Nadia M Hamdy, Amr Amin, Gamal Eldein Fathy Abd-Ellatef, Youssef Abdalla, Ali Abdalla, Dana Ahmad Saqr, Yi Lu, Wei Wu, Mariam I Gamal El-Din, Mohamed El-Shazly
{"title":"An Overview of Targeting Some Cancer Hallmarks with Plant Polyphenols: A Step Toward Precision.","authors":"Nadia M Hamdy, Amr Amin, Gamal Eldein Fathy Abd-Ellatef, Youssef Abdalla, Ali Abdalla, Dana Ahmad Saqr, Yi Lu, Wei Wu, Mariam I Gamal El-Din, Mohamed El-Shazly","doi":"10.1007/978-3-032-08530-6_8","DOIUrl":"10.1007/978-3-032-08530-6_8","url":null,"abstract":"<p><p>Polyphenols (PPs) are secondary metabolites that are present in more than 80% of plants. They possess a plethora of medicinal properties by modulating key pathological pathways, including epigenetics and those involved in oncogenesis or tumorigenesis. PPs have been shown to inhibit tumor cell proliferation, metastasis, and cancer cell resistance to chemotherapeutic medications. Their coadministration, either as plant-rich extracts or in advanced pharmaceutical formulations like nano-formulations, significantly impacts the tolerability, efficiency, and cytotoxicity of traditional chemotherapeutic drugs. Both clinical and preclinical studies, including in vitro and in vivo models, demonstrated the potent anticancer activity of PPs. Combining PPs with conventional chemotherapeutic agents has led to a significant improvement in the efficiency and safety index of these agents. Advances in PP nano-formulations have enhanced their bioavailability and therapeutic efficacy. The current chapter highlights the potential of PPs and recent advances in their formulation for targeting cancer.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"114 ","pages":"423-477"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889360","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}
Neera Raghav, Claudiu T Supuran, Alessio Nocentini
{"title":"Mechanisms of Carbonic Anhydrase Catalysis and Inhibition.","authors":"Neera Raghav, Claudiu T Supuran, Alessio Nocentini","doi":"10.1007/978-3-032-23172-7_2","DOIUrl":"10.1007/978-3-032-23172-7_2","url":null,"abstract":"<p><p>The catalytic mechanism of carbonic anhydrase (CA, EC 4.2.1.1) at least for the physiological CO<sub>2</sub> hydration is well understood, with the CO<sub>2</sub>-bicarbonate interconversion due to the nucleophilic attack of a zinc hydroxide species on the substrate molecule bound in a hydrophobic pocket, followed by a proton transfer reaction for the generation of the nucleophilic species of the enzyme, which is also the rate-determining one. There are five CA inhibition mechanisms described in detail to date, including (i) zinc-binding: (ii) anchoring to the zinc-bound water/hydroxide ion; (iii) occluding the active-site entrance; (iv) binding outside the active site; and (v) halogen-bond interaction with the proton shuttle of the enzyme. More than 50 different chemotypes were identified, which act in this way, whereas there are few compounds for which the inhibition mechanism is not clear yet. The many new classes of CA inhibitors also allowed the identification of isoform-selective agents for the many CA isoforms described in humans and thus, also the possibility of new pharmacological applications.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"123 ","pages":"17-28"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821127","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 Structural Role of Tropomyosin in Regulating Thin Filament Activation of Actin-Myosin Interaction.","authors":"William Lehman","doi":"10.1007/978-3-032-05273-5_3","DOIUrl":"10.1007/978-3-032-05273-5_3","url":null,"abstract":"<p><p>Myosin motor-heads projecting from muscle thick filaments interact cyclically with actin-based thin filament tracks, thereby driving inter-filament sliding that powers muscle contraction. Here, controlled recruitment of myosin heads from thick filaments leads pre-powerstroke myosin to bind weakly to actin. Myosin then isomerizes into strongly bound post-powerstroke conformations on actin, thus producing crossbridge motion in active muscles. In striated muscles, this process is regulated by a steric mechanism involving coiled-coil tropomyosin controlling access to myosin-binding sites on actin. Biochemical and structural studies suggest the regulatory mechanism involves tropomyosin occupying three average configurations on the actin thin filament, dependent on Ca<sup>2+</sup>, troponin, and myosin binding. Once Ca<sup>2+</sup>-activation of muscle occurs, tropomyosin pivots away from a troponin subunit-I (TnI) imposed B-state (myosin-blocking) position