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Physiological Systems in Promoting Frailty. 促进衰弱的生理系统。
IF 4.2 2区 医学 Q1 PHYSIOLOGY Pub Date : 2022-04-26 DOI: 10.1002/cphy.c210034
Laís R Perazza, Holly M Brown-Borg, LaDora V Thompson

Frailty is a complex syndrome affecting a growing sector of the global population as medical developments have advanced human mortality rates across the world. Our current understanding of frailty is derived from studies conducted in the laboratory as well as the clinic, which have generated largely phenotypic information. Far fewer studies have uncovered biological underpinnings driving the onset and progression of frailty, but the stage is set to advance the field with preclinical and clinical assessment tools, multiomics approaches together with physiological and biochemical methodologies. In this article, we provide comprehensive coverage of topics regarding frailty assessment, preclinical models, interventions, and challenges as well as clinical frameworks and prevalence. We also identify central biological mechanisms that may be at play including mitochondrial dysfunction, epigenetic alterations, and oxidative stress that in turn, affect metabolism, stress responses, and endocrine and neuromuscular systems. We review the role of metabolic syndrome, insulin resistance and visceral obesity, focusing on glucose homeostasis, adenosine monophosphate-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and nicotinamide adenine dinucleotide (NAD+ ) as critical players influencing the age-related loss of health. We further focus on how immunometabolic dysfunction associates with oxidative stress in promoting sarcopenia, a key contributor to slowness, weakness, and fatigue. We explore the biological mechanisms involved in stem cell exhaustion that affect regeneration and may contribute to the frailty-associated decline in resilience and adaptation to stress. Together, an overview of the interplay of aging biology with genetic, lifestyle, and environmental factors that contribute to frailty, as well as potential therapeutic targets to lower risk and slow the progression of ongoing disease is covered. © 2022 American Physiological Society. Compr Physiol 12:1-46, 2022.

虚弱是一种复杂的综合征,随着医学的发展,全球人类死亡率不断上升,影响着越来越多的全球人口。我们目前对虚弱的认识来自于实验室和临床研究,这些研究产生了大量的表型信息。但临床前和临床评估工具、多组学方法以及生理和生化方法已为推动该领域的发展奠定了基础。在这篇文章中,我们全面介绍了有关虚弱评估、临床前模型、干预措施、挑战以及临床框架和患病率的主题。我们还确定了可能起作用的核心生物机制,包括线粒体功能障碍、表观遗传学改变和氧化应激,这些反过来又会影响新陈代谢、应激反应以及内分泌和神经肌肉系统。我们回顾了代谢综合征、胰岛素抵抗和内脏肥胖的作用,重点关注葡萄糖稳态、单磷酸腺苷激活蛋白激酶(AMPK)、哺乳动物雷帕霉素靶标(mTOR)和烟酰胺腺嘌呤二核苷酸(NAD+),它们是影响与年龄相关的健康损失的关键因素。我们进一步关注免疫代谢功能障碍如何与氧化应激联系在一起,促进肌肉疏松症,这是导致迟钝、虚弱和疲劳的关键因素。我们探讨了干细胞衰竭所涉及的生物机制,干细胞衰竭会影响再生,并可能导致与虚弱相关的恢复力和压力适应能力下降。此外,我们还概述了衰老生物学与导致虚弱的遗传、生活方式和环境因素之间的相互作用,以及降低风险和减缓疾病进展的潜在治疗目标。© 2022 美国生理学会。Compr Physiol 12:1-46, 2022.
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引用次数: 0
Respiratory-Cardiovascular Interactions During Mechanical Ventilation: Physiology and Clinical Implications. 机械通气期间呼吸-心血管相互作用:生理学和临床意义。
IF 5.8 2区 医学 Q1 PHYSIOLOGY Pub Date : 2022-04-26 DOI: 10.1002/cphy.c210003
John Kreit

