Handbook of experimental pharmacology最新文献_第5页

UNC5B/Netrin Signaling as a Context-Dependent Regulator of Endothelial Homeostasis Across Vascular Beds. UNC5B/Netrin信号作为血管床内皮稳态的环境依赖性调节因子。

Handbook of experimental pharmacology Pub Date : 2026-07-11 DOI: 10.1007/164_2026_816

Jesús Juárez-Balarezo, Jorge Zúñiga-Hernández, Verónica Palma, Catalina Pía Prieto

{"title":"UNC5B/Netrin Signaling as a Context-Dependent Regulator of Endothelial Homeostasis Across Vascular Beds.","authors":"Jesús Juárez-Balarezo, Jorge Zúñiga-Hernández, Verónica Palma, Catalina Pía Prieto","doi":"10.1007/164_2026_816","DOIUrl":"https://doi.org/10.1007/164_2026_816","url":null,"abstract":"Blood vessels form a closed circulatory network that transports blood from the heart to peripheral tissues and back. Long-term vascular adaptation is mediated by angiogenesis, and the principal stages of this process have been systematically investigated, with particular emphasis on the microvascular bed and vessel sprouting. Angiogenesis is a fundamental adaptive process, tightly regulated by chemical, neural, and molecular mechanisms. Furthermore, the biological effects of several canonical regulators of vessel guidance, such as VEGF and bFGF, require precise regulation to ensure proper vascular network patterning and subsequent function. Emerging evidence suggests the need to adopt a broader perspective that incorporates new biological actors, such as the UNC5B (Uncoordinated-5 homolog b) receptor, a member of the Netrin family, which has been described as either pro- or anti-angiogenic depending on the specific vascular bed. However, the putative role and contribution of non-classical receptors, such as UNC5B, in the vascular patterning and endothelial stability via distinct intracellular signaling pathways have not been fully explored. Different forms of crosstalk among trophic mediators help maintain balanced angiogenic and barrier-stabilizing functions and a reparative microenvironment, which could be a potential therapeutic target depending on the vascular bed.Recent studies demonstrate that UNC5B function is shaped by tissue-specific molecular contexts, including ligand availability, co-receptor expression, and local signaling cues, positioning it as a context-dependent regulator of signaling balance. Transcriptomic analyses and experimental models reveal marked heterogeneity in UNC5B expression across endothelial subtypes, particularly in placental, retinal, and central nervous system vasculature, suggesting specialized roles in barrier maintenance and angiogenic fine-tuning.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420698","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}

引用次数: 0

Endothelial Cell Phenotypic Plasticity in Atherosclerosis. 动脉粥样硬化中的内皮细胞表型可塑性。

Handbook of experimental pharmacology Pub Date : 2026-06-19 DOI: 10.1007/164_2026_814

Laura Alonso-Herranz, Julián Albarrán-Juárez

{"title":"Endothelial Cell Phenotypic Plasticity in Atherosclerosis.","authors":"Laura Alonso-Herranz, Julián Albarrán-Juárez","doi":"10.1007/164_2026_814","DOIUrl":"https://doi.org/10.1007/164_2026_814","url":null,"abstract":"Atherosclerosis, the leading cause of cardiovascular death worldwide, is initiated by endothelial cells (ECs) dysfunction and sustained by maladaptive vascular remodeling. Far from being a uniform barrier, the endothelium is highly heterogeneous and phenotypically plastic. A central manifestation of this plasticity is endothelial-to-mesenchymal transition (EndMT), a dynamic continuum in which ECs progressively lose their endothelial identity and acquire mesenchymal, pro-fibrotic traits that contribute to every stage of atherosclerotic lesion development. This chapter reviews how atherogenic cues, including disturbed blood flow, oxidative stress, inflammation, and extracellular matrix stiffening, trigger EndMT, and how convergent signaling networks, notably TGF-β, together with Wnt/β-catenin, Notch, NF-κB/STAT3, and epigenetic regulators such as HDAC9, drive this process. These pathways are counterbalanced by protective mechanisms, including FGF and KLF2/KLF4 signaling, which help maintain endothelial homeostasis. We summarize evidence from in situ co-staining, genetic lineage tracing, epigenetic fate mapping, and single-cell multi-omics approaches, which collectively reveal distinct disease-associated EC subpopulations. We also review the in vitro, organ-on-a-chip, and murine models used to dissect EC plasticity. Finally, we discuss therapeutic and precision medicine strategies aimed at selectively reprogramming pathogenic endothelial states to promote plaque stabilization while preserving vascular integrity.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270587","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}