to a C-state position on actin, allowing initial weak myosin-binding to actin. The thin filament reconfiguration only partially relieves tropomyosin-troponin imposed steric inhibition of the myosin binding. However, the initial weak myosin-binding causes further tropomyosin translocation to an M-state position as myosin transitions from its pre-powerstroke to its post-powerstroke conformation, thereby fully activating the thin filament and resulting in contraction. This review summarizes the evolving structural evidence that has accumulated over many years, and which has shaped our current understanding of the troponin-tropomyosin steric regulatory mechanism that governs muscle contractility.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"113 ","pages":"59-80"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146012263","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}
Caitlin Johnston, Lyndall Briggs, Michelle Michie, Tara D Sutherland
{"title":"Biology and Molecular Structure of the α-Fibrous Silks in Bees, Ants, Wasps and Hornets (Hymenoptera).","authors":"Caitlin Johnston, Lyndall Briggs, Michelle Michie, Tara D Sutherland","doi":"10.1007/978-3-032-05273-5_14","DOIUrl":"10.1007/978-3-032-05273-5_14","url":null,"abstract":"<p><p>Larval aculeate insects (bees, ants and hornets) have evolved a silk for cocoon and nest construction based on entirely different design principles from the convergently evolved silk of spiders and silkworms. The silk is based on the coiled coil protein structure: a structure proposed in the 1950s by Francis Crick, where multiple α-helical proteins wrap around each other to form a supercoil. Whilst now recognised as a ubiquitous protein assembly motif, the purity of silk pulled from the honeybee silk gland made it one of the earliest experimentally validated examples of this structure. Here, we describe the current state of understanding of the relationship between the coiled coil structure and aculeate silk biology gained from early studies dating from the mid-twentieth century up to the present time. Further, efforts to replicate the natural material and functional materials generated from the silk are outlined. Finally, we consider the future of research in this area, focusing on mimicking natural silk and the use of recombinant silk for rational design of functional materials.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"113 ","pages":"475-492"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146012392","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":"Models of Intracellular Transport: Contradictions and Current Understanding.","authors":"Alexander A Mironov, Galina V Beznoussenko","doi":"10.1007/978-3-032-06936-8_8","DOIUrl":"10.1007/978-3-032-06936-8_8","url":null,"abstract":"<p><p>Intracellular transport is one of the most complex and debated topics in cell biology. Numerous models and their combinations have been proposed to explain experimental data on this process. This article describes our current understanding of the secretory pathway by analyzing different transport models. To identify the most realistic model, we identified observations that cannot be fully explained by the vesicular, diffusion, or cisterna maturation-progression models. The kiss-and-run model appears as the most powerful. From this perspective, vesicles at the ER exit sites are considered to be COPI-dependent. In cells with the central Golgi, the movement of carriers between the Golgi and peripheral structures occurs along microtubules via a bolus-like mechanism. In cells lacking microtubules, free ER-to-Golgi and Golgi-to-plasmalemma (or Golgi-to-endosome) carriers are extremely rare. Intra-Golgi transport relies heavily on temporary connections between cisternae, which subsequently break down. Cisternal perforations play a crucial role in this process. Cargo moves directionally through the Golgi stack, reaching the last two medial-cisternae and/or the trans-most cisterna, which function as the Golgi exit site. At this point, the dynamics of transport shifts from linear cargo movement to an exponential decay pattern. Post-Golgi carriers have to replace their own SNAREs with SNAREs that are able to facilitate their fusion with the plasmalemma.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"110 ","pages":"193-219"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145522879","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}
Elizabeth Berryman, Ariadna González Solís, Ethan Weiner, Marisa S Otegui
