Physiological reviews最新文献_第2页

Eukaryotic cell size regulation and its implications for cellular function and dysfunction. 真核细胞大小调节及其对细胞功能和功能障碍的影响。

IF 29.9 1区医学

Physiological reviews Pub Date : 2024-10-01 Epub Date: 2024-06-20 DOI: 10.1152/physrev.00046.2023

Yagya Chadha, Arohi Khurana, Kurt M Schmoller

{"title":"Eukaryotic cell size regulation and its implications for cellular function and dysfunction.","authors":"Yagya Chadha, Arohi Khurana, Kurt M Schmoller","doi":"10.1152/physrev.00046.2023","DOIUrl":"10.1152/physrev.00046.2023","url":null,"abstract":"Depending on cell type, environmental inputs, and disease, the cells in the human body can have widely different sizes. In recent years, it has become clear that cell size is a major regulator of cell function. However, we are only beginning to understand how the optimization of cell function determines a given cell's optimal size. Here, we review currently known size control strategies of eukaryotic cells and the intricate link of cell size to intracellular biomolecular scaling, organelle homeostasis, and cell cycle progression. We detail the cell size-dependent regulation of early development and the impact of cell size on cell differentiation. Given the importance of cell size for normal cellular physiology, cell size control must account for changing environmental conditions. We describe how cells sense environmental stimuli, such as nutrient availability, and accordingly adapt their size by regulating cell growth and cell cycle progression. Moreover, we discuss the correlation of pathological states with misregulation of cell size and how for a long time this was considered a downstream consequence of cellular dysfunction. We review newer studies that reveal a reversed causality, with misregulated cell size leading to pathophysiological phenotypes such as senescence and aging. In summary, we highlight the important roles of cell size in cellular function and dysfunction, which could have major implications for both diagnostics and treatment in the clinic.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"1679-1717"},"PeriodicalIF":29.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lung antimicrobial proteins and peptides: from host defense to therapeutic strategies. 肺部抗菌蛋白和肽：从宿主防御到治疗策略。

IF 29.9 1区医学

Physiological reviews Pub Date : 2024-10-01 Epub Date: 2024-07-25 DOI: 10.1152/physrev.00039.2023

Yuanpu Peter Di, Jenna Marie Kuhn, Maria Luisa Mangoni

{"title":"Lung antimicrobial proteins and peptides: from host defense to therapeutic strategies.","authors":"Yuanpu Peter Di, Jenna Marie Kuhn, Maria Luisa Mangoni","doi":"10.1152/physrev.00039.2023","DOIUrl":"10.1152/physrev.00039.2023","url":null,"abstract":"Representing severe morbidity and mortality globally, respiratory infections associated with chronic respiratory diseases, including complicated pneumonia, asthma, interstitial lung disease, and chronic obstructive pulmonary disease, are a major public health concern. Lung health and the prevention of pulmonary disease rely on the mechanisms of airway surface fluid secretion, mucociliary clearance, and adequate immune response to eradicate inhaled pathogens and particulate matter from the environment. The antimicrobial proteins and peptides contribute to maintaining an antimicrobial milieu in human lungs to eliminate pathogens and prevent them from causing pulmonary diseases. The predominant antimicrobial molecules of the lung environment include human α- and β-defensins and cathelicidins, among numerous other host defense molecules with antimicrobial and antibiofilm activity such as PLUNC (palate, lung, and nasal epithelium clone) family proteins, elafin, collectins, lactoferrin, lysozymes, mucins, secretory leukocyte proteinase inhibitor, surfactant proteins SP-A and SP-D, and RNases. It has been demonstrated that changes in antimicrobial molecule expression levels are associated with regulating inflammation, potentiating exacerbations, pathological changes, and modifications in chronic lung disease severity. Antimicrobial molecules also display roles in both anticancer and tumorigenic effects. Lung antimicrobial proteins and peptides are promising alternative therapeutics for treating and preventing multidrug-resistant bacterial infections and anticancer therapies.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"1643-1677"},"PeriodicalIF":29.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Understanding coenzyme Q. 了解辅酶 Q

IF 29.9 1区医学

Physiological reviews Pub Date : 2024-10-01 Epub Date: 2024-05-09 DOI: 10.1152/physrev.00040.2023

