Comprehensive Physiology最新文献_第3页

Photobiomodulation Alleviates Insulin Resistance Induced by Intermittent Hypoxia, Through Preservation of Adipose Tissue Insulin Signaling and Reduction of Hepatic Oxidative Stress in Mice. 光生物调节通过保存脂肪组织胰岛素信号和减少肝脏氧化应激减轻间歇性缺氧诱导的胰岛素抵抗。

IF 6.3 2区医学

Comprehensive Physiology Pub Date : 2026-06-01 DOI: 10.1002/cph4.70152

Stéphanie Paradis, Britanny Blachot-Minassian, Sophie Bouyon, Antoine Boutin, Amel Mohamadi, Guillaume Vial, Claire Arnaud, Elise Belaidi

{"title":"Photobiomodulation Alleviates Insulin Resistance Induced by Intermittent Hypoxia, Through Preservation of Adipose Tissue Insulin Signaling and Reduction of Hepatic Oxidative Stress in Mice.","authors":"Stéphanie Paradis, Britanny Blachot-Minassian, Sophie Bouyon, Antoine Boutin, Amel Mohamadi, Guillaume Vial, Claire Arnaud, Elise Belaidi","doi":"10.1002/cph4.70152","DOIUrl":"10.1002/cph4.70152","url":null,"abstract":"Aim: Chronic intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), contributes to metabolic diseases and enhances associated cardiovascular (CV) complications through oxidative stress and metabolic alterations. We hypothesize that photobiomodulation (PBM), a non-invasive low-level laser therapy, prevents IH-induced insulin resistance (IR), by preserving insulin signalization and reducing oxidative stress in insulin-sensitive organs.Methods: Male C57BL/6J mice were randomized in 4 groups, submitted to either 2-weeks IH (21%-5% FiO2, 60 s cycle, 8 h/day) or normoxia (N), with or without PBM (630 nm, 5 J/cm2, 32 mW, 120 s, 5 days/week). At day 11, insulin sensitivity was assessed by insulin tolerance test. Then, canonical insulin signaling pathway was explored by western-blot, and oxidative stress was assessed by measurement of enzymatic activity, O2·- content, and lipid and protein oxidation in liver, gastrocnemius (GC) muscle, and epididymal white adipose tissue (eWAT).Results: IH induces systemic IR, impairs insulin signaling in liver and eWAT, and increases hepatic O2·- content, while pro/anti-oxidant enzyme activities were unchanged. Interestingly, in IH group only, PBM significantly improves systemic insulin sensitivity, prevents eWAT insulin signaling alteration and decreases hepatic O2·- content.Conclusion: PBM alleviates systemic insulin resistance, restores eWAT insulin signaling, and limits hepatic oxidative stress induced by IH. By enhancing insulin sensitivity, PBM could be proposed as a new therapeutic strategy against OSA-associated metabolic comorbidities.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 3","pages":"e70152"},"PeriodicalIF":6.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148053207","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

Chronic Kidney Disease and the Gut Microbiota: An Expanding Confluence in the Development of the Disease. 慢性肾脏疾病和肠道微生物群：在疾病发展中不断扩大的融合。

IF 5.2 2区医学

Comprehensive Physiology Pub Date : 2026-06-01 DOI: 10.1002/cph4.70192

Muhammad Ahsan, Suheera Afzoon, Nandni, Ali Ahmed, Mubashirah, Priyanka, Habib Ul Rahman, Ali Raza Arif, Asra Faiz, Ibtisam Mirza, Nilay Bhatt

