Sub-cellular biochemistry最新文献

{"title":"The Intricate Interplay of Noncoding RNAs and the Gut Microbiome in Gastrointestinal and Endocrine-Related Cancers.","authors":"Sherien M El-Daly, Bahgat Fayed, Roba M Talaat, Shaimaa A Gouhar, Cinderella A Fahmy, Amira Mohamed Abd El-Jawad, Nadia M Hamdy, Zakaria Y Abd Elmageed","doi":"10.1007/978-3-032-08530-6_2","DOIUrl":"10.1007/978-3-032-08530-6_2","url":null,"abstract":"<p><p>The human gut microbiome and noncoding RNAs (ncRNAs) represent interconnected regulatory networks that profoundly influence cancer development, particularly in gastrointestinal and endocrine-related malignancies. This chapter delineates the intricate interplay of microbiome-ncRNA crosstalk in the context of gastrointestinal and endocrine-related cancers.The chapter begins with a comprehensive overview of the taxonomic and functional landscape of the healthy adult gut microbiome. The gut microbiome, comprising trillions of microorganisms, plays a crucial role in endocrine regulation through hormone metabolism, synthesis of bioactive compounds, and modulation of immune responses, thereby establishing a critical crosstalk with the host endocrine system. Dysbiosis, or microbial imbalance, has been linked to endocrine dysfunction and the pathogenesis of various diseases, including gastrointestinal and endocrine-related cancers.We then elucidate the classifications of noncoding RNAs and their function as key molecular regulators in cellular communication, gene expression, and disease progression. NcRNAs contribute significantly to the development and progression of endocrine-related malignancies. The intricate crosstalk between the gut microbiome and host ncRNAs demonstrates how gut dysbiosis can disrupt host ncRNA expression patterns, thereby affecting oncogenic pathways, immune surveillance, and metabolic reprogramming linked to tumor initiation, progression, and metastasis. Conversely, host-derived ncRNAs, secreted into the gut lumen, can directly shape microbial gene expression. In this section, we explore how dysregulation of this axis contributes to carcinogenesis through the promotion of chronic inflammation, epithelial barrier dysfunction, and oncogenic signaling. Therapeutic strategies targeting this interplay, including probiotics, prebiotics, fecal microbiota transplantation, and dietary interventions, are introduced in the context of restoring microbial balance.This comprehensive chapter provides crucial insights into the molecular mechanisms governing microbiome-ncRNA interactions and their implications for cancer biology, offering new perspectives for therapeutic interventions in gastrointestinal and endocrine-related malignancies.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"114 ","pages":"61-121"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational Approaches and Structure-Based Drug Design of CAIs.","authors":"Alessandro Bonardi, Paola Gratteri","doi":"10.1007/978-3-032-23172-7_4","DOIUrl":"10.1007/978-3-032-23172-7_4","url":null,"abstract":"<p><p>Human carbonic anhydrases (hCAs) are emerging as increasingly relevant therapeutic targets due to their involvement in a broad spectrum of pathological conditions, ranging from glaucoma and epilepsy to cancer, neuroinflammation, metabolic disorders, and obesity. The coexistence of 15 isoforms with distinct catalytic activities and tissue distributions makes selectivity a central challenge in the development of CA inhibitors (CAIs). Recent advances in computational chemistry, artificial intelligence (AI), machine learning (ML), and Structure-Based Drug Design (SBDD) have significantly accelerated the identification of new chemotypes and selective modulators.This chapter provides a comprehensive overview of in silico strategies applied to CAIs, including pharmacophore modeling, Virtual Screening, docking, molecular dynamics (MD), MM-GBSA, and AI-driven predictive modeling. Case studies illustrate how Ligand-Based and Structure-Based approaches have led to the discovery of selective inhibitors for hCAs. A special emphasis is placed on structure-function relationships, including peculiar active-site features responsible for isoform differentiation and exploitable for rational ligand design.Furthermore, the chapter highlights recent ML- and DL-based frameworks trained on large biochemical datasets, capable of predicting potency and selectivity with high accuracy. Notably, the integration of explainable AI tools and experimental validation demonstrates the potential of computational pipelines in guiding hit identification and optimization.Overall, this chapter underscores the increasingly synergistic role of computational methodologies and AI in the development of selective CAIs.