Ying Wang, Noah Lilienfeldt, Siegfried Hekimi

{"title":"Understanding coenzyme Q.","authors":"Ying Wang, Noah Lilienfeldt, Siegfried Hekimi","doi":"10.1152/physrev.00040.2023","DOIUrl":"10.1152/physrev.00040.2023","url":null,"abstract":"Coenzyme Q (CoQ), also known as ubiquinone, comprises a benzoquinone head group and a long isoprenoid side chain. It is thus extremely hydrophobic and resides in membranes. It is best known for its complex function as an electron transporter in the mitochondrial electron transport chain (ETC) but is also required for several other crucial cellular processes. In fact, CoQ appears to be central to the entire redox balance of the cell. Remarkably, its structure and therefore its properties have not changed from bacteria to vertebrates. In metazoans, it is synthesized in all cells and is found in most, and maybe all, biological membranes. CoQ is also known as a nutritional supplement, mostly because of its involvement with antioxidant defenses. However, whether there is any health benefit from oral consumption of CoQ is not well established. Here we review the function of CoQ as a redox-active molecule in the ETC and other enzymatic systems, its role as a prooxidant in reactive oxygen species generation, and its separate involvement in antioxidant mechanisms. We also review CoQ biosynthesis, which is particularly complex because of its extreme hydrophobicity, as well as the biological consequences of primary and secondary CoQ deficiency, including in human patients. Primary CoQ deficiency is a rare inborn condition due to mutation in CoQ biosynthetic genes. Secondary CoQ deficiency is much more common, as it accompanies a variety of pathological conditions, including mitochondrial disorders as well as aging. In this context, we discuss the importance, but also the great difficulty, of alleviating CoQ deficiency by CoQ supplementation.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"1533-1610"},"PeriodicalIF":29.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140898396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multiscale structure and function of the aortic valve apparatus. 主动脉瓣装置的多尺度结构和功能。

IF 29.9 1区医学

Physiological reviews Pub Date : 2024-10-01 Epub Date: 2023-09-21 DOI: 10.1152/physrev.00038.2022

Hussam El-Nashar, Malak Sabry, Yuan-Tsan Tseng, Nadine Francis, Najma Latif, Kim H Parker, James E Moore, Magdi H Yacoub

{"title":"Multiscale structure and function of the aortic valve apparatus.","authors":"Hussam El-Nashar, Malak Sabry, Yuan-Tsan Tseng, Nadine Francis, Najma Latif, Kim H Parker, James E Moore, Magdi H Yacoub","doi":"10.1152/physrev.00038.2022","DOIUrl":"10.1152/physrev.00038.2022","url":null,"abstract":"Whereas studying the aortic valve in isolation has facilitated the development of life-saving procedures and technologies, the dynamic interplay of the aortic valve and its surrounding structures is vital to preserving their function across the wide range of conditions encountered in an active lifestyle. Our view is that these structures should be viewed as an integrated functional unit, here referred to as the aortic valve apparatus (AVA). The coupling of the aortic valve and root, left ventricular outflow tract, and blood circulation is crucial for AVA's functions: unidirectional flow out of the left ventricle, coronary perfusion, reservoir function, and support of left ventricular function. In this review, we explore the multiscale biological and physical phenomena that underlie the simultaneous fulfillment of these functions. A brief overview of the tools used to investigate the AVA, such as medical imaging modalities, experimental methods, and computational modeling, specifically fluid-structure interaction (FSI) simulations, is included. Some pathologies affecting the AVA are explored, and insights are provided on treatments and interventions that aim to maintain quality of life. The concepts explained in this article support the idea of AVA being an integrated functional unit and help identify unanswered research questions. Incorporating phenomena through the molecular, micro, meso, and whole tissue scales is crucial for understanding the sophisticated normal functions and diseases of the AVA.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"1487-1532"},"PeriodicalIF":29.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41145423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

REDOX SIGNALLING IN THE PANCREAS IN HEALTH AND DISEASE 胰腺中的氧化还原信号在健康和疾病中的作用

IF 33.6 1区医学

Physiological reviews Pub Date : 2024-09-26 DOI: 10.1152/physrev.00044.2023

Juan Sastre, Salvador Pérez, Luis Sabater, Sergio Rius-Pérez

引用次数: 0

The liver as a central "hub" of the immune system: pathophysiological implications 肝脏是免疫系统的中心 "枢纽"：病理生理学意义

