Physiology (Bethesda, Md.)最新文献_第2页

Lymphatic Matters in Heart Disease: Systemic and Cardiac Perspectives. 心脏病中的淋巴问题：系统和心脏的观点。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2027-01-01 Epub Date: 2026-05-13 DOI: 10.1152/physiol.00057.2025

Benjamin Kelly, Tobias Wang, Vibeke E Hjortdal, Donna M B Boedtkjer

{"title":"Lymphatic Matters in Heart Disease: Systemic and Cardiac Perspectives.","authors":"Benjamin Kelly, Tobias Wang, Vibeke E Hjortdal, Donna M B Boedtkjer","doi":"10.1152/physiol.00057.2025","DOIUrl":"10.1152/physiol.00057.2025","url":null,"abstract":"The lymphatic system plays a fundamental role in cardiovascular physiology by maintaining whole body fluid balance, facilitating immune trafficking, and enabling lipid transport. Through these functions, lymphatic performance is tightly coupled to cardiovascular health, and disturbances in lymphatic flow, pumping, or lympho-venous return can directly influence the development and progression of heart disease. This review examines the relationship between the lymphatic and cardiovascular systems with an emphasis on systemic lymphatic function and its relevance to cardiovascular pathology. We describe the structure and physiology of the human lymphatic vasculature, including mechanisms governing lymph formation, transport, and return to the venous circulation, and discuss how these processes are challenged in conditions such as heart failure, venous congestion, and altered hemodynamics. Clinical and experimental evidence linking lymphatic dysfunction to edema, inflammation, and impaired organ function across multiple cardiovascular disease states, including heart failure, atherosclerosis, congenital heart disease, and heart transplantation, is considered. In addition, comparative and translational perspectives are presented, illustrating how diverse vertebrate lymphatic strategies inform fundamental principles of lymphatic regulation and translational cardiovascular research. Finally, emerging imaging modalities and therapeutic approaches targeting lymphatic structure and function are discussed as potential avenues for improving the diagnosis and treatment of cardiovascular disease. Together, this review positions the lymphatic system as an integral, system-level contributor to cardiovascular physiology and disease, underscoring the need to consider lymphatic function alongside the blood circulation in both research and clinical practice.","PeriodicalId":520753,"journal":{"name":"Physiology (Bethesda, Md.)","volume":" ","pages":"0"},"PeriodicalIF":10.3,"publicationDate":"2027-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147937259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel Roles of GPCRs in the Renal Collecting Duct. gpcr在肾集管中的新作用。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2026-11-01 Epub Date: 2026-04-17 DOI: 10.1152/physiol.00005.2026

Mackenzie K Kui, Jessica J Zhang, Jennifer L Pluznick

引用次数: 0

Brown Adipose Tissue Thermogenesis. 褐色脂肪组织产热。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2026-11-01 Epub Date: 2026-03-12 DOI: 10.1152/physiol.00002.2026

Denis P Blondin

{"title":"Brown Adipose Tissue Thermogenesis.","authors":"Denis P Blondin","doi":"10.1152/physiol.00002.2026","DOIUrl":"10.1152/physiol.00002.2026","url":null,"abstract":"Human brown adipose tissue (BAT) has emerged as a metabolically dynamic organ with the potential to influence thermoregulation, substrate utilization, and cardiometabolic health. This review synthesizes current knowledge on the biomolecular features of human BAT, physiological and pharmacological strategies to stimulate energy dissipation, the tools used to measure its function in vivo, and its role in thermoregulation and metabolic disease. Molecular profiling reveals that human BAT contains heterogeneous thermogenic adipocytes with multilocular lipid droplets, rich innervation and vascularization, compartmentalized mitochondria, and, beyond its hallmark expression of uncoupling protein 1 (UCP1), the capacity to recruit broader oxidative and futile-cycle pathways. Anatomically, BAT is distributed across several depots with distinct recruitment potential that varies widely between individuals. Cold exposure remains the most potent activator, although nutritional and pharmacological stimuli can also modulate BAT activity. Advances in imaging have expanded the ability to quantify BAT thermogenesis, from gold-standard [15O]O2 and [11C]acetate PET to multitracer and multimodal approaches aimed at capturing oxidative flux and heat production. These methods indicate that human BAT contributes modestly to lipid and glucose clearance and whole body energy expenditure, yet spontaneous uptake of [18F]fluorodeoxyglucose remains consistently associated with lower adiposity and reduced cardiometabolic risk. Major uncertainties persist regarding the true thermogenic capacity of human BAT, the functional relevance of beige adipocytes, the balance between UCP1-dependent and UCP1-independent heat-producing pathways, and the most reliable metrics of in vivo activation. Addressing these known unknowns will require integrated, multimodal approaches to define when, where, and how human BAT contributes to metabolic health.","PeriodicalId":520753,"journal":{"name":"Physiology (Bethesda, Md.)","volume":" ","pages":"0"},"PeriodicalIF":10.3,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147439102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Carotid Body Chemoreceptors: from Mountain to Space. 颈动脉体化学感受器：从高山到太空。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2026-11-01 Epub Date: 2026-05-13 DOI: 10.1152/physiol.00011.2026

David C Andrade, Camila Salazar-Ardiles, Bayron García-Ordenes, Jose Bueno, Alexis Arce-Alvarez, Maria Rodriguez-Fernandez, Rodrigo Iturriaga, Gregoire P Millet

引用次数: 0

Regulatory and Physiological Roles of lncRNAs in Tumor Immunotherapy Response. lncrna在肿瘤免疫治疗反应中的调控和生理作用。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2026-11-01 Epub Date: 2026-04-06 DOI: 10.1152/physiol.00058.2025

