Physiological reviews最新文献_第9页

Protease-activated receptors in health and disease. 健康和疾病中的蛋白酶激活受体。

IF 29.9 1区医学

Physiological reviews Pub Date : 2023-01-01 Epub Date: 2022-07-28 DOI: 10.1152/physrev.00044.2021

Chloe J Peach, Laura E Edgington-Mitchell, Nigel W Bunnett, Brian L Schmidt

{"title":"Protease-activated receptors in health and disease.","authors":"Chloe J Peach, Laura E Edgington-Mitchell, Nigel W Bunnett, Brian L Schmidt","doi":"10.1152/physrev.00044.2021","DOIUrl":"10.1152/physrev.00044.2021","url":null,"abstract":"Proteases are signaling molecules that specifically control cellular functions by cleaving protease-activated receptors (PARs). The four known PARs are members of the large family of G protein-coupled receptors. These transmembrane receptors control most physiological and pathological processes and are the target of a large proportion of therapeutic drugs. Signaling proteases include enzymes from the circulation; from immune, inflammatory epithelial, and cancer cells; as well as from commensal and pathogenic bacteria. Advances in our understanding of the structure and function of PARs provide insights into how diverse proteases activate these receptors to regulate physiological and pathological processes in most tissues and organ systems. The realization that proteases and PARs are key mediators of disease, coupled with advances in understanding the atomic level structure of PARs and their mechanisms of signaling in subcellular microdomains, has spurred the development of antagonists, some of which have advanced to the clinic. Herein we review the discovery, structure, and function of this receptor system, highlight the contribution of PARs to homeostatic control, and discuss the potential of PAR antagonists for the treatment of major diseases.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 1","pages":"717-785"},"PeriodicalIF":29.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9662810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9602459","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

Cortical-subcortical interactions in goal-directed behavior. 目标定向行为中的皮层-皮层下相互作用

IF 29.9 1区医学

Physiological reviews Pub Date : 2023-01-01 Epub Date: 2022-06-30 DOI: 10.1152/physrev.00048.2021

K Guadalupe Cruz, Yi Ning Leow, Nhat Minh Le, Elie Adam, Rafiq Huda, Mriganka Sur

{"title":"Cortical-subcortical interactions in goal-directed behavior.","authors":"K Guadalupe Cruz, Yi Ning Leow, Nhat Minh Le, Elie Adam, Rafiq Huda, Mriganka Sur","doi":"10.1152/physrev.00048.2021","DOIUrl":"10.1152/physrev.00048.2021","url":null,"abstract":"Flexibly selecting appropriate actions in response to complex, ever-changing environments requires both cortical and subcortical regions, which are typically described as participating in a strict hierarchy. In this traditional view, highly specialized subcortical circuits allow for efficient responses to salient stimuli, at the cost of adaptability and context specificity, which are attributed to the neocortex. Their interactions are often described as the cortex providing top-down command signals for subcortical structures to implement; however, as available technologies develop, studies increasingly demonstrate that behavior is represented by brainwide activity and that even subcortical structures contain early signals of choice, suggesting that behavioral functions emerge as a result of different regions interacting as truly collaborative networks. In this review, we discuss the field's evolving understanding of how cortical and subcortical regions in placental mammals interact cooperatively, not only via top-down cortical-subcortical inputs but through bottom-up interactions, especially via the thalamus. We describe our current understanding of the circuitry of both the cortex and two exemplar subcortical structures, the superior colliculus and striatum, to identify which information is prioritized by which regions. We then describe the functional circuits these regions form with one another, and the thalamus, to create parallel loops and complex networks for brainwide information flow. Finally, we challenge the classic view that functional modules are contained within specific brain regions; instead, we propose that certain regions prioritize specific types of information over others, but the subnetworks they form, defined by their anatomical connections and functional dynamics, are the basis of true specialization.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 1","pages":"347-389"},"PeriodicalIF":29.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9401464","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 choroid plexus: a missing link in our understanding of brain development and function. 脉络丛：我们了解大脑发育和功能的一个缺失环节。

IF 33.6 1区医学

Physiological reviews Pub Date : 2023-01-01 Epub Date: 2022-09-29 DOI: 10.1152/physrev.00060.2021

Norman R Saunders, Katarzyna M Dziegielewska, Ryann M Fame, Maria K Lehtinen, Shane A Liddelow

