Comprehensive Physiology最新文献_第7页

Lactobacillus Is Associated With Disease in Pulmonary Arterial Hypertension: A Prospective Cohort Study. 乳酸杆菌与肺动脉高压疾病相关：一项前瞻性队列研究

IF 6.3 2区医学

Comprehensive Physiology Pub Date : 2026-06-01 DOI: 10.1002/cph4.70161

Arun Jose, Senu Apewokin, Nicholas J Ollberding, Qing Duan, Jennifer Trannguyen, Sasha Z Prisco, Thenappan Thenappan, Anna R Hemnes, Jean M Elwing

{"title":"Lactobacillus Is Associated With Disease in Pulmonary Arterial Hypertension: A Prospective Cohort Study.","authors":"Arun Jose, Senu Apewokin, Nicholas J Ollberding, Qing Duan, Jennifer Trannguyen, Sasha Z Prisco, Thenappan Thenappan, Anna R Hemnes, Jean M Elwing","doi":"10.1002/cph4.70161","DOIUrl":"10.1002/cph4.70161","url":null,"abstract":"Background: Gut dysbiosis and gut-derived metabolites have been linked to pulmonary arterial hypertension. However, associations between specific microbes, and corresponding metabolites, with pulmonary arterial hypertension disease severity is limited.Methods: This was a prospective cohort study of patients with pulmonary arterial hypertension undergoing right heart catheterization, with pulmonary artery blood subject to nuclear magnetic resonance metabolomics, and simultaneous stool sample shotgun metagenomics. Validation of metabolite levels with disease severity was done in an independent cohort of pulmonary arterial hypertension patients with blood samples from right heart catheterization testing.Results: The presence of Lactobacillus species in the gut microbiome of pulmonary arterial hypertension patients was associated with less severe pulmonary hemodynamics and echocardiographic right ventricular dysfunction. Higher threonine levels were associated with more favorable pulmonary hemodynamic characteristics in both prospective and independent validation cohorts of pulmonary arterial hypertension patients.Conclusions: Detectable Lactobacillus species in the gut microbiome of pulmonary arterial hypertension patients are associated with more favorable pulmonary hemodynamic and right ventricular characteristics. Circulating gut-derived metabolites may also be involved. Further investigation into the relationship between gut microbial Lactobacillus, circulating metabolites, disease severity, and clinical outcomes in pulmonary arterial hypertension may be warranted.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 3","pages":"e70161"},"PeriodicalIF":6.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764479","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

The Mitochondrial-Autophagy Axis in MASLD: Mechanisms, Crosstalk, and Therapeutic Targets. 线粒体-自噬轴在MASLD：机制，串扰和治疗靶点。

IF 6.3 2区医学

Comprehensive Physiology Pub Date : 2026-06-01 DOI: 10.1002/cph4.70155

Gaurab Bhaduri, Anchin Kalia, Banshi Saboo, Sanjay Bandyopadhyay

{"title":"The Mitochondrial-Autophagy Axis in MASLD: Mechanisms, Crosstalk, and Therapeutic Targets.","authors":"Gaurab Bhaduri, Anchin Kalia, Banshi Saboo, Sanjay Bandyopadhyay","doi":"10.1002/cph4.70155","DOIUrl":"10.1002/cph4.70155","url":null,"abstract":"Background: This review seeks to integrate contemporary evidence regarding mitochondrial dysfunction and autophagic regulation in metabolic dysfunction associated steatotic liver disease (MASLD), elucidating mechanistic pathways, indigenous determinants, and emerging therapeutic targets.Methods: A thorough search was performed in PubMed, Scopus, EMBASE, Web of Science, and Google Scholar. Research publications on mitochondrial activity, oxidative phosphorylation, fatty acid oxidation, mitophagy, lipophagy, and associated autophagic pathways in MASLD or MASH were incorporated.Results: This review integrates findings that show mitochondrial dysfunction is a key mediator of MASLD progression. Mitochondrial dysfunction due to fatty acid oxidation, electron transport chain uncoupling, increased reactive oxygen species, and was found to be associated with steatosis, inflammation, and fibrosis. Simultaneous inhibition of autophagy, including lipophagy and mitophagy, contributes to lipid accumulation and persistence of dysfunctional mitochondria. Novel mediators of MASLD progression include gut dysbiosis, ferroptosis, and mitoDAMP signaling.Conclusion: In summary, the results indicate that mitochondrial dysfunction and autophagy dysregulation are interdependent mediators of MASLD pathogenesis. Their interaction mediates metabolic overload to oxidative stress, inflammation, and fibrotic remodeling. The understanding of these mechanisms provides a common platform for MASLD progression and suggests mitochondrial quality control, autophagy modulation, and associated metabolic pathways as promising targets for future MASLD therapeutic and preventive strategies.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 3","pages":"e70155"},"PeriodicalIF":6.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764682","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

