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":"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":"https://doi.org/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":"Computational Approaches and Structure-Based Drug Design of CAIs.","authors":"Alessandro Bonardi, Paola Gratteri","doi":"10.1007/978-3-032-23172-7_4","DOIUrl":"https://doi.org/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":"https://doi.org/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":"Structural Biology of Actin: Interplay Between Molecular Assembly, Conformational Polymorphism and ATPase.","authors":"Yuichiro Maéda, Toshiro Oda, Akihiro Narita, Yusuke Kanematsu, Mitsusada Iwasa, Shuichi Takeda","doi":"10.1007/978-3-032-05273-5_4","DOIUrl":"https://doi.org/10.1007/978-3-032-05273-5_4","url":null,"abstract":"<p><p>Actin was first identified as a major muscle protein with two key activities: polymerization and ATPase. Although the significance of these activities in muscle contraction was unclear, subsequent cell biological studies revealed that actin is abundant also in non-muscle cells, where it drives dynamic remodeling through ATP-dependent treadmilling. Biochemical studies revealed that the polymerization coupled with ATP hydrolysis produces two distinct F-actin states: a stable ADP-P_i state and an unstable ADP state. The transition between the ADP-P_i and ADP states (i.e., P_i release) likely generates the free energy that drives treadmilling.In this chapter, we introduce our structural biological studies of these states and the mechanisms underlying their formation. Our F-actin model showed that polymerization induces a rotation between its two rigid domains, shifting actin from a twisted G-form to a flat F-form. We also resolved the cryo-EM structure of cofilin-decorated F-actin, in which actin adopts a distinct C-form. Analysis of PDB data classified actin structures into four conformations: G-, F-, C-, and O-forms, each linked to specific functions-G-form for nucleotide exchange, F-form for ATP hydrolysis, and C-form for filament severing. High-resolution F-form structures further elucidated the ATP hydrolysis pathway and the basis for the stability of the ADP-P_i state.Despite these advances, key questions remain. Although the global structure of F-form actin is identical across nucleotide states, its properties differ: ATP/ADP-P_i states are stable and cofilin-resistant, whereas the ADP state is prone to depolymerization and cofilin-mediated severing. We suggest that each state should be characterized by the distinct nature of conformational fluctuations from F-form back to G-form.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"113 ","pages":"81-112"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146011843","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":"The Impact of Ageing on Fibrillar Collagens.","authors":"Elizabeth G Canty-Laird, Himadri S Gupta, Helen L Birch","doi":"10.1007/978-3-032-05273-5_12","DOIUrl":"https://doi.org/10.1007/978-3-032-05273-5_12","url":null,"abstract":"<p><p>The world population is ageing rapidly. The over-60s now outnumber the under- 5s, and 1 in 6 people will be over 60 by 2030 (WHO). Collagen is a key structural component of many tissues and organs, and although a fraction of the collagenous component of tissues is remarkably long-lived, it progressively accumulates damage over a lifetime. The capacity for new collagen synthesis and post-translational modification is altered and dysregulated during ageing. The mature crosslinks that stabilise collagenous tissues can remain stable or increase with age, whereas age-related glycation end-products can increase and affect tissue biomechanics. At the fibrillar nanoscale, changes associated with ageing and disease influence fibril deformation and stress transfer in a tissue-specific manner. Age-related loss of collagen can be caused by proteolytic degradation, but normal collagen turnover is also affected by ageing and its dysregulation is detrimental to tissue homeostasis. Age-related accumulation of senescent cells may contribute to the aberrant turnover of collagen during ageing. Finally, collagen itself may hold the key to counteracting some of the detrimental effects of ageing, with ingested hydrolysed collagen peptides demonstrating beneficial effects on skin and the musculoskeletal system.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"113 ","pages":"377-412"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146011870","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":"The Many Lives of a Single Sequence: Functional Plasticity Through Amyloid Polymorphism.","authors":"Mariana Pigozzi Cali, Jim Monistrol, Fabio Strati, Janina Schiller, Rinat Indig, Ronja Markworth, Meytal Landau","doi":"10.1007/978-3-032-05273-5_16","DOIUrl":"https://doi.org/10.1007/978-3-032-05273-5_16","url":null,"abstract":"<p><p>Amyloids play critical functional roles in biology, including microbial virulence, innate immunity, and cellular organization, broadening their traditional association with neurodegenerative and systemic diseases. This chapter explores the structural and functional plasticity of amyloids, emphasizing how a single protein sequence can adopt multiple fibrillar conformations, termed polymorphs, each with distinct biological outcomes. We synthesise recent high-resolution structural insights from cryo-EM, NMR, and microcrystallography that elucidate the polymorphic behaviour of amyloids in both pathogenic and functional contexts. Particular focus is placed on bacterial functional amyloids that stabilise biofilms and modulate host-pathogen interactions and on antimicrobial peptides that form reversible fibrils with cytotoxic or immune-stimulatory functions. We also highlight the emerging paradigm of amyloid-nucleic acid co-assemblies and their role in immune recognition, autoimmunity, and possibly the origin of life. By examining structure-function relationships across a broad evolutionary spectrum, we argue that amyloid polymorphism constitutes a general mechanism of biological regulation. Understanding how these fibrils shift between states, including cross-β, cross-α, nanotubular, or phase-separated condensates, offers insight into their dual roles in health and disease. This perspective repositions amyloids not merely as pathological end-products but as versatile, ancient scaffolds for structural adaptation and functional innovation.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"113 ","pages":"521-558"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146012233","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":"https://doi.org/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":"Golgi Fragmentation as a Potential Link Between SARS-CoV-2 Infection and Alzheimer's Disease: Mechanisms and Implications for Neurodegeneration in Long COVID.","authors":"Yanzhuang Wang, Sam Gandy","doi":"10.1007/978-3-032-16833-7_19","DOIUrl":"https://doi.org/10.1007/978-3-032-16833-7_19","url":null,"abstract":"<p><p>The COVID-19 pandemic has impacted millions of people worldwide, and recent studies have shown that SARS-CoV-2 infection can lead to an Alzheimer's-like neuropathological and biomarker phenotype, as well as clinical symptoms of \"brain fog\". This raises an intriguing question: \"How and where might the molecular pathways underlying SARS-CoV-2 infection and Alzheimer's disease (AD) converge?\" One common feature of both SARS-CoV-2 infection and AD is the alteration of the endomembrane system, particularly the fragmentation of the Golgi apparatus. In this review article, we summarize the existing literature on SARS-CoV-2 infection biology and speculate about the potential mechanisms linking Golgi defects, SARS-CoV-2 infection, and neurodegeneration.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"111 ","pages":"463-482"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259478","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}