Current Opinion in Physiology最新文献

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Mechanisms of microRNA trafficking to mitochondria in the heart microRNA转运至心脏线粒体的机制

IF 1.9 Q2 PHYSIOLOGY

Current Opinion in Physiology

Pub Date : 2025-09-01 Epub Date: 2025-08-08 DOI: 10.1016/j.cophys.2025.100848

Diego Quiroga , Rachel Daniel , Samarjit Das

MicroRNAs (miRNAs) are essential post-transcriptional regulators of gene expression, and accumulating evidence supports their presence and function within mitochondria. These mitochondrial microRNAs (MitomiRs) modulate key processes such as oxidative phosphorylation, ATP production, calcium homeostasis, and reactive oxygen species balance in cardiac tissue. Despite growing recognition of their importance, the mechanisms governing miRNA trafficking to mitochondria remain incompletely understood. This review explores the current knowledge on miRNA biogenesis, mitochondrial import pathways — including the roles of Argonaute 2 (AGO2), the Translocase of the Outer/Inner Mitochondrial Membrane (TOM/TIM) complexes, and Polynucleotide Phosphorylase (PNPase) — and the regulatory impact of specific MitomiRs, such as miR-181c, miR-210, miR-378, let-7b, and miR-1. Understanding how these molecules influence mitochondrial function provides insight into their therapeutic potential in cardiovascular disease.

MicroRNAs （miRNAs）是基因表达的重要转录后调控因子，越来越多的证据支持它们在线粒体内的存在和功能。这些线粒体microRNAs （MitomiRs）调节心脏组织中氧化磷酸化、ATP产生、钙稳态和活性氧平衡等关键过程。尽管人们越来越认识到它们的重要性，但控制miRNA运输到线粒体的机制仍然不完全清楚。这篇综述探讨了目前关于miRNA生物发生、线粒体进口途径的知识-包括Argonaute 2 （AGO2）、线粒体外/内膜转位酶（TOM/TIM）复合物和多核苷酸磷酸化酶（PNPase）的作用-以及特定mitomir的调节作用，如miR-181c、miR-210、miR-378、let-7b和miR-1。了解这些分子如何影响线粒体功能，有助于深入了解它们在心血管疾病中的治疗潜力。

引用次数: 0

Circadian control of cellular constituent turnover and growth 细胞成分周转和生长的昼夜节律控制

IF 2.5 Q2 PHYSIOLOGY

Current Opinion in Physiology

Pub Date : 2025-09-01 Epub Date: 2025-05-27 DOI: 10.1016/j.cophys.2025.100837

Jeffrey J Kelu

The circadian clock synchronises biological processes with environmental cues, optimising fitness and energy efficiency. Among these, cell growth regulation is a critical yet underexplored area. While primarily linked to rhythmic cell division, cell growth also arises from the cyclic accumulation of cellular components driving volume expansion. This review highlights advances in understanding how the circadian clock regulates the synthesis and degradation of key cellular constituents, particularly RNAs and proteins, in both homeostatic and growing cells. These processes are essential for maintaining cellular homeostasis and supporting tissue development and regeneration. Further exploration of circadian turnover and its integration with cellular growth pathways could pave the way for chronotherapeutic strategies.

生物钟与环境线索同步生物过程，优化健康和能量效率。其中，细胞生长调控是一个关键但尚未充分探索的领域。虽然主要与细胞分裂节律有关，但细胞生长也源于驱动体积扩张的细胞成分的循环积累。这篇综述强调了在了解生物钟如何调节稳态和生长细胞中关键细胞成分的合成和降解方面的进展，特别是rna和蛋白质。这些过程对于维持细胞稳态和支持组织发育和再生至关重要。进一步探索昼夜节律转换及其与细胞生长途径的整合可以为时间治疗策略铺平道路。

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Noncoding RNA in cancer: pathogenesis to therapeutic targets 非编码RNA在癌症中的作用：发病机制和治疗靶点

