Advances in experimental medicine and biology最新文献

{"title":"ABCA4 c.5461-6T>C Causes Stargardt Disease Through Exon Skipping.","authors":"Mathieu Quinodoz, Ana Belén Iglesias-Romero, Francesca Cancellieri, Karolina Kaminska, Hendrik P N Scholl, Maximilian Pfau, Carlo Rivolta","doi":"10.1007/978-3-031-76550-6_10","DOIUrl":"10.1007/978-3-031-76550-6_10","url":null,"abstract":"<p><p>Stargardt disease (STGD1) is an inherited retinal dystrophy that follows an autosomal recessive inheritance in which photoreceptors degenerate, leading to progressive vision loss that starts from the central retina. The severity of symptoms can vary considerably depending on the mutations: they range from severe childhood-onset to late-onset milder forms, the latter being caused by specific hypomorphic variants. In this study, we describe a novel non-canonical splicing variant: NM_000350.3:c.5461-6T>C. This variant was found in compound heterozygosity with a frequent pathogenic hypomorphic variant, p.Gly1961Glu, in a patient with Stargardt disease and her affected brother. In silico tools predicted a low effect on splicing, but experimental validation, in contrast, showed this DNA change to be causing severe splicing alterations.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"57-62"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389584","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":"Oral Diseases Are Associated with Cognitive Decline and Dementia.","authors":"Chenyi Gao, Jing Kang","doi":"10.1007/978-3-031-79146-8_11","DOIUrl":"10.1007/978-3-031-79146-8_11","url":null,"abstract":"<p><p>Common oral diseases, including periodontitis and dental caries, and their endpoint as tooth loss are controllable yet highly prevalent among adults worldwide. Cognitive decline also poses significant global public health challenges during the aging process, especially the pathological form of cognitive decline such as dementia. Dementia is irreversible and is one of the leading causes of death, disability, and dependency in the aging population. Emerging research suggests a bidirectional association between oral diseases and cognitive decline or dementia. This potential link has implications for designing better oral care plans for patients with dementia and recognizing oral diseases as modifiable risk factors for dementia prevention.This chapter provides an overview of the association between oral diseases and cognitive decline, followed by a discussion of current evidence on such associations in two directions: (1) the impact of cognitive decline or dementia on oral health and (2) the role of oral diseases as modifiable risk factors for dementia. We critically evaluate several hypotheses regarding the underlying mechanisms of this association, including (1) life-course hypothesis, (2) shared inflammation and bacterial infection mechanisms, (3) malnourishment mechanism, (4) pain pathway, and (5) sensory feedback pathway.However, the association between oral diseases and cognitive decline or dementia remains controversial due to limited high-quality evidence, particularly from biomedical research. Much of the existing evidence is from observational studies prone to confounding bias, with inconclusive questions about causation and the direction of causality.This chapter concludes by emphasizing the need for future studies with robust methodological designs, including randomized controlled trials, biomedical studies, and innovative research techniques such as Mendelian randomization. Such studies are crucial for disease prevention and enhancing patient care and quality of life. By providing a comprehensive overview, this chapter contributes to an advanced understanding of this field, addresses current study gaps, and suggests future research directions.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1472 ","pages":"171-183"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668806","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":"Assessment of ABCA4 Genetic Variants: Current Landscape and Future Prospects.","authors":"Senem Cevik, Subhasis B Biswas, Esther E Biswas-Fiss","doi":"10.1007/978-3-031-76550-6_11","DOIUrl":"10.1007/978-3-031-76550-6_11","url":null,"abstract":"<p><p>Genetic variants of ABCA4 are associated with a spectrum of inherited retinal degenerations, causing progressive vision loss due to rod and cone photoreceptor death and retinal pigment epithelium atrophy, ultimately leading to blindness. Understanding the functional implications and assessing the pathogenicity of the extensive number of ABCA4 variants, which exceed 3000, remains a formidable challenge. A substantial proportion of these variants remain categorized as variants of uncertain significance (VUS) or exhibit conflicting clinical interpretations (CI). Determining variant pathogenicity is imperative for clinicians to assess long-term outcomes and facilitate precise patient enrollment in ongoing clinical trials. This review aims to provide an overview of the current methodologies used to assess the functional characteristics of ABCA4 variants.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"63-67"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389588","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":"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":"10.1007/978-3-031-76550-6_26","url":null,"abstract":"<p><p>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.</p>","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}

