Physiological reviews最新文献

The influence of extracellular vesicles on tumor evolution and resistance to therapy. 细胞外囊泡对肿瘤演变和耐药性的影响。

IF 29.9 1区医学

Physiological reviews Pub Date : 2025-07-01 Epub Date: 2025-02-21 DOI: 10.1152/physrev.00019.2024

Enrique Bastón, Juan García-Agulló, Héctor Peinado

{"title":"The influence of extracellular vesicles on tumor evolution and resistance to therapy.","authors":"Enrique Bastón, Juan García-Agulló, Héctor Peinado","doi":"10.1152/physrev.00019.2024","DOIUrl":"10.1152/physrev.00019.2024","url":null,"abstract":"Disruption of cellular communication that regulates normal physiology is often a key factor in the development of disease, including cancer. Extracellular vesicles (EVs) are mediators of cell-cell communication, modulating local and distant microenvironments and playing an important role influencing tumor progression at both early and late stages. Indeed, EV-mediated communication participates in the initial steps of primary tumor transformation and proliferation as well as the preparation of the premetastatic niche and subsequent metastasis. In this context, the presence of DNA in EVs (EV-DNA) is particularly intriguing, with important biological implications and significant potential as a biomarker in liquid biopsies. In this review we discuss the mechanisms involved in EV-shed DNA and the potential impact in tumor evolution. In addition, it has become apparent in recent years that the secretion of EVs also influences the behavior of the surrounding microenvironment. An important unresolved challenge in oncology is the resistance of tumors to treatment, one of the primary causes of high cancer mortality. The role of EVs in therapy resistance has garnered considerable interest. In the latter part of this review, we also examine the potential involvement of EVs in resistance to therapy.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"1173-1212"},"PeriodicalIF":29.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468772","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

Extracellular vesicles and the lung: from disease pathogenesis to biomarkers and treatments. 细胞外囊泡与肺部疾病：从发病机制到生物标志物和治疗。

IF 29.9 1区医学

Physiological reviews Pub Date : 2025-07-01 Epub Date: 2025-03-24 DOI: 10.1152/physrev.00032.2024

Kyong-Su Park, Cecilia Lässer, Jan Lötvall

{"title":"Extracellular vesicles and the lung: from disease pathogenesis to biomarkers and treatments.","authors":"Kyong-Su Park, Cecilia Lässer, Jan Lötvall","doi":"10.1152/physrev.00032.2024","DOIUrl":"10.1152/physrev.00032.2024","url":null,"abstract":"Nanosized extracellular vesicles (EVs) are released by all cells to convey cell-to-cell communication. EVs, including exosomes and microvesicles, carry an array of bioactive molecules, such as proteins and RNAs, encapsulated by a membrane lipid bilayer. Epithelial cells, endothelial cells, and various immune cells in the lung contribute to the pool of EVs in the lung microenvironment and carry molecules reflecting their cellular origin. EVs can maintain lung health by regulating immune responses, inducing tissue repair, and maintaining lung homeostasis. They can be detected in lung tissues and biofluids such as bronchoalveolar lavage fluid and blood, offering information about disease processes, and can function as disease biomarkers. Here, we discuss the role of EVs in lung homeostasis and pulmonary diseases such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, pulmonary fibrosis, and lung injury. The mechanistic involvement of EVs in pathogenesis and their potential as disease biomarkers are discussed. Finally, the pulmonary field benefits from EVs as clinical therapeutics in severe pulmonary inflammatory disease, as EVs from mesenchymal stem cells attenuate severe respiratory inflammation in multiple clinical trials. Further, EVs can be engineered to carry therapeutic molecules for enhanced and broadened therapeutic opportunities, such as the anti-inflammatory molecule CD24. Finally, we discuss the emerging opportunity of using different types of EVs for treating severe respiratory conditions.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"1733-1821"},"PeriodicalIF":29.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693102","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

TPCs: FROM PLANT TO HUMAN. TPCs：从植物到人类。

IF 29.9 1区医学

Physiological reviews Pub Date : 2025-07-01 Epub Date: 2025-04-03 DOI: 10.1152/physrev.00044.2024

