Physiological reviews最新文献

英文中文

Proglucagon-derived Peptides: Human Physiology and Therapeutic Potential 胰高血糖素衍生肽：人体生理学和治疗潜力

IF 33.6 1区医学 Q1 PHYSIOLOGY

Physiological reviews

Pub Date : 2025-07-28 DOI: 10.1152/physrev.00057.2024

Lærke S. Gasbjerg, Casper K. Nielsen, Malte P. Suppli, Magnus F. G. Grøendahl, Jens J. Holst, Filip K. Knop, Palle B. Jeppesen, Asger B. Lund

Physiological Reviews, Ahead of Print.

《生理评论》，出版前。

引用次数: 0

Metabolic adaptations in cancer progression 癌症进展中的代谢适应

IF 33.6 1区医学 Q1 PHYSIOLOGY

Physiological reviews

Pub Date : 2025-07-28 DOI: 10.1152/physrev.00037.2024

Yiming Peng-Winkler, Sarah-Maria Fendt

Physiological Reviews, Ahead of Print.

《生理评论》，出版前。

引用次数: 0

Angiocrine and Pericrine Signaling: How Endothelial Cells and Pericytes Drive Cancer Progression and Therapy Resistance. 血管分泌和周分泌信号传导：内皮细胞和周细胞如何驱动癌症进展和治疗耐药性。

IF 33.6 1区医学 Q1 PHYSIOLOGY

Physiological reviews

Pub Date : 2025-07-23 DOI: 10.1152/physrev.00046.2024

Alexander M Jordan,Rebecca J G Drake,Kairbaan M Hodivala-Dilke

The emergence of treatment resistance and metastasis are significant challenges that need to be addressed to improve cancer patient outcomes. Greater insight into the mechanisms regulating these processes is needed to identify novel targets for the development of effective treatments. The importance of blood vessel interactions, including endothelial angiocrine and pericyte pericrine signals, with surrounding tissues, has been well established in regulating several normal physiological functions, including angiogenesis, metabolism, wound healing and development. They have also been implicated in the mechanisms of cancer growth, metastatic dissemination, regulation of the immune microenvironment and therapeutic resistance. This review provides an overview of the angiocrine and pericrine processes that regulate cancer, the tumor microenvironment and therapy responses. It highlights that endothelial cells and pericytes are not only important in maintaining blood vessel structure in cancer, but that their signaling roles are a pivotal regulatory element harnessed by tumors, some of which could be targeted for alternative cancer treatment strategies. Here, we summarize current research targeting angiocrine and pericrine signaling in cancer and propose new approaches for thorough exploration of these networks to further disentangle the intricate mechanisms at play.

治疗耐药和转移的出现是改善癌症患者预后需要解决的重大挑战。需要更深入地了解调节这些过程的机制，以确定开发有效治疗的新靶点。血管相互作用的重要性，包括内皮血管分泌和周细胞周分泌信号，与周围组织，在调节一些正常的生理功能，包括血管生成，代谢，伤口愈合和发育已经得到了很好的确立。它们还涉及癌症生长、转移性传播、免疫微环境调节和治疗耐药性的机制。本文综述了调节癌症、肿瘤微环境和治疗反应的血管分泌和周分泌过程。它强调了内皮细胞和周细胞不仅在维持癌症血管结构中很重要，而且它们的信号作用是肿瘤利用的关键调节元件，其中一些可以作为替代癌症治疗策略的靶点。在这里，我们总结了目前针对血管分泌和周分泌信号在癌症中的研究，并提出了深入探索这些网络的新方法，以进一步解开其复杂的机制。

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引用次数: 0

Sensing molecular carbon dioxide - a translational focus for respiratory disease 传感分子二氧化碳——呼吸系统疾病的转化焦点

IF 33.6 1区医学 Q1 PHYSIOLOGY

Physiological reviews

Pub Date : 2025-07-16 DOI: 10.1152/physrev.00022.2024

István Vadász, Eoin P Cummins, Deborah H. Brotherton, S Marina Casalino Matsuda, Laura A. Dada, Ori Green, Dustin T. King, Vitalii Kryvenko, Masahiko Shigemura, Peter H. S. Sporn, Moritz J. Strowitzki, Martin J. Cann, Jacob I. Sznajder

Physiological Reviews, Ahead of Print.

