Physiology (Bethesda, Md.)最新文献

RNA-Protein Complexes and Their Role in Cell Fate. rna -蛋白复合物及其在细胞命运中的作用。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2027-01-01 Epub Date: 2026-06-26 DOI: 10.1152/physiol.00018.2026

Kaito Masaki, Malvin Leonardo Pardi, Hirohide Saito

引用次数: 0

The Iron Lung: Ferroptosis and Iron Regulation in Aging and Lung Diseases. 铁肺：铁下垂和铁在衰老和肺部疾病中的调节。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2027-01-01 Epub Date: 2026-06-27 DOI: 10.1152/physiol.00062.2025

Maunick Lefin Koloko Ngassie, Yamillie Ortiz, Preetham Ravi, Daniel A Pfeffer-Kleemann, Niyati A Borkar, Christina M Pabelick, Y S Prakash

{"title":"The Iron Lung: Ferroptosis and Iron Regulation in Aging and Lung Diseases.","authors":"Maunick Lefin Koloko Ngassie, Yamillie Ortiz, Preetham Ravi, Daniel A Pfeffer-Kleemann, Niyati A Borkar, Christina M Pabelick, Y S Prakash","doi":"10.1152/physiol.00062.2025","DOIUrl":"10.1152/physiol.00062.2025","url":null,"abstract":"Iron is an important metal element regulating biological processes such as gene expression, electron transport, cell proliferation, differentiation and division, and cellular respiration. Regulation of iron levels is therefore critical, with excess iron accumulation leading to iron-dependent lipid peroxidation and cell death (ferroptosis). Factors such as aging and environmental exposures (e.g., high/low oxygen, particulate iron) can disrupt iron homeostasis. Iron-dependent processes influence downstream pathways such as inflammation, mitochondrial energetics, and remodeling (proliferation, fibrosis), pathways involved in lung diseases particularly at the extremes of age, from hyperoxic lung injury in neonates to chronic diseases such as asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis (PF) that increase with age. Although these diseases involve structural and functional changes in bronchial versus alveolar compartments, including airway hyperreactivity, altered mucus production, cell proliferation and migration, increased extracellular matrix (ECM) remodeling, senescence, and metabolic dysregulation, the casual or consequential links between iron dysregulation and disease pathology, particularly with aging, are still being investigated. The aim of this topical review is to 1) highlight current knowledge regarding iron regulation in normal lung versus lung diseases, 2) identify known roles of iron in lung homeostasis and the contribution of iron dysregulation in lung diseases with aging, and 3) explore the potential benefit of targeting iron regulation and/or ferroptosis in lung diseases.","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148341585","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

Recent Advances in the Pathophysiology of Hypertension. 高血压病理生理学的最新进展。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2027-01-01 Epub Date: 2026-05-19 DOI: 10.1152/physiol.00019.2023

Augusto C Montezano, Raquel D Sarafian, Francisco J Rios, Zachariel Blaikie, Livia L Camargo, Milad Rasouli, Rhian M Touyz

引用次数: 0

Evolution of Adaptive Nonshivering Thermogenesis in Mammals. 哺乳动物适应性非寒颤产热的进化。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2027-01-01 Epub Date: 2026-06-29 DOI: 10.1152/physiol.00020.2026

Michaela Keuper, Martin Jastroch

{"title":"Evolution of Adaptive Nonshivering Thermogenesis in Mammals.","authors":"Michaela Keuper, Martin Jastroch","doi":"10.1152/physiol.00020.2026","DOIUrl":"10.1152/physiol.00020.2026","url":null,"abstract":"Endothermy depends on the ability to generate heat beyond basal metabolic output. The transition from incidental metabolic heat production to regulated adaptive thermogenesis represents a critical yet poorly understood milestone in vertebrate evolution. In vertebrates, adaptive thermogenesis includes shivering thermogenesis and nonshivering thermogenesis (NST), the latter involving molecular mechanisms that release energy in the form of heat independently of muscle contraction. This review synthesizes physiological, comparative, and evolutionary findings on adaptive NST, with a focus on adipose-based thermogenesis mediated by its unique mitochondrial uncoupling protein 1 (UCP1). We highlight a two-stage evolutionary model in which a prethermogenic adipose program governing UCP1 expression preceded the emergence of efficient UCP1-mediated thermogenesis in eutherian mammals. The source of NST and underlying mechanisms in other tissues and in noneutherian endothermic vertebrates are less well understood. We discuss proposed UCP1-independent sources of cellular heat production in adipose tissue and muscle. Although these pathways can increase cellular energy expenditure, evidence supporting their role as dedicated and regulated thermogenic mechanisms remains limited to date. Collectively, these findings suggest that adaptive NST is not a singular conserved mechanism but a diverse and context-dependent evolutionary strategy with important implications for understanding human physiology and disease.","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7619422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148348618","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

