Advances in experimental medicine and biology最新文献_第3页

Astrocytes in Primary Familial Brain Calcification (PFBC): Emphasis on the Importance of Induced Pluripotent Stem Cell-Derived Human Astrocyte Models. 星形胶质细胞在原发性家族性脑钙化（PFBC）：强调诱导多能干细胞衍生的人类星形胶质细胞模型的重要性。

4区医学

Advances in experimental medicine and biology Pub Date : 2025-01-23 DOI: 10.1007/5584_2024_840

Ebru Kavakli, Nazli Gul, Onur Can Begentas, Erkan Kiris

{"title":"Astrocytes in Primary Familial Brain Calcification (PFBC): Emphasis on the Importance of Induced Pluripotent Stem Cell-Derived Human Astrocyte Models.","authors":"Ebru Kavakli, Nazli Gul, Onur Can Begentas, Erkan Kiris","doi":"10.1007/5584_2024_840","DOIUrl":"https://doi.org/10.1007/5584_2024_840","url":null,"abstract":"Primary familial brain calcification (PFBC) is a rare, progressive central nervous system (CNS) disorder without a cure, and the current treatment methodologies primarily aim to relieve neurological and psychiatric symptoms of the patients. The disease is characterized by abnormal bilateral calcifications in the brain, however, our mechanistic understanding of the biology of the disease is still limited. Determining the roles of the specific cell types and molecular mechanisms involved in the pathophysiological processes of the disease is of great importance for the development of novel and effective treatment methodologies. There is a growing interest in the involvement of astrocytes in PFBC, as recent studies have suggested that astrocytes play a central role in the disease and that functional defects in these cells are critical for the development and progression of the disease. This review aims to discuss recent findings on the roles of astrocytes in PFBC pathophysiology, with a focus on known expression and roles of PFBC genes in astrocytes. Additionally, we discuss the importance of human astrocytes for PFBC disease modeling, and astrocytes as a potential therapeutic target in PFBC. Utilization of species-specific and physiologically relevant PFBC model systems can open new avenues for basic research, drug development, and regenerative medicine.","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998397","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

Establishment of a 3D-Printed Tissue-on-a-Chip Model for Live Imaging of Bacterial Infections. 建立用于细菌感染实时成像的3d打印组织芯片模型。

4区医学

Advances in experimental medicine and biology Pub Date : 2025-01-18 DOI: 10.1007/5584_2024_829

Albert Fuglsang-Madsen, Janus Anders Juul Haagensen, Charlotte De Rudder, Filipa Bica Simões, Søren Molin, Helle Krogh Johansen

{"title":"Establishment of a 3D-Printed Tissue-on-a-Chip Model for Live Imaging of Bacterial Infections.","authors":"Albert Fuglsang-Madsen, Janus Anders Juul Haagensen, Charlotte De Rudder, Filipa Bica Simões, Søren Molin, Helle Krogh Johansen","doi":"10.1007/5584_2024_829","DOIUrl":"https://doi.org/10.1007/5584_2024_829","url":null,"abstract":"Despite advances in healthcare, bacterial pathogens remain a severe global health threat, exacerbated by rising antibiotic resistance. Lower respiratory tract infections, with their high death toll, are of particular concern. Accurately replicating host-pathogen interactions in laboratory models is crucial for understanding these diseases and evaluating new therapies. In this communication, we briefly present existing in vivo models for cystic fibrosis and their limitations in replicating human respiratory infections. We then present a novel, 3D-printed, cytocompatible microfluidic lung-on-a-chip device, designed to simulate the human lung environment, and with possible use in recapitulating general infectious diseases.Our device enables the colonisation of fully differentiated lung epithelia at an air-liquid interface with Pseudomonas aeruginosa, a key pathogen in many severe infections. By incorporating dynamic flow, we replicate the clearance of bacterial toxins and planktonic cells, simulating both acute and chronic infections. This platform supports real-time monitoring of therapeutic interventions, mimics repeated drug administrations as in clinical settings, and facilitates the analysis of colony-forming units and cytokine secretion over time. Our findings indicate that this lung-on-a-chip device has significant potential for advancing infectious disease research, in optimizing treatment strategies against infections and in developing novel treatments.","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998409","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