{"title":"The choroid plexus: a missing link in our understanding of brain development and function.","authors":"Norman R Saunders, Katarzyna M Dziegielewska, Ryann M Fame, Maria K Lehtinen, Shane A Liddelow","doi":"10.1152/physrev.00060.2021","DOIUrl":"10.1152/physrev.00060.2021","url":null,"abstract":"Studies of the choroid plexus lag behind those of the more widely known blood-brain barrier, despite a much longer history. This review has two overall aims. The first is to outline long-standing areas of research where there are unanswered questions, such as control of cerebrospinal fluid (CSF) secretion and blood flow. The second aim is to review research over the past 10 years where the focus has shifted to the idea that there are choroid plexuses located in each of the brain's ventricles that make specific contributions to brain development and function through molecules they generate for delivery via the CSF. These factors appear to be particularly important for aspects of normal brain growth. Most research carried out during the twentieth century dealt with the choroid plexus, a brain barrier interface making critical contributions to the composition and stability of the brain's internal environment throughout life. More recent research in the twenty-first century has shown the importance of choroid plexus-generated CSF in neurogenesis, influence of sex and other hormones on choroid plexus function, and choroid plexus involvement in circadian rhythms and sleep. The advancement of technologies to facilitate delivery of brain-specific therapies via the CSF to treat neurological disorders is a rapidly growing area of research. Conversely, understanding the basic mechanisms and implications of how maternal drug exposure during pregnancy impacts the developing brain represents another key area of research.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 1","pages":"919-956"},"PeriodicalIF":33.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9678431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9101150","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: 8

Clonal hematopoiesis, somatic mosaicism, and age-associated disease. 克隆造血、体细胞嵌合和年龄相关疾病。

IF 29.9 1区医学

Physiological reviews Pub Date : 2023-01-01 Epub Date: 2022-09-01 DOI: 10.1152/physrev.00004.2022

Megan A Evans, Kenneth Walsh

{"title":"Clonal hematopoiesis, somatic mosaicism, and age-associated disease.","authors":"Megan A Evans, Kenneth Walsh","doi":"10.1152/physrev.00004.2022","DOIUrl":"10.1152/physrev.00004.2022","url":null,"abstract":"Somatic mosaicism, the occurrence of multiple genetically distinct cell clones within the same tissue, is an evitable consequence of human aging. The hematopoietic system is no exception to this, where studies have revealed the presence of expanded blood cell clones carrying mutations in preleukemic driver genes and/or genetic alterations in chromosomes. This phenomenon is referred to as clonal hematopoiesis and is remarkably prevalent in elderly individuals. While clonal hematopoiesis represents an early step toward a hematological malignancy, most individuals will never develop blood cancer. Somewhat unexpectedly, epidemiological studies have found that clonal hematopoiesis is associated with an increase in the risk of all-cause mortality and age-related disease, particularly in the cardiovascular system. Studies using murine models of clonal hematopoiesis have begun to shed light on this relationship, suggesting that driver mutations in mature blood cells can causally contribute to aging and disease by augmenting inflammatory processes. Here we provide an up-to-date review of clonal hematopoiesis within the context of somatic mosaicism and aging and describe recent epidemiological studies that have reported associations with age-related disease. We will also discuss the experimental studies that have provided important mechanistic insight into how driver mutations promote age-related disease and how this knowledge could be leveraged to treat individuals with clonal hematopoiesis.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"103 1","pages":"649-716"},"PeriodicalIF":29.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9639777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10702900","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

Circadian clocks of the kidney: function, mechanism, and regulation. 肾脏的昼夜节律：功能、机制和调节。

IF 33.6 1区医学

Physiological reviews Pub Date : 2022-10-01 Epub Date: 2022-05-16 DOI: 10.1152/physrev.00045.2021

Hannah M Costello, Jermaine G Johnston, Alexandria Juffre, G Ryan Crislip, Michelle L Gumz

引用次数: 19

Complex physiology and clinical implications of time-restricted eating. 限时进食的复杂生理学和临床意义。

IF 33.6 1区医学

Physiological reviews Pub Date : 2022-10-01 Epub Date: 2022-07-14 DOI: 10.1152/physrev.00006.2022

Max C Petersen, Molly R Gallop, Stephany Flores Ramos, Amir Zarrinpar, Josiane L Broussard, Maria Chondronikola, Amandine Chaix, Samuel Klein