Two Pulses per Beat: Parallel Energetics of Myocardium and Coronary Wall. 每搏两次：心肌和冠状动脉壁的平行能量学。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2027-01-01 Epub Date: 2026-07-23 DOI: 10.1152/physiol.00023.2026

Manuel F Muñoz, L Fernando Santana

{"title":"Two Pulses per Beat: Parallel Energetics of Myocardium and Coronary Wall.","authors":"Manuel F Muñoz, L Fernando Santana","doi":"10.1152/physiol.00023.2026","DOIUrl":"10.1152/physiol.00023.2026","url":null,"abstract":"Each heartbeat is initiated by a sinoatrial node action potential that propagates through the myocardial syncytium, triggering sequential contraction of the four chambers and propelling blood through the coronary, pulmonary, and systemic circulations. This mechanical event is fueled by two coupled energetic pulses: one in the working myocardium, where ATP is consumed by Ca2+ cycling, cross-bridge cycling, and ion pumping, and a second in the coronary vascular wall, where smooth muscle cells (SMCs), endothelial cells, and pericytes expend ATP to maintain tone, manage Ca2+, and coordinate perfusion against systolic compression that arrests their blood supply. Cardiac myocytes and coronary SMCs share the same actomyosin machinery but are activated differently. In myocytes, beat-to-beat Ca2+ transients drive Ca2+ binding to troponin C to permit synchronous contraction; in coronary SMCs, Ca2+/calmodulin activates myosin light chain kinase (MLCK), which phosphorylates myosin to sustain tone. In both cell types, ATP availability sets the ceiling on excitability: when the energetic budget is met, ion pumps, SERCA, and ATP-sensitive channels operate within range and electrical behavior is stable; when it is not, excitability fails. Biosensor measurements reveal beat-to-beat ATP gains and dips in sinoatrial node and ventricular myocytes across systole and diastole. The vascular wall undergoes its own synchronous cycle: systolic compression arrests perfusion while MLCK, SERCA, and Kir2.1-mediated retrograde signaling compete for a diastolic replenishment window that narrows with each heart rate increment. We propose that cardiac energetics must treat these pulses as coequal, reframing heart failure as a vascular and computational disease of the coronary wall.","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":"148582078","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

Ion Channels as Gatekeepers of Fertility: from Uterine Kir7.1 to Sperm CatSper. 离子通道作为生育能力的看门人：从子宫Kir7.1到精子CatSper。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2027-01-01 Epub Date: 2026-06-09 DOI: 10.1152/physiol.00015.2026

Qingwei Niu, Polina V Lishko

{"title":"Ion Channels as Gatekeepers of Fertility: from Uterine Kir7.1 to Sperm CatSper.","authors":"Qingwei Niu, Polina V Lishko","doi":"10.1152/physiol.00015.2026","DOIUrl":"10.1152/physiol.00015.2026","url":null,"abstract":"Ion channels coordinate diverse physiological functions through tightly regulated fluxes of Ca2+, K+, Na+, Cl-, and H+ across both plasma and intracellular membranes. In the reproductive system, ion channels have emerged as key regulators of processes essential for reproductive success. They control epithelial transport and ciliary activity in the oviduct, regulate uterine smooth muscle contractility and receptivity, and orchestrate sperm capacitation, hyperactivation, acrosome reaction, and fertilization. These functions require precise spatial and temporal integration of environmental cues, including bioactive lipids, pH, temperature, and mechanical forces encountered throughout the reproductive tract. Dysregulation of ion channel activity has been increasingly linked to infertility, pregnancy complications, and other reproductive disorders. Recent advances in live-cell imaging, superresolution microscopy, electrophysiology, and cryo-electron microscopy have transformed our understanding of ion channel architecture, regulation, and organization within specialized membrane microdomains in reproductive tissues. In this review, we highlight recent discoveries of ion channels and their regulatory mechanisms specifically in reproductive tissues, with a focus on emerging roles of potassium channel Kir7.1 in uterine physiology and calcium channel CatSper in sperm motility, and discuss emerging questions that will guide future research in reproductive ion channel biology.","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13341003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148207641","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