Miriam G Jasiulionis, Eduardo M Reis

引用次数: 0

ADAMTS and ADAMTSL Mutations in Connective Tissue Disorders. 结缔组织疾病中的ADAMTS和ADAMTSL突变。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2026-11-01 Epub Date: 2026-03-31 DOI: 10.1152/physiol.00043.2025

Ana D Alcocer, Elizabeth H Rush, Timothy J Mead

{"title":"ADAMTS and ADAMTSL Mutations in Connective Tissue Disorders.","authors":"Ana D Alcocer, Elizabeth H Rush, Timothy J Mead","doi":"10.1152/physiol.00043.2025","DOIUrl":"10.1152/physiol.00043.2025","url":null,"abstract":"The a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family is made up of extracellular matrix (ECM) proteins and enzymes involved in regulating tissue structure and function. The ECM is a network of proteins and polysaccharides surrounding the cells that provide support and maintain cellular function. Mutations to proteins in the ECM lead to systemic connective tissue disorders by disrupting the structural integrity and maintenance of the ECM, resulting in ocular, musculoskeletal, skin, and cardiovascular abnormalities. Mutations that arise from the ADAMTS family lead to specific connective tissue disorders with distinct clinical characteristics. Here, we detail these distinct clinical features of major connective tissue disorders that arise from mutations in the ADAMTS family proteins. These include Ehlers-Danlos syndrome arising from mutations in ADAMTS2, geleophysic dysplasia from ADAMTSL2, Weill-Marchesani syndrome from ADAMTS10 and ADAMTS17, ectopia lentis from ADAMTSL4, thoracic aortic aneurysms and dissection from ADAMTSL6, valvular disease in ADAMTS19, and a further connective tissue disorder from mutations in ADAMTS6. This review details the mechanisms in which mutations to these ADAMTS genes impair the structure of the ECM, leading to the variety of phenotypic outcomes seen in connective tissue disorders.","PeriodicalId":520753,"journal":{"name":"Physiology (Bethesda, Md.)","volume":" ","pages":"0"},"PeriodicalIF":10.3,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13157330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147597505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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 Impact of Antigen Presentation on BBB Disruption and Neuroinflammation. 抗原呈递对血脑屏障破坏和神经炎症的影响。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2026-11-01 Epub Date: 2026-03-31 DOI: 10.1152/physiol.00041.2025

Mark A Maynes, Aaron J Johnson

引用次数: 0

An Update on Inborn Errors of V(D)J Recombination. V(D)J重组的先天性错误研究进展。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2026-11-01 Epub Date: 2026-03-28 DOI: 10.1152/physiol.00004.2026

Ina Schim van der Loeff, Manisha Ahuja, Rui Chen, Eleonora Patane, Sophie Hambleton

{"title":"An Update on Inborn Errors of V(D)J Recombination.","authors":"Ina Schim van der Loeff, Manisha Ahuja, Rui Chen, Eleonora Patane, Sophie Hambleton","doi":"10.1152/physiol.00004.2026","DOIUrl":"10.1152/physiol.00004.2026","url":null,"abstract":"V(D)J recombination is the fundamental process by which developing T and B lymphocytes generate diverse antigen receptors, enabling adaptive immunity. This tightly regulated program operates exclusively in lymphoid precursors during G1 phase and depends on the lymphocyte-specific RAG1-RAG2 recombinase to introduce programmed DNA double-strand breaks at recombination signal sequences, followed by repair through the classical nonhomologous end joining (c-NHEJ) pathway. Disruption of any step in this molecular choreography compromises antigen receptor diversity and underlies a spectrum of inborn errors of immunity (IEIs), ranging from severe combined immunodeficiency (SCID) to immune dysregulation with autoimmunity and granulomatous disease. In this review, we place disorders of V(D)J recombination within the broader framework of T-cell development, detailing the temporal waves of recombinase activity, chromatin accessibility, and DNA damage responses that guide thymocyte differentiation. We discuss pathogenic variants affecting the cleavage phase [RAG1, RAG2, and the recently identified RAG cochaperone NudC domain-containing 3 (NUDCD3)], end processing (ARTEMIS), ligation and repair (LIG4, XLF, XRCC4, PRKDC), and genome surveillance pathways (ATM, MRN complex, RNF168), highlighting genotype-phenotype correlations and mechanisms driving immune deficiency and dysregulation. We briefly review recent diagnostic advances, including newborn screening using T-cell receptor excision circles, repertoire sequencing, and functional assays, alongside current therapeutic strategies. Finally, we outline key unanswered questions and argue that continued integration of clinical observation with molecular discovery is essential to improve outcomes and deepen understanding of adaptive immune development.","PeriodicalId":520753,"journal":{"name":"Physiology (Bethesda, Md.)","volume":" ","pages":"0"},"PeriodicalIF":10.3,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7619016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147535595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cardiopulmonary and Immune Effects of Environmental Particulate Exposures. 环境微粒暴露对心肺和免疫的影响。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2026-11-01 Epub Date: 2026-03-19 DOI: 10.1152/physiol.00064.2025

Matthew J Mears, Eleanor J Mohler, Priya Bandaru, Evan W Neczypor, Matthew W Gorr, Loren E Wold

引用次数: 0

Physiology in Perspective. 《透视生理学》。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2026-11-01 Epub Date: 2026-09-18 DOI: 10.1152/physiol.90085.2026

Amanda Heidt

引用次数: 0