Positive-pressure inspiration and positive end-expiratory pressure (PEEP) increase pleural, alveolar, lung transmural, and intra-abdominal pressure, which decrease right and left ventricular (RV; LV) preload and LV afterload and increase RV afterload. The magnitude and clinical significance of the resulting changes in ventricular function are determined by the delivered tidal volume, the total level of PEEP, the compliance of the lungs and chest wall, intravascular volume, baseline RV and LV function, and intra-abdominal pressure. In mechanically ventilated patients, the most important, adverse consequences of respiratory-cardiovascular interactions are a PEEP-induced reduction in cardiac output, systemic oxygen delivery, and blood pressure; RV dysfunction in patients with ARDS; and acute hemodynamic collapse in patients with pulmonary hypertension. On the other hand, the hemodynamic changes produced by respiratory-cardiovascular interactions can be beneficial when used to assess volume responsiveness in hypotensive patients and by reducing dyspnea and improving hypoxemia in patients with cardiogenic pulmonary edema. Thus, a thorough understanding of the physiological principles underlying respiratory-cardiovascular interactions is essential if critical care practitioners are to anticipate, recognize, manage, and utilize their hemodynamic effects. © 2022 American Physiological Society. Compr Physiol 12:1-24, 2022.

正压吸气和呼气末正压(PEEP)增加胸膜压、肺泡压、肺跨壁压和腹内压,降低左右心室压(RV);LV)预负荷和LV后负荷,并增加RV后负荷。由此引起的心室功能改变的程度和临床意义取决于所输送的潮气量、PEEP总水平、肺和胸壁顺应性、血管内容积、基线左室和左室功能以及腹内压。在机械通气患者中,呼吸-心血管相互作用最重要的不良后果是peep诱导的心输出量、全身氧输送和血压的减少;ARDS患者右心室功能障碍的研究肺动脉高压患者的急性血流动力学衰竭。另一方面,当用于评估低血压患者的容量反应性,以及通过减轻心源性肺水肿患者的呼吸困难和改善低氧血症时,呼吸-心血管相互作用产生的血流动力学变化是有益的。因此,如果重症监护医生要预测、识别、管理和利用呼吸-心血管相互作用的生理原理,透彻理解呼吸-心血管相互作用的生理原理是必不可少的。©2022美国生理学会。物理学报(英文版),2012。
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引用次数: 3
Molecular Modeling is an Enabling Approach to Complement and Enhance Channelopathy Research. 分子模型是补充和加强通道病研究的一种有利方法。
IF 5.8 2区 医学 Q1 PHYSIOLOGY Pub Date : 2022-03-29 DOI: 10.1002/cphy.c190047
Michael T Zimmermann

Hundreds of human membrane proteins form channels that transport necessary ions and compounds, including drugs and metabolites, yet details of their normal function or how function is altered by genetic variants to cause diseases are often unknown. Without this knowledge, researchers are less equipped to develop approaches to diagnose and treat channelopathies. High-resolution computational approaches such as molecular modeling enable researchers to investigate channelopathy protein function, facilitate detailed hypothesis generation, and produce data that is difficult to gather experimentally. Molecular modeling can be tailored to each physiologic context that a protein may act within, some of which may currently be difficult or impossible to assay experimentally. Because many genomic variants are observed in channelopathy proteins from high-throughput sequencing studies, methods with mechanistic value are needed to interpret their effects. The eminent field of structural bioinformatics integrates techniques from multiple disciplines including molecular modeling, computational chemistry, biophysics, and biochemistry, to develop mechanistic hypotheses and enhance the information available for understanding function. Molecular modeling and simulation access 3D and time-dependent information, not currently predictable from sequence. Thus, molecular modeling is valuable for increasing the resolution with which the natural function of protein channels can be investigated, and for interpreting how genomic variants alter them to produce physiologic changes that manifest as channelopathies. © 2022 American Physiological Society. Compr Physiol 12:3141-3166, 2022.