Dietary Modulation of CMA: Implications for Cancer Prevention and Therapy. 膳食调节CMA：对癌症预防和治疗的意义。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2027-01-01 Epub Date: 2026-07-18 DOI: 10.1152/physiol.00014.2026

Cecilia Sanchez-Felipe, Esperanza Arias, Julio Madrigal-Matute

{"title":"Dietary Modulation of CMA: Implications for Cancer Prevention and Therapy.","authors":"Cecilia Sanchez-Felipe, Esperanza Arias, Julio Madrigal-Matute","doi":"10.1152/physiol.00014.2026","DOIUrl":"10.1152/physiol.00014.2026","url":null,"abstract":"Chaperone-mediated autophagy (CMA) is a selective lysosomal degradation pathway that links nutrient availability to intracellular proteostasis through the targeted turnover of selective proteins. Through this selective control of protein quality, CMA participates in the regulation of metabolic adaptation, cellular homeostasis, and stress responses. CMA is highly responsive to nutritional cues, including caloric restriction (CR), fasting, and changes in macronutrient composition, positioning this pathway as a key mediator of cellular adaptation to metabolic stress. In cancer, CMA displays context-dependent functions that influence tumor metabolism, genomic stability, and survival under adverse microenvironmental conditions. These dual roles suggest that dietary modulation of CMA may shape tumor initiation and progression through effects on cellular proteostasis and metabolic plasticity. In this review, we summarize current knowledge on the molecular mechanisms by which nutritional signals regulate CMA and discuss the physiological implications of nutrition-driven CMA modulation for cancer prevention and therapy.","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148498641","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

Optimized Cardiac Health by Exercise: Cardiomyocytes and Immune Microenvironment. 通过运动优化心脏健康：心肌细胞和免疫微环境。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2027-01-01 Epub Date: 2026-04-19 DOI: 10.1152/physiol.00008.2026

Shuqin Liu, Meiyu Hu, Xinpeng Li, Guoping Li, Dragos Cretoiu, T Scott Bowen, Joost P G Sluijter, Yihua Bei, Junjie Xiao

{"title":"Optimized Cardiac Health by Exercise: Cardiomyocytes and Immune Microenvironment.","authors":"Shuqin Liu, Meiyu Hu, Xinpeng Li, Guoping Li, Dragos Cretoiu, T Scott Bowen, Joost P G Sluijter, Yihua Bei, Junjie Xiao","doi":"10.1152/physiol.00008.2026","DOIUrl":"10.1152/physiol.00008.2026","url":null,"abstract":"Exercise is a highly cost-effective and nonpharmacological intervention for maintaining cardiovascular health and treating heart disease. Exercise can protect the heart through multiple effects, including the regulation of cardiomyocytes and noncardiomyocytes. Immune cells can be regulated upon exercise under both physiological and pathological conditions. The present review presents the current knowledge and research advances about how exercise protects the heart, especially deciphering the regulation of cardiomyocytes and the immune microenvironment by exercise. This review introduces the effect of exercise on the infiltration, phenotypic plasticity, and activation of innate and adaptive immune cells, alongside their interactions with other cellular components within the cardiac immune microenvironment. Moreover, we address the role of lymphatic vessels in regulating immune cell trafficking and activation, as well as the effects of exercise on cardiac lymphangiogenesis. It further discusses the application of multiomics approaches in investigating exercise-induced cardiac adaptations, explores potential therapeutic strategies targeting the cardiac immune microenvironment, and highlights the cardiotoxicity risks associated with excessive exercise. A deep understanding of the effects of exercise on cardiomyocytes and cardiac immune microenvironment will pave the way to promote exercise interventions and the development of exercise mimetics in the treatment of heart diseases.","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":"147725497","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

Is Insulin Resistance an Adaptive Response? Clues from Nature. 胰岛素抵抗是一种适应性反应吗？来自大自然的线索。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2027-01-01 Epub Date: 2026-06-02 DOI: 10.1152/physiol.00059.2025