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"123 ","pages":"59-79"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Applications of Carbonic Anhydrase Inhibitors in Ophthalmology.","authors":"Simone Giovannuzzi, Alessio Nocentini, Claudiu T Supuran","doi":"10.1007/978-3-032-23172-7_5","DOIUrl":"10.1007/978-3-032-23172-7_5","url":null,"abstract":"<p><p>Ophthalmology is the branch of medicine devoted to the study, diagnosis, and treatment of disorders affecting the eye and visual system, as glaucoma is. It is a leading cause of irreversible blindness worldwide and is commonly diagnosed solely in advanced stages of the disease when important and irreversible losses of visual field have already occurred. One of the major therapeutic options for its management is based on the inhibition of the metalloenzyme Carbonic Anhydrases. Indeed, CA inhibitors (CAIs) diminish ocular hypertension in glaucomatous patients by mainly reducing the rate of bicarbonate formation and thus, the secretion of the aqueous humor. This chapter presents an overview of the current CAIs used for treating glaucoma and introduces the latest pharmaceutical advancements in this field.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"123 ","pages":"81-99"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Golgi Retention and Oncogenic Signaling of KIT Tyrosine Kinase in Gastrointestinal Stromal Tumor.","authors":"Yuuki Obata, Toshirou Nishida","doi":"10.1007/978-3-032-16833-7_16","DOIUrl":"10.1007/978-3-032-16833-7_16","url":null,"abstract":"<p><p>KIT, a receptor protein tyrosine kinase (RTK), is localized in the plasma membrane and binds stem cell factor. A cancer-causing permanently active mutant of KIT (KIT^mut) accumulates aberrantly in intracellular compartments. Oncogenic RTK mutants other than KIT^mut also exhibit characteristic organelle localization, unlike their wild-type counterparts. However, the precise subcellular localization of RTK^mut and its biological significance in oncogenic signaling remain unclear. Recent studies have shown that in gastrointestinal stromal tumors (GISTs), KIT^mut is inappropriately retained in the Golgi/trans-Golgi network (TGN) area in a manner dependent on its tyrosine kinase activity. It is trapped in the biosynthetic secretory pathway in which normal RTK trafficking occurs. Importantly, KIT^mut is activated and exerts oncogenic signaling predominantly in the Golgi/TGN of GIST cells. Recently, key players in the Golgi retention of KIT^mut have been reported, but they are unlikely to be involved in the intracellular retention of other RTKs, suggesting that the retention of individual RTKs is regulated by different molecular mechanisms. Here, we review the present knowledge on KIT retention in the Golgi/TGN region in GISTs, molecular mechanisms underlying this retention, and the aberrant localization of other RTK mutants. We also discuss strategies for the medical development of RTK inhibition by blocking intracellular trafficking.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"111 ","pages":"381-412"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial Extent and Heterogeneity of Water at Phospholipid Membranes Revealed by Molecular Dynamics.","authors":"Giancarlo Franzese","doi":"10.1007/978-3-032-24159-7_5","DOIUrl":"https://doi.org/10.1007/978-3-032-24159-7_5","url":null,"abstract":"<p><p>Water at phospholipid membrane interfaces critically influences membrane stability, permeability, and biomolecular interactions, yet the spatial extent and nature of membrane-induced perturbations remain incompletely characterized. Here we review atomistic molecular dynamics simulations of dimyristoylphosphatidylcholine (DMPC) bilayers across varying hydration levels to elucidate water behavior at the membrane interface. The results reveal that while water dynamics recover bulk-like behavior approximately 1.2 nm from the membrane, structural anomalies persist up to ~2.5 nm, indicating a decoupling of structural and dynamical properties. We identify distinct populations of inner, bound, and unbound water with heterogeneous structural and dynamical characteristics; bound water forms stable hydrogen bonds with lipids and exhibits markedly slowed dynamics, whereas unbound water progressively attains bulk-like behavior. Bound and unbound water form an interface marked by a sudden change in their properties: bound water, as well as inner water, is structurally and dynamically membrane-like, while unbound water is bulk-like. These findings refine the concept of hydration water and have important implications for understanding membrane functionality, biomolecular interactions, and improving computational models of biological systems.