{"title":"Current advances in protein phosphatases in kidney disease","authors":"Marina Rousseau, Pedro Geraldes","doi":"10.1016/j.cophys.2025.100828","DOIUrl":"10.1016/j.cophys.2025.100828","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"44 ","pages":"Article 100828"},"PeriodicalIF":2.5,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892203","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}
Achala Theres P Moncy , Samarjit Das , Hannah R Vasanthi
{"title":"Emerging role of exosomal-microRNA in obesity","authors":"Achala Theres P Moncy , Samarjit Das , Hannah R Vasanthi","doi":"10.1016/j.cophys.2025.100827","DOIUrl":"10.1016/j.cophys.2025.100827","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"44 ","pages":"Article 100827"},"PeriodicalIF":2.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882590","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}
Mohit Kumar, Arnab Saha, Agasou Alfonso Rameau, Susmita Sil, Shilpa Buch
{"title":"Role of extracellular vesicle–mediated neurodegeneration in substance use disorders","authors":"Mohit Kumar, Arnab Saha, Agasou Alfonso Rameau, Susmita Sil, Shilpa Buch","doi":"10.1016/j.cophys.2025.100826","DOIUrl":"10.1016/j.cophys.2025.100826","url":null,"abstract":"<div><div>Substance use disorders (SUDs) remain a complicated and widespread public health problem, characterized by obsessive drug and alcohol use, despite adverse consequences. Emerging research suggests that the extracellular vesicles (EVs) play a critical role in mediating drug addiction and several neurodegenerative processes associated with SUDs. EVs, which include exosomes, microvesicles, and apoptotic bodies, are lipid-bilayered vesicles that facilitate intracellular communication throughout the host by shuttling bioactive molecules, such as proteins, lipids, DNA fragments, and RNA, including both coding and noncoding RNAs across recipient cells. The current review is a comprehensive analysis highlighting the potential role of EVs in the onset and progression of SUD, specifically in the context of cocaine, cannabis, methamphetamine, opiates, alcohol, and tobacco. The goal is to offer valuable insights into the underlying mechanism(s) involving EVs in the pathogenesis of SUD, ultimately paving the way for new therapeutic avenues.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"44 ","pages":"Article 100826"},"PeriodicalIF":2.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808563","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}
Mingliang Pan , Zhixin Li , Xiaohong Wang , Liying Zhan , Guo-Chang Fan
{"title":"Noncoding RNAs in myocardial ischemia/reperfusion injury and repair","authors":"Mingliang Pan , Zhixin Li , Xiaohong Wang , Liying Zhan , Guo-Chang Fan","doi":"10.1016/j.cophys.2025.100825","DOIUrl":"10.1016/j.cophys.2025.100825","url":null,"abstract":"<div><div>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<em>.</em> 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.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"44 ","pages":"Article 100825"},"PeriodicalIF":2.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808564","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}
{"title":"Dual-specificity phosphatases: an update on their activity regulation and roles in metabolic diseases","authors":"Caroline De Roo, Erin McLean, Ruijie Liu","doi":"10.1016/j.cophys.2025.100816","DOIUrl":"10.1016/j.cophys.2025.100816","url":null,"abstract":"<div><div>Reversible protein phosphorylation is catalyzed by both protein kinases and phosphatases, affecting cellular signal transduction in physiological and pathological processes. In contrast to protein kinases, the substrates and <em>in vivo</em> function of approximately 200 phosphatases are less characterized. The big family of protein phosphatases consists of serine/threonine phosphatases, tyrosine phosphatases, and dual-specificity phosphatases (DUSPs), which dephosphorylate both serine/threonine, and tyrosine residues within the target proteins. Over the last two decades, progress in the study of DUSPs allows for not only a better understanding of their activation and signaling termination but also the effect of their abnormal expression in the development of various diseases, such as diabetes, cancer, neurodegenerative disorders, and nonalcoholic fatty liver disease. The focus of this minireview is to discuss current understanding of transcriptional and post-translational regulation of DUSPs, as well as their emerging roles in energy metabolism.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"44 ","pages":"Article 100816"},"PeriodicalIF":2.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725259","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}
Sayam Ghosal , Bernadett R Bodnár , Brachyahu M Kestecher , Ákos Nagy , Tamás László , Bora Yilmaz , Yixuan Zeng , Adrienn Szabó , Csaba Bödör , Edit I Buzás , Xabier Osteikoetxea
{"title":"Revolutionizing therapeutics: unleashing the power of extracellular vesicles for disease intervention","authors":"Sayam Ghosal , Bernadett R Bodnár , Brachyahu M Kestecher , Ákos Nagy , Tamás László , Bora Yilmaz , Yixuan Zeng , Adrienn Szabó , Csaba Bödör , Edit I Buzás , Xabier Osteikoetxea","doi":"10.1016/j.cophys.2025.100815","DOIUrl":"10.1016/j.cophys.2025.100815","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) have emerged as a significant tool in therapeutic applications, exhibiting low immunogenicity and the ability to traverse biological barriers. EV-based treatments show great potential in various diseases, including oncology, neurodegeneration, and cardiovascular conditions. In cancer research, EVs play a role in tumor growth, spread, and resistance to chemotherapy, with modified EVs showing promise in improving drug delivery to challenging cancers such as glioblastoma. For neurodegeneration, EVs aid in protecting neurons and restoring motor function. Likewise, in cardiovascular diseases, EVs participate in tissue repair and heart protection. The effectiveness of EV-based vaccines, exemplified by a clinically approved meningococcal serogroup B MenB-4C vaccine, further underscores the therapeutic value of this approach. This review examines the progress in EV-based therapeutics and their future potential.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"43 ","pages":"Article 100815"},"PeriodicalIF":2.5,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143149275","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}