Yvonne Eileen Klingl, Arnas Petrauskas, Dawid Jaślan, Christian Grimm

{"title":"TPCs: FROM PLANT TO HUMAN.","authors":"Yvonne Eileen Klingl, Arnas Petrauskas, Dawid Jaślan, Christian Grimm","doi":"10.1152/physrev.00044.2024","DOIUrl":"10.1152/physrev.00044.2024","url":null,"abstract":"In 2005, the Arabidopsis thaliana two-pore channel TPC1 channel was identified as a vacuolar Ca2+-release channel. In 2009, three independent groups published studies on mammalian TPCs as nicotinic acid adenine dinucleotide phosphate (NAADP)-activated endolysosomal Ca2+ release channels, results that were eventually challenged by two other groups, claiming mammalian TPCs to be phosphatidylinositol-3,5-bisphosphate [PI(3,5)P2]-activated Na+ channels. By now this dispute seems to have been largely reconciled. Lipophilic small molecule agonists of TPC2, mimicking either the NAADP or the PI(3,5)P2 mode of channel activation, revealed, together with structural evidence, that TPC2 can change its selectivity for Ca2+ versus Na+ in a ligand-dependent fashion (N- vs. P-type activation). Furthermore, the NAADP-binding proteins Jupiter microtubule-associated homolog 2 protein (JPT2) and Lsm12 were discovered, corroborating the hypothesis that NAADP activation of TPCs only works in the presence of these auxiliary NAADP-binding proteins. Pathophysiologically, loss or gain of function of TPCs has effects on autophagy, exocytosis, endocytosis, and intracellular trafficking, e.g., LDL cholesterol trafficking leading to fatty liver disease or viral and bacterial toxin trafficking, corroborating the roles of TPCs in infectious diseases such as Ebola or COVID-19. Defects in the trafficking of epidermal growth factor receptor and β1-integrin suggested roles in cancer. In neurodegenerative lysosomal storage disease models, P-type activation of TPC2 was found to have beneficial effects on both in vitro and in vivo hallmarks of Niemann-Pick disease type C1, Batten disease, and mucolipidosis type IV. Here, we cover the latest on the structure, function, physiology, and pathophysiology of these channels with a focus initially on plants followed by mammalian TPCs, and we discuss their potential as drug targets, including currently available pharmacology.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"1695-1732"},"PeriodicalIF":29.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803970","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

The flux of energy in critical illness and the obesity paradox. 危重疾病中的能量流动和肥胖悖论。

IF 29.9 1区医学

Physiological reviews Pub Date : 2025-07-01 Epub Date: 2025-02-21 DOI: 10.1152/physrev.00029.2024

Ariel Jaitovich, Jesse B Hall

{"title":"The flux of energy in critical illness and the obesity paradox.","authors":"Ariel Jaitovich, Jesse B Hall","doi":"10.1152/physrev.00029.2024","DOIUrl":"10.1152/physrev.00029.2024","url":null,"abstract":"During critical illness, systemic inflammation causes organ-specific metabolic changes. In the immune and inflammatory compartments, predominantly anabolic reprogramming supports cellular replication and inflammatory response execution. Pari passu, catabolism of adipose tissue and skeletal muscle supplies carbon skeletons and enthalpy for inflammatory and immune cell anabolism. The liver plays a key role during these metabolic shifts in enabling adequate supply of glucose and ketone bodies to the circulation. Although often perceived as passive surrogates of prehospitalization frailty, body mass constituents are active parties of an overarching metabolic trade-off that is key for survival after acute insults. Muscle and adipose tissue remodel in response to critical illness and thus profoundly influence the systemic metabolic landscape during and after hospitalization. Whether obesity's effect on patient systemic metabolism and survival is paradoxically beneficial or not remains controversial. Substrate-induced epigenetic changes lead to abnormal transcriptional programs that in turn regulate metabolic pathways critical to patient survival. We present a summary of major mechanisms involved in the flux of energy in critical illness from body mass into immune response execution and suggest future research avenues focused on perturbed immune-metabolic and epigenetic programs that could lead to improved understanding of these processes, and eventually to better outcomes for the critically ill.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"1487-1552"},"PeriodicalIF":29.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468771","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

Sex differences in the metabolism of glucose and fatty acids by adipose tissue and skeletal muscle in humans. 人类脂肪组织和骨骼肌代谢葡萄糖和脂肪酸的性别差异。

IF 29.9 1区医学

Physiological reviews Pub Date : 2025-07-01 Epub Date: 2025-01-27 DOI: 10.1152/physrev.00008.2024

Damla N Costa, Sylvia Santosa, Michael D Jensen

{"title":"Sex differences in the metabolism of glucose and fatty acids by adipose tissue and skeletal muscle in humans.","authors":"Damla N Costa, Sylvia Santosa, Michael D Jensen","doi":"10.1152/physrev.00008.2024","DOIUrl":"10.1152/physrev.00008.2024","url":null,"abstract":"Adult males and females have markedly different body composition, and energy expenditure and have different degrees of risk for metabolic diseases. A major aspect of metabolic regulation involves the appropriate storage and disposal of glucose and fatty acids. The use of sophisticated calorimetry, tracer, and imaging techniques has provided insight into the complex metabolism of these substrates showing that the regulation of these processes varies tremendously throughout the day, from the overnight fasting condition to meal ingestion, to the effects of physical activity. The sexual dimorphism in substrate metabolism is most readily observed in how fatty acids are stored and mobilized. The objective of this review is to provide a comprehensive and critical summary of the reported sex differences in the mobilization, oxidation, and storage of fat and carbohydrate in adipose tissue and skeletal muscle. We will describe how adipose tissue lipolysis differs between sexes and how this varies between fed, fasted, and exercise conditions. We will also review what is known about endogenous and exogenous fatty acid storage in adipose tissue and muscle, as well as how oxidation compares between men and women in response to exercise. What has been learned about the cellular level regulation of these processes will be described. Although glucose metabolism exhibits fewer differences between men and women, we will also review the existing knowledge on this topic.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"897-934"},"PeriodicalIF":29.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047709","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