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"116 ","pages":"99-118"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Noncoding RNAs: A Novel Frontier in Liver Cancer Research and Therapy: Implications for Precision Oncology.","authors":"Al-Aliaa M Sallam, Mahmoud A Elrebehy, Ibrahim M Elazab, Mohamed S Elballal, Ola E Elazazy, Samah S Abbas, Manar M El Tabaa, Shih-Min Hsia, Miguel Angel Chávez-Fumagalli, Nadia M Hamdy","doi":"10.1007/978-3-032-08530-6_5","DOIUrl":"10.1007/978-3-032-08530-6_5","url":null,"abstract":"<p><p>There is an urgent need for reliable noninvasive indicators of the occurrence and course of liver disease. According to research conducted in recent decades, the risk scores for liver-related complications can be determined by utilizing the genetic and epigenetic components involved in the development of liver disease. This might potentially indicate the feasibility of implementing programs for target screening and monitoring of complications.Precision medicine may be used to treat liver illnesses, thanks to recent advancements in our knowledge of the epigenetics of liver cells. In a multicellular organism, each cell has a distinct phenotype, even if they all have the same genetics. Chromatin states determined by epigenetic processes are necessary for this heritable yet dynamic cell identity. Genetic, environmental, and metabolic factors that determine DNA accessibility to the transcriptional machinery governing gene expression and cellular states in various liver illnesses can alter the epigenomic landscapes unique to the liver. Noncoding RNAs (ncRNAs) are examples of the epigenetic regulation of chromatin. The coordinated actions of numerous epigenetic factors that modify nucleosome positioning and structure (remodelers), create epigenetic marks in DNA and histones (writers), identify and interpret the marks (readers), and eliminate these marks (erasers) preserve this epigenetic information.Here, we summarize the literature on how epigenetic changes contribute to the development of liver cancers. Along with talking about the potential of epigenetic therapy approaches, we also address their usefulness as epigenetic biomarkers for the diagnosis and prognosis of hepatocellular carcinoma.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"114 ","pages":"237-297"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COPI Vesicle and Tubule Formation at the Golgi Complex.","authors":"Kunyou Park, Jia-Shu Yang, Victor W Hsu, Seung-Yeol Park","doi":"10.1007/978-3-032-16833-7_2","DOIUrl":"10.1007/978-3-032-16833-7_2","url":null,"abstract":"<p><p>The Coat Protein I (COPI) complex forms both vesicles and tubules for transport at the Golgi complex. Anterograde Golgi transport occurs with the Golgi cisternae acting as carriers, a process known as cisternal maturation, while COPI vesicles transport in the retrograde direction. The cargoes of retrograde transport include Golgi glycosylation enzymes, enabling these enzymes to maintain their distributions as residents of the cis, medial, and trans cisternae of the Golgi. COPI also forms tubules that connect the Golgi cisternae, which enables a faster mode of anterograde Golgi transport than that mediated by cisternal maturation. Recent advancements in our understanding of COPI vesicle formation have significantly contributed to the current view of Golgi transport. Particularly, the discovery of COPI tubules has provided new insights into how Golgi transport occurs.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"111 ","pages":"37-47"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of Glycan Modification by Glycosyltransferases in the Golgi Apparatus.","authors":"Hirokazu Yagi, Seigo Tateo, Koichi Kato","doi":"10.1007/978-3-032-16833-7_11","DOIUrl":"10.1007/978-3-032-16833-7_11","url":null,"abstract":"<p><p>Protein glycosylation, a fundamental modification critical for diverse biological functions, is well orchestrated within the Golgi apparatus, a central organelle in the secretory pathway. This review explores the mechanisms by which the Golgi governs protein-specific glycan modification, emphasizing the spatial organization of glycosyltransferases within the Golgi and the regulated transport of glycoproteins through its compartments. Specificity arises from the strategic localization of glycosyltransferases within the Golgi, enabling them to recognize both glycan structures and protein domains on their substrates. Advanced imaging reveals a complex and dynamic organization within the Golgi, challenging traditional models and highlighting specialized zones. Regulated transport of glycoproteins through the Golgi is critical for controlling their access to modifying enzymes. Specific sequence motifs within glycoproteins can act as 'passport sequence', directing them to distinct Golgi regions and influencing glycosylation by altering their proximity to specific enzymes and accessory proteins. These mechanisms support the hypothesis that sequence-dependent signals within substrate proteins influence their trafficking, enabling precise glycosylation as they transit the Golgi. Understanding these processes provides new insights into how glycan diversity is generated and regulated within the Golgi, highlighting the interplay between enzyme localization, protein trafficking, and the dynamic organization of this essential organelle.