{"title":"Chronic Kidney Disease and the Gut Microbiota: An Expanding Confluence in the Development of the Disease.","authors":"Muhammad Ahsan, Suheera Afzoon, Nandni, Ali Ahmed, Mubashirah, Priyanka, Habib Ul Rahman, Ali Raza Arif, Asra Faiz, Ibtisam Mirza, Nilay Bhatt","doi":"10.1002/cph4.70192","DOIUrl":"10.1002/cph4.70192","url":null,"abstract":"Purpose: Chronic kidney disease (CKD) remains a major global health burden despite advances in conventional therapies. This review synthesizes current clinical and experimental evidence on the bidirectional relationship between CKD and gut microbial dysbiosis, emphasizing mechanisms, measurable outcomes, and therapeutic interventions.Methods: A narrative review of recent clinical and experimental studies was conducted to explore alterations in gut microbial composition, generation of uremic toxins, and the impact of CKD therapies on microbial balance. Emerging microbiota-targeted interventions were also examined.Results: Studies consistently report reduced microbial diversity, loss of short-chain fatty acid (SCFA)-producing taxa, and enrichment of proteolytic, toxin-producing bacteria in CKD. Gut-derived metabolites such as indoxyl sulfate (IS), p-cresyl sulfate (pCS), and trimethylamine N-oxide (TMAO) are linked to oxidative stress, RAAS activation, and fibrogenesis. In human trials, microbiota-directed therapies show modest biochemical benefits: a meta-analysis of 21 randomized studies reported mean reductions in serum BUN (8.5 mg/dL) and CRP (1.4 mg/L) with probiotic or synbiotic supplementation, while inulin (10 g/day) in stage 3-4 CKD reduced serum pCS by 25% and increased fecal butyrate by 40%. However, most mechanistic data derive from animal and in vitro models, and human evidence remains heterogeneous and underpowered. Stage-specific differences are evident-early CKD shows subtler dysbiosis, while advanced CKD and dialysis populations exhibit profound microbial shifts and variable responsiveness.Conclusion: The gut microbiota is a promising, modifiable contributor to CKD pathophysiology. Stage-stratified longitudinal studies are needed to establish causality and therapeutic efficacy.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 3","pages":"e70192"},"PeriodicalIF":5.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148197761","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

Lung-Muscle Interaction in ARDS: Implications for Injury, Recovery, and Long-Term Outcomes. ARDS肺-肌肉相互作用：对损伤、恢复和长期预后的影响。

IF 6.3 2区医学

Comprehensive Physiology Pub Date : 2026-06-01 DOI: 10.1002/cph4.70201

Luciano Amarelle, Matías Pécora, Verónica Hermida, Martín Angulo

{"title":"Lung-Muscle Interaction in ARDS: Implications for Injury, Recovery, and Long-Term Outcomes.","authors":"Luciano Amarelle, Matías Pécora, Verónica Hermida, Martín Angulo","doi":"10.1002/cph4.70201","DOIUrl":"10.1002/cph4.70201","url":null,"abstract":"Acute respiratory distress syndrome (ARDS) is increasingly recognized as a systemic syndrome in which the consequences of lung injury extend beyond the respiratory system. Among its extra-pulmonary manifestations, skeletal muscle dysfunction has emerged as a major determinant of short- and long-term outcomes. Accumulating evidence supports a bidirectional lung-muscle interaction in ARDS, involving both peripheral and respiratory muscles. The injured lung may promote muscle atrophy, weakness, contractile dysfunction, and impaired regeneration through multiple upstream drivers, including systemic inflammation, altered gas exchange, respiratory support strategies, immobilization, and pharmacologic exposures. These factors converge on downstream intramuscular pathways such as enhanced proteolysis, impaired protein synthesis, and mitochondrial dysfunction. In turn, skeletal muscle dysfunction may adversely affect the respiratory system through direct mechanical effects of respiratory muscle weakness or excessive inspiratory effort, as well as through indirect systemic mechanisms involving inflammatory and endocrine signaling. Thus, skeletal muscle should be viewed not only as a target of ARDS-related insults, but also as a biologically active organ that may influence injury propagation, recovery, and long-term functional outcomes. In this review, we examine the physiological basis of lung-muscle communication and discuss how these interactions become dysregulated in ARDS and acute lung injury. A better understanding of this integrated lung-muscle axis may help redefine supportive care in ARDS and design strategies aimed at preserving both pulmonary and muscular function.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 3","pages":"e70201"},"PeriodicalIF":6.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148307348","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

Myostatin Signaling in Skeletal Muscle: Implications for Athletic Performance. 骨骼肌中的肌肉生长抑制素信号传导：对运动表现的影响。

IF 6.3 2区医学

Comprehensive Physiology Pub Date : 2026-06-01 DOI: 10.1002/cph4.70190

Srishti Chandel, Deenathayalan Uvarajan, Mahalaxmi Iyer, Dibbanti HariKrishna Reddy, Zothan Siama, Bupesh Giridharan, Arul Narayanasamy, John M, Arvinder Wander, Balachandar Vellingiri

