Physiological reviews最新文献_第2页

Frontiers in the physiology of male pattern androgenetic alopecia: Beyond the androgen horizon. 男性型雄激素性脱发的生理学前沿：超越雄激素水平。

IF 33.6 1区医学

Physiological reviews Pub Date : 2025-07-10 DOI: 10.1152/physrev.00005.2024

Sabrina Altendorf,Marta Bertolini,Alizée Le Riche,Antonella Tosti,Ralf Paus

{"title":"Frontiers in the physiology of male pattern androgenetic alopecia: Beyond the androgen horizon.","authors":"Sabrina Altendorf,Marta Bertolini,Alizée Le Riche,Antonella Tosti,Ralf Paus","doi":"10.1152/physrev.00005.2024","DOIUrl":"https://doi.org/10.1152/physrev.00005.2024","url":null,"abstract":"Male pattern androgenetic alopecia (mpAGA), the most common form of hair loss in men, represents a heritable, androgen-dependent complex trait distinct from female pattern hair loss. Despite the psychosocial burden of mpAGA in some affected individuals and associations with other morbidities, we portray mpAGA as an essentially physiological phenomenon in which defined hair follicle (HF) populations in developmentally preprogrammed scalp skin regions undergo a dramatic, but reversible (mini-)organ transformation in genetically predisposed individuals. Histologically, mpAGA exhibits progressive HF miniaturization (terminal-to-vellus conversion) and anagen shortening. Clinically, this results in a characteristic balding pattern of frontotemporal and vertex scalp skin, associated with telogen effluvium. It remains unclear how exactly androgens induce this phenotype, since neither androgen receptor polymorphisms nor changes in androgen serum or local androgen skin levels persuasively explain it. It also is as yet unresolved if mpAGA-associated HF transformation and hair cycle changes are primarily driven by the HF mesenchyme, e.g. by excessive emigration and/or reduced inductive potential of dermal papilla fibroblasts, or by intraepithelial events such as prostaglandin D2-dependent reduced HF epithelial stem cell progenitor generation. While critically revisiting our limited current understanding of mpAGA physiology and the role of mpAGA-associated genes we discuss potential targets for future therapeutic intervention beyond androgens and highlight selected dysregulated signaling pathways in mpAGA. We underscore mpAGA as an instructive, accessible model for interrogating under-investigated physiological roles of immune cells, oxidative stress, aging/senescence, and the microbiome in human organ remodeling and hair cycle regulation, and define major open research questions beyond androgen receptor- mediated signaling.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"111 1","pages":""},"PeriodicalIF":33.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594353","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

Type I Interferons in health and disease-Molecular aspects and clinical implications. I型干扰素在健康和疾病中的作用——分子方面和临床意义。

IF 33.6 1区医学

Physiological reviews Pub Date : 2025-07-10 DOI: 10.1152/physrev.00047.2024

Clio P Mavragani,Mary K Crow

{"title":"Type I Interferons in health and disease-Molecular aspects and clinical implications.","authors":"Clio P Mavragani,Mary K Crow","doi":"10.1152/physrev.00047.2024","DOIUrl":"https://doi.org/10.1152/physrev.00047.2024","url":null,"abstract":"Type I interferons (IFNs), particularly IFNα and IFNβ, play a crucial role in the human immune response against viral infections. This review delves into the multifaceted antiviral, immunomodulatory and antitumor physiological roles of type I IFNs, while describing their contribution to the pathogenesis of various disease pathologies including cancer, systemic and organ specific autoimmunity, neuroinflammation and atherosclerosis. Genetic determinants influencing activation of type I IFN pathways and therapeutic interventions either targeting or stimulating these pathways in the context of autoimmunity and cancer respectively are also discussed. Ultimately, the current understanding of the role of type I IFNs as biomarkers indicative of distinct clinical and serological phenotypes, their correlation with disease activity, their predictive role in therapeutic outcomes across diverse clinical scenarios, as well as the challenges associated with their implementation in clinical practice, are thoroughly addressed. Together, these insights underscore the significant potential of type I IFNs, as mediators and therapeutic targets, to reshape clinical decision-making, while highlighting the urgent need for robust, standardized methodologies for assessment of type I IFNs and their integration into routine practice.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"4 1","pages":""},"PeriodicalIF":33.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594355","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 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

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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139471/pdf/","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":"OA","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

Programmed cell death and tissue regeneration: A link that should be resolved 程序性细胞死亡和组织再生：一个应该解决的联系

IF 33.6 1区医学

Physiological reviews Pub Date : 2025-06-18 DOI: 10.1152/physrev.00036.2024

Gelina S Kopeina, Anastasia Yu Efimenko, Vsevolod A. Tkachuk, Boris Zhivotovsky

引用次数: 0

Glycerolipid Cycling in Thermogenesis, Energy Homeostasis and Signaling 产热、能量稳态和信号传导中的甘油脂循环

IF 33.6 1区医学

Physiological reviews Pub Date : 2025-06-10 DOI: 10.1152/physrev.00024.2024

Pegah Poursharifi, S.R. Murthy Madiraju, Abel Oppong, Shingo Kajimura, Christopher J Nolan, Denis P. Blondin, Marc Prentki

引用次数: 0

The physiopathology of brain-derived neurotrophic factor 脑源性神经营养因子的生理病理