Comprehensive Physiology最新文献

Tet Methylcytosine Dioxygenase 2 (TET2) Mutation Drives a Global Hypermethylation Signature in Patients With Pulmonary Arterial Hypertension (PAH): Correlation With Altered Gene Expression Relevant to a Common T Cell Phenotype. Tet甲基胞嘧啶双加氧酶2 （TET2）突变驱动肺动脉高压（PAH）患者的整体高甲基化特征：与普通T细胞表型相关的基因表达改变相关

IF 4.2 2区医学

Comprehensive Physiology Pub Date : 2025-04-01 DOI: 10.1002/cph4.70011

Charles C T Hindmarch, François Potus, Ruaa Al-Qazazi, Benjamin P Ott, William C Nichols, Michael J Rauh, Stephen L Archer

{"title":"Tet Methylcytosine Dioxygenase 2 (TET2) Mutation Drives a Global Hypermethylation Signature in Patients With Pulmonary Arterial Hypertension (PAH): Correlation With Altered Gene Expression Relevant to a Common T Cell Phenotype.","authors":"Charles C T Hindmarch, François Potus, Ruaa Al-Qazazi, Benjamin P Ott, William C Nichols, Michael J Rauh, Stephen L Archer","doi":"10.1002/cph4.70011","DOIUrl":"https://doi.org/10.1002/cph4.70011","url":null,"abstract":"Epigenetic changes in gene expression due to DNA methylation regulate pulmonary vascular structure and function. Genetic or acquired alterations in DNA methylation/demethylation can promote the development of pulmonary arterial hypertension (PAH). Here, we performed epigenome-wide mapping of DNA methylation in whole blood from 10 healthy people and 19 age/sex-matched PAH patients from the PAH Biobank. Exome sequencing confirmed the absence of known mutations in PAH-associated gene variants identifying subjects with or without mutations of TET2, a putative PAH gene encoding the demethylating enzyme, TET2. DNA of patients with PAH and no TET2 mutation was hypermethylated compared to healthy controls. Patients with PAH and a TET2 mutation had greater DNA CpG methylation than mutation-free PAH patients. Unique Differentially Methylated Regions (DMR) were more common in patients with PAH with TET2 mutations (1164) than in PAH without mutations (262). We correlated methylome findings with a public PAH transcriptomic RNA dataset, prioritizing targets that are both hypermethylated in our cohort and downregulated at the RNA level. Relative to controls, functional analysis reveals enriched functions related to T cell differentiation in PAH patients with a TET2 mutation. We identified genes with downregulated expression that were hypermethylated in PAH patients (with or without a TET2 mutation). In both cases, a conserved T cell phenotype emerged. Pan-chromosomal hypermethylation in PAH is greatest in patients with TET2 mutations. Observed hypermethylation of genes involved in the pathogenesis of PAH, such as EIF2AK4, and transcription factors that regulate T cell development, such as TCF7, merit further study and may contribute to the inflammation in PAH.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"15 2","pages":"e70011"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12021535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Redefining Macrophage Heterogeneity in Atherosclerosis: A Focus on Possible Therapeutic Implications. 重新定义动脉粥样硬化中的巨噬细胞异质性：关注可能的治疗意义。

IF 4.2 2区医学

Comprehensive Physiology Pub Date : 2025-04-01 DOI: 10.1002/cph4.70008

Babunageswararao Kanuri, Krishna P Maremanda, Dipanjan Chattopadhyay, M Faadiel Essop, Man Kit Sam Lee, Andrew J Murphy, Prabhakara R Nagareddy