{"title":"Myostatin Signaling in Skeletal Muscle: Implications for Athletic Performance.","authors":"Srishti Chandel, Deenathayalan Uvarajan, Mahalaxmi Iyer, Dibbanti HariKrishna Reddy, Zothan Siama, Bupesh Giridharan, Arul Narayanasamy, John M, Arvinder Wander, Balachandar Vellingiri","doi":"10.1002/cph4.70190","DOIUrl":"10.1002/cph4.70190","url":null,"abstract":"Myostatin, encoded by the MSTN gene, is a critical negative regulator of skeletal muscle growth and plays a central role in maintaining muscle homeostasis. It regulates satellite cell proliferation, differentiation, and protein synthesis through both Smad-dependent and non-Smad signaling pathways. Overexpression of myostatin promotes muscle atrophy and delays recovery, whereas reduced myostatin activity enhances protein synthesis and muscle regeneration, primarily by modulating the IGF-1/Akt/mTOR signaling pathway. Modulation of myostatin has been associated with improved metabolic function, increased insulin sensitivity, enhanced musculoskeletal adaptation, and improved performance sustainability. Genetic variations in MSTN and its receptors activin-type II receptor A (ACVR2A) and activin type II receptor B (ACVR2B) R2B contribute to inter-individual differences in muscle morphology, fiber-type distribution, and athletic performance. Specific polymorphisms, including rs1805086 and rs11333758, have been associated with variations in muscle strength, hypertrophy, and endurance capacity. Despite extensive research, a comprehensive evaluation of the relationship between MSTN signaling, skeletal muscle mass, and athletic performance remains limited. This review provides an integrated overview of myogenesis, MSTN-mediated signaling pathways, genetic polymorphisms, endocrine interactions, and therapeutic modulation strategies. We further discuss the implications of MSTN in muscle hypertrophy, inflammation, and sports performance, highlighting future research directions in precision sports genomics and translational muscle biology.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 3","pages":"e70190"},"PeriodicalIF":6.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283431","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

IF 5.2 2区医学

Comprehensive Physiology Pub Date : 2026-06-01 DOI: 10.1002/cph4.70146

Wei-Lan Yin, Lei Peng, Jing-Hong Zhang, Xiao-Ling Huang, Wei-Guo Yin

{"title":"Hyperlipid-Related Alzheimer's Disease: Potential Role of CircUCK2/miR-24-3p/p38 Axis in Neuronal Damage.","authors":"Wei-Lan Yin, Lei Peng, Jing-Hong Zhang, Xiao-Ling Huang, Wei-Guo Yin","doi":"10.1002/cph4.70146","DOIUrl":"10.1002/cph4.70146","url":null,"abstract":"Background: Accumulating empirical evidence underscores that hyperlipidemia may fuel the pathological progression of Alzheimer's disease (AD) by triggering inflammatory signaling cascades and promoting amyloid-β (Aβ) fibrillogenesis. The CircUCK2/miR-24-3p/p38 regulatory axis has been identified as a key molecular node in these biological processes, yet its specific functions in AD associated with abnormal lipid metabolism remain incompletely delineated.Methods: We recruited 50 AD patients and 50 healthy individuals from the Neurology Department of the Affiliated Hospital of the University of South China. Logistic regression analysis was employed to explore the correlation between blood lipid concentrations and AD susceptibility, while Pearson correlation analysis was used to assess the association between lipid levels and Aβ deposition. Dual-luciferase reporter assays confirmed the mutual regulatory relationships among CircUCK2, miR-24-3p, and p38. Additionally, we evaluated inflammatory responses, neuronal damage, and the activation status of p38. A hyperlipidemic mouse model was established to examine the expression levels of AD-related biomarkers.Results: Elevated blood lipid levels were closely correlated with increased AD risk and enhanced Aβ deposition. CircUCK2 was found to induce p38 phosphorylation by targeting miR-24-3p, thereby augmenting autophagic flux, mitigating inflammatory reactions, and suppressing apoptotic pathways in hyperlipidemic cells. Furthermore, p38 activation reduced the levels of pro-inflammatory mediators, downregulated the expression of Aβ42 and P-tau181, and improved learning and memory capabilities in mice.Conclusion: Hyperlipidemia accelerates Aβ deposition and neuronal injury, potentially exacerbating AD progression. The CircUCK2/miR-24-3p/p38 signaling pathway may serve as a promising therapeutic target for AD intervention.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 3","pages":"e70146"},"PeriodicalIF":5.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148223579","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

Restoring the Cardiopulmonary Unit: A Coupling-Centric Review of Pharmacotherapy in Pulmonary Vascular Disease. 恢复心肺功能：以肺血管疾病药物治疗为中心的综述。

IF 6.3 2区医学

Comprehensive Physiology Pub Date : 2026-06-01 DOI: 10.1002/cph4.70160

Niloofar Khoshnam Rad, Tayebeh Lakzaei, Hamidreza Abtahi, Tayebe Mohammad Alizade