Dynamic Modulation of the Gut Microbiome in Neurodegenerative Diseases: Mechanisms, Therapeutic Potential, and Clinical Perspective. 神经退行性疾病中肠道微生物组的动态调节：机制、治疗潜力和临床前景。

IF 6.3 2区医学

Comprehensive Physiology Pub Date : 2026-06-01 DOI: 10.1002/cph4.70165

Shilpa Devi, Nabendu Debnath, Pooja Yadav, Shree Satyavolu, Ashok Kumar Yadav, Neetu Tyagi

{"title":"Dynamic Modulation of the Gut Microbiome in Neurodegenerative Diseases: Mechanisms, Therapeutic Potential, and Clinical Perspective.","authors":"Shilpa Devi, Nabendu Debnath, Pooja Yadav, Shree Satyavolu, Ashok Kumar Yadav, Neetu Tyagi","doi":"10.1002/cph4.70165","DOIUrl":"10.1002/cph4.70165","url":null,"abstract":"The gut and brain communicate bidirectionally through the gut microbiota, forming a complex network often referred to as the \"microbiota-gut-brain axis.\" The gastrointestinal microbiome produces various metabolites, including short-chain fatty acids (SCFAs), tryptophan-derived compounds, and secondary bile acids. Research indicates that disruptions in the intestinal microbiota (dysbiosis) and impaired gut-brain axis are associated with various neurological conditions. The central nervous system (CNS) influences digestive processes via the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS). On the other hand, the gut reciprocally affects brain function through microbial metabolites, neuroactive substances, and intestinal hormones via multiple pathways, including neural (vagal), immune, and endocrine signaling; however, only a subset of metabolites can directly access the CNS due to blood-brain barrier (BBB) selectivity. These microbial metabolites can directly or indirectly influence the CNS and modulate neuro-immune signaling by activating receptors, such as the aryl hydrocarbon receptor (AhR) and G protein-coupled receptors (GPCRs). By acting as ligands for these receptors, metabolites modulate neural signaling and exert neuroprotective effects. This review discusses how probiotic-derived metabolites modulate the gut-brain axis and provide neuroprotective effects, focusing on the receptors they activate and their downstream signaling pathways involved in neuroprotection.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 3","pages":"e70165"},"PeriodicalIF":6.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980764","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

Extracellular Vesicles as Drivers of Lung Endothelial Dysfunction in ARDS: Mechanisms and Therapeutic Opportunities. 细胞外囊泡作为急性呼吸窘迫综合征肺内皮功能障碍的驱动因素：机制和治疗机会。

IF 6.3 2区医学

Comprehensive Physiology Pub Date : 2026-06-01 DOI: 10.1002/cph4.70179

Mohammed Yaman Al Matni, Patrick Belvitch, Steven M Dudek, Eleftheria Letsiou

{"title":"Extracellular Vesicles as Drivers of Lung Endothelial Dysfunction in ARDS: Mechanisms and Therapeutic Opportunities.","authors":"Mohammed Yaman Al Matni, Patrick Belvitch, Steven M Dudek, Eleftheria Letsiou","doi":"10.1002/cph4.70179","DOIUrl":"10.1002/cph4.70179","url":null,"abstract":"Acute respiratory distress syndrome (ARDS) is a complex, life-threatening condition that can arise from both direct pulmonary insults-such as pneumonia and aspiration-and indirect extrapulmonary causes including sepsis and trauma. A key driver of ARDS pathogenesis is the disruption of the lung endothelial barrier. Over the past several decades, extensive research has elucidated numerous mechanisms underlying the endothelial cell (EC) dysfunction in the acute lung injury (ALI) pathophysiology that occurs during ARDS. A range of EC modulators have been identified, as well as therapeutic strategies aimed at restoring EC integrity. More recently, extracellular vesicles (EVs) have emerged as critical mediators in ARDS pathogenesis, acting as potent regulators of endothelial function. EVs originating either locally in the lung or from distant tissues can reach the pulmonary vasculature, where they amplify inflammatory signaling and disrupt EC barrier integrity, thereby exacerbating injury and disease severity. This review summarizes recent advances in understanding how EVs from diverse cellular, tissue, and organ sources contribute to endothelial dysfunction in ALI pathophysiology. It also explores emerging endothelial-targeted therapies for ARDS, spanning preclinical and clinical stages, that may counteract EV-mediated pathogenic mechanisms, and highlights key gaps that remain to be addressed.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 3","pages":"e70179"},"PeriodicalIF":6.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13238324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148162043","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

