Advances in experimental medicine and biology最新文献

{"title":"Ocular Tissue-Specific Amino Acid Metabolism in Gyrate Atrophy.","authors":"Artjola Puja, Jinyu Lu, Jianhai Du","doi":"10.1007/978-3-031-76550-6_46","DOIUrl":"10.1007/978-3-031-76550-6_46","url":null,"abstract":"<p><p>Deficiency of the mitochondrial enzyme ornithine aminotransferase (OAT) causes gyrate atrophy of the choroid and retina (GACR), a rare autosomal inherited disorder characterized by a substantial elevation in plasma ornithine and progressive chorioretinal degeneration. While OAT is expressed in many tissues, the deficiency mainly affects the retinal pigment epithelium (RPE)/choroid and retina, progressing from the periphery to the macula. RPE has been identified as the initial site of damage in GACR. Amino acid metabolism is crucial for the RPE function and its support for retinal metabolism. In GACR, in addition to ornithine, the metabolism of multiple amino acids is disrupted. This review explores the tissue-specific differences in amino acid metabolism between macular and peripheral ocular regions that may contribute to the pathophysiology of the disease.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"279-284"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photoreceptor Disc Morphogenesis: Who Are the Conductors of This Highly Metronomic Process?","authors":"Roly Megaw","doi":"10.1007/978-3-031-76550-6_50","DOIUrl":"10.1007/978-3-031-76550-6_50","url":null,"abstract":"<p><p>To ensure that normal vision is maintained, the photoreceptor must continually renew its outer segment, a massive expanse of ciliary membrane extending from the tip of its connecting cilium. The outer segment is organised into hundreds of flattened discs, the formation of which is highly regulated. Disc morphogenesis requires the metronomic assembly of an actin cytoskeletal network to initiate the necessary membrane deformation and subsequent network disassembly to allow disc completion. Disruption of disc turnover, due to human mutations, results in an inherited retinal dystrophy (IRD), a leading cause of visual loss in children and working adults. This chapter will describe the structural evidence that disc formation is actin-driven and discuss what is known of the molecular mechanisms that govern the process.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"305-308"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389821","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}

{"title":"The Oral Microbiome and Us.","authors":"Naile Dame-Teixeira, Thuy Do, Dongmei Deng","doi":"10.1007/978-3-031-79146-8_1","DOIUrl":"10.1007/978-3-031-79146-8_1","url":null,"abstract":"<p><p>Oral and systemic human health depend on the symbiotic relationship between the human host and its microbiome. As the second most diverse site of the human microbiome, the oral cavity is instrumental in symbiotic relationships, transforming nutrients and acting as the human body's initial barrier against pathogens. However, under certain conditions, the typically beneficial oral microbiome can become harmful. Systemic inflammatory diseases can send signals through the oral-gut axis, such as cytokines and host defensins, altering gene expression and, consequently, the composition of the oral microbiome. These changes can be responsible for causing oral diseases, such as periodontitis and candidiasis. Evidence of metabolic syndrome, including obesity, hypertension, hyperglycemia, and dyslipidemia, exacerbates oral microbiome dysbiosis. On the other hand, the oral microbiota can also influence systemic health. Inflammatory processes in the gingival structures caused by a dysbiotic oral microbiome are linked to worsen glycemic levels in diabetics, premature birth, and rheumatoid arthritis, among others. The idea for this book emerged from the need to explore the multifaceted nature of this relationship in its various dimensions. We discuss multispecies characteristics from an ecological perspective, focusing on how the host affects the microbiome and vice versa. Understanding how the oral microbiome influences human health will guide tailored strategies for disease prevention and treatment, which is discussed in the last section of the book. Looking ahead, predictive health and disease models will enable personalized therapies centered on restoring the healthy human microbiome.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1472 ","pages":"3-9"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668844","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}