数以百计的人体膜蛋白形成通道,运输必要的离子和化合物,包括药物和代谢物,但其正常功能的细节或功能如何被基因变异改变而导致疾病,往往是未知的。没有这方面的知识,研究人员就无法开发出诊断和治疗经络病变的方法。高分辨率的计算方法,如分子建模,使研究人员能够研究通道病蛋白的功能,促进详细的假设生成,并产生难以通过实验收集的数据。分子模型可以根据蛋白质可能发挥作用的每个生理环境进行定制,其中一些可能目前难以或不可能通过实验进行分析。由于在高通量测序研究中,在通道病蛋白中观察到许多基因组变异,因此需要具有机制价值的方法来解释其影响。结构生物信息学的杰出领域整合了包括分子建模、计算化学、生物物理学和生物化学在内的多个学科的技术,以发展机制假设并增强可用于理解功能的信息。分子建模和模拟访问三维和时间相关的信息,目前不能从序列预测。因此,分子模型对于提高研究蛋白质通道自然功能的分辨率,以及解释基因组变异如何改变它们以产生表现为通道病变的生理变化是有价值的。©2022美国生理学会。中国生物医学工程学报(英文版),2016。
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引用次数: 0
Oxidative Stress and Redox Signaling in the Pathophysiology of Liver Diseases. 肝脏疾病病理生理学中的氧化应激和氧化还原信号转导。
IF 5.8 2区 医学 Q1 PHYSIOLOGY Pub Date : 2022-03-29 DOI: 10.1002/cphy.c200021
Raja Gopal Reddy Mooli, Dhanunjay Mukhi, Sadeesh K Ramakrishnan

The increased production of derivatives of molecular oxygen and nitrogen in the form of reactive oxygen species (ROS) and reactive nitrogen species (RNS) lead to molecular damage called oxidative stress. Under normal physiological conditions, the ROS generation is tightly regulated in different cells and cellular compartments. Any disturbance in the balance between the cellular generation of ROS and antioxidant balance leads to oxidative stress. In this article, we discuss the sources of ROS (endogenous and exogenous) and antioxidant mechanisms. We also focus on the pathophysiological significance of oxidative stress in various cell types of the liver. Oxidative stress is implicated in the development and progression of various liver diseases. We narrate the master regulators of ROS-mediated signaling and their contribution to liver diseases. Nonalcoholic fatty liver diseases (NAFLD) are influenced by a "multiple parallel-hit model" in which oxidative stress plays a central role. We highlight the recent findings on the role of oxidative stress in the spectrum of NAFLD, including fibrosis and liver cancer. Finally, we provide a brief overview of oxidative stress biomarkers and their therapeutic applications in various liver-related disorders. Overall, the article sheds light on the significance of oxidative stress in the pathophysiology of the liver. © 2022 American Physiological Society. Compr Physiol 12:3167-3192, 2022.

分子氧和氮的衍生物以活性氧(ROS)和活性氮(RNS)的形式产生,它们的增加会导致被称为氧化应激的分子损伤。在正常生理条件下,ROS 的生成在不同的细胞和细胞间隙中受到严格调控。细胞产生的 ROS 与抗氧化平衡之间的任何失调都会导致氧化应激。本文将讨论 ROS 的来源(内源性和外源性)和抗氧化机制。我们还重点讨论了氧化应激在肝脏各类细胞中的病理生理意义。氧化应激与各种肝脏疾病的发生和发展有关。我们讲述了 ROS 介导的信号转导的主调节因子及其对肝病的影响。非酒精性脂肪肝(NAFLD)受 "多重平行打击模型 "的影响,其中氧化应激起着核心作用。我们重点介绍了氧化应激在非酒精性脂肪肝(包括肝纤维化和肝癌)中的作用的最新发现。最后,我们简要概述了氧化应激生物标志物及其在各种肝脏相关疾病中的治疗应用。总之,文章揭示了氧化应激在肝脏病理生理学中的重要意义。© 2022 美国生理学会。Compr Physiol 12:3167-3192, 2022.
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引用次数: 0
Computational and Experimental Analysis of Genetic Variants. 遗传变异的计算与实验分析。
IF 5.8 2区 医学 Q1 PHYSIOLOGY Pub Date : 2022-03-29 DOI: 10.1002/cphy.c210012
Jeremy W Prokop, Vladislav Jdanov, Lane Savage, Michele Morris, Neil Lamb, Elizabeth VanSickle, Cynthia L Stenger, Surender Rajasekaran, Caleb P Bupp

Genomics has grown exponentially over the last decade. Common variants are associated with physiological changes through statistical strategies such as Genome-Wide Association Studies (GWAS) and quantitative trail loci (QTL). Rare variants are associated with diseases through extensive filtering tools, including population genomics and trio-based sequencing (parents and probands). However, the genomic associations require follow-up analyses to narrow causal variants, identify genes that are influenced, and to determine the physiological changes. Large quantities of data exist that can be used to connect variants to gene changes, cell types, protein pathways, clinical phenotypes, and animal models that establish physiological genomics. This data combined with bioinformatics including evolutionary analysis, structural insights, and gene regulation can yield testable hypotheses for mechanisms of genomic variants. Molecular biology, biochemistry, cell culture, CRISPR editing, and animal models can test the hypotheses to give molecular variant mechanisms. Variant characterizations can be a significant component of educating future professionals at the undergraduate, graduate, or medical training programs through teaching the basic concepts and terminology of genetics while learning independent research hypothesis design. This article goes through the computational and experimental analysis strategies of variant characterization and provides examples of these tools applied in publications. © 2022 American Physiological Society. Compr Physiol 12:3303-3336, 2022.