引用次数: 0

Mechanisms of Actions of Physiological, Pharmacological, and Toxicological Dietary Bioactive Inorganic Boron. 膳食生物活性无机硼的生理、药理学和毒理学作用机制。

Handbook of experimental pharmacology Pub Date : 2026-06-19 DOI: 10.1007/164_2026_808

Forrest H Nielsen

引用次数: 0

BNCT Plus Luminescence: New Paradigm for Boron-Containing Drug Design. BNCT加发光：含硼药物设计的新范式。

Handbook of experimental pharmacology Pub Date : 2026-06-19 DOI: 10.1007/164_2026_809

Xin Liu, Deshuang Tu, Chang-Sheng Lu, Hong Yan

{"title":"BNCT Plus Luminescence: New Paradigm for Boron-Containing Drug Design.","authors":"Xin Liu, Deshuang Tu, Chang-Sheng Lu, Hong Yan","doi":"10.1007/164_2026_809","DOIUrl":"https://doi.org/10.1007/164_2026_809","url":null,"abstract":"Boron neutron capture therapy (BNCT) is an emerging modality for cancer treatment, where the development of advanced boron-containing drugs is crucial. Recent years have seen the application of boron-containing drugs exhibiting high boron content, excellent tumor-targeting ability, low toxicity, and good biocompatibility in BNCT for diverse cancers, including skin, breast, and brain tumors. Nevertheless, challenges persist in boron-containing drug development, notably the inability to monitor drug distribution in vivo, which impedes the precise application of neutron irradiation. Fluorescence imaging, recognized for its capacity to detect biomolecules in real time and multiple dimensions, has emerged as a promising solution. Consequently, researchers have proposed designing \"luminescent boron-containing drugs\" to enable precise spatial and concentration mapping via fluorescence imaging. This chapter provides a concise overview of BNCT, boron-containing drugs, and fluorescence imaging, followed by a detailed discussion on molecular design strategies and applications of photo-functional boron-containing drugs for integrated imaging diagnosis and BNCT treatment. Within this framework, advanced boron-containing drugs incorporating fluorescence imaging capabilities-such as near-infrared, two-photon absorption, and fluorescence lifetime imaging-are being developed. With ongoing research efforts, fluorescence-imaging boron-containing drugs hold significant potential for future clinical BNCT, ultimately benefiting patients.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271412","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}

引用次数: 0

Endothelial Dysfunction and Neurovascular Alterations in Autism Spectrum Disorder. 自闭症谱系障碍的内皮功能障碍和神经血管改变。

Handbook of experimental pharmacology Pub Date : 2026-06-19 DOI: 10.1007/164_2026_812

Jorge Manzo

{"title":"Endothelial Dysfunction and Neurovascular Alterations in Autism Spectrum Disorder.","authors":"Jorge Manzo","doi":"10.1007/164_2026_812","DOIUrl":"https://doi.org/10.1007/164_2026_812","url":null,"abstract":"The traditional view of autism spectrum disorder (ASD) has largely focused on neuronal mechanisms as the primary drivers of atypical neurodevelopment. However, increasing evidence suggests that vascular and neurovascular processes also contribute to the developmental trajectories associated with the condition. In particular, endothelial cells have emerged as active regulators of brain development through their roles in angiogenesis, blood-brain barrier (BBB) formation, neurovascular signaling, and interactions with the immune system. This chapter examines the growing body of evidence supporting a neurovascular perspective of ASD, in which endothelial dysfunction is considered a biologically meaningful component of pathophysiology rather than a secondary consequence of neural alterations. Evidence from both human studies and experimental models indicates that disturbances in vascular development, BBB integrity, VEGF signaling, endothelial metabolism, and neuroimmune communication can influence brain maturation and behavior. Particular attention is given to prenatal and perinatal factors, including maternal inflammation, placental dysfunction, and environmental exposures that affect endothelial development during critical periods of neurodevelopment. The chapter also explores the contribution of oxidative and nitrosative stress, endothelial adhesion molecules, and the neurovascular unit as mechanisms linking vascular and neural dysfunction. By integrating findings across molecular, cellular, developmental, and systems-level studies, this work advances a framework in which vascular and neural processes are tightly interconnected throughout brain development. This perspective not only provides new insight into the biological heterogeneity of ASD but also highlights the endothelium and the neurovascular unit as promising targets for biomarker discovery and future therapeutic intervention.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270579","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}

