Physiological reviews最新文献_第5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

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

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 28.7 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":28.7,"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

Navigating the multifaceted intricacies of the Na⁺-Cl^- cotransporter, a highly regulated key effector in the control of hydromineral homeostasis. 驾驭 Na+-Cl- 共转运体的多面复杂性，它是控制水矿物质平衡的高度调节和关键效应器。

IF 29.9 1区医学

Physiological reviews Pub Date : 2024-07-01 Epub Date: 2024-02-08 DOI: 10.1152/physrev.00027.2023

A V Rioux, T R Nsimba-Batomene, S Slimani, N A D Bergeron, M A M Gravel, S V Schreiber, M J Fiola, L Haydock, A P Garneau, P Isenring

{"title":"Navigating the multifaceted intricacies of the Na+-Cl- cotransporter, a highly regulated key effector in the control of hydromineral homeostasis.","authors":"A V Rioux, T R Nsimba-Batomene, S Slimani, N A D Bergeron, M A M Gravel, S V Schreiber, M J Fiola, L Haydock, A P Garneau, P Isenring","doi":"10.1152/physrev.00027.2023","DOIUrl":"10.1152/physrev.00027.2023","url":null,"abstract":"The Na+-Cl- cotransporter (NCC; SLC12A3) is a highly regulated integral membrane protein that is known to exist as three splice variants in primates. Its primary role in the kidney is to mediate the cosymport of Na+ and Cl- across the apical membrane of the distal convoluted tubule. Through this role and the involvement of other ion transport systems, NCC allows the systemic circulation to reclaim a fraction of the ultrafiltered Na+, K+, Cl-, and Mg+ loads in exchange for Ca2+ and [Formula: see text]. The physiological relevance of the Na+-Cl- cotransport mechanism in humans is illustrated by several abnormalities that result from NCC inactivation through the administration of thiazides or in the setting of hereditary disorders. The purpose of the present review is to discuss the molecular mechanisms and overall roles of Na+-Cl- cotransport as the main topics of interest. On reading the narrative proposed, one will realize that the knowledge gained in regard to these themes will continue to progress unrelentingly no matter how refined it has now become.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"1147-1204"},"PeriodicalIF":29.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11381001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139703235","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

Physiological basis for xenotransplantation from genetically modified pigs to humans. 转基因猪向人类异种移植的生理基础：综述。

IF 29.9 1区医学

Physiological reviews Pub Date : 2024-07-01 Epub Date: 2024-03-22 DOI: 10.1152/physrev.00041.2023

Leigh Peterson, Magdi H Yacoub, David Ayares, Kazuhiko Yamada, Daniel Eisenson, Bartley P Griffith, Muhammad M Mohiuddin, Willard Eyestone, J Craig Venter, Ryszard T Smolenski, Martine Rothblatt

{"title":"Physiological basis for xenotransplantation from genetically modified pigs to humans.","authors":"Leigh Peterson, Magdi H Yacoub, David Ayares, Kazuhiko Yamada, Daniel Eisenson, Bartley P Griffith, Muhammad M Mohiuddin, Willard Eyestone, J Craig Venter, Ryszard T Smolenski, Martine Rothblatt","doi":"10.1152/physrev.00041.2023","DOIUrl":"10.1152/physrev.00041.2023","url":null,"abstract":"The collective efforts of scientists over multiple decades have led to advancements in molecular and cellular biology-based technologies including genetic engineering and animal cloning that are now being harnessed to enhance the suitability of pig organs for xenotransplantation into humans. Using organs sourced from pigs with multiple gene deletions and human transgene insertions, investigators have overcome formidable immunological and physiological barriers in pig-to-nonhuman primate (NHP) xenotransplantation and achieved prolonged pig xenograft survival. These studies informed the design of Revivicor's (Revivicor Inc, Blacksburg, VA) genetically engineered pigs with 10 genetic modifications (10 GE) (including the inactivation of 4 endogenous porcine genes and insertion of 6 human transgenes), whose hearts and kidneys have now been studied in preclinical human xenotransplantation models with brain-dead recipients. Additionally, the first two clinical cases of pig-to-human heart xenotransplantation were recently performed with hearts from this 10 GE pig at the University of Maryland. Although this review focuses on xenotransplantation of hearts and kidneys, multiple organs, tissues, and cell types from genetically engineered pigs will provide much-needed therapeutic interventions in the future.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"1409-1459"},"PeriodicalIF":29.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11390123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140185347","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

Neurobiology and systems biology of stress resilience. 压力复原力的神经生物学和系统生物学。

IF 29.9 1区医学

Physiological reviews Pub Date : 2024-07-01 Epub Date: 2024-03-14 DOI: 10.1152/physrev.00042.2023