IF 2.5 Q2 PHYSIOLOGY

Current Opinion in Physiology

Pub Date : 2025-09-01 Epub Date: 2025-06-30 DOI: 10.1016/j.cophys.2025.100847

Arpita Ghosh Mitra

In the human genome, most transcribed RNA does not translate into protein, yet it plays a crucial role in gene expression regulation. This ‘dark matter of the genome’ is called noncoding RNAs (ncRNAs), which are involved in the pathogenesis of different diseases, viz., cancer. According to the length of nucleotides, ncRNAs are categorised into long ncRNAs (lncRNAs) or small ncRNAs. Recent emerging studies are exploring the massive role of ncRNAs behind pathophysiology and the scope of utilising these huge segments as diagnostic and prognostic indicators, as well as therapeutic targets of cancer. This brief and succinct review will focus on recent publications on the status and major contribution of ncRNAs in cancer, ranging from pathogenesis and diagnosis to prognosis and therapy.

在人类基因组中，大多数转录的RNA不转化为蛋白质，但它在基因表达调控中起着至关重要的作用。这种“基因组的暗物质”被称为非编码rna (ncRNAs)，它与不同疾病（如癌症）的发病机制有关。根据核苷酸的长度，ncrna分为长ncrna （lncrna）和小ncrna。最近的新兴研究正在探索ncrna在病理生理学中的巨大作用，以及利用这些巨大片段作为诊断和预后指标以及癌症治疗靶点的范围。这篇简短的综述将集中在最近发表的关于ncrna在癌症中的地位和主要贡献的文章，从发病机制和诊断到预后和治疗。

引用次数: 0

Mitochondrial ncRNAs beyond the mitochondrion: coordinators of organelle crosstalk 线粒体外的线粒体ncrna：细胞器串扰的协调者

IF 2.5 Q2 PHYSIOLOGY

Current Opinion in Physiology

Pub Date : 2025-09-01 Epub Date: 2025-05-08 DOI: 10.1016/j.cophys.2025.100831

Sidhant Khatri, Anna Blumental-Perry

The mitochondrion contains its own genome that encodes subunits of respiratory complexes, components of the translation machinery, and numerous noncoding RNAs (ncRNAs). Some of these ncRNAs are antisense transcripts of their respective genes, regulating their maturation within mitochondria. Others facilitate mitochondria-to-nucleus communication, conveying mitochondrial status to the nucleus and coordinating synergy between the genomes. The first known mito-ncRNAs that exit mitochondria were those generated from the control regions of the mitochondrial genome. Recent evidence suggests that this phenomenon is broader, encompassing multiple mitochondrial sense and antisense transcripts and mito-tRNAs. mito-ncRNAs are regulated by the proliferative state of the cell, physiological stresses, and viral infections. Both within and outside the organelle, mito-ncRNAs serve as scaffolds for protein complex assembly, as modulators of promoter occupancy, heterochromatin states, nucleolar functions, and spliceosome selectivity, and as precursors and regulators of miRNA networks. Here, we summarize and discuss current knowledge regarding mito-ncRNA-mediated signaling pathways.

线粒体包含自己的基因组，该基因组编码呼吸复合物的亚基、翻译机制的组成部分和许多非编码rna （ncRNAs）。其中一些ncrna是它们各自基因的反义转录本，在线粒体内调节它们的成熟。另一些则促进线粒体与细胞核之间的通信，将线粒体状态传递给细胞核，并协调基因组之间的协同作用。已知的第一个退出线粒体的mito- ncrna是那些从线粒体基因组的控制区域产生的。最近的证据表明，这种现象是更广泛的，包括多种线粒体正、反义转录物和mito- trna。mito-ncRNAs受细胞增殖状态、生理应激和病毒感染的调节。在细胞器内外，mito-ncRNAs都是蛋白质复合物组装的支架，是启动子占用、异染色质状态、核仁功能和剪接体选择性的调节剂，也是miRNA网络的前体和调节剂。在这里，我们总结和讨论当前关于mitto - ncrna介导的信号通路的知识。