《生理评论》，出版前。

引用次数: 0

Diaphragm Muscle: A Pump That Can Not Fail. 横膈肌：一个不能失败的泵。

IF 33.6 1区医学 Q1 PHYSIOLOGY

Physiological reviews

Pub Date : 2025-07-11 DOI: 10.1152/physrev.00043.2024

Gary C Sieck,Matthew J Fogarty

In mammals, breathing requires an inspiratory pump to generate a negative intrathoracic pressure and thus pull air into the lungs for gas exchange. Exclusively in mammals, the diaphragm muscle (DIAm) is the major inspiratory pump, which separates the thoracic and abdominal cavities. With DIAm contraction a negative intrathoracic and positive abdominal pressure are generated (i.e., transdiaphragmatic pressure (Pdi). During breathing,the DIAm is very active, with a duty cycle (time active vs inactive) similar to that of the heart. Like the heart, this is a pump that cannot fail! Thus, in controlling breathing, the nervous system must activate DIAm to accomplish pump function while avoiding fatigue. The timing of DIAm activations must also be coordinated with activation of the upper airway muscles (the pipes) to avoid airway occlusion and aspiration, the intercostal and abdominal muscles to appropriately stiffen the body cavities. Similarly, neural control and coordination of the DIAm in non-ventilatory behaviors (airway protection, swallowing, vocalization and voiding) is equally complex, with coordinated activation of the DIAm and abdominal muscles. It is becoming increasingly clear that impaired non-ventilatory functions underlie the pathophysiology of a variety of medical conditions. In this review, we will delve into the detailed mechanistic underpinnings of the neural control of the DIAm and the symphonic coordination of its activation during breathing and other behaviors. We will attempt to move the field from considering the DIAm only as an inspiratory pump, emphasising neural control of airway, intercostal and abdominal muscles that must be coordinated with DIAm activation.

在哺乳动物中，呼吸需要一个吸气泵来产生负的胸内压，从而将空气吸入肺部进行气体交换。在哺乳动物中，隔膜肌（DIAm）是分隔胸腔和腹腔的主要吸气泵。DIAm收缩产生胸内负压和腹正压（即经膈压（Pdi））。在呼吸过程中，DIAm非常活跃，具有与心脏相似的占空比（活跃与不活跃的时间）。就像心脏一样，这是一个不能失败的泵！因此，在控制呼吸时，神经系统必须激活DIAm来完成泵功能，同时避免疲劳。DIAm的激活时间也必须与上气道肌肉（管道）的激活相协调，以避免气道闭塞和误吸，肋间肌和腹肌适当地硬化体腔。同样，在非通气行为（气道保护、吞咽、发声和排尿）中，DIAm的神经控制和协调也同样复杂，DIAm和腹部肌肉协同激活。越来越清楚的是，受损的非通气功能是各种医疗条件的病理生理学基础。在这篇综述中，我们将深入研究DIAm的神经控制及其在呼吸和其他行为中激活的交响协调的详细机制基础。我们将尝试改变将DIAm仅仅视为吸入泵的观点，强调气道、肋间肌和腹肌的神经控制必须与DIAm的激活相协调。

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引用次数: 0

Recent advances in alcohol metabolism: from the gut to the brain. 酒精代谢的最新进展：从肠道到大脑。

IF 33.6 1区医学 Q1 PHYSIOLOGY

Physiological reviews

Pub Date : 2025-07-10 DOI: 10.1152/physrev.00053.2024

Modan R Goldman,Mariel Molina-Castro,Jumar C Etkins,Theodore L Koide,Vijay A Ramchandani,Martin H Plawecki,Julie A Mennella,Marta Yanina Pepino

Globally, alcohol is the most widely used psychoactive drug and a leading cause of premature death among individuals aged 15-49 years. Understanding the absorption, distribution, metabolism, and excretion of alcohol in the human body, otherwise known as alcohol pharmacokinetics, is essential for predicting its behavioral effects and toxic consequences. This review examines the evolutionary origins of alcohol consumption and metabolism, focusing on the activity of alcohol dehydrogenase enzymes across species, which serve as key catalysts in alcohol oxidation. It also highlights recent advances in understanding central alcohol metabolism and updates on the potential clinical significance of non-oxidative pathways of alcohol metabolism and endogenous alcohol production, particularly in the context of liver disease. In addition, the review inspects factors that modulate alcohol metabolism, including genetic polymorphisms, biological sex, food intake, women's reproductive status, and clinical interventions such as medications and metabolic surgeries. Understanding these sources of variability in alcohol metabolism is crucial for identifying individual risk factors and tailoring strategies to reduce alcohol-related harm. This comprehensive review offers a current perspective on alcohol pharmacokinetics, valuable insights into its implications for health, behavior, and potential innovative therapeutic targets.

在全球范围内，酒精是使用最广泛的精神药物，也是15-49岁人群过早死亡的主要原因。了解酒精在人体内的吸收、分布、代谢和排泄，也称为酒精药代动力学，对于预测其行为效应和毒性后果至关重要。这篇综述探讨了酒精消耗和代谢的进化起源，重点是跨物种的酒精脱氢酶的活性，它是酒精氧化的关键催化剂。它还强调了在理解中枢酒精代谢方面的最新进展，以及酒精代谢和内源性酒精产生的非氧化途径的潜在临床意义的最新进展，特别是在肝脏疾病的背景下。此外，该综述还考察了调节酒精代谢的因素，包括基因多态性、生物性别、食物摄入、女性生殖状况以及药物和代谢手术等临床干预措施。了解这些酒精代谢变异性的来源对于确定个体风险因素和制定减少酒精相关危害的策略至关重要。这篇全面的综述提供了当前酒精药代动力学的观点，对其对健康、行为和潜在创新治疗靶点的影响有价值的见解。

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引用次数: 0

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 Q1 PHYSIOLOGY

Physiological reviews

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

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

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.