{"title":"Restoring the Cardiopulmonary Unit: A Coupling-Centric Review of Pharmacotherapy in Pulmonary Vascular Disease.","authors":"Niloofar Khoshnam Rad, Tayebeh Lakzaei, Hamidreza Abtahi, Tayebe Mohammad Alizade","doi":"10.1002/cph4.70160","DOIUrl":"10.1002/cph4.70160","url":null,"abstract":"The clinical trajectory of pulmonary vascular disease (PVD) is governed by the functional and molecular integration of the right ventricle (RV) and pulmonary vasculature-the cardiopulmonary unit. Right ventricular-pulmonary arterial (RV-PA) coupling (Ees/Ea) is the principal determinant of survival. This review synthesizes contemporary pathophysiology and therapeutics through the lens of RV-PA coupling, reflecting the recognition of active heart-lung crosstalk. Advancing beyond traditional reviews, this article (1) formalizes a phenotype-guided treatment algorithm based on coupling derangement, (2) integrates emerging concepts of molecular crosstalk mediated by extracellular vesicles, and (3) positions sotatercept as a \"coupling drug\" targeting both components of the cardiopulmonary unit. We detail maladaptive pathways-including metabolic reprogramming, inflammation, fibrosis, and sex hormone signaling-that degrade RV contractility (Ees) under chronic pressure overload. The pharmacotherapeutic landscape is critically evaluated: from established vasodilators that indirectly support the RV by reducing afterload (Ea) to transformative disease-modifying agents like sotatercept that reverse vascular remodeling and the emerging frontier of direct RV-targeted therapies. We argue that the future of PVD management lies in a precision-based strategy using deep phenotyping to classify patients by dominant coupling derangements and matching them with mechanism-based therapies. The paradigm must shift beyond symptomatic vasodilation toward regimens explicitly designed to restore the physiological balance of the cardiopulmonary unit, carefully distinguishing between validated standards of care and investigational approaches.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 3","pages":"e70160"},"PeriodicalIF":6.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811894","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

Glycolytic Signaling Pathways and Anti-Glycolytic Therapy for Cancer: Research and Perspectives. 肿瘤的糖酵解信号通路和抗糖酵解治疗：研究与展望。

IF 6.3 2区医学

Comprehensive Physiology Pub Date : 2026-06-01 DOI: 10.1002/cph4.70177

Xiang Li, Siqi Li, Dingding Li, Yan Xi, Qihong Gu, Jiahao Liu, Shiqiang Hou, Xinyang Zhang, Chunjin Jin, Minfeng Yang, Minjie Chu

{"title":"Glycolytic Signaling Pathways and Anti-Glycolytic Therapy for Cancer: Research and Perspectives.","authors":"Xiang Li, Siqi Li, Dingding Li, Yan Xi, Qihong Gu, Jiahao Liu, Shiqiang Hou, Xinyang Zhang, Chunjin Jin, Minfeng Yang, Minjie Chu","doi":"10.1002/cph4.70177","DOIUrl":"10.1002/cph4.70177","url":null,"abstract":"The Warburg effect refers to a metabolic reprogramming process characterized by enhanced glycolysis and lactate production, even in the presence of adequate oxygen. This phenomenon is a critical adaptation enabling tumor cells to satisfy their elevated energy and biosynthetic requirements. This review synthesizes key regulators within the glycolytic signaling pathways and examines the dynamic interplay between glycolysis and other metabolic processes, including oxidative phosphorylation (OXPHOS) and fatty acid metabolism. Special emphasis is placed on how intravital imaging provides real-time insights into these metabolic alterations. Furthermore, this review underscores the central role of glycolysis in the tumor metabolic network and its contribution to resistance mechanisms against chemotherapy and radiotherapy. Finally, it discusses the latest developments in targeted therapies, reviewing the clinical progress of glycolysis inhibitors (e.g., curcumin, docetaxel) and exploring future directions for combining metabolic interventions with immunotherapy and other innovative approaches. These insights promise to offer novel perspectives on tumor metabolic reprogramming and the evolution of precision therapies.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 3","pages":"e70177"},"PeriodicalIF":6.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971273","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

An Integrated Lumped Parameter Model and Computational Fluid Dynamics Framework for Predicting Hemodynamic Parameters in Pulmonary Vein Stenosis. 预测肺静脉狭窄血流动力学参数的综合集总参数模型和计算流体动力学框架。