{"title":"The Detection Limits of Legionella According to the EU Directive 2020/2184. Could That Be Too Permissive?","authors":"G Bertolino, L Marras, V Coroneo","doi":"10.1007/5584_2023_790","DOIUrl":"10.1007/5584_2023_790","url":null,"abstract":"<p><strong>Introduction: </strong>The problem of detecting legionella after a case of legionellosis from the source of environmental contamination has been known since a long time ago. Legionella is a bacterium present in various natural and artificial habitats and especially in surface fresh waters. It is found in greater concentration in warm waters, at temperatures between 20 °C and 42 °C. The greatest risk factor for humans is represented by the presence of Legionella in water distribution systems in hospitals, medical equipment (e.g. respirators, dialyzers, inhalers, humidifiers, water, massage equipment used in balneotherapy) and turbines used in dental practices, especially for hospitalized individuals. In the EU directive 2020/2184, issued by the European parliament on 16/12/2020, the concentration of Legionella was added to the parameters to be determined in assessing the quality of drinking water intended for human consumption. The objectives were to improve the quality standard of drinking water, reduce the consumption of bottled water and consequently reduce plastic waste. The WHO notes that Legionella causes the greatest burden from a health point of view and it is included among the parameters that require careful monitoring with a limit of less than 1000 CFU/L. The aim of this report was to evaluate the new EU directive 2020/2184 on the light of our laboratory experience.</p><p><strong>Materials and methods: </strong>A total of 459 samples were processed at our Hygiene of food Laboratory - Department of Medical Sciences and Public Health. All statistical analyses were conducted using the SPSS statistical package (version 23 for Windows. SPSS, Inc. Chicago, Ill).</p><p><strong>Results and discussion: </strong>Of the 67 structures examined where the cases occurred, 35 showed samples with at least one over-threshold value considering the reference value of 100 CFU/L, whereas using the new limit of 1000 CFU/L, only 25 structures resulted as having at least one sample above the threshold. In our experience as a regional reference laboratory for Legionella research, the increase from 100 CFU/L to 1,000 CFU/L could lead to a lower alert level. In fact, in the period between October 2017 and October 2021, the median value of CFU/L in presence of a case was 0 (0-100). Despite the large amount of studies on Legionella only a few relate the withdrawals and the consequent CFU/L with the confirmed cases of legionellosis, as in our analysis. The 75° percentile values of the Legionella concentration equal to 100 CFU/L in all samples associated with cases and clusters leads us to hypothesize that the limit equal to 1000 CFU/L that will be introduced for environmental monitoring as per recent European regulations may not be sufficiently protective for minimizing risk in the population, especially in healthcare facilities where fragile patients are assisted.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":" ","pages":"23-30"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41096809","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}

{"title":"Microenvironmental Regulation of Dormancy in Breast Cancer Metastasis: \"An Ally that Changes Allegiances\".","authors":"Evrim Ceren Kabak, Sok Lin Foo, Maria Rafaeva, Ivan Martin, Mohamed Bentires-Alj","doi":"10.1007/978-3-031-70875-6_18","DOIUrl":"10.1007/978-3-031-70875-6_18","url":null,"abstract":"<p><p>Breast cancer remission after treatment is sometimes long-lasting, but in about 30% of cases, there is a relapse after a so-called dormant state. Cellular cancer dormancy, the propensity of disseminated tumor cells (DTCs) to remain in a nonproliferative state for an extended period, presents an opportunity for therapeutic intervention that may prevent reawakening and the lethal consequences of metastatic outgrowth. Therefore, identification of dormant DTCs and detailed characterization of cancer cell-intrinsic and niche-specific [i.e., tumor microenvironment (TME) mediated] mechanisms influencing dormancy in different metastatic organs are of great importance in breast cancer. Several microenvironmental drivers of DTC dormancy in metastatic organs, such as the lung, bone, liver, and brain, have been identified using in vivo models and/or in vitro three-dimensional culture systems. TME induction and persistence of dormancy in these organs are mainly mediated by signals from immune cells, stromal cells, and extracellular matrix components of the TME. Alterations of the TME have been shown to reawaken dormant DTCs. Efforts to capitalize on these findings often face translational challenges due to limited availability of representative patient samples and difficulty in designing dormancy-targeting clinical trials. In this chapter, we discuss current approaches to identify dormant DTCs and provide insights into cell-extrinsic (i.e., TME) mechanisms driving breast cancer cell dormancy in distant organs.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1464 ","pages":"373-395"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998456","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}

{"title":"Desmosome and Hemidesmosome Disassembly in Retinal Pigmented Epithelium: Intersection with the Exosome Pathway.","authors":"Mikael Klingeborn, Emily D Reese","doi":"10.1007/978-3-031-76550-6_56","DOIUrl":"10.1007/978-3-031-76550-6_56","url":null,"abstract":"<p><p>The retinal pigmented epithelium (RPE) forms the outer blood-retinal barrier, and like other epithelia it has several different types of cell-cell junctions, such as desmosomes. The RPE provides key metabolic and nutrient support to photoreceptors and the function of normal vision. The RPE is a principal location of disease-associated changes in age-related macular degeneration (AMD), due to its essential role in visual homeostasis. There are no robust early indicators of AMD or disease progression, a need that could be filled by the development of early AMD biomarkers. Exosomes are lipid bilayer membrane vesicles of nanometer sizes that are released via a dedicated machinery by all cells and carry out a multitude of functions related to cellular signaling and waste management. In the RPE, they are released from both the apical and basal sides, and the cargo composition reflects this polarization. We have recently shown that exosomes released from the basolateral side of RPE cells under chronic oxidative stress conditions contain desmosome and hemidesmosome proteins. Here we discuss the composition of desmosomes and hemidesmosomes in the RPE, and the potential of these exosome-associated components as biomarkers of early RPE dysfunction preceding AMD symptoms detectable in the current clinical setting. How cargo loading into basolateral exosomes is controlled in polarized epithelia such as RPE, is also discussed.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"339-343"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389645","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}