基因组学在过去十年中呈指数级增长。通过全基因组关联研究(GWAS)和定量追踪位点(QTL)等统计策略,常见变异与生理变化相关。通过广泛的过滤工具,包括群体基因组学和基于三人的测序(父母和先证者),罕见变异与疾病相关。然而,基因组关联需要后续分析,以缩小因果变异,识别受影响的基因,并确定生理变化。存在大量数据,可用于将变异与基因变化、细胞类型、蛋白质途径、临床表型和建立生理基因组学的动物模型联系起来。这些数据与生物信息学相结合,包括进化分析、结构洞察和基因调控,可以为基因组变异的机制产生可测试的假设。分子生物学、生物化学、细胞培养、CRISPR编辑和动物模型可以验证这些假设,从而给出分子变异机制。在学习独立研究假设设计的同时,通过教授遗传学的基本概念和术语,变体特征可以成为教育本科生、研究生或医学培训项目中未来专业人员的重要组成部分。本文介绍了变异表征的计算和实验分析策略,并提供了这些工具在出版物中应用的示例。©2022美国生理学会。中国生物医学工程学报(英文版),2012。
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引用次数: 4
Polycystic Ovary Syndrome and the Neuroendocrine Consequences of Androgen Excess. 多囊卵巢综合征和雄激素过量的神经内分泌后果。
IF 5.8 2区 医学 Q1 PHYSIOLOGY Pub Date : 2022-03-29 DOI: 10.1002/cphy.c210025
Mauro S B Silva, Rebecca E Campbell

Polycystic ovary syndrome (PCOS) is a major endocrine disorder strongly associated with androgen excess and frequently leading to female infertility. Although classically considered an ovarian disease, altered neuroendocrine control of gonadotropin-releasing hormone (GnRH) neurons in the brain and abnormal gonadotropin secretion may underpin PCOS presentation. Defective regulation of GnRH pulse generation in PCOS promotes high luteinizing hormone (LH) pulsatile secretion, which in turn overstimulates ovarian androgen production. Early and emerging evidence from preclinical models suggests that maternal androgen excess programs abnormalities in developing neuroendocrine circuits that are associated with PCOS pathology, and that these abnormalities are sustained by postpubertal elevation of endogenous androgen levels. This article will discuss experimental evidence, from the clinic and in preclinical animal models, that has significantly contributed to our understanding of how androgen excess influences the assembly and maintenance of neuroendocrine impairments in the female brain. Abnormal central gamma-aminobutyric acid (GABA) signaling has been identified in both patients and preclinical models as a possible link between androgen excess and elevated GnRH/LH secretion. Enhanced GABAergic innervation and drive to GnRH neurons is suspected to contribute to the pathogenesis and early manifestation of neuroendocrine derangement in PCOS. Accordingly, this article also provides an overview of GABA regulation of GnRH neuron function from prenatal development to adulthood to discuss possible avenues for future discovery research and therapeutic interventions. © 2022 American Physiological Society. Compr Physiol 12:3347-3369, 2022.