IF 33.6 1区医学

Physiological reviews Pub Date : 2024-09-19 DOI: 10.1152/physrev.00004.2023

Vincenzo Ronca, Alessio Gerussi, Paul Collins, Alessandro Parente, Ye Htun Oo, Pietro Invernizzi

引用次数: 0

Nanodomain cAMP signalling in cardiac pathophysiology: potential for developing targeted therapeutic interventions. 心脏病理生理学中的纳米域 cAMP 信号：开发靶向治疗干预的潜力。

IF 29.9 1区医学

Physiological reviews Pub Date : 2024-08-08 DOI: 10.1152/physrev.00013.2024

Manuela Zaccolo, Duangnapa Kovanich

{"title":"Nanodomain cAMP signalling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.","authors":"Manuela Zaccolo, Duangnapa Kovanich","doi":"10.1152/physrev.00013.2024","DOIUrl":"10.1152/physrev.00013.2024","url":null,"abstract":"3', 5'-cyclic adenosine monophosphate (cAMP) mediates the effects of sympathetic stimulation on the rate and strength of cardiac contraction. Beyond this pivotal role, in cardiac myocytes cAMP also orchestrates a diverse array of reactions to various stimuli. To ensure specificity of response, the cAMP signaling pathway is intricately organized into multiple, spatially confined, subcellular domains, each governing a distinct cellular function. In this review, we describe the molecular components of the cAMP signalling pathway, how they organized are inside the intracellular space and how they achieve exquisite regulation of signalling within nanometer-size domains. We delineate the key experimental findings that lead to the current model of compartmentalised cAMP signaling and we offer an overview of our present understanding of how cAMP nanodomains are structured and regulated within cardiac myocytes. Furthermore, we discuss how compartmentalized cAMP signaling is affected in cardiac disease and consider the potential therapeutic opportunities arising from understanding such organization. By exploiting the nuances of compartmentalized cAMP signaling, novel and more effective therapeutic strategies for managing cardiac conditions may emerge. Finally, we highlight the unresolved questions and hurdles that must be addressed to translate these insights into interventions that may benefit patients.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":""},"PeriodicalIF":29.9,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hepatic glucagon action: beyond glucose mobilization. 肝脏胰高血糖素的作用--超越葡萄糖动员。

IF 33.6 1区医学

Physiological reviews Pub Date : 2024-07-01 Epub Date: 2024-02-01 DOI: 10.1152/physrev.00028.2023

Sarina Kajani, Rhianna C Laker, Ekaterina Ratkova, Sarah Will, Christopher J Rhodes

{"title":"Hepatic glucagon action: beyond glucose mobilization.","authors":"Sarina Kajani, Rhianna C Laker, Ekaterina Ratkova, Sarah Will, Christopher J Rhodes","doi":"10.1152/physrev.00028.2023","DOIUrl":"10.1152/physrev.00028.2023","url":null,"abstract":"Glucagon's ability to promote hepatic glucose production has been known for over a century, with initial observations touting this hormone as a diabetogenic agent. However, glucagon receptor agonism [when balanced with an incretin, including glucagon-like peptide 1 (GLP-1) to dampen glucose excursions] is now being developed as a promising therapeutic target in the treatment of metabolic diseases, like metabolic dysfunction-associated steatotic disease/metabolic dysfunction-associated steatohepatitis (MASLD/MASH), and may also have benefit for obesity and chronic kidney disease. Conventionally regarded as the opposing tag-team partner of the anabolic mediator insulin, glucagon is gradually emerging as more than just a \"catabolic hormone.\" Glucagon action on glucose homeostasis within the liver has been well characterized. However, growing evidence, in part thanks to new and sensitive \"omics\" technologies, has implicated glucagon as more than just a \"glucose liberator.\" Elucidation of glucagon's capacity to increase fatty acid oxidation while attenuating endogenous lipid synthesis speaks to the dichotomous nature of the hormone. Furthermore, glucagon action is not limited to just glucose homeostasis and lipid metabolism, as traditionally reported. Glucagon plays key regulatory roles in hepatic amino acid and ketone body metabolism, as well as mitochondrial turnover and function, indicating broader glucagon signaling consequences for metabolic homeostasis mediated by the liver. Here we examine the broadening role of glucagon signaling within the hepatocyte and question the current dogma, to appreciate glucagon as more than just that \"catabolic hormone.\"","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"1021-1060"},"PeriodicalIF":33.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139651525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Proteomics of the heart. 心脏蛋白质组学