{"title":"Redefining Macrophage Heterogeneity in Atherosclerosis: A Focus on Possible Therapeutic Implications.","authors":"Babunageswararao Kanuri, Krishna P Maremanda, Dipanjan Chattopadhyay, M Faadiel Essop, Man Kit Sam Lee, Andrew J Murphy, Prabhakara R Nagareddy","doi":"10.1002/cph4.70008","DOIUrl":"10.1002/cph4.70008","url":null,"abstract":"Atherosclerosis is a lipid disorder where modified lipids (especially oxidized LDL) induce macrophage foam cell formation in the aorta. Its pathogenesis involves a continuum of persistent inflammation accompanied by dysregulated anti-inflammatory responses. Changes in the immune cell status due to differences in the lesional microenvironment are crucial in terms of plaque development, its progression, and plaque rupture. Ly6Chi monocytes generated through both medullary and extramedullary cascades act as one of the major sources of plaque macrophages and thereby foam cells. Both monocytes and monocyte-derived macrophages also participate in pathological events in atherosclerosis-associated multiple organ systems through inter-organ communications. For years, macrophage phenotypes M1 and M2 have been shown to perpetuate inflammatory and resolution responses; nevertheless, such a dualistic classification is too simplistic and contains severe drawbacks. As the lesion microenvironment is enriched with multiple mediators that possess the ability to activate macrophages to diverse phenotypes, it is obvious that such cells should demonstrate substantial heterogeneity. Considerable research in this regard has indicated the presence of additional macrophage phenotypes that are exclusive to atherosclerotic plaques, namely Mox, M4, Mhem, and M(Hb) type. Furthermore, although the concept of macrophage clusters has come to the fore in recent years with the evolution of high-dimensional techniques, classifications based on such 'OMICS' approaches require extensive functional validation as well as metabolic phenotyping. Bearing this in mind, the current review provides an overview of the status of different macrophage populations and their role during atherosclerosis and also outlines possible therapeutic implications.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"15 2","pages":"e70008"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synergistic Effects of Riluzole and Sodium Butyrate on Barrier Function and Disease Progression of Amyotrophic Lateral Sclerosis Through the Gut-Neuron Axis. 利鲁唑和丁酸钠通过肠-神经元轴对肌萎缩侧索硬化症屏障功能和疾病进展的协同作用。

IF 4.2 2区医学

Comprehensive Physiology Pub Date : 2025-04-01 DOI: 10.1002/cph4.70009

Yongguo Zhang, KaReisha Robinson, Yinglin Xia, Jun Sun

{"title":"Synergistic Effects of Riluzole and Sodium Butyrate on Barrier Function and Disease Progression of Amyotrophic Lateral Sclerosis Through the Gut-Neuron Axis.","authors":"Yongguo Zhang, KaReisha Robinson, Yinglin Xia, Jun Sun","doi":"10.1002/cph4.70009","DOIUrl":"10.1002/cph4.70009","url":null,"abstract":"Emerging evidence has shown that gut-brain barrier dysfunction occurs at the early stages of ALS. Previous studies demonstrated that sodium butyrate significantly prolonged the life span of ALS mice. Riluzole is the first FDA-approved drug for ALS treatment. We hypothesize that Riluzole and sodium butyrate combined treatment further decreases aggregation of the h-SOD1G93A, restores the gut-brain barrier function, and delays ALS progression. SOD1G93A mice (9-10-week-old) were treated with Riluzole (10 mg/kg, I.P. daily), sodium butyrate (2% in drinking water), or Riluzole and sodium butyrate combination for 6 weeks. The Riluzole/butyrate combination showed a significantly longer rotarod time, increased grip strength, and enhanced intestinal barrier, as compared with Riluzole or sodium butyrate-only treatment. More reduction of h-SOD1G93A aggregation was observed in the colon, spinal cord lumbar, and brain cortex with Riluzole and sodium butyrate combination, compared with Riluzole or sodium butyrate-only treatment. Tight junction proteins (ZO-1 and Claudin-5) significantly increased in the colon, spinal cord lumbar, and brain cortex of mice with Riluzole and sodium butyrate treatment. The Riluzole and sodium butyrate combination reduced serum lipopolysaccharides and h-SOD1G93A aggregation, and inflammatory cytokines more than those in Riluzole or sodium butyrate-only treatment. Overall, Riluzole and sodium butyrate treatment is more effective than either Riluzole or sodium butyrate-only in delaying ALS progress. It provides a potential therapeutic strategy and mechanism by restoring barrier function through the gut-brain axis for ALS.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"15 2","pages":"e70009"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sex and Depot Specific Adipocyte Proteome Profiling In Vivo via Intracellular Proximity Labeling. 性别和储存特异性脂肪细胞蛋白质组分析在体内通过细胞内接近标记。

IF 4.2 2区医学

Comprehensive Physiology Pub Date : 2025-04-01 DOI: 10.1002/cph4.70007

Taylor L Simonian, Amanda S Meyer, Jinjin Guo, Jihui Sha, James A Wohlschlegel, Ilia A Droujinine, Norbert Perrimon, Andrew P McMahon