多囊卵巢综合征(PCOS)是一种与雄激素过多密切相关的主要内分泌疾病,常导致女性不孕。虽然传统上认为PCOS是卵巢疾病,但大脑中促性腺激素释放激素(GnRH)神经元的神经内分泌控制改变和促性腺激素分泌异常可能是PCOS的基础。多囊卵巢综合征中GnRH脉冲产生的调节缺陷促进高黄体生成素(LH)脉冲分泌,这反过来过度刺激卵巢雄激素的产生。来自临床前模型的早期和新出现的证据表明,母体雄激素过量会导致与多囊卵巢综合征病理相关的发育中的神经内分泌回路异常,而这些异常是由青春期后内源性雄激素水平升高维持的。本文将讨论来自临床和临床前动物模型的实验证据,这些证据对我们理解雄激素过量如何影响女性大脑中神经内分泌损伤的组装和维持有重要贡献。中枢γ -氨基丁酸(GABA)信号异常已在患者和临床前模型中被确定为雄激素过量和GnRH/LH分泌升高之间的可能联系。gaba能神经支配的增强和GnRH神经元的驱动可能与PCOS神经内分泌紊乱的发病机制和早期表现有关。因此,本文也提供了从产前发育到成年期GABA调节GnRH神经元功能的概述,以讨论未来发现研究和治疗干预的可能途径。©2022美国生理学会。中国生物医学工程学报(英文版),2012。
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引用次数: 4
Cell Networks in Endocrine/Neuroendocrine Gland Function. 内分泌/神经内分泌腺功能中的细胞网络。
IF 5.8 2区 医学 Q1 PHYSIOLOGY Pub Date : 2022-03-29 DOI: 10.1002/cphy.c210031
Nathalie C Guérineau, Pauline Campos, Paul R Le Tissier, David J Hodson, Patrice Mollard

Reproduction, growth, stress, and metabolism are determined by endocrine/neuroendocrine systems that regulate circulating hormone concentrations. All these systems generate rhythms and changes in hormone pulsatility observed in a variety of pathophysiological states. Thus, the output of endocrine/neuroendocrine systems must be regulated within a narrow window of effective hormone concentrations but must also maintain a capacity for plasticity to respond to changing physiological demands. Remarkably most endocrinologists still have a "textbook" view of endocrine gland organization which has emanated from 20th century histological studies on thin 2D tissue sections. However, 21st -century technological advances, including in-depth 3D imaging of specific cell types have vastly changed our knowledge. We now know that various levels of multicellular organization can be found across different glands, that organizational motifs can vary between species and can be modified to enhance or decrease hormonal release. This article focuses on how the organization of cells regulates hormone output using three endocrine/neuroendocrine glands that present different levels of organization and complexity: the adrenal medulla, with a single neuroendocrine cell type; the anterior pituitary, with multiple intermingled cell types; and the pancreas with multiple intermingled cell types organized into distinct functional units. We give an overview of recent methodologies that allow the study of the different components within endocrine systems, particularly their temporal and spatial relationships. We believe the emerging findings about network organization, and its impact on hormone secretion, are crucial to understanding how homeostatic regulation of endocrine axes is carried out within endocrine organs themselves. © 2022 American Physiological Society. Compr Physiol 12:3371-3415, 2022.

生殖、生长、应激和代谢是由调节循环激素浓度的内分泌/神经内分泌系统决定的。在各种病理生理状态下,所有这些系统都会产生节律和激素搏动的变化。因此,内分泌/神经内分泌系统的输出必须在一个狭窄的有效激素浓度窗口内调节,但也必须保持可塑性的能力,以应对不断变化的生理需求。值得注意的是,大多数内分泌学家仍然对内分泌腺组织持“教科书”式的观点,这种观点源于20世纪对薄二维组织切片的组织学研究。然而,21世纪的技术进步,包括特定细胞类型的深入3D成像,极大地改变了我们的知识。我们现在知道,在不同的腺体中可以发现不同水平的多细胞组织,不同物种的组织结构也不同,可以通过修改来增强或减少激素的释放。本文主要研究细胞组织如何通过三种不同组织和复杂程度的内分泌/神经内分泌腺来调节激素输出:肾上腺髓质,具有单一的神经内分泌细胞类型;垂体前叶,具有多种混杂的细胞类型;胰腺有多种混杂的细胞类型组成不同的功能单位。我们给出了最近的方法,允许研究内分泌系统内的不同组成部分,特别是它们的时间和空间关系的概述。我们相信关于网络组织及其对激素分泌的影响的新发现对于理解内分泌轴在内分泌器官内部如何进行稳态调节至关重要。©2022美国生理学会。中国生物医学工程学报(英文版),2016。
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引用次数: 0
Developmental Effects of Electronic Cigarette Use. 电子烟使用对发育的影响。
IF 5.8 2区 医学 Q1 PHYSIOLOGY Pub Date : 2022-03-29 DOI: 10.1002/cphy.c210018
Joseph M Collaco, Sharon A McGrath-Morrow