{"title":"Post-Golgi Trafficking in Plant Cells.","authors":"Elizabeth Berryman, Ariadna González Solís, Ethan Weiner, Marisa S Otegui","doi":"10.1007/978-3-032-06936-8_11","DOIUrl":"10.1007/978-3-032-06936-8_11","url":null,"abstract":"<p><p>Post-Golgi trafficking in plants regulates transport to and from the cell surface, vacuolar trafficking, and recycling pathways within the endomembrane system. Endosomes serve as central hubs in these pathways, managing the composition of lipids and proteins in the plasma membrane and vacuole in response to developmental signals or environmental changes. Once internalized via endocytosis, plasma membrane proteins are directed to the trans-Golgi Network (TGN), which acts as an early endosome. From the TGN, proteins can either be sent back to the plasma membrane or trafficked to multivesicular endosomes (MVEs) for further sorting and ultimate delivery to the vacuole for degradation. Key molecular assemblies such as the retromer, the ESCRT (Endosomal Sorting Complex Required for Transport) machinery, small GTPases, adaptor proteins, and SNAREs associate with distinct domains of endosomal membranes to facilitate protein sorting and membrane remodeling. This review focuses on the roles of endosomes in post-Golgi trafficking, mechanisms of cargo sorting, and membrane remodeling.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"110 ","pages":"267-286"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145522877","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":"Unconventional Protein Transport Across the Golgi Ribbon.","authors":"Jaakko Saraste, Kristian Prydz","doi":"10.1007/978-3-032-06936-8_4","DOIUrl":"10.1007/978-3-032-06936-8_4","url":null,"abstract":"<p><p>In addition to the classical secretory pathway, which involves the transport of endoplasmic reticulum (ER)-derived cargo through the cisternal stacks of the Golgi apparatus, several Golgi-independent transport routes contribute to the delivery of membrane-bound and soluble proteins to the plasma membrane (PM) or the extracellular space. Some of these transport events bypassing the Golgi stacks-collectively referred to as unconventional protein secretion (UcPS)-employ vesicular intermediates. However, the nature of these intermediates and the intracellular pathways utilized by various unconventional cargo are only partly understood. Notably, beyond its role in conventional secretory trafficking at the ER-Golgi interface, the intermediate compartment (IC) has been identified at the crossroads of two distinct vesicular UcPS pathways, participating in the sorting and Golgi-independent trafficking of both ER-synthesized (ER translocation signal-containing) and leaderless cytoplasmic cargo. Additionally, findings indicating that the IC directly interacts with the endocytic recycling system may help clarify how various unconventional cargo proteins reach the cell surface. Given that the central IC elements and recycling endosomes (REs)-defined by the GTPases Rab1 and Rab11, respectively-are closely associated with, and may even link the Golgi stacks, this chapter explores the connection between the classical and unconventional secretory routes and their potential divergence at the level of the Golgi ribbon.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"110 ","pages":"67-93"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145522826","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":"Water Under Molecular Crowding: From Femtosecond H-Bond Networks Dynamics to Biological Function.","authors":"Xiao You","doi":"10.1007/978-3-032-24159-7_7","DOIUrl":"https://doi.org/10.1007/978-3-032-24159-7_7","url":null,"abstract":"<p><p>Cells are densely packed with macromolecules, creating a crowded environment that fundamentally alters water's hydrogen bond (H-bond) networks. H-bond networks, typically dynamic and tetrahedral in bulk water, are disrupted by macromolecular surfaces, confinement, and competitive solute interactions. Subtle shifts in H-bond lifetimes, connectivity, and reorientation dynamics cascade into large-scale biological consequences-modulating protein folding, enzymatic function, and liquid-liquid phase separation. This chapter highlights how recent advances in time-resolved vibrational spectroscopy (e.g., 2D IR) and molecular dynamics (MD) simulations unravel crowding's effects on water structure and dynamics. Emphasis is placed on how these techniques elucidate interfacial water's heterogeneous and slowed dynamics in cytoplasm-like environments, at membrane surfaces, and within membraneless biomolecular condensates. We discuss how these dynamic perturbations reshape free energy landscapes and modulate biomolecular function. Finally, the chapter proposes integrative frameworks to connect ultrafast spectroscopic and simulation data with mesoscale biophysical models. Such multiscale approaches are essential to capture the full implications of hydration under crowding, offering a pathway to understand how life is organized at the molecular level in its physiologically crowded native state.