引用次数: 0

Molecular Mechanisms of Endothelial Shear Stress Mechanotransduction in Health and Disease. 内皮剪切应力在健康和疾病中的机械转导的分子机制。

Handbook of experimental pharmacology Pub Date : 2026-06-19 DOI: 10.1007/164_2026_815

Jesus H Beltran-Ornelas, Min Jeong Cho, Gavin Power, Jaume Padilla, Luis A Martinez-Lemus

{"title":"Molecular Mechanisms of Endothelial Shear Stress Mechanotransduction in Health and Disease.","authors":"Jesus H Beltran-Ornelas, Min Jeong Cho, Gavin Power, Jaume Padilla, Luis A Martinez-Lemus","doi":"10.1007/164_2026_815","DOIUrl":"https://doi.org/10.1007/164_2026_815","url":null,"abstract":"Endothelial cells translate hemodynamic forces into biochemical signals that regulate vascular homeostasis through a process called mechanotransduction. Over the past decades, the study of this physiological process has received significant attention, leading to the identification of molecular structures that detect changes in shear stress. However, the functional capacity of these mechanosensors is compromised under conditions such as obesity, diabetes, and aging, resulting in impaired mechanotransduction. Such impaired mechanotransduction leads to endothelial dysfunction, a key early component of cardiovascular disease. This highlights the importance of studying the molecular and cellular mechanisms underlying endothelial mechanotransduction and its dysfunction. In this chapter, putative molecular components of endothelial mechanotransduction, their signaling pathways, and alterations under both physiological and pathological conditions will be discussed. Accurate identification of these components and a deep understanding of the mechanotransduction mechanisms in which they participate are needed to develop novel therapeutics for cardiovascular disease.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270839","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}

引用次数: 0

Calcium Fructoborate: Unique Among Other Boron-Carbohydrate Complexes from Nature: Biochemical Roles and Pharmacological Potential. 果糖硼酸钙：独特的其他硼-碳水化合物从自然界：生化作用和药理学潜力。

Handbook of experimental pharmacology Pub Date : 2026-05-26 DOI: 10.1007/164_2026_810

Ion Romulus Scorei, Andrei Biţă, George Dan Mogoşanu, John M Hunter

{"title":"Calcium Fructoborate: Unique Among Other Boron-Carbohydrate Complexes from Nature: Biochemical Roles and Pharmacological Potential.","authors":"Ion Romulus Scorei, Andrei Biţă, George Dan Mogoşanu, John M Hunter","doi":"10.1007/164_2026_810","DOIUrl":"https://doi.org/10.1007/164_2026_810","url":null,"abstract":"Boron (B) is a trace element with distinctive coordination chemistry that enables the formation of reversible esters with cis-diol-containing ligands, particularly carbohydrates and polyols. Among naturally occurring B-carbohydrate complexes, calcium fructoborate (CaFB) is the most extensively studied and clinically evaluated and is widely used as a nutraceutical ingredient. Initially identified in fruits and vegetables and subsequently developed as a stable Ca salt, CaFB provides a practical model for understanding how B's biological effects may depend on chemical form in addition to elemental intake. Chemically, CaFB comprises mono- and di-ester fructoborates stabilized by Ca, supporting aqueous handling and storage stability. After ingestion, CaFB contributes primarily to systemic B exposure (predominantly as boric acid following gastrointestinal hydrolysis), while any distal-gut availability of intact B-carbohydrate species remains a plausible but currently unconfirmed possibility in humans and requires direct, speciation-aware assessment. Biologically, preclinical and clinical data indicate that CaFB may influence inflammatory tone, oxidative stress pathways, and aspects of bone and cardiovascular physiology, with a favorable safety profile within studied dose ranges at commonly used doses. In contrast, other naturally occurring B-carbohydrate species (e.g., polyol-borates) underscore the breadth of B chemistry in foods but remain less characterized and less clinically validated. Overall, CaFB stands out as supported by preliminary clinical evidence for nutritional B delivery, with documented tolerability and evidence of biological activity across multiple systems.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015178","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}

引用次数: 0

Endothelial Dysfunction in Vascular Inflammation: The Role of NLRP3, NLRP10, AIM2, TLR9, and PANoptosis. 血管炎症中的内皮功能障碍：NLRP3、NLRP10、AIM2、TLR9和PANoptosis的作用。

Handbook of experimental pharmacology Pub Date : 2026-05-26 DOI: 10.1007/164_2026_802