Embryonic Mammary Gland Morphogenesis. 胚胎乳腺形态发生。

4区医学

Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-70875-6_2

Satu-Marja Myllymäki, Qiang Lan, Marja L Mikkola

{"title":"Embryonic Mammary Gland Morphogenesis.","authors":"Satu-Marja Myllymäki, Qiang Lan, Marja L Mikkola","doi":"10.1007/978-3-031-70875-6_2","DOIUrl":"https://doi.org/10.1007/978-3-031-70875-6_2","url":null,"abstract":"Embryonic mammary gland development unfolds with the specification of bilateral mammary lines, thereafter progressing through placode, bud, and sprout stages before branching morphogenesis. Extensive epithelial-mesenchymal interactions guide morphogenesis from embryogenesis to adulthood. Two distinct mesenchymal tissues are involved, the primary mammary mesenchyme that harbors mammary inductive capacity, and the secondary mesenchyme, the precursor of the adult stroma. Placode and bud stages are morphologically similar with other ectodermal appendages like the hair follicle, reflecting the mammary gland's assumed evolutionary origin from an ancestral hair follicle-associated glandular unit. The shared features extend to signalling cascades such as the Wnt/β-catenin, fibroblast growth factor (Fgf), and ectodysplasin (Eda) pathways, while pathways unique to mammary gland include parathyroid hormone-like hormone (Pthlh) signalling and Hedgehog activity suppression. Mammary gland branching is highly non-stereotypic, achieved by the dynamic use of two distinct modes of branching: tip bifurcation and side branching and stochastic branch point formation. The cellular mechanisms driving the initial morphogenetic steps are slowly beginning to be unravelled. During placode and bud stages, mammary primordium predominantly grows through cell influx, while sprouting correlates with heightened proliferation. Branch elongation is driven by directional cell migration combined with differential cell motility and proliferation supplying the reservoir of migratory cells, whereas a bifurcating tip is associated with localized repression of the cell cycle and cell motility. Numerous similarities exist between embryonic programs and breast tumorigenesis, spanning cellular plasticity, epithelial-stromal interactions, and molecular regulators. Understanding embryonic mammogenesis may provide insights into how normal developmental processes can go awry, leading to malignancy, or how they can be reversed to prevent cancer progression.","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1464 ","pages":"9-27"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998449","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

The Roles of Myeloid Cells in Breast Cancer Progression. 骨髓细胞在乳腺癌进展中的作用。

4区医学

Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-70875-6_19

Charlotte Helena Rivas, Fengshuo Liu, Xiang H-F Zhang

{"title":"The Roles of Myeloid Cells in Breast Cancer Progression.","authors":"Charlotte Helena Rivas, Fengshuo Liu, Xiang H-F Zhang","doi":"10.1007/978-3-031-70875-6_19","DOIUrl":"https://doi.org/10.1007/978-3-031-70875-6_19","url":null,"abstract":"This chapter reviews tumor-associated myeloid cells, including macrophages, neutrophils, and other innate immune cells, and their multifaceted roles in supporting breast cancer progression and metastasis. In primary tumors, myeloid cells play key roles in promoting tumor epithelial-mesenchymal transition (EMT) and invasion. They can facilitate intravasation (entry into the bloodstream) and colonization, disrupting the endothelial cell layer and reshaping the extracellular matrix. They can also stimulate angiogenesis, suppress immune cell responses, and enhance cancer cell adaptability. In the bloodstream, circulating myeloid cells enable the survival of disseminated tumor cells via immunosuppressive effects and physical shielding. At the metastatic sites, they prime the premetastatic niche, facilitate tumor cell extravasation, and support successful colonization and outgrowth. Mechanistically, myeloid cells enhance cancer cell survival, dormancy escape, proliferation, and mesenchymal-epithelial transition (MET). Nonetheless, substantial gaps in our understanding persist regarding the functional and spatiotemporal diversity, as well as the evolutionary patterns, of myeloid cells during metastatic progression. Myeloid cell plasticity and differential responses to therapies present key barriers to successful treatments. Identifying specific pro-tumoral myeloid cell subpopulations and disrupting their interactions with cancer cells represent promising therapeutic opportunities. Emerging evidence suggests combining immunomodulators or stromal normalizers with conventional therapies could help overcome therapy-induced immunosuppression and improve patient outcomes. Overall, further elucidating myeloid cell heterogeneity and function throughout the process of breast cancer progression and metastasis will enable more effective therapeutic targeting of these critical stromal cells.","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1464 ","pages":"397-412"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998398","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

E-Cadherin-Mediated Cell-Cell Adhesion and Invasive Lobular Breast Cancer. e -钙粘蛋白介导的细胞粘附与浸润性小叶乳腺癌。

4区医学

Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-70875-6_14

Esme Bullock, Valerie G Brunton

{"title":"E-Cadherin-Mediated Cell-Cell Adhesion and Invasive Lobular Breast Cancer.","authors":"Esme Bullock, Valerie G Brunton","doi":"10.1007/978-3-031-70875-6_14","DOIUrl":"https://doi.org/10.1007/978-3-031-70875-6_14","url":null,"abstract":"E-cadherin is a transmembrane protein and central component of adherens junctions (AJs). The extracellular domain of E-cadherin forms homotypic interactions with E-cadherin on adjacent cells, facilitating the formation of cell-cell adhesions, known as AJs, between neighbouring cells. The intracellular domain of E-cadherin interacts with α-, β- and p120-catenins, linking the AJs to the actin cytoskeleton. Functional AJs maintain epithelial tissue identity and integrity. Transcriptional downregulation of E-cadherin is the first step in epithelial-to-mesenchymal transition (EMT), a process essential in development and tissue repair, which, in breast cancer, can contribute to tumour progression and metastasis. In addition, loss-of-function mutations in E-cadherin are a defining feature of invasive lobular breast cancer (also known as invasive lobular carcinoma (ILC)), the second most common histological subtype of breast cancer. ILC displays a discohesive, single-file invasive growth pattern due to the loss of functional AJs. Despite being so prevalent, until recently there has been limited ILC-focused research and historically ILC patients have often been excluded from clinical trials. Despite displaying a number of good prognostic indicators, such as low grade and high rates of estrogen receptor positivity, ILC patients tend to have similar or poorer outcomes relative to the most common subtype of breast cancer, invasive ductal carcinoma (IDC). In ILC, E-cadherin loss promotes hyperactivation of growth factor receptors, in particular insulin-like growth factor 1 receptor, anoikis resistance and synthetic lethality with ROS1 inhibition. These features introduce clinical vulnerabilities that could potentially be exploited to improve outcomes for ILC patients, for whom there are currently limited tailored treatments available.","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1464 ","pages":"259-275"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998448","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