{"title":"Sex-specific effects of environmental pollutants on pulmonary immune responses","authors":"Sylvia S Sanchez, Fenna CM Sillé","doi":"10.1016/j.cophys.2025.100813","DOIUrl":"10.1016/j.cophys.2025.100813","url":null,"abstract":"<div><div>Environmental pollutants can adversely impact various physiological processes, affecting systems such as the respiratory and immune systems. Immune responses are influenced by various factors, including age, hormonal status, genetic background, and, notably, sex, with effects extending to both innate and adaptive immunity. External factors, like environmental pollutants, can also disrupt innate and/or adaptive immunity and compromise pathogen recognition and memory against future infections. Furthermore, environmental pollutants can play a pivotal role in the development and exacerbation of many chronic respiratory diseases. It is becoming increasingly evident that environmental pollutants elicit sex-specific effects across different species. This review highlights recent findings on the intricate interplay between sex differences and immune-related effects induced by environmental pollutants, with a particular focus on the dysregulation of pulmonary immune responses.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"43 ","pages":"Article 100813"},"PeriodicalIF":2.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349036","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}
{"title":"Circadian rhythms in renal metabolism","authors":"Yohan Bignon, Dmitri Firsov","doi":"10.1016/j.cophys.2025.100814","DOIUrl":"10.1016/j.cophys.2025.100814","url":null,"abstract":"<div><div>The kidney has one of the highest resting metabolic rates among human tissues. Most of the produced ATP is used for solutes and water reabsorption along the renal tubule. However, circadian rhythmicity in the glomerular filtration rate results in substantial circadian variations in the amounts of solutes and water to be reabsorbed at a given circadian time. Moreover, circadian rhythmicity in the renal blood flow causes circadian oscillations in available oxygen and metabolic substrates in kidney tissue. Collectively, this suggests that processes involved in energy consumption and energy production in the kidney follow circadian rhythms that parallel those in tubular reabsorption. In this review, we summarize recent progress in the identification of rhythmic renal metabolic pathways that are entrained by the intrinsic tubular circadian clock.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"43 ","pages":"Article 100814"},"PeriodicalIF":2.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143149274","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}
Patricia Xander , Mariana O Gonçalves, Ana C Torrecilhas
{"title":"Extracellular vesicles released by Trypanosoma cruzi and Leishmania spp.: protozoan parasite–host interaction mechanism","authors":"Patricia Xander , Mariana O Gonçalves, Ana C Torrecilhas","doi":"10.1016/j.cophys.2024.100792","DOIUrl":"10.1016/j.cophys.2024.100792","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) released by the protozoa parasites <em>Trypanosoma cruzi</em> and <em>Leishmania</em> spp. and host communication have received increased attention and achieved greater significance in recent years. This review focuses on the operation and consequences of the communication channel, which provides important insights into a variety of infectious disease characteristics and host immune responses. We highlight the most important discoveries, explain the underlying mechanisms, and discuss the implications for basic science and potential treatments. These EVs play a critical role in the parasite's ability to spread infection and alter the host’s immune response. However, there are some gaps in the research in this field, particularly in functional biological features that could help us understand the conditions and mechanisms underlying protozoan EV release. Therefore, more research is needed, as understanding the mechanisms underlying pathogen–host interaction is critical to treating endemic parasitic diseases. Given that EVs are promising candidates for vaccination, diagnosis, and therapy, this could lay the groundwork for the development of novel therapeutic approaches. Furthermore, there is no vaccine available for Chagas disease, which is extremely difficult to treat and manage.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"43 ","pages":"Article 100792"},"PeriodicalIF":2.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143149305","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}
{"title":"The two-sided impact of beta-adrenergic receptor ligands on inflammation","authors":"Paulina Dragan, Dorota Latek","doi":"10.1016/j.cophys.2024.100779","DOIUrl":"10.1016/j.cophys.2024.100779","url":null,"abstract":"<div><div>Beta-adrenergic receptors (β-ARs) encompass three distinct subtypes, which participate in modulating inflammatory responses. Both agonists and antagonists of these receptors are used to treat numerous diseases and have often been observed to have a protective role on different kinds of tissues. β-AR antagonists are used to treat cardiovascular diseases and chronic obstructive pulmonary disease but may worsen inflammation in neurodegenerative disorders. However, two β-AR antagonists, carvedilol and nebivolol, can attenuate the formation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. Many β-AR agonists have proved to mediate anti-inflammatory signals, especially in regard to suppressing the inflammatory response of macrophages or providing protective effects in cases of hypoxia. The activation of beta-adrenergic receptors can, however, be a double-edged sword, as their overactivation may result in cardiac inflammation. Here, we aim to provide an overview of recent advances in studying the connection between β-ARs and inflammation.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"41 ","pages":"Article 100779"},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142416298","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}