Electronic cigarettes have gained widespread acceptance among adolescents and young adults. As a result of this popularity, there are concerns regarding the potential harm of primary, secondhand and thirdhand electronic cigarette exposures on fetal and postnatal development. In vitro studies have shown that constituents in electronic cigarette liquids, including nicotine, flavorings, and carrier agents can alter cellular processes and growth. Additionally, aerosolized electronic cigarette emissions have been shown to disrupt organ development and immune responses in preclinical studies. In clinical studies, an association between electronic cigarette use and frequent respiratory symptoms, greater asthma severity and impaired mucociliary clearance has been demonstrated with adolescent and young adult users of electronic cigarettes having twice the frequency of cough, mucus production, or bronchitis compared to nonusers. Along with the popularity of electronic cigarette use, secondhand electronic cigarette exposure has increased substantially; with almost one-fourth of middle and high school children reporting exposure to secondhand vapors. The health consequences of secondhand electronic cigarette exposure on children and other vulnerable populations are poorly understood but detectable levels of cotinine have been measured in nonusers. Pregnant women and their offspring are another vulnerable group at increased risk for health consequences from electronic cigarette exposure. Nicotine crosses the placenta and can disrupt brain and lung development in preclinical studies. This article will focus on the physiological and health effects associated with primary or secondhand exposure to electronic cigarettes. It is expected that with ongoing availability of electronic cigarettes as well as the accumulation of additional follow-up time for long-term outcomes, the risks associated with exposure will become better clarified. © 2022 American Physiological Society. Compr Physiol 12:3337-3346, 2022.

电子烟在青少年和年轻人中得到了广泛的接受。由于电子烟的流行,人们担心接触一手、二手和三手电子烟对胎儿和产后发育的潜在危害。体外研究表明,电子烟液体中的成分,包括尼古丁、调味剂和载体剂,可以改变细胞的过程和生长。此外,在临床前研究中,雾化电子烟的排放物已被证明会破坏器官发育和免疫反应。在临床研究中,电子烟的使用与频繁的呼吸道症状、更严重的哮喘严重程度和粘膜纤毛清除受损之间存在关联,与不使用电子烟的青少年和年轻成人相比,电子烟使用者咳嗽、产生粘液或支气管炎的频率是前者的两倍。随着电子烟使用的普及,二手电子烟暴露量大幅增加;近四分之一的中学生和高中生报告接触二手烟。接触二手电子烟对儿童和其他弱势群体的健康影响尚不清楚,但在不使用电子烟的人群中测量了可替宁的可检测水平。孕妇及其后代是另一个易受电子烟危害的弱势群体。临床前研究显示,尼古丁会穿过胎盘,扰乱大脑和肺部的发育。这篇文章将重点讨论与初次或二手接触电子烟有关的生理和健康影响。预计随着电子烟的持续可获得性以及对长期结果的额外随访时间的积累,与接触相关的风险将得到更好的阐明。©2022美国生理学会。中国生物医学工程学报(英文版),2012。
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引用次数: 0
State of Knowledge on Molecular Adaptations to Exercise in Humans: Historical Perspectives and Future Directions. 关于人类运动分子适应性的知识现状:历史展望与未来方向。
IF 4.2 2区 医学 Q1 PHYSIOLOGY Pub Date : 2022-03-09 DOI: 10.1002/cphy.c200033
Kaleen M Lavin, Paul M Coen, Liliana C Baptista, Margaret B Bell, Devin Drummer, Sara A Harper, Manoel E Lixandrão, Jeremy S McAdam, Samia M O'Bryan, Sofhia Ramos, Lisa M Roberts, Rick B Vega, Bret H Goodpaster, Marcas M Bamman, Thomas W Buford

For centuries, regular exercise has been acknowledged as a potent stimulus to promote, maintain, and restore healthy functioning of nearly every physiological system of the human body. With advancing understanding of the complexity of human physiology, continually evolving methodological possibilities, and an increasingly dire public health situation, the study of exercise as a preventative or therapeutic treatment has never been more interdisciplinary, or more impactful. During the early stages of the NIH Common Fund Molecular Transducers of Physical Activity Consortium (MoTrPAC) Initiative, the field is well-positioned to build substantially upon the existing understanding of the mechanisms underlying benefits associated with exercise. Thus, we present a comprehensive body of the knowledge detailing the current literature basis surrounding the molecular adaptations to exercise in humans to provide a view of the state of the field at this critical juncture, as well as a resource for scientists bringing external expertise to the field of exercise physiology. In reviewing current literature related to molecular and cellular processes underlying exercise-induced benefits and adaptations, we also draw attention to existing knowledge gaps warranting continued research effort. © 2021 American Physiological Society. Compr Physiol 12:3193-3279, 2022.