Importance of Choriocapillaris Replacement in Therapeutic Strategies for Age-Related Macular Degeneration.

4区医学

Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_64

Emma L Burton, Victoria E Tovell, Peter Coffey

{"title":"Importance of Choriocapillaris Replacement in Therapeutic Strategies for Age-Related Macular Degeneration.","authors":"Emma L Burton, Victoria E Tovell, Peter Coffey","doi":"10.1007/978-3-031-76550-6_64","DOIUrl":"https://doi.org/10.1007/978-3-031-76550-6_64","url":null,"abstract":"Age-related macular degeneration (AMD) is a progressive disease of the retina, characterised by the degeneration of several cell layers, including the choriocapillaris (CC), retinal pigment epithelium (RPE) and photoreceptors (PR). Because of this, cell replacement therapies have the potential to treat AMD. Previous research has predominantly focussed on the development of a transplantable pluripotent stem cell-derived RPE monolayer, owing to RPE degeneration early in AMD. However, there is now increasing evidence for CC atrophy early in the pathogenesis of AMD. Given the crucial role of the CC in retinal homeostasis, there is significant potential to expand research into CC replacement with the hope of advancing current cell therapies. The RPE and CC have a highly interconnected relationship, and thus, the replacement of one of these cell layers while the other remains dysfunctional may not be optimal for the long-term rescue of vision in AMD. Therefore, one approach would be to replace both the RPE and CC as a combined cell therapy. Here, we outline the importance of CC in health and disease, as well as potential considerations when building a tissue-engineered CC-like vascular network, with a particular focus on pericytes.","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"389-393"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389736","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

Riboflavin, Retbindin, and Riboflavin Transporters in the Retina. 视网膜中的核黄素、视黄醛和核黄素转运体

4区医学

Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_77

Xue Zhao, Muna I Naash, Muayyad R Al-Ubaidi

引用次数: 0

Molecular Components of Vesicle Cycling at the Rod Photoreceptor Ribbon Synapse.

4区医学

Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_54

Christin Hanke-Gogokhia, Thomas E Zapadka, Stella Finkelstein, Vadim Y Arshavsky, Jonathan B Demb

引用次数: 0

Assessment of ABCA4 Genetic Variants: Current Landscape and Future Prospects.

4区医学

Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_11

Senem Cevik, Subhasis B Biswas, Esther E Biswas-Fiss

引用次数: 0

Noninvasive Assessment of Ocular Structure in the Elderly 13-Lined Ground Squirrel.

4区医学

Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_26

Hannah M Follett, Ching Tzu Yu, Owen R Bowie, Chloe Guillaume, Phyllis Summerfelt, Emma Warr, Dana K Merriman, Joseph Carroll

{"title":"Noninvasive Assessment of Ocular Structure in the Elderly 13-Lined Ground Squirrel.","authors":"Hannah M Follett, Ching Tzu Yu, Owen R Bowie, Chloe Guillaume, Phyllis Summerfelt, Emma Warr, Dana K Merriman, Joseph Carroll","doi":"10.1007/978-3-031-76550-6_26","DOIUrl":"https://doi.org/10.1007/978-3-031-76550-6_26","url":null,"abstract":"The 13-lined ground squirrel (13-LGS) is an attractive model for vision research due to its cone-dominance, accessibility, and amenability to noninvasive retinal imaging. The ability to interpret results from longitudinal studies in this animal model is limited by a lack of normative data from aged animals. To address this, we used noninvasive imaging to characterize structural changes in the anterior segment and retina in 20 13-LGS aged 5-8 years of age. Our imaging revealed multiple age-related changes in the 13-LGS eye. Phenotypes include lens opacifications, loss of normal cone structure surrounding the optic nerve head, abnormal near-infrared reflectance and short-wavelength fundus autofluorescence signal, altered and disrupted retinal lamination, choroidal thinning, and cone mosaic disruptions and reflectivity alterations. While these qualitative observations were considered abnormal, quantitative measures of retinal thickness and cone density in elderly eyes were comparable to those of young controls. Age-related changes in ocular media and retinal structure in the 13-LGS need to be considered in future longitudinal studies.","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"157-162"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389706","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