Comprehensive Physiology最新文献_第2页

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

{"title":"Vagal Sensory Gut-Brain Pathways That Control Eating-Satiety and Beyond.","authors":"Rebeca Mendez-Hernandez, Isadora Braga, Avnika Bali, Mingxin Yang, Guillaume de Lartigue","doi":"10.1002/cph4.70010","DOIUrl":"10.1002/cph4.70010","url":null,"abstract":"The vagus nerve is the body's primary sensory conduit from gut to brain, traditionally viewed as a passive relay for satiety signals. However, emerging evidence reveals a far more complex system-one that actively encodes diverse aspects of meal-related information, from mechanical stretch to nutrient content, metabolic state, and even microbial metabolites. This review challenges the view of vagal afferent neurons (VANs) as simple meal-termination sensors and highlights their specialized subpopulations, diverse sensory modalities, and downstream brain circuits, which shape feeding behavior, metabolism, and cognition. We integrate recent advances from single-cell transcriptomics, neural circuit mapping, and functional imaging to examine how VANs contribute to gut-brain communication beyond satiety, including their roles in food reward and memory formation. By synthesizing the latest research and highlighting emerging directions for the field, this review provides a comprehensive update on vagal sensory pathways and their role as integrators of meal information.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"15 2","pages":"e70010"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976413","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

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

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

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

Type 2 Diabetes Mellitus: A Comprehensive Review of Pathophysiology, Comorbidities, and Emerging Therapies. 2型糖尿病：病理生理学、合并症和新疗法的综合综述。

IF 4.2 2区医学

Comprehensive Physiology Pub Date : 2025-02-01 DOI: 10.1002/cph4.70003

Aditi Singh, Sucharita Shadangi, Pulkit Kr Gupta, Soumendra Rana

{"title":"Type 2 Diabetes Mellitus: A Comprehensive Review of Pathophysiology, Comorbidities, and Emerging Therapies.","authors":"Aditi Singh, Sucharita Shadangi, Pulkit Kr Gupta, Soumendra Rana","doi":"10.1002/cph4.70003","DOIUrl":"10.1002/cph4.70003","url":null,"abstract":"Humans are perhaps evolutionarily engineered to get deeply addicted to sugar, as it not only provides energy but also helps in storing fats, which helps in survival during starvation. Additionally, sugars (glucose and fructose) stimulate the feel-good factor, as they trigger the secretion of serotonin and dopamine in the brain, associated with the reward sensation, uplifting the mood in general. However, when consumed in excess, it contributes to energy imbalance, weight gain, and obesity, leading to the onset of a complex metabolic disorder, generally referred to as diabetes. Type 2 diabetes mellitus (T2DM) is one of the most prevalent forms of diabetes, nearly affecting all age groups. T2DM is clinically diagnosed with a cardinal sign of chronic hyperglycemia (excessive sugar in the blood). Chronic hyperglycemia, coupled with dysfunctions of pancreatic β-cells, insulin resistance, and immune inflammation, further exacerbate the pathology of T2DM. Uncontrolled T2DM, a major public health concern, also contributes significantly toward the onset and progression of several micro- and macrovascular diseases, such as diabetic retinopathy, nephropathy, neuropathy, atherosclerosis, and cardiovascular diseases, including cancer. The current review discusses the epidemiology, causative factors, pathophysiology, and associated comorbidities, including the existing and emerging therapies related to T2DM. It also provides a future roadmap for alternative drug discovery for the management of T2DM.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"15 1","pages":"e70003"},"PeriodicalIF":4.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467104","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

The Role of Chronic Stress in the Pathogenesis of Ischemic Heart Disease in Women. 慢性应激在女性缺血性心脏病发病机制中的作用。

IF 4.2 2区医学

Comprehensive Physiology Pub Date : 2025-02-01 DOI: 10.1002/cph4.70000

Megan Cairns, Erna Marais, Danzil Joseph, M Faadiel Essop

{"title":"The Role of Chronic Stress in the Pathogenesis of Ischemic Heart Disease in Women.","authors":"Megan Cairns, Erna Marais, Danzil Joseph, M Faadiel Essop","doi":"10.1002/cph4.70000","DOIUrl":"10.1002/cph4.70000","url":null,"abstract":"Psychological stress has emerged as a critical risk factor for cardiovascular disease, especially in women. While female participation in clinical research has improved, sex-specific data analysis and reporting often remain inadequate, limiting our ability to draw definitive conclusions for women. Conversely, preclinical studies consistently demonstrate adverse effects of stress on female health, yet the molecular mechanisms underlying this association remain elusive. Evidence suggests that female IHD pathogenesis is more complex than in males, involving multiple factors, including inflammation, contractile dysfunction, bioenergetic impairment, and remodeling. However, many of these mechanisms are primarily derived from male studies, and molecular investigations in female models are limited, hindering our understanding of the underlying biological pathways. This is particularly concerning given the increasing prevalence of ischemic heart disease in postmenopausal women. In order to fully elucidate the impact of stress on female cardiac health and develop targeted interventions, further preclinical research on female models is essential.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"15 1","pages":"e70000"},"PeriodicalIF":4.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11793136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188572","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