{"title":"Sex and Depot Specific Adipocyte Proteome Profiling In Vivo via Intracellular Proximity Labeling.","authors":"Taylor L Simonian, Amanda S Meyer, Jinjin Guo, Jihui Sha, James A Wohlschlegel, Ilia A Droujinine, Norbert Perrimon, Andrew P McMahon","doi":"10.1002/cph4.70007","DOIUrl":"10.1002/cph4.70007","url":null,"abstract":"Adipose tissue has varying distributions and metabolic properties between the sexes. Inherent sex-specific differences in adipocytes may heighten the risk of metabolic disease in males. Analysis of the adipocyte proteome can potentially provide important insight. To enable cell-type specific proteomic profiling in vivo, we genetically engineered a mouse line for cell-type specific production of a promiscuous biotin ligase (BirA*G3) facilitating the rapid isolation of biotinylated cell-type specific proteomes. Adipocyte-specific activation of cytoplasmic BirA*G3 led to robust biotinylation of adipocyte proteins across all major fat depots. Comparison of brown adipose tissue (BAT) and subcutaneous white adipose tissue (SAT) proteomes identified 229 brown adipose-enriched and 35 white adipose-enriched proteins. Regional comparison of white fat depots revealed additional differences across depots. Comparison of male and female depots identified sexually dimorphic adipose proteins: AHNAK predominating in the male and ACOT2 in the female. These findings validate the genetic model and highlight insights to be gained through targeted profiling of adipocytes. The genetic tool adds to existing approaches for in vivo proximity profiling of cell-type specific proteome programs.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"15 2","pages":"e70007"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Vagal Sensory Gut-Brain Pathways That Control Eating-Satiety and Beyond. 迷走神经感觉肠-脑通路控制进食饱腹感及其他。

IF 4.2 2区医学

Comprehensive Physiology Pub Date : 2025-04-01 DOI: 10.1002/cph4.70010

Rebeca Mendez-Hernandez, Isadora Braga, Avnika Bali, Mingxin Yang, Guillaume de Lartigue

引用次数: 0

p21-Activated Kinase 1 (Pak1) as an Element in Functional and Dysfunctional Interplay Among the Myocardium, Adipose Tissue, and Pancreatic Beta Cells. p21活化激酶1 （Pak1）是心肌、脂肪组织和胰腺细胞之间功能和功能失调相互作用的一个因素。

IF 4.2 2区医学

Comprehensive Physiology Pub Date : 2025-04-01 DOI: 10.1002/cph4.70006

Paola C Rosas, R John Solaro

{"title":"p21-Activated Kinase 1 (Pak1) as an Element in Functional and Dysfunctional Interplay Among the Myocardium, Adipose Tissue, and Pancreatic Beta Cells.","authors":"Paola C Rosas, R John Solaro","doi":"10.1002/cph4.70006","DOIUrl":"10.1002/cph4.70006","url":null,"abstract":"This review focuses on p21-activated kinase 1 (Pak1), a multifunctional, highly conserved enzyme that regulates multiple downstream effectors present in many tissues. Upstream signaling via Ras-related small G-proteins, Cdc42/Rac1 promotes the activity of Pak1. Our hypothesis is that this signaling cascade is an important element in communication among the myocardium, adipose tissue, and pancreatic β-cells. Evidence indicates that a shared property of these tissues is that structure/function stability requires homeostatic Pak1 activity. Increases or decreases in Pak1 activity may promote dysfunction or increase susceptibility to stressors. Evidence that increased levels of Pak1 activity may be protective provides support for efforts to develop therapeutic approaches activating Pak1 with potential use in prevalent disorders associated with obesity, diabetes, and myocardial dysfunction. On the other hand, since increased Pak1 activity is associated with cancer progression, there has been a significant effort to develop Pak1 inhibitors. These opposing therapeutic approaches highlight the need for a deep understanding of Pak1 signaling in relation to the development of effective and selective therapies with minimal or absent off-target effects.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"15 2","pages":"e70006"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Glucagon-Like Peptide-1 Links Ingestion, Homeostasis, and the Heart. 胰高血糖素样肽-1连接摄取、体内平衡和心脏。

IF 4.2 2区医学

Comprehensive Physiology Pub Date : 2025-02-01 DOI: 10.1002/cph4.7

Jean-Philippe Krieger, Derek Daniels, Shin Lee, Svetlana Mastitskaya, Wolfgang Langhans