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引用次数: 0

Intersection of sex and circadian biology 性别与昼夜生物学的交叉

IF 2.5 Q2 PHYSIOLOGY

Current Opinion in Physiology

Pub Date : 2025-09-01 Epub Date: 2025-05-30 DOI: 10.1016/j.cophys.2025.100834

Georgios K Paschos, Ronan Lordan, Garret A FitzGerald

The circadian clock aligns behavior and physiology with environmental rhythms, and its disruption has been associated with increased risk of metabolic and neurological diseases. This review examines the emerging trends and mounting evidence demonstrating that there are sex-specific differences in circadian physiology relevant to health. Preclinical and clinical studies indicate that females exhibit greater circadian resilience, robust transcriptional rhythms, and resistance to clock perturbation compared to males. These influences affect susceptibility to metabolic conditions and responses to circadian perturbations like shift work. Notably, sex differences in response to alcohol consumption and cancer chronotherapy have emerged as fields of significant interest. Future research must consider both sexes to refine existing interventions and uncover the complex mechanisms of circadian physiology for more inclusive therapeutic strategies.

生理时钟使行为和生理与环境节律保持一致，它的破坏与代谢和神经疾病的风险增加有关。这篇综述研究了新兴趋势和越来越多的证据，表明与健康相关的生理昼夜节律存在性别特异性差异。临床前和临床研究表明，与男性相比，女性表现出更强的生理弹性、强大的转录节律和对时钟扰动的抵抗力。这些影响影响对代谢条件的易感性和对昼夜节律扰动（如倒班工作）的反应。值得注意的是，性别差异对酒精消费和癌症时间疗法的反应已经成为人们非常感兴趣的领域。未来的研究必须考虑两性，以完善现有的干预措施，并揭示昼夜生理的复杂机制，以获得更具包容性的治疗策略。

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SHP2 happens, just sail with it: the role of the protein tyrosine phosphatase SHP2 in autoimmune and autoinflammatory diseases 蛋白酪氨酸磷酸酶SHP2在自身免疫性和自身炎症性疾病中的作用

IF 2.5 Q2 PHYSIOLOGY

Current Opinion in Physiology

Pub Date : 2025-09-01 Epub Date: 2025-05-26 DOI: 10.1016/j.cophys.2025.100833

Samantha Le Sommer , Maria I Kontaridis

Autoimmune and autoinflammatory diseases are a diverse group of disorders that stem from aberrant immune responses against self. While autoimmune disorders are characterized by lymphocyte-driven antigen-specific responses, autoinflammatory diseases are driven by chronic activation of the innate immune system. However, to date, both groups of disorders lack clear understanding for their onset and the functional mechanisms conducive to their pathology and have few efficacious, safe, and/or curative treatment options for patients. The SH2 domain–containing protein tyrosine phosphatase (SHP2), the protein encoded by the PTPN11 gene, is a nodal enzyme involved in embryogenesis, development, proliferation, differentiation, and survival of cells. Mutations in PTPN11 are associated with the development of congenital disorders as well as several types of cancers. Recently, links between autoimmunity and genetic developmental disorders have also revealed a key role for SHP2 activity in autoimmune–autoinflammatory pathophysiology. Its association with these disorders has begun to unravel the molecular mechanisms that contribute to the onset of autoimmunity. In this review, we will discuss the emergent role of SHP2 in autoimmunity and the current known and unknown molecular mechanisms of its regulation in these processes and propose the translational impact it may have as a therapeutic in the near future.

自身免疫性疾病和自身炎症性疾病是一组不同的疾病，源于对自身的异常免疫反应。自身免疫性疾病的特点是淋巴细胞驱动的抗原特异性反应，而自身炎症性疾病是由先天免疫系统的慢性激活驱动的。然而，迄今为止，这两组疾病对其发病和有助于其病理的功能机制缺乏明确的认识，并且对患者缺乏有效、安全和/或治愈的治疗选择。SH2结构域蛋白酪氨酸磷酸酶（SHP2）是由PTPN11基因编码的蛋白，是一种参与胚胎发生、发育、增殖、分化和细胞存活的节点酶。PTPN11的突变与先天性疾病的发展以及几种类型的癌症有关。最近，自身免疫和遗传性发育障碍之间的联系也揭示了SHP2活性在自身免疫-自身炎症病理生理中的关键作用。它与这些疾病的关联已经开始揭示导致自身免疫发病的分子机制。在这篇综述中，我们将讨论SHP2在自身免疫中的新兴作用，以及目前已知和未知的SHP2在这些过程中的调节分子机制，并提出它在不久的将来可能作为一种治疗方法的翻译影响。