Raffael Kalisch, Scott J Russo, Marianne B Müller

{"title":"Neurobiology and systems biology of stress resilience.","authors":"Raffael Kalisch, Scott J Russo, Marianne B Müller","doi":"10.1152/physrev.00042.2023","DOIUrl":"10.1152/physrev.00042.2023","url":null,"abstract":"Stress resilience is the phenomenon that some people maintain their mental health despite exposure to adversity or show only temporary impairments followed by quick recovery. Resilience research attempts to unravel the factors and mechanisms that make resilience possible and to harness its insights for the development of preventative interventions in individuals at risk for acquiring stress-related dysfunctions. Biological resilience research has been lagging behind the psychological and social sciences but has seen a massive surge in recent years. At the same time, progress in this field has been hampered by methodological challenges related to finding suitable operationalizations and study designs, replicating findings, and modeling resilience in animals. We embed a review of behavioral, neuroimaging, neurobiological, and systems biological findings in adults in a critical methods discussion. We find preliminary evidence that hippocampus-based pattern separation and prefrontal-based cognitive control functions protect against the development of pathological fears in the aftermath of singular, event-type stressors [as found in fear-related disorders, including simpler forms of posttraumatic stress disorder (PTSD)] by facilitating the perception of safety. Reward system-based pursuit and savoring of positive reinforcers appear to protect against the development of more generalized dysfunctions of the anxious-depressive spectrum resulting from more severe or longer-lasting stressors (as in depression, generalized or comorbid anxiety, or severe PTSD). Links between preserved functioning of these neural systems under stress and neuroplasticity, immunoregulation, gut microbiome composition, and integrity of the gut barrier and the blood-brain barrier are beginning to emerge. On this basis, avenues for biological interventions are pointed out.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"1205-1263"},"PeriodicalIF":29.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11381009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140120382","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

A versatile delivery vehicle for cellular oxygen and fuels, or metabolic sensor? - A review and perspective on the functions of myoglobin 细胞氧气和燃料的多功能输送工具，还是代谢传感器？- 肌红蛋白功能的回顾与展望

IF 33.6 1区医学

Physiological reviews Pub Date : 2024-05-02 DOI: 10.1152/physrev.00031.2023

Kiran Kumar Adepu, Andriy Anishkin, Sean H. Adams, Sree V Chintapalli

引用次数: 0

Neuronal glucose sensing mechanisms and circuits in the control of insulin and glucagon secretion 控制胰岛素和胰高血糖素分泌的神经元葡萄糖传感机制和回路

IF 33.6 1区医学

Physiological reviews Pub Date : 2024-04-25 DOI: 10.1152/physrev.00038.2023

Bernard Thorens

{"title":"Neuronal glucose sensing mechanisms and circuits in the control of insulin and glucagon secretion","authors":"Bernard Thorens","doi":"10.1152/physrev.00038.2023","DOIUrl":"https://doi.org/10.1152/physrev.00038.2023","url":null,"abstract":"Glucose homeostasis is mainly under the control of the pancreatic islet hormones insulin and glucagon, which, respectively, stimulate glucose uptake and utilization by liver, fat, and muscle or glucose production by the liver. The balance between the secretion of these hormones is under the control of blood glucose concentrations. Indeed, pancreatic islet b-cells and a-cells can sense variations in glycemia and respond by an appropriate secretory response to restore euglycemia. However, the secretory activity of these cells is also under multiple additional metabolic, hormonal, and neuronal signals that combine to ensure the perfect control of glycemia over a lifetime. The central nervous system (CNS), which has an almost absolute requirement for glucose as a source of metabolic energy and, thus, a vital interest in ensuring that glycemic levels never fall below ~5mM, is equipped with populations of neurons responsive to changes in glucose concentrations. These neurons control pancreatic islet cells secretion activity in multiple ways: through both branches of the autonomic nervous system, through the hypothalamic-pituitary-adrenal axis, and by secreting vasopressin (AVP) in the blood at the level of the posterior pituitary. Here, we will present the autonomic innervation of the pancreatic islets; the mechanisms of neurons activation by a rise or a fall in glucose concentration; how current viral tracing, chemogenetic, and optogenetic techniques allow to integrate specific glucose sensing neurons in defined neuronal circuits that control endocrine pancreas function. Finally, how genetic screens in mice can untangle the diversity of the hypothalamic mechanisms controlling the response to hypoglycemia.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"23 1","pages":""},"PeriodicalIF":33.6,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140648916","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