Advances in experimental medicine and biology最新文献

{"title":"An Overview of Circular RNAs.","authors":"Julia Mester-Tonczar, Ena Hasimbegovic","doi":"10.1007/978-981-96-9428-0_1","DOIUrl":"https://doi.org/10.1007/978-981-96-9428-0_1","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) are a class of endogenous, covalently closed RNA molecules. Unlike linear RNAs, circRNAs are formed through noncanonical splicing, during which a downstream donor site is ligated with an upstream splice acceptor site, building a backsplice junction (BSJ), the distinguishing feature of circRNAs. The inherent feature of circRNAs is their lack of 5' cap structures and 3' poly(A) tails, which are typically found in linear RNAs. Due to their resistance to exonucleases, they exhibit increased stability compared to linear RNAs. In the past, circRNAs have been shown to be evolutionarily conserved and possess cell-type and tissue-specific expression patterns. The various important biological functions of circRNAs, including their roles as protein inhibitors (microRNA (miRNAs) sponges) and regulators of RNA-binding proteins (RBPs), have made them interesting biomolecules for the scientific community. However, due to the novelty of this research field, many obstacles are still present, arising from the lack of consensus on the precise methodological standards for reliable identification and nomenclature of newly identified circRNAs, inherent limitations of the applied methodologies, and the open questions regarding the mechanisms of action of this class of RNAs. This chapter will provide a brief summary of the discovery of circRNAs and the early related research. We will outline the importance of RNA sequencing technologies in circRNA research and highlight the more recent findings in this field, with a special focus on the different functions of circRNAs. Finally, we will discuss key challenges associated with circRNA research.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1485 ","pages":"3-18"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938775","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":"Iron and Pregnancy.","authors":"Veena Sangkhae, Elizabeta Nemeth","doi":"10.1007/978-3-031-92033-2_21","DOIUrl":"https://doi.org/10.1007/978-3-031-92033-2_21","url":null,"abstract":"<p><p>Iron is essential for nearly all living organisms, but iron requirements vary throughout one's lifetime. Pregnancy is a period notable for vastly increased iron requirements. Iron is needed to support maternal adaptations throughout pregnancy and to enable the growth and development of both the placenta and fetus. Insufficient iron has long been linked to adverse pregnancy outcomes; thus, universal iron supplementation is common practice before and during pregnancy. In high-income countries, however, where foods are often iron-fortified and red meat consumption is common, too much iron supplementation during pregnancy has become a concern, as iron excess has also been linked to adverse pregnancy outcomes. Advances in clinical management have enabled more women with iron-related disorders to conceive; thus, it is important to understand iron physiology and how iron disorders affect pregnant women and their offspring to help inform clinical practice and optimize outcomes. This chapter will address the physiologic iron homeostasis of pregnancy and discuss what is currently known about iron-related disease and their consequences on human pregnancy.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1480 ","pages":"327-343"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551640","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":"Impact of Developmental Alcohol Exposure on Sleep Physiology.","authors":"Valentina Licheri, Jonathan L Brigman","doi":"10.1007/978-3-031-81908-7_6","DOIUrl":"10.1007/978-3-031-81908-7_6","url":null,"abstract":"<p><p>The present chapter summarizes the clinical and preclinical findings collected to date, showing the impact of developmental alcohol exposure on sleep physiology. Sleep is a complex physiological process that plays a pivotal role in maintaining overall health and well-being via its involvement in regulating physiological, cognitive, and emotional functions. Clinical studies consistently report a high prevalence of sleep disturbances in children and adolescents diagnosed with fetal alcohol spectrum disorders (FASDs), including short sleep duration, sleep anxiety, bedtime resistance, increased sleep fragmentation, and parasomnias. It is established that alcohol consumption during gestation impairs brain development, leading to structural and functional alterations that may affect sleep architecture. In addition, clinical investigations have found a significant correlation between sleep-wake cycle disruptions and cognitive impairments after developmental alcohol exposure, and sleep disturbances are increasingly recognized as a substantial problem among FASD patients. However, the molecular mechanisms underlying these disturbances are poorly understood. Surprisingly, few studies with animal models of FASDs have characterized the effect of developmental ethanol exposure on sleep physiology, and these have focused on high doses. This chapter provides an overview of the current knowledge, reports the sleep disturbances in FASD patients, and then summarizes the gap in understanding the molecular and physiological mechanisms.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1473 ","pages":"111-127"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699403","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":"Molecular Components of Vesicle Cycling at the Rod Photoreceptor Ribbon Synapse.","authors":"Christin Hanke-Gogokhia, Thomas E Zapadka, Stella Finkelstein, Vadim Y Arshavsky, Jonathan B Demb","doi":"10.1007/978-3-031-76550-6_54","DOIUrl":"10.1007/978-3-031-76550-6_54","url":null,"abstract":"<p><p>Rod photoreceptors are light-sensitive neurons of the retina that support vision in dim light. A rod cell consists of an outer segment for phototransduction, an inner segment and soma for energy production and protein synthesis, and a synaptic terminal for vesicle release onto second-order neurons-bipolar and horizontal cells. Mouse rods contain a single ribbon synaptic release site, where vesicles filled with glutamate are released at a rate of up to ~20 vesicles/synapse/second. This high release rate requires a fine balance between synaptic vesicle exocytosis and endocytosis. Here, we review the properties of synaptic transmission and highlight proteins essential for synaptic vesicle recycling at the rod ribbon synapse.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"325-330"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389696","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":"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}