{"title":"Glucagon-Like Peptide-1 Links Ingestion, Homeostasis, and the Heart.","authors":"Jean-Philippe Krieger, Derek Daniels, Shin Lee, Svetlana Mastitskaya, Wolfgang Langhans","doi":"10.1002/cph4.7","DOIUrl":"10.1002/cph4.7","url":null,"abstract":"Glucagon-like peptide-1 (GLP-1), a hormone released from enteroendocrine cells in the distal small and large intestines in response to nutrients and other stimuli, not only controls eating and insulin release, but is also involved in drinking control as well as renal and cardiovascular functions. Moreover, GLP-1 functions as a central nervous system peptide transmitter, produced by preproglucagon (PPG) neurons in the hindbrain. Intestinal GLP-1 inhibits eating by activating vagal sensory neurons directly, via GLP-1 receptors (GLP-1Rs), but presumably also indirectly, by triggering the release of serotonin from enterochromaffin cells. GLP-1 enhances glucose-dependent insulin release via a vago-vagal reflex and by direct action on beta cells. Finally, intestinal GLP-1 acts on the kidneys to modulate electrolyte and water movements, and on the heart, where it provides numerous benefits, including anti-inflammatory, antiatherogenic, and vasodilatory effects, as well as protection against ischemia/reperfusion injury and arrhythmias. Hindbrain PPG neurons receive multiple inputs and project to many GLP-1R-expressing brain areas involved in reward, autonomic functions, and stress. PPG neuron-derived GLP-1 is involved in the termination of large meals and is implicated in the inhibition of water intake. This review details GLP-1's roles in these interconnected systems, highlighting recent findings and unresolved issues, and integrating them to discuss the physiological and pathological relevance of endogenous GLP-1 in coordinating these functions. As eating poses significant threats to metabolic, fluid, and immune homeostasis, the body needs mechanisms to mitigate these challenges while sustaining essential nutrient intake. Endogenous GLP-1 plays a crucial role in this \"ingestive homeostasis.\"","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"15 1","pages":"e7"},"PeriodicalIF":4.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immune Regulatory Crosstalk in Adipose Tissue Thermogenesis. 脂肪组织产热中的免疫调节串扰。

IF 4.2 2区医学

Comprehensive Physiology Pub Date : 2025-02-01 DOI: 10.1002/cph4.70001

Ramazan Yildiz, Khatanzul Ganbold, Njeri Z R Sparman, Prashant Rajbhandari

{"title":"Immune Regulatory Crosstalk in Adipose Tissue Thermogenesis.","authors":"Ramazan Yildiz, Khatanzul Ganbold, Njeri Z R Sparman, Prashant Rajbhandari","doi":"10.1002/cph4.70001","DOIUrl":"10.1002/cph4.70001","url":null,"abstract":"Brown adipose tissue (BAT) and thermogenic beige fat within white adipose tissue (WAT), collectively known as adaptive thermogenic fat, dissipate energy as heat, offering promising therapeutic potential to combat obesity and metabolic disorders. The specific biological functions of these fat depots are determined by their unique interaction with the microenvironments, composed of immune cells, endothelial cells, pericytes, and nerve fibers. Immune cells residing in these depots play a key role in regulating energy expenditure and systemic energy homeostasis. The dynamic microenvironment of thermogenic fat depots is essential for maintaining tissue health and function. Immune cells infiltrate both BAT and beige WAT, contributing to their homeostasis and activation through intricate cellular communications. Emerging evidence underscores the importance of various immune cell populations in regulating thermogenic adipose tissue, though many remain undercharacterized. This review provides a comprehensive overview of the immune cells that regulate adaptive thermogenesis and their complex interactions within the adipose niche, highlighting their potential to influence metabolic health and contribute to therapeutic interventions for obesity and metabolic syndrome.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"15 1","pages":"e70001"},"PeriodicalIF":4.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Introducing the "New" Comprehensive Physiology: A Journal Focused on Interorgan Communication in Health and Disease. 介绍“新”综合生理学：专注于健康和疾病的器官间通讯的杂志。

IF 4.2 2区医学

Comprehensive Physiology Pub Date : 2025-02-01 DOI: 10.1002/cph4.9

J Usha Raj

引用次数: 0

Myeloid-Mesenchymal Crosstalk in Lung Fibrosis. 肺纤维化中的骨髓-间质串扰。

IF 4.2 2区医学

Comprehensive Physiology Pub Date : 2025-02-01 DOI: 10.1002/cph4.70004

Aritra Bhattacharyya, Preeti Yadav, Mallar Bhattacharya

引用次数: 0