice inactivated for the αvβ5 integrin synchronizing phagocytosis, MerTK<sup>CR</sup> knockin mice devoid of the MerTK internalization receptor cleavage site, and Pre-mRNA Processing Factors 31 knockout mice, PRPF splicing factor mutations constituting the second most important cause of autosomic dominant retinitis pigmentosa in patients. Failure in mitochondrial activity and energetic metabolism has been detected in all three models. Signs of cellular stress and increasing oxidative processes were observed in β5<sup>-/-</sup> and Prpf31<sup>+/-</sup> RPE cells, while MerTK<sup>CR</sup> mutants seem to be sensitive to light-derived stress associated with augmented retinal inflammation. Taken together, these results highlight some common pathological mechanisms in these mice, as well as particular features related to the specific function of each protein.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"259-263"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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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