IF 29.9 1区医学

Physiological reviews Pub Date : 2024-07-01 Epub Date: 2024-02-01 DOI: 10.1152/physrev.00026.2023

Oleg A Karpov, Aleksandr Stotland, Koen Raedschelders, Blandine Chazarin, Lizhuo Ai, Christopher I Murray, Jennifer E Van Eyk

{"title":"Proteomics of the heart.","authors":"Oleg A Karpov, Aleksandr Stotland, Koen Raedschelders, Blandine Chazarin, Lizhuo Ai, Christopher I Murray, Jennifer E Van Eyk","doi":"10.1152/physrev.00026.2023","DOIUrl":"10.1152/physrev.00026.2023","url":null,"abstract":"Mass spectrometry-based proteomics is a sophisticated identification tool specializing in portraying protein dynamics at a molecular level. Proteomics provides biologists with a snapshot of context-dependent protein and proteoform expression, structural conformations, dynamic turnover, and protein-protein interactions. Cardiac proteomics can offer a broader and deeper understanding of the molecular mechanisms that underscore cardiovascular disease, and it is foundational to the development of future therapeutic interventions. This review encapsulates the evolution, current technologies, and future perspectives of proteomic-based mass spectrometry as it applies to the study of the heart. Key technological advancements have allowed researchers to study proteomes at a single-cell level and employ robot-assisted automation systems for enhanced sample preparation techniques, and the increase in fidelity of the mass spectrometers has allowed for the unambiguous identification of numerous dynamic posttranslational modifications. Animal models of cardiovascular disease, ranging from early animal experiments to current sophisticated models of heart failure with preserved ejection fraction, have provided the tools to study a challenging organ in the laboratory. Further technological development will pave the way for the implementation of proteomics even closer within the clinical setting, allowing not only scientists but also patients to benefit from an understanding of protein interplay as it relates to cardiac disease physiology.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"931-982"},"PeriodicalIF":29.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11381016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139651526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Computational modeling of cardiac electrophysiology and arrhythmogenesis: toward clinical translation. 心脏电生理学和心律失常发生的计算建模。

IF 29.9 1区医学

Physiological reviews Pub Date : 2024-07-01 Epub Date: 2023-12-28 DOI: 10.1152/physrev.00017.2023

Natalia A Trayanova, Aurore Lyon, Julie Shade, Jordi Heijman

{"title":"Computational modeling of cardiac electrophysiology and arrhythmogenesis: toward clinical translation.","authors":"Natalia A Trayanova, Aurore Lyon, Julie Shade, Jordi Heijman","doi":"10.1152/physrev.00017.2023","DOIUrl":"10.1152/physrev.00017.2023","url":null,"abstract":"The complexity of cardiac electrophysiology, involving dynamic changes in numerous components across multiple spatial (from ion channel to organ) and temporal (from milliseconds to days) scales, makes an intuitive or empirical analysis of cardiac arrhythmogenesis challenging. Multiscale mechanistic computational models of cardiac electrophysiology provide precise control over individual parameters, and their reproducibility enables a thorough assessment of arrhythmia mechanisms. This review provides a comprehensive analysis of models of cardiac electrophysiology and arrhythmias, from the single cell to the organ level, and how they can be leveraged to better understand rhythm disorders in cardiac disease and to improve heart patient care. Key issues related to model development based on experimental data are discussed, and major families of human cardiomyocyte models and their applications are highlighted. An overview of organ-level computational modeling of cardiac electrophysiology and its clinical applications in personalized arrhythmia risk assessment and patient-specific therapy of atrial and ventricular arrhythmias is provided. The advancements presented here highlight how patient-specific computational models of the heart reconstructed from patient data have achieved success in predicting risk of sudden cardiac death and guiding optimal treatments of heart rhythm disorders. Finally, an outlook toward potential future advances, including the combination of mechanistic modeling and machine learning/artificial intelligence, is provided. As the field of cardiology is embarking on a journey toward precision medicine, personalized modeling of the heart is expected to become a key technology to guide pharmaceutical therapy, deployment of devices, and surgical interventions.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"1265-1333"},"PeriodicalIF":29.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11381036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139049219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0