Advances in experimental medicine and biology最新文献

{"title":"Recent Advances in the Role of Non-coding RNAs in Fetal Alcohol Spectrum Disorders.","authors":"Ariana N Pritha, Andrea A Pasmay, Shahani Noor","doi":"10.1007/978-3-031-81908-7_7","DOIUrl":"10.1007/978-3-031-81908-7_7","url":null,"abstract":"<p><p>Despite numerous preclinical studies modeling fetal alcohol spectrum disorder (FASD)-associated neurodevelopmental deficits to date, a comprehensive molecular landscape dictating these deficits remains poorly understood. Non-coding RNAs constitute a substantial layer of epigenetic regulation of gene expression at the transcriptional, post-transcriptional, translational, and post-translational levels. Yet, little is known about the differential expression of non-coding RNAs in the context of prenatal alcohol exposure (PAE) that are mechanistically linked with FASD-related neurobehavior deficits. This chapter reviews our current knowledge from preclinical studies in non-coding RNA-mediated molecular mechanisms that may underlie FASD pathophysiology. This chapter also summarizes relevant clinical evidence and current efforts in utilizing these non-coding RNA molecules as biomarkers of PAE-associated deficits impacting central nervous system (CNS) function. Unraveling the diverse roles of various species of non-coding RNAs is critical to enhancing our comprehension of these intricate molecular pathways. Understanding these pathways would likely contribute to identifying critical molecular target(s) for developing efficient treatment strategies and prognostic and diagnostic markers fostering advancements in treating and managing FASD-related CNS dysfunction.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1473 ","pages":"129-155"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699349","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":"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":"10.1007/5584_2024_829","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":" ","pages":"69-85"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","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}

{"title":"Clinical Implications of Breast Cancer Intrinsic Subtypes.","authors":"Alejandro Rios-Hoyo, Naing-Lin Shan, Philipp L Karn, Lajos Pusztai","doi":"10.1007/978-3-031-70875-6_21","DOIUrl":"10.1007/978-3-031-70875-6_21","url":null,"abstract":"<p><p>Estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) breast cancers have different genomic architecture and show large-scale gene expression differences consistent with different cellular origins, which is reflected in the luminal (i.e., ER+) versus basal-like (i.e., ER-) molecular class nomenclature. These two major molecular subtypes have distinct epidemiological risk factors and different clinical behaviors. Luminal cancers can be subdivided further based on proliferative activity and ER signaling. Those with a high expression of proliferation-related genes and a low expression of ER-associated genes, called luminal B, have a high risk of early recurrence (i.e., within 5 years), derive significant benefit from adjuvant chemotherapy, and may benefit from adding immunotherapy to chemotherapy. This subset of luminal cancers is identified as the genomic high-risk ER+ cancers by the MammaPrint, Oncotype DX Recurrence Score, EndoPredict, Prosigna, and several other molecular prognostic assays. Luminal A cancers are characterized by low proliferation and high ER-related gene expression. They tend to have excellent prognosis with adjuvant endocrine therapy. Adjuvant chemotherapy may not improve their outcome further. These cancers correspond to the genomic low-risk categories. However, these cancers remain at risk for distant recurrence for extended periods of time, and over 50% of distant recurrences occur after 5 years. Basal-like cancers are uniformly highly proliferative and tend to recur within 3-5 years of diagnosis. In the absence of therapy, basal-like breast cancers have the worst survival, but these also include many highly chemotherapy-sensitive cancers. Basal-like cancers are often treated with preoperative chemotherapy combined with an immune checkpoint inhibitor which results in 60-65% pathologic complete response rates that herald excellent long-term survival. Patients with residual cancer after neoadjuvant therapy can receive additional postoperative chemotherapy that improves their survival. Currently, there is no clinically actionable molecular subclassification for basal-like cancers, although cancers with high androgen receptor (AR)-related gene expression and those with high levels of immune infiltration have better prognosis, but currently their treatment is not different from basal-like cancers in general. A clinically important, minor subset of breast cancers are characterized by frequent HER2 gene amplification and high expression of a few dozen genes, many residing on the HER2 amplicon. This is an important subset because of the highly effective HER2 targeted therapies which are synergistic with endocrine therapy and chemotherapy. The clinical behavior of HER2-enriched cancers is dominated by the underlying ER subtype. ER+/HER2-enriched cancers tend to have more indolent course and lesser chemotherapy sensitivity than their ER counterparts.