IF 6.3 2区医学

Comprehensive Physiology Pub Date : 2026-06-01 DOI: 10.1002/cph4.70185

Alessia Di Nardo, David A Romero, Rachel D Vanderlaan, Cristina H Amon

{"title":"An Integrated Lumped Parameter Model and Computational Fluid Dynamics Framework for Predicting Hemodynamic Parameters in Pulmonary Vein Stenosis.","authors":"Alessia Di Nardo, David A Romero, Rachel D Vanderlaan, Cristina H Amon","doi":"10.1002/cph4.70185","DOIUrl":"10.1002/cph4.70185","url":null,"abstract":"Pediatric pulmonary vein stenosis (PVS) is a progressive vascular disease associated with poor long-term outcomes. A growing body of evidence supports a relationship between the mechanisms of PVS pathogenesis and atypical hemodynamic conditions within the pulmonary veins; however, there is still a limited understanding of how this hemodynamic environment changes in different presentations of PVS. We propose a novel framework for the study of hemodynamics within the pulmonary veins that integrates computational fluid dynamics (CFD) models with a lumped parameter model (LPM) of the surrounding cardiovascular system. Model coupling is accomplished through surrogate model representation of the CFD domain, allowing for computationally efficient LPM parameter optimization for LPM calibration to specified target values of pressure and volume. The framework was employed to simulate five patient-representative scenarios including varying degrees of stenosis severity, varying number of stenotic veins, and the presence of left-to-right shunt physiology. The distribution of time-averaged wall shear stress (TAWSS) within the proximal pulmonary veins was assessed, as well as predicted flows, pressures, and volumes within the pulmonary arteries, veins, and ventricles.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 3","pages":"e70185"},"PeriodicalIF":6.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148053202","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

Beyond the Gut: How the Thymus Reshapes the Immune Landscape of Inflammatory Bowel Disease. 超越肠道：胸腺如何重塑炎症性肠病的免疫景观。

IF 6.3 2区医学

Comprehensive Physiology Pub Date : 2026-06-01 DOI: 10.1002/cph4.70188

Yannan Ma, Hengqian Liu, Zuo Zhang, Yuanyuan Li, Qian Dai, Jianyun Zhou, Xia Xie, Hongli Zhou

{"title":"Beyond the Gut: How the Thymus Reshapes the Immune Landscape of Inflammatory Bowel Disease.","authors":"Yannan Ma, Hengqian Liu, Zuo Zhang, Yuanyuan Li, Qian Dai, Jianyun Zhou, Xia Xie, Hongli Zhou","doi":"10.1002/cph4.70188","DOIUrl":"10.1002/cph4.70188","url":null,"abstract":"Inflammatory bowel disease (IBD) comprises a group of chronic inflammatory disorders of the gastrointestinal tract driven by immune dysregulation. In recent years, increasing attention has been directed toward the role of the thymus in the pathogenesis of IBD. However, a comprehensive and systematic review on this topic remains lacking. This article focuses on the immunoregulatory function of the thymus in IBD, emphasizing its pivotal role in maintaining intestinal immune homeostasis through the development and function of regulatory T cells (Tregs). We systematically review the mechanisms by which the thymic microenvironment, transcription factors, signaling pathways, and intercellular interactions regulate Treg homeostasis. Additionally, we propose the concept of the \"gut-thymus axis,\" elucidating how intestinal microbiota dysbiosis can impair thymic structure and function-primarily via TLR signaling pathways-thereby reducing Treg output, establishing a pro-inflammatory positive feedback loop, and exacerbating IBD progression. We further note that although thymus-targeted therapeutic strategies have been extensively explored-including thymectomy, ex vivo expansion and in vivo induction of Tregs, molecular targeting of signaling pathways, and thymic microenvironment remodeling-the translational maturity of these strategies varies considerably. In summary, thymic dysfunction may contribute to the pathogenesis of IBD by disrupting Treg-mediated central immune tolerance; nevertheless, its core pathogenic role in human IBD requires further clinical validation. Future research leveraging emerging technologies such as single-cell omics and organoid models may further elucidate gut-thymus crosstalk mechanisms and offer theoretical foundations and therapeutic targets for precision immunotherapy in IBD.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 3","pages":"e70188"},"PeriodicalIF":6.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136255","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

Epigenetic Perspectives on Maternal Gut Microbiota's Impact on Embryonic and Fetal Development. 母体肠道菌群对胚胎和胎儿发育影响的表观遗传学观点。

IF 6.3 2区医学

Comprehensive Physiology Pub Date : 2026-06-01 DOI: 10.1002/cph4.70163

Shoulong Xu, Yanjiao Huang, Chenyue Hu, Wenli Ding, Zhenwei Pu, Qiang Li, Zhiliang Xu

引用次数: 0