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Mitochondrial connection to Alzheimer’s disease and heart failure 线粒体与阿尔茨海默病和心力衰竭有关

IF 2.5 Q2 PHYSIOLOGY

Current Opinion in Physiology

Pub Date : 2025-06-01 Epub Date: 2025-05-02 DOI: 10.1016/j.cophys.2025.100830

Anupriya Sinha , Natasha Jaiswal , Pooja Jadiya , Dhanendra Tomar

The brain and heart are intricately linked, with dysfunction in one organ often affecting the other. Cardiovascular diseases (CVDs), particularly heart failure, impair cerebral blood flow, contributing to cognitive decline and increasing dementia risk. Conversely, Alzheimer’s disease (AD), marked by amyloid-beta plaques and tau tangles, impacts cardiac function. A shared mechanism between AD and CVDs is mitochondrial dysfunction, which disrupts energy production and oxidative balance, worsening both neurodegeneration and heart health. This interdependence underscores the potential for mitochondria-targeted therapies to address both conditions. With an aging population facing rising incidences of AD and CVDs, understanding these interconnected pathways and the central role of mitochondria could inform new therapeutic strategies and improve outcomes in both neurodegenerative and cardiovascular diseases.

大脑和心脏有着错综复杂的联系，一个器官的功能障碍往往会影响到另一个器官。心血管疾病（cvd），特别是心力衰竭，损害脑血流，导致认知能力下降，增加痴呆风险。相反，以淀粉样斑块和tau蛋白缠结为标志的阿尔茨海默病（AD）会影响心脏功能。AD和cvd的共同机制是线粒体功能障碍，线粒体功能障碍破坏能量产生和氧化平衡，使神经变性和心脏健康恶化。这种相互依赖性强调了线粒体靶向治疗解决这两种疾病的潜力。随着老龄化人口面临AD和cvd发病率的上升，了解这些相互关联的途径和线粒体的核心作用可以为神经退行性疾病和心血管疾病提供新的治疗策略和改善结果。

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Current advances in protein phosphatases in kidney disease 蛋白质磷酸酶在肾脏疾病中的研究进展

IF 2.5 Q2 PHYSIOLOGY

Current Opinion in Physiology

Pub Date : 2025-06-01 Epub Date: 2025-04-20 DOI: 10.1016/j.cophys.2025.100828

Marina Rousseau, Pedro Geraldes

Chronic kidney disease (CKD) affects a large portion of the global population and is characterized by alterations in kidney function. Unfortunately, patients who progress to end-stage kidney disease have little chance of kidney function reversal and will ultimately need dialysis or a kidney transplant. Therefore, understanding the underlying mechanisms of CKD progression is critical for developing new therapies. Protein phosphatases are essential regulators of signal transduction in the normal function of cells. The deregulation of different protein phosphatases has been associated with kidney disease onset and progression. This review aims to highlight the recent advances in the role of protein phosphatases in kidney health and disease. Mainly, attention will be brought to three of the four main families of protein phosphatases (serine/threonine, protein tyrosine, and dual-specificity phosphatases). Since kidney disease encompasses a wide range of pathologies, this review will focus on glomerulopathies, diabetic kidney disease, acute kidney injury, and advanced CKD/fibrosis.

慢性肾脏疾病（CKD）影响全球人口的很大一部分，其特征是肾功能改变。不幸的是，进展到终末期肾病的患者几乎没有机会逆转肾功能，最终将需要透析或肾移植。因此，了解CKD进展的潜在机制对于开发新疗法至关重要。蛋白磷酸酶是细胞正常功能中信号转导的重要调节因子。不同蛋白磷酸酶的失调与肾脏疾病的发生和发展有关。本文综述了蛋白磷酸酶在肾脏健康和疾病中的作用的最新进展。主要关注蛋白磷酸酶的四个主要家族中的三个（丝氨酸/苏氨酸，蛋白酪氨酸和双特异性磷酸酶）。由于肾脏疾病包括广泛的病理，本综述将重点关注肾小球病变、糖尿病肾病、急性肾损伤和晚期CKD/纤维化。