{"title":"Complex physiology and clinical implications of time-restricted eating.","authors":"Max C Petersen, Molly R Gallop, Stephany Flores Ramos, Amir Zarrinpar, Josiane L Broussard, Maria Chondronikola, Amandine Chaix, Samuel Klein","doi":"10.1152/physrev.00006.2022","DOIUrl":"10.1152/physrev.00006.2022","url":null,"abstract":"Time-restricted eating (TRE) is a dietary intervention that limits food consumption to a specific time window each day. The effect of TRE on body weight and physiological functions has been extensively studied in rodent models, which have shown considerable therapeutic effects of TRE and important interactions among time of eating, circadian biology, and metabolic homeostasis. In contrast, it is difficult to make firm conclusions regarding the effect of TRE in people because of the heterogeneity in results, TRE regimens, and study populations. In this review, we 1) provide a background of the history of meal consumption in people and the normal physiology of eating and fasting; 2) discuss the interaction between circadian molecular metabolism and TRE; 3) integrate the results of preclinical and clinical studies that evaluated the effects of TRE on body weight and physiological functions; 4) summarize other time-related dietary interventions that have been studied in people; and 4) identify current gaps in knowledge and provide a framework for future research directions.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"102 4","pages":"1991-2034"},"PeriodicalIF":33.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9423781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9585851","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

Human temperature regulation under heat stress in health, disease, and injury. 人体在健康、疾病和伤害的热应激下的温度调节。

IF 29.9 1区医学

Physiological reviews Pub Date : 2022-10-01 Epub Date: 2022-06-09 DOI: 10.1152/physrev.00047.2021

Matthew N Cramer, Daniel Gagnon, Orlando Laitano, Craig G Crandall

{"title":"Human temperature regulation under heat stress in health, disease, and injury.","authors":"Matthew N Cramer, Daniel Gagnon, Orlando Laitano, Craig G Crandall","doi":"10.1152/physrev.00047.2021","DOIUrl":"10.1152/physrev.00047.2021","url":null,"abstract":"The human body constantly exchanges heat with the environment. Temperature regulation is a homeostatic feedback control system that ensures deep body temperature is maintained within narrow limits despite wide variations in environmental conditions and activity-related elevations in metabolic heat production. Extensive research has been performed to study the physiological regulation of deep body temperature. This review focuses on healthy and disordered human temperature regulation during heat stress. Central to this discussion is the notion that various morphological features, intrinsic factors, diseases, and injuries independently and interactively influence deep body temperature during exercise and/or exposure to hot ambient temperatures. The first sections review fundamental aspects of the human heat stress response, including the biophysical principles governing heat balance and the autonomic control of heat loss thermoeffectors. Next, we discuss the effects of different intrinsic factors (morphology, heat adaptation, biological sex, and age), diseases (neurological, cardiovascular, metabolic, and genetic), and injuries (spinal cord injury, deep burns, and heat stroke), with emphasis on the mechanisms by which these factors enhance or disturb the regulation of deep body temperature during heat stress. We conclude with key unanswered questions in this field of research.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"102 4","pages":"1907-1989"},"PeriodicalIF":29.9,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9394784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9302681","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

Albumin uptake and processing by the proximal tubule: physiological, pathological, and therapeutic implications. 近端小管对白蛋白的摄取和处理:生理、病理和治疗意义。

IF 33.6 1区医学

Physiological reviews Pub Date : 2022-10-01 DOI: 10.1152/physrev.00014.2021

Bruce A Molitoris, Ruben M Sandoval, Shiv Pratap S Yadav, Mark C Wagner

{"title":"Albumin uptake and processing by the proximal tubule: physiological, pathological, and therapeutic implications.","authors":"Bruce A Molitoris, Ruben M Sandoval, Shiv Pratap S Yadav, Mark C Wagner","doi":"10.1152/physrev.00014.2021","DOIUrl":"https://doi.org/10.1152/physrev.00014.2021","url":null,"abstract":"For nearly 50 years the proximal tubule (PT) has been known to reabsorb, process, and either catabolize or transcytose albumin from the glomerular filtrate. Innovative techniques and approaches have provided insights into these processes. Several genetic diseases, nonselective PT cell defects, chronic kidney disease (CKD), and acute PT injury lead to significant albuminuria, reaching nephrotic range. Albumin is also known to stimulate PT injury cascades. Thus, the mechanisms of albumin reabsorption, catabolism, and transcytosis are being reexamined with the use of techniques that allow for novel molecular and cellular discoveries. Megalin, a scavenger receptor, cubilin, amnionless, and Dab2 form a nonselective multireceptor complex that mediates albumin binding and uptake and directs proteins for lysosomal degradation after endocytosis. Albumin transcytosis is mediated by a pH-dependent binding affinity to the neonatal Fc receptor (FcRn) in the endosomal compartments. This reclamation pathway rescues albumin from urinary losses and cellular catabolism, extending its serum half-life. Albumin that has been altered by oxidation, glycation, or carbamylation or because of other bound ligands that do not bind to FcRn traffics to the lysosome. This molecular sorting mechanism reclaims physiological albumin and eliminates potentially toxic albumin. The clinical importance of PT albumin metabolism has also increased as albumin is now being used to bind therapeutic agents to extend their half-life and minimize filtration and kidney injury. The purpose of this review is to update and integrate evolving information regarding the reabsorption and processing of albumin by proximal tubule cells including discussion of genetic disorders and therapeutic considerations.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"102 4","pages":"1625-1667"},"PeriodicalIF":33.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9505336","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: 34