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"116 ","pages":"147-167"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991286","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":"Intermediate Filaments: Structure-Mechanics Crosstalk.","authors":"Sarah Köster, Harald Herrmann","doi":"10.1007/978-3-032-05273-5_7","DOIUrl":"https://doi.org/10.1007/978-3-032-05273-5_7","url":null,"abstract":"<p><p>Intermediate filaments (IFs) possess unique mechanical properties that distinguish them from actin filaments and microtubules. In particular, they exhibit high flexibility, pronounced extensibility, and complete stability during biochemical extractions from cells and tissues. These characteristics stem from their molecular structure, which is typical of fibrous proteins. A defining feature is the central ~300 amino acid long α-helical segment with a distinct hydrophobic sequence pattern, facilitating the formation of a parallel coiled-coil dimer. Under low ionic strength conditions, two such dimers interact via their basic amino-terminal domains with the acidic coiled-coil domains to form distinct, rod-like tetrameric complexes. Upon addition of salt, the tetramers first assemble laterally into full-width, unit-length filaments, which then anneal longitudinally into micrometer-long filaments with a characteristic, 10-nm diameter. Advanced experimental techniques enable us to measure piconewton forces and micrometer length scales. By combining, for example, optical tweezers or atomic force microscopy with sophisticated data analysis and numeric modeling, we have deepened our understanding of the structure-mechanics relationship in IFs, including their force-extension behavior and the low bending rigidity. These findings enable us to hypothesize about the mechanical roles of these filaments within the living cell and speculate about biomimetic, synthetic materials.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"113 ","pages":"163-191"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146012353","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":"Association of Golgi Stacks and Recycling Endosomes Ensures Post-Golgi Trafficking.","authors":"Akiko K Satoh","doi":"10.1007/978-3-032-06936-8_5","DOIUrl":"10.1007/978-3-032-06936-8_5","url":null,"abstract":"<p><p>The trans-Golgi network (TGN) has traditionally been considered the primary sorting hub for newly synthesized proteins, whereas recycling endosomes (REs) are recognized as intermediate stations for endocytosed materials before their return to the plasma membrane. However, over the past two decades, functional overlaps between the TGN and RE have become evident, with both playing roles in the exocytic and endocytic pathways. Recent studies have shown that REs can transition between two distinct states: Golgi-associated RE (GA-RE) and free-RE. Detachment and reattachment of REs to Golgi stacks are commonly observed. In plants, it has been established that there are two types of TGNs: Golgi-associated TGN and Golgi-independent TGN. The dynamics of REs in animal cells strongly resemble those in plant TGNs. Together with their molecular similarities, these findings suggest that REs may be equivalent to at least some parts of the TGN. Given that the TGN is now understood to be composed of distinct zones, REs could represent the trans-most zone of the TGN.GA-REs receive newly synthesized glycosylphosphatidylinositol-anchored proteins (GPI-APs) but not vesicular stomatitis virus G protein (VSV-G) from the trans-Golgi cisternae. Upon detachment from the Golgi stacks, free-REs serve as post-Golgi carriers for GPI-APs. Besides cargo sorting, the TGN/RE system may play a key role in regulating the spatial distribution of Golgi stacks within cells. We propose that the dynamic balance between the association and separation of Golgi stacks and TGNs/REs is crucial for determining the cell-wide arrangement of Golgi stacks, along with the organization of microtubules and the lateral-linking activity of Golgi stacks.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"110 ","pages":"95-107"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145522893","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}