男性型雄激素性脱发（mpAGA）是男性最常见的脱发形式，是一种可遗传的、雄激素依赖性的复杂特征，与女性型脱发不同。尽管mpAGA对一些受影响的个体造成心理社会负担，并与其他疾病有关，但我们将mpAGA描述为一种本质上的生理现象，在这种生理现象中，发育预先编程的头皮皮肤区域的定义毛囊（HF）群体在遗传易感个体中经历了戏剧性的，但可逆的（微型）器官转化。组织学上，mpAGA表现出进行性HF小型化（终末到肌腱转化）和生长原缩短。临床上，这导致前额颞部和头皮顶点皮肤的特征性秃顶，并伴有休止期积液。目前尚不清楚雄激素究竟是如何诱导这种表型的，因为雄激素受体多态性、雄激素血清或局部雄激素皮肤水平的变化都不能令人信服地解释它。此外，mpaga相关的HF转化和毛发周期变化是否主要由HF间质驱动，例如，真皮乳头成纤维细胞的过度迁移和/或诱导电位降低，或上皮内事件，如前列腺素d2依赖性的HF上皮干细胞祖细胞生成减少，目前尚不清楚。在批判性地回顾我们目前对mpAGA生理学和mpAGA相关基因作用的有限理解的同时，我们讨论了除雄激素外未来治疗干预的潜在目标，并强调了mpAGA中选择的失调信号通路。我们强调mpAGA是一个指导性的、可访问的模型，用于询问免疫细胞、氧化应激、衰老/衰老和微生物组在人体器官重塑和头发周期调节中的生理作用，并定义了雄激素受体介导的信号传导之外的主要开放研究问题。

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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 Q1 PHYSIOLOGY

Physiological reviews

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

Clio P Mavragani,Mary K Crow

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.

I型干扰素（ifn），特别是IFNα和IFNβ，在人类对抗病毒感染的免疫反应中起着至关重要的作用。这篇综述深入探讨了I型ifn在多方面的抗病毒、免疫调节和抗肿瘤的生理作用，同时描述了它们在各种疾病病理的发病机制中的贡献，包括癌症、全身和器官特异性自身免疫、神经炎症和动脉粥样硬化。本文还讨论了影响I型IFN通路激活的遗传决定因素，以及在自身免疫和癌症的背景下靶向或刺激这些通路的治疗干预措施。最后，对I型ifn作为不同临床和血清学表型的生物标志物的作用的当前理解，它们与疾病活动性的相关性，它们在不同临床情况下治疗结果的预测作用，以及与它们在临床实践中实施相关的挑战，都得到了彻底的解决。总之，这些见解强调了I型ifn作为介质和治疗靶点的巨大潜力，以重塑临床决策，同时强调了迫切需要强有力的、标准化的方法来评估I型ifn并将其纳入常规实践。

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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 Q1 PHYSIOLOGY

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

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.

调节正常生理的细胞通讯中断通常是包括癌症在内的疾病发展的关键因素。细胞外囊泡（EVs）是细胞间通讯的介质，调节局部和远处微环境，并在肿瘤早期和晚期的进展中发挥重要作用。事实上，ev介导的通讯参与了原发肿瘤转化和增殖的初始步骤，以及转移前生态位的准备和随后的转移。在这种情况下，ev中DNA的存在（EV-DNA）特别有趣，具有重要的生物学意义和作为液体活检生物标志物的巨大潜力。在这篇综述中，我们将讨论EV-shed DNA的机制及其在肿瘤进化中的潜在影响。此外，近年来发现，电动汽车的分泌也会影响周围微环境的行为。肿瘤对治疗的抵抗是肿瘤学中一个重要的未解决的挑战，这是癌症高死亡率的主要原因之一。ev在治疗耐药中的作用引起了相当大的兴趣。在本综述的后半部分，我们还将研究ev在治疗耐药中的潜在参与。

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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 Q1 PHYSIOLOGY

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

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.

所有细胞都会释放纳米级细胞外囊泡 (EV)，以传递细胞间的通讯。细胞外小泡（包括外泌体和微囊泡）携带一系列生物活性分子，如蛋白质和 RNA，由膜脂质双分子层包裹。肺部的上皮细胞、内皮细胞和各种免疫细胞构成了肺部微环境中的EVs库，并携带反映其细胞来源的分子。EVs 可通过调节免疫反应、诱导组织修复和维持肺部平衡来维持肺部健康。它们可在肺组织和生物流体（如支气管肺泡灌洗液和血液）中被检测到，提供有关疾病过程的信息，并可作为疾病的生物标记物。在此，我们将讨论 EVs 在肺稳态和肺部疾病（如哮喘、慢性阻塞性肺病、囊性纤维化、特发性肺纤维化和肺损伤）中的作用。我们还讨论了 EVs 参与发病机制的机理及其作为疾病生物标志物的潜力。最后，在多项临床试验中，来自间充质干细胞的 EVs 可减轻严重的呼吸道炎症。此外，EVs 可被设计为携带治疗分子，以增强和扩大治疗机会，如抗炎分子 CD24。最后，我们讨论了利用不同类型的 EV 治疗严重呼吸系统疾病的新机遇。

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引用次数: 0

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