Adhesion G protein-coupled receptors: structure, signaling, physiology, and pathophysiology. 粘附G蛋白偶联受体：结构、信号传导、生理学和病理生理学。

IF 33.6 1区医学

Physiological reviews Pub Date : 2022-10-01 Epub Date: 2022-04-25 DOI: 10.1152/physrev.00027.2021

Trisha Lala, Randy A Hall

{"title":"Adhesion G protein-coupled receptors: structure, signaling, physiology, and pathophysiology.","authors":"Trisha Lala, Randy A Hall","doi":"10.1152/physrev.00027.2021","DOIUrl":"10.1152/physrev.00027.2021","url":null,"abstract":"Adhesion G protein-coupled receptors (AGPCRs) are a family of 33 receptors in humans exhibiting a conserved general structure but diverse expression patterns and physiological functions. The large NH2 termini characteristic of AGPCRs confer unique properties to each receptor and possess a variety of distinct domains that can bind to a diverse array of extracellular proteins and components of the extracellular matrix. The traditional view of AGPCRs, as implied by their name, is that their core function is the mediation of adhesion. In recent years, though, many surprising advances have been made regarding AGPCR signaling mechanisms, activation by mechanosensory forces, and stimulation by small-molecule ligands such as steroid hormones and bioactive lipids. Thus, a new view of AGPCRs has begun to emerge in which these receptors are seen as massive signaling platforms that are crucial for the integration of adhesive, mechanosensory, and chemical stimuli. This review article describes the recent advances that have led to this new understanding of AGPCR function and also discusses new insights into the physiological actions of these receptors as well as their roles in human disease.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"102 4","pages":"1587-1624"},"PeriodicalIF":33.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10528523","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: 15

Physiology and pathophysiology of human airway mucus. 人类气道粘液的生理学和病理生理学。

IF 33.6 1区医学

Physiological reviews Pub Date : 2022-10-01 Epub Date: 2022-01-10 DOI: 10.1152/physrev.00004.2021

David B Hill, Brian Button, Michael Rubinstein, Richard C Boucher

{"title":"Physiology and pathophysiology of human airway mucus.","authors":"David B Hill, Brian Button, Michael Rubinstein, Richard C Boucher","doi":"10.1152/physrev.00004.2021","DOIUrl":"10.1152/physrev.00004.2021","url":null,"abstract":"The mucus clearance system is the dominant mechanical host defense system of the human lung. Mucus is cleared from the lung by cilia and airflow, including both two-phase gas-liquid pumping and cough-dependent mechanisms, and mucus transport rates are heavily dependent on mucus concentration. Importantly, mucus transport rates are accurately predicted by the gel-on-brush model of the mucociliary apparatus from the relative osmotic moduli of the mucus and periciliary-glycocalyceal (PCL-G) layers. The fluid available to hydrate mucus is generated by transepithelial fluid transport. Feedback interactions between mucus concentrations and cilia beating, via purinergic signaling, coordinate Na+ absorptive vs Cl- secretory rates to maintain mucus hydration in health. In disease, mucus becomes hyperconcentrated (dehydrated). Multiple mechanisms derange the ion transport pathways that normally hydrate mucus in muco-obstructive lung diseases, e.g., cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), non-CF bronchiectasis (NCFB), and primary ciliary dyskinesia (PCD). A key step in muco-obstructive disease pathogenesis is the osmotic compression of the mucus layer onto the airway surface with the formation of adherent mucus plaques and plugs, particularly in distal airways. Mucus plaques create locally hypoxic conditions and produce airflow obstruction, inflammation, infection, and, ultimately, airway wall damage. Therapies to clear adherent mucus with hydrating and mucolytic agents are rational, and strategies to develop these agents are reviewed.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"102 4","pages":"1757-1836"},"PeriodicalIF":33.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9665957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10668248","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: 47