Karen L Sweazea

{"title":"Is Insulin Resistance an Adaptive Response? Clues from Nature.","authors":"Karen L Sweazea","doi":"10.1152/physiol.00059.2025","DOIUrl":"10.1152/physiol.00059.2025","url":null,"abstract":"Insulin is an evolutionarily conserved peptide hormone best known for regulating glucose homeostasis, yet its physiological roles extend well beyond glucose regulation. Across the animal kingdom, insulin signaling influences such diverse physiological processes as growth and development, stress responses, cognition, learning, memory formation, sodium balance, thermoregulation, reproduction, and vision. Although traditional laboratory models have advanced our understanding of insulin signaling and diabetes pathophysiology, they represent a relatively narrow perspective on the diversity of glucose regulation strategies and roles of insulin observed in the animal kingdom. Examination of insulin resistance through a comparative physiology lens provides a broader evolutionary framework for understanding how insulin signaling pathways and nutrient regulation have been conserved or modified across species in response to various environmental pressures. Evidence from this approach demonstrates diverse glucose regulation strategies noting that insulin resistance can at times function as an adaptive response to various stressors, even in humans. Several recent reviews have explored the evolution of insulin resistance and adaptive insulin resistance, although most have focused on a limited subset of vertebrates. Therefore, the intent of the present review is not to reproduce these efforts but to synthesize evidence across taxa, highlighting the diversity of strategies for glucose regulation and adaptive insulin resistance in vertebrates through the lens of comparative physiology. By examining insulin signaling within an evolutionary context, this review aims to identify unifying principles that challenge conventional paradigms of insulin resistance as solely pathological and instead position it as a context-dependent physiological adaptation across species.","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":"148146037","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

Multicellular Cross Talk and Therapeutic Vaccines in Heart Failure. 心力衰竭的多细胞串扰和治疗性疫苗

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2027-01-01 Epub Date: 2026-04-29 DOI: 10.1152/physiol.00007.2026

Manami Katoh, Seitaro Nomura, Toshiyuki Ko, Jin Komuro, Hiroki Hayashi, Hironori Nakagami, Issei Komuro

{"title":"Multicellular Cross Talk and Therapeutic Vaccines in Heart Failure.","authors":"Manami Katoh, Seitaro Nomura, Toshiyuki Ko, Jin Komuro, Hiroki Hayashi, Hironori Nakagami, Issei Komuro","doi":"10.1152/physiol.00007.2026","DOIUrl":"10.1152/physiol.00007.2026","url":null,"abstract":"Heart failure (HF) remains a leading cause of morbidity and mortality worldwide despite major advances in pharmacological and device-based therapies. A central limitation of current treatments is their predominant focus on neurohumoral modulation rather than the intrinsic biological processes driving cardiac remodeling. Recent progress in genetics, single-cell and spatial omics, and systems biology has fundamentally reshaped our understanding of HF, revealing it as a heterogeneous, multicellular syndrome characterized by disrupted intercellular communication within the cardiac cellular ecosystem. Endothelial cells, fibroblasts, immune cells, and cardiomyocytes engage in dynamic signaling networks that coordinate myocardial structure, metabolism, and function; pathological remodeling emerges when these networks become maladaptive. Circulating biomarkers increasingly serve as readouts of these intercellular interactions, reflecting senescence, inflammation, fibrosis, and metabolic stress. Among them, insulin-like growth factor-binding protein 7 (IGFBP7) has emerged as a key mediator linking endothelial cell senescence to cardiomyocyte metabolic dysfunction. In parallel, stress-activated fibroblast subpopulations drive HF progression through paracrine signaling pathways such as the MYC-CXCL1-CXCR2 axis. These insights open new therapeutic opportunities beyond conventional pharmacology. Immunization-based strategies targeting pathological intercellular communication represent a novel paradigm for disease-modifying HF therapy. Peptide-based vaccines that neutralize circulating mediators or eliminate pathogenic cell populations have demonstrated efficacy in preclinical models and early clinical studies. In this review, we integrate emerging trends in HF research with recent advances in multicellular biology and therapeutic vaccination, proposing immunization as a unifying strategy to target cardiac remodeling at its roots.","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":"147795784","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