几个世纪以来,经常锻炼被认为是促进、维持和恢复人体几乎所有生理系统健康功能的有效刺激。随着人们对人体生理学复杂性的认识不断加深,方法论的可能性不断发展,以及日益严峻的公共卫生形势,将运动作为预防或治疗手段的研究从未像现在这样跨学科,也从未像现在这样影响深远。在美国国立卫生研究院共同基金(NIH Common Fund)"体育锻炼分子传导者联盟"(MoTrPAC)计划的早期阶段,该领域已做好充分准备,在现有对运动相关益处的内在机制的理解的基础上进行深入研究。因此,我们提出了一个全面的知识体系,详细介绍了当前围绕人类运动分子适应性的文献基础,以在这一关键时刻提供该领域的现状,并为将外部专业知识引入运动生理学领域的科学家提供资源。在回顾与运动引起的益处和适应性的分子和细胞过程相关的现有文献时,我们还提请注意需要继续研究的现有知识差距。© 2021 美国生理学会。Compr Physiol 12:3193-3279, 2022.
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引用次数: 0
The Cardiac Na+ -Ca2+ Exchanger: From Structure to Function. 心脏Na+ -Ca2+交换器:从结构到功能。
IF 5.8 2区 医学 Q1 PHYSIOLOGY Pub Date : 2021-12-29 DOI: 10.1002/cphy.c200031
Michela Ottolia, Scott John, Adina Hazan, Joshua I Goldhaber

Ca2+ homeostasis is essential for cell function and survival. As such, the cytosolic Ca2+ concentration is tightly controlled by a wide number of specialized Ca2+ handling proteins. One among them is the Na+ -Ca2+ exchanger (NCX), a ubiquitous plasma membrane transporter that exploits the electrochemical gradient of Na+ to drive Ca2+ out of the cell, against its concentration gradient. In this critical role, this secondary transporter guides vital physiological processes such as Ca2+ homeostasis, muscle contraction, bone formation, and memory to name a few. Herein, we review the progress made in recent years about the structure of the mammalian NCX and how it relates to function. Particular emphasis will be given to the mammalian cardiac isoform, NCX1.1, due to the extensive studies conducted on this protein. Given the degree of conservation among the eukaryotic exchangers, the information highlighted herein will provide a foundation for our understanding of this transporter family. We will discuss gene structure, alternative splicing, topology, regulatory mechanisms, and NCX's functional role on cardiac physiology. Throughout this article, we will attempt to highlight important milestones in the field and controversial topics where future studies are required. © 2021 American Physiological Society. Compr Physiol 12:1-37, 2021.

Ca2+稳态对细胞功能和存活至关重要。因此,细胞质内Ca2+浓度受到大量专门的Ca2+处理蛋白的严格控制。其中之一是Na+ -Ca2+交换器(NCX),这是一种普遍存在的质膜转运体,利用Na+的电化学梯度将Ca2+驱逐出细胞,而不是其浓度梯度。在这一关键作用下,这种二级转运蛋白指导重要的生理过程,如Ca2+稳态、肌肉收缩、骨形成和记忆等。本文就近年来有关哺乳动物NCX结构及其与功能关系的研究进展进行综述。由于对该蛋白进行了广泛的研究,因此将特别强调哺乳动物心脏异构体NCX1.1。鉴于真核交换体之间的保守程度,本文强调的信息将为我们理解这种转运体家族提供基础。我们将讨论基因结构、选择性剪接、拓扑结构、调控机制以及NCX在心脏生理学中的功能作用。在这篇文章中,我们将试图强调该领域的重要里程碑和未来需要研究的有争议的话题。©2021美国生理学会。中国生物医学工程学报(英文版),2012。
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引用次数: 10
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Comprehensive Physiology
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