{"title":"The Impact of Diet and Nutrition on the Oral Microbiome.","authors":"Simona Santonocito, Alessandro Polizzi, Gaetano Isola","doi":"10.1007/978-3-031-79146-8_4","DOIUrl":"10.1007/978-3-031-79146-8_4","url":null,"abstract":"<p><p>At present, it is well known that oral health is essential for the well-being of the body as a whole, thanks to the increasing awareness of how various oral diseases, including periodontal disease, oral carcinomas, and other conditions, have a close connection with various systemic disorders. In recent decades, studies on the oral microbiome have increasingly emphasized how the balance between the host and the microbial species that coexist there is essential for oral health at all stages of life. However, there are many factors capable of interfering with that balance, and diet is precisely one of them. The real influence of diet on the oral microbiota, and consequently on oral health, has been much debated. In this context, the observation of two key periods in human history, the Neolithic and the Industrial Revolution, has proved to be diriment. The foods and processing techniques that emerged in these two historical periods, in association with changes in customs and habits, significantly altered the central constituents of the human diet, including macronutrient proportions, glycemic load, fatty acid composition, sodium and potassium levels, micronutrient levels, dietary pH, and fiber content taken in by human beings. The introduction of these foods into the daily human routine has been linked to a decline in oral health and an increase of several other diseases, including cardiovascular diseases, inflammatory bowel disease, rheumatic diseases, many cancers, and obesity. The aim of this chapter is to update the current knowledge and further discuss the role of diet and nutrition on oral health.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1472 ","pages":"53-69"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668811","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":"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":"10.1007/978-3-031-76550-6_64","url":null,"abstract":"<p><p>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.</p>","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}

{"title":"Exploring Innovative Approaches to Isolate a One-Component c-di-GMP Transducer: A Pilot Study.","authors":"Chiara Scribani Rossi, Giacomo Parisi, Alessandro Paiardini, Serena Rinaldo","doi":"10.1007/5584_2023_787","DOIUrl":"10.1007/5584_2023_787","url":null,"abstract":"<p><p>Environmental nutrients control bacterial biofilm homeostasis, by regulating the intracellular levels of c-di-GMP. One component transducers can sense different classes of small molecules through a periplasmic domain; the nutrient recognition triggers the subsequent regulation of the downstream cytosolic diguanylate cyclase (GGDEF) or phosphodiesterase (EAL) domains, via transmembrane helix(ces), to finally change c-di-GMP levels.Protein studies on such transducers have been mainly carried out on isolated domains due to the presence of the transmembrane portion. Nevertheless, the cleavage of GGDEF and EAL-containing proteins could be detrimental since both tertiary and quaternary structures could be allosterically controlled; to by-pass this limitation, studies on the corresponding full-length proteins are highly desired.We have in silico selected a GGDEF-EAL transducer from Dyella thiooxydans (ann. A0A160N0B7), whose periplasmic binding domain was predicted to bind to arginine, a nutrient often associated with chronic infections and biofilm. This protein has been used as an in vitro tool for the identification of the best approach for its isolation, including (i) protein engineering to produce a water-soluble version via QTY (Glutamine, Threonine, and Tyrosine) code or (ii) nanodiscs assembly. The results on this \"prototype\" may represent the proof-of-concept for future isolation of other transmembrane proteins sharing the same architecture, including more complex nutrient-based transducers controlling c-di-GMP levels.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":" ","pages":"9-21"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10052193","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":"Riboflavin, Retbindin, and Riboflavin Transporters in the Retina.","authors":"Xue Zhao, Muna I Naash, Muayyad R Al-Ubaidi","doi":"10.1007/978-3-031-76550-6_77","DOIUrl":"10.1007/978-3-031-76550-6_77","url":null,"abstract":"<p><p>The retina is the most metabolically active tissue in the body. It harbors high levels of flavins due to their involvement as enzymatic co-factors in energy production. Flavins are delivered to the body via specific transporters, the ablation of which leads to riboflavin transporter deficiency (RTD) and ariboflavinosis in humans. RTD leads to embryonic lethality in mice, and in humans, it has detrimental effects on the nervous system, causing neurologic abnormalities. However, the reports on the effects of RTD on retinal homeostasis are limited despite the fact that the retina maintains high levels of riboflavin and its derivatives. We have identified retbindin (Rtbdn) as a retina-specific riboflavin-binding protein, ablation of which leads to reduced flavin levels associated with retinal degeneration in mice. To focus attention on the role of flavins in retinal homeostasis, herein, we discuss the specific functions of flavins and Rtbdn and their protective roles in maintaining retinal health.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"471-475"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389783","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":"A Comprehensive Review of the Mechanisms and Clinical Development of Monoclonal Antibodies in Cancer Therapy.","authors":"Selen Gencsoy Eker, Gizem Inetas Yengin, Cansu Tatar, Gulperi Oktem","doi":"10.1007/5584_2024_838","DOIUrl":"10.1007/5584_2024_838","url":null,"abstract":"<p><p>Cancer is still the disease that ranks first in human mortality in the twenty-first century. In the last 20 years, the concept of molecular targeted therapy has come to the fore with the use of small molecule agents or signal transduction inhibitors that show anticancer effects for certain types of cancer. Monoclonal antibodies, which have a therapeutic effect, especially by providing signal transduction inhibition, are used clinically as first-line treatment in various types of cancer. Molecular targeted therapies are critical for eliminating the adverse effects and drug resistance problems that occur in traditional cancer treatments. This review summarizes current information on various targeted therapeutic agents, including the structure and classification of monoclonal antibodies, their production methods and mechanisms of action, the monoclonal antibodies used in clinical trials, the complement system mechanism and cancer relationship, and the relationship between complement-dependent cytotoxicity and monoclonal antibodies.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":" ","pages":"181-203"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811867","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":"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":"10.1007/978-3-031-70875-6_14","url":null,"abstract":"<p><p>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.</p>","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}