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1464 ","pages":"435-448"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998427","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":"Precise Gene Editing Technologies in Retinal Applications.","authors":"Mehri Ahmadian, Iskalen Cansu Topcu Okan, Gokce Uyanik, Markus Tschopp, Cavit Agca","doi":"10.1007/978-3-031-76550-6_20","DOIUrl":"10.1007/978-3-031-76550-6_20","url":null,"abstract":"<p><p>Gene therapy is emerging as a promising treatment for inherited retinal diseases (IRDs). One of the first successful applications of gene therapy for IRDs was the gene replacement therapy for the RPE65 mutation. This therapy delivers a functional copy of the RPE65 gene to patients via AAV vectors, rather than targeting the mutation itself. Gene editing technologies have advanced significantly in recent years, allowing it to make precise in vivo modifications to the genetic code. After the discovery of CRISPR-Cas9, other gene editing technologies such as base editing and prime editing have been developed by modifying and combining the original CRISPR-Cas9 technology with other methods. Moreover, recently discovered CRISPR-Cas systems allow RNA editing to correct mutations at the posttranscriptional level. These technologies have potential applications in various fields, including inherited retinal diseases. This mini-review evaluates and summarizes the most current advancements in genome editing methods, including prime editing, base editing, and RNA editing, and their applications on retinal diseases.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"119-123"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389824","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 Autoimmune Regulator (AIRE) Gene, The Master Activator of Self-Antigen Expression in the Thymus.","authors":"Matthieu Giraud, Pärt Peterson","doi":"10.1007/978-3-031-77921-3_7","DOIUrl":"10.1007/978-3-031-77921-3_7","url":null,"abstract":"<p><p>It has been more than 20 years since the AIRE gene was discovered. The mutations in the AIRE gene cause a rare and life-threatening autoimmune disease with severe manifestations against a variety of organs. Since the identification of the AIRE gene in 1997, more than two decades of investigations have revealed key insights into the role of AIRE and its mode of action. These studies have shown that AIRE uniquely induces the expression of thousands of tissue-restricted self-antigens in the thymus. These self-antigens are presented to developing T cells, resulting in the deletion of the self-reactive T cells and the generation of regulatory T cells. Thus, AIRE is a master guardian in establishing and maintaining central immune tolerance.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1471 ","pages":"199-221"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603351","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":"Interaction of the Systemic Inflammatory State, Inflammatory Mediators, and the Oral Microbiome.","authors":"Mariana Caldas Oliveira Mattos, Amanda Vivacqua, Valeria Martins Araújo Carneiro, Daniela Correa Grisi, Maria do Carmo Machado Guimarães","doi":"10.1007/978-3-031-79146-8_8","DOIUrl":"10.1007/978-3-031-79146-8_8","url":null,"abstract":"<p><p>Humans are biological units that host numerous microbial symbionts and their genomes, which together form a superorganism or holobiont. Changes in the balance of the oral ecosystem can have consequences for both general and oral health, such as cavities, gingivitis, and periodontitis. Periodontitis is initiated by a synergistic and dysbiotic microbial community that causes local inflammation and destruction of the tooth's supporting tissues, potentially leading to systemic inflammation. This inflammation caused by periodontal disease has been associated with various systemic alterations, and the immune system is largely responsible for the body's exacerbated response, which can induce and exacerbate chronic conditions. Studies indicate that subgingival microorganisms found in periodontitis reach the bloodstream and are distributed throughout the body and, therefore, can be found in distant tissues and organs. Among all diseases associated with periodontal disease, diabetes mellitus presents the strongest and most elucidated link, and its bidirectional relationship has already been demonstrated. Chronic hyperglycemia favors the worsening of periodontal parameters, while the aggravation of periodontal parameters can promote an increase in glycemic indexes. Other systemic diseases have been related to periodontitis, such as Alzheimer's, chronic kidney disease, atherosclerosis, and respiratory diseases. The importance of periodontal control may suggest a reduction in the chances of developing chronic inflammatory diseases because these two alterations often share inflammatory pathways and, for this reason, may influence each other.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1472 ","pages":"121-132"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668832","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 PRPH2 D2 Loop: Biochemical Insights and Implications in Disease.","authors":"Larissa Ikelle, Muayyad R Al-Ubaidi, Muna I Naash","doi":"10.1007/978-3-031-76550-6_52","DOIUrl":"10.1007/978-3-031-76550-6_52","url":null,"abstract":"<p><p>PRPH2 is a glycosylated tetraspanin protein that plays a crucial role in outer segment morphogenesis. The protein induces membrane curvature at the rim and orchestrates proper disc elaboration by forming a complex network of homo- and hetero-oligomers, primarily mediated through its EC2/D2 loop. This loop, a functionally and structurally essential domain shared by all tetraspanins, is divided into two subdomains responsible for diverse interactions. Pathological mutations in the EC2/D2 loop account for nearly 70% of all PRPH2 mutations, resulting in a spectrum of heterogenous disease phenotypes. In this chapter, we provide an overview of the structural elements of the EC2/D2 loop of PRPH2 and explore the cellular and biochemical consequences of known mutations.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"313-317"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389637","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":"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}