Molecular dissection of the role of ACE2 in glucose homeostasis. ACE2在葡萄糖稳态中作用的分子解剖。

IF 29.9 1区医学

Physiological reviews Pub Date : 2025-07-01 Epub Date: 2025-02-07 DOI: 10.1152/physrev.00027.2024

Kavaljit H Chhabra, Robin Shoemaker, Chandana B Herath, Merlin C Thomas, Catalin M Filipeanu, Eric Lazartigues

{"title":"Molecular dissection of the role of ACE2 in glucose homeostasis.","authors":"Kavaljit H Chhabra, Robin Shoemaker, Chandana B Herath, Merlin C Thomas, Catalin M Filipeanu, Eric Lazartigues","doi":"10.1152/physrev.00027.2024","DOIUrl":"10.1152/physrev.00027.2024","url":null,"abstract":"Angiotensin-converting enzyme 2 (ACE2) was discovered 25 years ago as a negative regulator of the renin-angiotensin system, opposing the effects of angiotensin II. Beyond its well-demonstrated roles in cardiovascular regulation and COVID-19 pathology, ACE2 is involved in a plethora of physiopathological processes. In this review, we summarize the latest discoveries on the role of ACE2 in glucose homeostasis and regulation of metabolism. In the endocrine pancreas, ACE2 is expressed at low levels in β-cells, but loss of its expression inhibits glucose-stimulated insulin secretion and impairs glucose tolerance. Conversely, overexpression of ACE2 improved glycemia, suggesting that recombinant ACE2 might be a future therapy for diabetes. In the skeletal muscle of ACE2-deficient mice a progressive triglyceride accumulation was observed, whereas in diabetic kidney the initial increase in ACE2 is followed by a chronic reduction of expression in kidney tubules and impairment of glucose metabolism. At the intestinal level dysregulation of the enzyme alters the amino acid absorption and intestinal microbiome, whereas at the hepatic level ACE2 protects against diabetic fatty liver disease. Not least, ACE2 is upregulated in adipocytes in response to nutritional stimuli, and administration of recombinant ACE2 decreased body weight and increased thermogenesis. In addition to tissue-specific regulation of ACE2 function, the enzyme undergoes complex cellular posttranslational modifications that are changed during diabetes evolution, with at least proteolytic cleavage and ubiquitination leading to modifications in ACE2 activity. Detailed characterization of ACE2 in a cellular and tissue-specific manner holds promise for improving therapeutic outcomes in diabetes and metabolic disorders.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"935-973"},"PeriodicalIF":29.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12124467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371048","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

Deconstructing the GWAS library - Next Generation GWAS 解构GWAS库-下一代GWAS

IF 33.6 1区医学

Physiological reviews Pub Date : 2025-05-23 DOI: 10.1152/physrev.00025.2024

Weirui Zhang, Svenja Koslowski, Marouane Benzaki, Chang Jie Mick Lee, Yike Zhu, Michelle C.E Mak, Yonglin Zhu, Shaun S.E Loong, Guillaume Lettre, Chukwuemeka George Anene-Nzelu, Roger Foo

引用次数: 0

Immunotherapy for atherosclerosis 动脉粥样硬化的免疫治疗

IF 33.6 1区医学

Physiological reviews Pub Date : 2025-05-21 DOI: 10.1152/physrev.00016.2024

Claudia Monaco, Coleen A. McNamara, Bram Slütter, Amanda C. Foks, Stefan Bekiranov, Willem J.M. Mulder, Isabel Gonçalves, Esther Lutgens

引用次数: 0

Cysteine-based redox sensors in the cardiovascular system - from identification to physiology and drug discovery. 心血管系统中基于半胱氨酸的氧化还原传感器——从鉴定到生理学和药物发现。

IF 33.6 1区医学

Physiological reviews Pub Date : 2025-05-08 DOI: 10.1152/physrev.00051.2024

Joseph R Burgoyne,Philip Eaton

引用次数: 0

Central nervous system mechanisms of salt-sensitive hypertension 盐敏感性高血压的中枢神经系统机制