{"title":"Melanoma Cell Adhesion Molecule (CD 146) in Endometrial Physiology and Disorder.","authors":"Priyanka Hilage, Mrunal N Damle, Rakesh Kumar Sharma, Meghnad G Joshi","doi":"10.1007/5584_2024_826","DOIUrl":"10.1007/5584_2024_826","url":null,"abstract":"<p><p>The human endometrium, the innermost lining of the uterus, is the anatomic prerequisite for pregnancy. It is the only dynamic tissue that undergoes more than 400 cycles of regeneration throughout the reproductive life of women. Key to this function are endometrial stem cells as well as cell adhesion molecules. Melanoma cell adhesion molecule (MCAM/CD146/MUC18) is a membrane glycoprotein of the mucin family and a key cell adhesion protein, highly expressed by endometrial cells. CD146 is a significant molecule pivotal in endometrial physiology, assisting tissue regeneration and angiogenesis. Endometrium also acts as a culprit in causing several endometrial dysfunctions, such as endometriosis, endometrial hyperplasia, and endometrial carcinoma, due to interrupted molecular and functional mechanisms. Though most of the endometrial dysfunctions arise as a result of endocrine disturbance, it has a major pathological role associated with angiogenesis. It has already been proven that CD146 is a potential marker for the diagnosis of angiogenic dysfunctions and malignancy, including endometrial cancer. However, its mechanistic role in causing the pathology is a mystery. This chapter explores the role of CD146 in normal and pathological endometrial conditions and the therapeutic implications of CD146.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":" ","pages":"131-148"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455653","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}

{"title":"Monocytes in Retinal Degeneration: Little Cells with a Big Impact.","authors":"Kaitryn E Ronning, Marie E Burns, Florian Sennlaub","doi":"10.1007/978-3-031-76550-6_22","DOIUrl":"10.1007/978-3-031-76550-6_22","url":null,"abstract":"<p><p>Inflammation has been strongly implicated in retinal degenerative disorders, including inherited retinal degenerations (IRDs) and age-related macular degeneration (AMD). Microglia are the only immune cells in the retina during normal function, but during damage and disease, monocytes are able to invade the retina. Despite similarities to microglia, monocyte-derived cells (MdCs) may play a distinct and often pathogenic role in disease. Recent technological advances are rapidly improving our ability to investigate monocytic cells, yet many questions remain. Still, it is clear monocytes play an important role during retinal degenerative disorders and they are an exciting target for the development of therapeutic interventions.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"133-137"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389701","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}

{"title":"Identification of Unexpected Pathomechanisms Underlying the Human Usher Syndrome.","authors":"Uwe Wolfrum, Joshua Linnert, Baran E Güler, Joshua Klein, Jacques S Fritze, Nicole Wenck, Kerstin Nagel-Wolfrum","doi":"10.1007/978-3-031-76550-6_28","DOIUrl":"10.1007/978-3-031-76550-6_28","url":null,"abstract":"<p><p>Human Usher syndrome (USH) is the most common form of hereditary deaf-blindness, characterized by inner ear defects and late-onset vision loss. USH is a complex genetic disorder, clinically and genetically heterogeneous. To date, there is no treatment for the ocular phenotype of any USH subtype, as the underlying pathomechanisms of the disease in the eye are far from being understood. We aim to elucidate the function of USH proteins to gain insight into the pathomechanisms leading to the retinal phenotype in USH. Here, we focus on the USH1 proteins SANS (USH1G) and harmonin (USH1C), and the USH2C protein ADGRV1. Results from affinity capture approaches revealed putative interacting proteins to these USH proteins, indicative of diverse various unexpected molecular pathways and modules. Functional studies in both cellular and animal models confirmed the roles of SANS in the pre-mRNA splicing of other retinal genes, especially USH genes and harmonin as a suppressor of the canonical Wnt signaling. Additionally, ADGRV1 showed characteristics of a metabotropic mechanoreceptor regulating cell adhesions, Ca²⁺ homeostasis of the cell, and autophagy. The dysfunction of these pathways and processes may contribute to the development of USH and are novel potential targets for future therapies.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"171-175"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389728","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}

{"title":"Megabase Deletion of the Human EYS Locus Using CRISPR/Cas9.","authors":"Bruna Lopes da Costa, Anders Steen Knudsen, C Henrique Alves, Stephen H Tsang, Peter M J Quinn","doi":"10.1007/978-3-031-76550-6_18","DOIUrl":"10.1007/978-3-031-76550-6_18","url":null,"abstract":"<p><p>Mutations in the Eyes Shut Homolog (EYS) gene are associated with autosomal recessive retinitis pigmentosa (arRP). To date, four retinal isoforms of EYS have been identified. However, the precise retinal function of EYS is not fully understood, but it has apparent roles in retinal morphogenesis, architecture, and ciliary transport. Clustered-regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated (Cas) nuclease-mediated approaches are powerful tools for genome engineering in mammalian cells. The use of paired CRISPR/Cas9-induced double-strand breaks (DSBs) using dual single guide RNAs (sgRNA) can lead to precise genomic deletions. In this study, we developed a dual sgRNA strategy to facilitate CRISPR/Cas9-mediated deletion of 1,988,210 bp of the EYS locus, removing the four currently identified human retinal EYS isoforms. This approach can be used to produce EYSdel induced pluripotent stem cell (iPSC) lines to explore the function of EYS in human iPSC-derived retinal organoids.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"107-111"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389774","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}