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"111 ","pages":"251-267"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into Microtubule Nucleation at the Golgi Apparatus.","authors":"Rosa M Rios, María P Gavilán","doi":"10.1007/978-3-032-16833-7_12","DOIUrl":"10.1007/978-3-032-16833-7_12","url":null,"abstract":"<p><p>The arrangement of microtubule (MT) networks is essential for various cellular processes including chromosome segregation during cell division, organelle positioning and transport, and the maintenance of cell polarity and morphology. The configuration of MT arrays heavily depends on the sites of MT assembly and anchoring of their minus ends. These sites are often organized into specialized structures known as microtubule-organizing centers (MTOCs). The nucleation activity of MTOCs relies on MT-nucleating factors, such as γ-tubulin-containing complexes, their associated activators and receptors, and proteins that anchor and stabilize MT minus ends.Traditionally, the centrosome has been considered the primary MTOC in animal cells. However, recent research has revealed significant contributions from other subcellular structures in shaping MT networks. Notably, the Golgi Apparatus (GA) has emerged as a prominent alternative MTOC, operating in a diverse range of organisms from Drosophila to humans and across various cell types, from undifferentiated cells to highly specialized ones. This novel activity expands the functional repertoire of the GA, complementing its central role in secretion with essential contributions to MT cytoskeleton configuration.This chapter offers a comprehensive overview of the current understanding of MT formation at the GA, including how this process is coordinated with the centrosome. It also explores the specific functions of Golgi-nucleated MTs and their participation in generating the complex MT networks of specialized cells, such as neurons, muscle cells, and pancreatic cells.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"111 ","pages":"271-315"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug Design of Carbonic Anhydrase Inhibitors.","authors":"Neera Raghav, Niccolò Paoletti, Claudiu T Supuran","doi":"10.1007/978-3-032-23172-7_3","DOIUrl":"10.1007/978-3-032-23172-7_3","url":null,"abstract":"<p><p>Carbonic anhydrases (CAs) are ubiquitous zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide and play essential roles in numerous physiological and pathological processes. Over the past decades, carbonic anhydrase inhibitors (CAIs) have emerged as valuable therapeutic agents for the treatment of a variety of human disorders, including glaucoma, epilepsy, altitude sickness, and, more recently, cancer and infectious diseases. This chapter provides a comprehensive overview of the principles and strategies underlying the rational design and synthesis of CA inhibitors. The two fundamental medicinal chemistry approaches for CAI development, the \"ring approach\" and the \"tail approach,\" are discussed in detail, emphasizing the versatility and effectiveness of these strategies in optimizing binding affinity and enhancing isoform selectivity. Both classical zinc-binding inhibitors, such as sulfonamides and related chemotypes, and nonclassical inhibitors acting through alternative mechanisms are discussed. Among nonclassical inhibitors, particular attention is devoted to natural product-derived scaffolds, such as coumarins and polyamines, which have gained considerable interest due to their selective inhibition of the tumor-associated isoforms hCA IX/hCA XII, and hCA IV, respectively. The chapter also evaluates the increasing number of recently reported nonclassical chemotypes for which X-ray crystal structures in adduct with the enzymes are however not available. Finally, an overview of the main synthetic methodologies employed for the preparation of the different classes of CA inhibitors is presented, providing practical insights into the chemical strategies most commonly used in this field.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"123 ","pages":"29-57"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}