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Noncoding RNAs in myocardial ischemia/reperfusion injury and repair 非编码rna在心肌缺血/再灌注损伤及修复中的作用

IF 2.5 Q2 PHYSIOLOGY

Current Opinion in Physiology

Pub Date : 2025-06-01 Epub Date: 2025-03-21 DOI: 10.1016/j.cophys.2025.100825

Mingliang Pan , Zhixin Li , Xiaohong Wang , Liying Zhan , Guo-Chang Fan

Myocardial ischemia/reperfusion (I/R) usually triggers a series of molecular and cellular changes, which yield excessive oxidative stress and massive cardiomyocyte death, leading to sterile inflammation, cardiac fibrosis, and, eventually, heart failure. Over the past two decades, numerous studies have demonstrated that noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), involve almost every aspect of adverse cardiac remodeling induced by I/R. They have emerged as key regulators in the process of cardiac cell death (i.e. apoptosis, necroptosis, ferroptosis, pyroptosis, and PANoptosis), fibrosis, angiogenesis, and immune responses during myocardial I/R. Herein, this review summarizes recent advancements on ncRNA-mediated regulation of cardiac cell death, cardiac angiogenesis, fibrosis, and macrophage function as well as intercellular communication following myocardial I/R. Finally, the therapeutic potential of ncRNAs for treating myocardial I/R injury and future research directions are also discussed.

心肌缺血/再灌注（I/R）通常会引发一系列分子和细胞变化，产生过度氧化应激和大量心肌细胞死亡，导致无菌炎症、心脏纤维化，最终导致心力衰竭。在过去的二十年中，大量研究表明，非编码rna (ncRNAs)，包括microRNAs （miRNAs）、长链非编码rna （lncRNAs）和环状rna (circRNAs)，几乎涉及I/R诱导的不良心脏重构的各个方面。在心肌I/R过程中，它们在心肌细胞死亡（即凋亡、坏死坏死、铁下垂、焦下垂和PANoptosis）、纤维化、血管生成和免疫反应过程中发挥关键调节作用。本文综述了心肌I/R后ncrna介导的心肌细胞死亡、血管生成、纤维化、巨噬细胞功能以及细胞间通讯调控的最新进展。最后，讨论了ncrna在心肌I/R损伤中的治疗潜力及未来的研究方向。

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Emerging role of exosomal-microRNA in obesity 外泌体微rna在肥胖中的新作用

IF 2.5 Q2 PHYSIOLOGY

Current Opinion in Physiology

Pub Date : 2025-06-01 Epub Date: 2025-04-11 DOI: 10.1016/j.cophys.2025.100827

Achala Theres P Moncy , Samarjit Das , Hannah R Vasanthi

Exosomes are small extracellular vesicles released by every living cell in the human body and can be found in the circulation of almost every biological fluids. They majorly serve as a communication channel between cells. Exosomal-microRNAs (miRNAs) are gaining wide attention in several pathophysiological conditions, and are considered as early diagnostic and therapeutic targets. Recently, exosomal-miRNAs have been identified as key players during obesity and co-existing risk elements, unraveling their pivotal role in the progression of obesity-induced pathophysiological conditions. In this review, the latest developments in the role of exosomal cargo, specifically miRNAs, in obesity are highlighted. Additionally, we discuss their potential significance as early biomarkers and potential therapeutic targets for diagnosing and managing obesity and related diseases.

外泌体是由人体每一个活细胞释放的小细胞外囊泡，几乎在每一种生物液体的循环中都能找到。它们主要作为细胞间的通讯通道。外泌体微rna （miRNAs）在多种病理生理条件下受到广泛关注，被认为是早期诊断和治疗的靶点。最近，外泌体mirna已被确定为肥胖和共存风险因素的关键参与者，揭示了它们在肥胖诱导的病理生理状况进展中的关键作用。在这篇综述中，重点介绍了外泌体货物，特别是mirna在肥胖中的作用的最新进展。此外，我们还讨论了它们作为诊断和管理肥胖及相关疾病的早期生物标志物和潜在治疗靶点的潜在意义。

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