Diana L Silva-Velasco, Rinaldo R Dos Passos, Raiana Anjos Moraes, Tiago Tomazini Gonçalves, Stephanie Wilczynski, Tianxin Zhang, Stephanie Randar, Jeremiah Tobin, Mark J Uline, Fernanda Priviero, R Clinton Webb

引用次数: 0

Pulmonary Arterial Hypertension and Endothelial Dysfunction. 肺动脉高压和内皮功能障碍。

Handbook of experimental pharmacology Pub Date : 2026-05-26 DOI: 10.1007/164_2026_806

Maria Eduarda de Sá Freire Onofre, Renata Trabach Santos, Fernanda Ferreira Cruz, Patricia Rieken Macêdo Rocco, Pedro Leme Silva

{"title":"Pulmonary Arterial Hypertension and Endothelial Dysfunction.","authors":"Maria Eduarda de Sá Freire Onofre, Renata Trabach Santos, Fernanda Ferreira Cruz, Patricia Rieken Macêdo Rocco, Pedro Leme Silva","doi":"10.1007/164_2026_806","DOIUrl":"https://doi.org/10.1007/164_2026_806","url":null,"abstract":"Pulmonary hypertension is a progressive and multifactorial disorder associated with a broad spectrum of cardiovascular and respiratory conditions. The updated definition proposed at the World Symposium on Pulmonary Hypertension (mean pulmonary arterial pressure 20 mmHg, pulmonary arterial wedge pressure ≤15 mmHg, and pulmonary vascular resistance ≥3 Wood units) has improved diagnostic sensitivity, enabling earlier recognition of disease onset and progression. This review discusses the central role of endothelial dysfunction in pulmonary vascular homeostasis and examines the dynamic interplay between pulmonary arterial smooth muscle cells and the extracellular matrix under both physiological and pathological conditions. Key mechanisms underlying vascular remodeling, including intimal proliferation, medial hypertrophy, and extracellular matrix reorganization, are explored as major contributors to increased pulmonary vascular resistance and right ventricular overload. Experimental models of pulmonary hypertension are critically evaluated regarding their translational relevance, methodological strengths, and limitations in reproducing human disease phenotypes. In addition, current evidence-based therapeutic strategies are appraised in the context of recent randomized clinical trials, with emphasis on risk stratification and disease-targeted interventions. Finally, emerging experimental therapies and novel translational approaches are discussed, highlighting future perspectives for precision medicine and advanced vascular-targeted treatments in pulmonary hypertension.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015267","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}

引用次数: 0

Boron-Containing Compounds (BCCs) as Antibacterials. 含硼化合物（BCCs）作为抗菌剂。

Handbook of experimental pharmacology Pub Date : 2026-05-26 DOI: 10.1007/164_2026_807

Ahmet Kilic, Marvin A Soriano-Ursúa, Rahime Soylemez

{"title":"Boron-Containing Compounds (BCCs) as Antibacterials.","authors":"Ahmet Kilic, Marvin A Soriano-Ursúa, Rahime Soylemez","doi":"10.1007/164_2026_807","DOIUrl":"https://doi.org/10.1007/164_2026_807","url":null,"abstract":"Recently, new bacteria have emerged due to environmental problems caused by many factors. At this point, opportunistic pathogens that previously posed no threat have undergone a shift in their geographical distribution over time due to climate-related factors. Thus, developing new antibiotic resistance (AMR) strains has become an important objective. In this context, developing new antibacterial agents to control these new bacteria is considered a very important goal. However, it is also crucial to prevent the reproduction or growth of these bacteria and to ensure their safety in animal cells for use in patients. For this, there is an urgent need to develop potential drug candidates that have demonstrated beneficial results in vivo and in vitro medicinal applications. In recent years, crucial studies have shown new antibiotic drug candidates; among these, boron-containing compounds (BCCs) exhibit promising developments and are beginning to be used in the design of pharmacologically active molecules. Studies have shown that the use of BCCs as effective antibiotic drug candidates, and as a result, it has been determined that they exhibit antibacterial activities through various mechanisms of action. However, due to the mistaken belief among some researchers that boron is toxic, the applications of BCCs in different health fields were delayed for a certain period. On the other hand, experimental and clinical studies on different applications of BCCs as antibiotic drug candidates have shown them as safe agents used in animals, including humans; moreover, they are versatile molecules and can play an effective role in antibacterial drug design. This chapter focuses on identifying BCCs as antibiotic drug candidates, their antibacterial properties, and additional data regarding their pharmacology profiles.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015188","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}

引用次数: 0