SLC and ABC Transporters in Lung Cancer: Orchestrators of Malignancy and Therapeutic Resistance. 肺癌中的SLC和ABC转运蛋白：恶性肿瘤和治疗耐药性的协调者。

IF 6.3 2区医学

Comprehensive Physiology Pub Date : 2026-04-01 DOI: 10.1002/cph4.70111

Ping Li, Minlei Dong, Binxin Chen, Jun Luo, Huidi Jiang, Nengming Lin

{"title":"SLC and ABC Transporters in Lung Cancer: Orchestrators of Malignancy and Therapeutic Resistance.","authors":"Ping Li, Minlei Dong, Binxin Chen, Jun Luo, Huidi Jiang, Nengming Lin","doi":"10.1002/cph4.70111","DOIUrl":"10.1002/cph4.70111","url":null,"abstract":"Background: Lung cancer remains a leading cause of global cancer mortality, with therapeutic efficacy significantly hampered by intrinsic and acquired therapy resistance. Solute carrier (SLC) and ATP-binding cassette (ABC) transporters have emerged as pivotal regulators orchestrating the transmembrane transport of diverse substrates to critically influence lung cancer progression and treatment response.Scope of review: This review systematically examines the pathophysiological roles of key transporters in lung cancer progression and therapeutic response, with a particular emphasis on their functions in mediating crosstalk within the tumor microenvironment (TME). It assesses the current knowledge in this field, elucidates the underlying molecular mechanisms, and highlights potential avenues for future research and clinical translation.Major conclusions: SLC and ABC transporters critically contribute to the aggressiveness of lung cancer by orchestrating multiple facets of its malignant phenotype. This encompasses promoting cell proliferation, suppressing cell death, facilitating tumor invasion and metastasis, sustaining cancer stem cell (CSC) self-renewal, and modulating chemotherapy sensitivity and resistance. Furthermore, they mediate immunosuppression within the TME through dynamic crosstalk with resident stromal and immune cells. Thus, the substantial involvement of SLC and ABC transporters in lung cancer pathogenesis and therapeutic resistance definitively positions them as pivotal molecular vulnerabilities and actionable targets for developing novel therapeutic strategies to overcome drug resistance and improve clinical outcomes.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 2","pages":"e70111"},"PeriodicalIF":6.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147316190","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

Threshold Effects of Dietary Components on Global NAFLD Burden: Modulating Role of Socioeconomic Development. 膳食成分对全球NAFLD负担的阈值效应：社会经济发展的调节作用

IF 6.3 2区医学

Comprehensive Physiology Pub Date : 2026-04-01 DOI: 10.1002/cph4.70135

Yanqi Kou, Junyi Yang, Guojia Yuan, Guohui Zhong, Fengyu Chen, Mouji Liang, Yujie Huang, Kun He, Ying Lin, Zongchen Huang, Xiaolan Wu, Shicai Ye, Yuping Yang

{"title":"Threshold Effects of Dietary Components on Global NAFLD Burden: Modulating Role of Socioeconomic Development.","authors":"Yanqi Kou, Junyi Yang, Guojia Yuan, Guohui Zhong, Fengyu Chen, Mouji Liang, Yujie Huang, Kun He, Ying Lin, Zongchen Huang, Xiaolan Wu, Shicai Ye, Yuping Yang","doi":"10.1002/cph4.70135","DOIUrl":"10.1002/cph4.70135","url":null,"abstract":"Non-alcoholic fatty liver disease (NAFLD) affects approximately 25% of the adult population worldwide. This study quantifies the global NAFLD burden attributable to 10 dietary components across diverse populations.Methods: This study integrated 2018 data from the Global Dietary Database (GDD) and the Global Burden of Disease (GBD) study to analyze correlations of dietary nutrients with the incidence and prevalence of NAFLD across 185 countries. Nonlinear relationships were explored using generalized additive models (GAM), with findings subsequently validated against National Health and Nutrition Examination Survey (NHANES) data. Additionally, Spearman correlation analysis was performed to assess associations between sociodemographic development (SDI) and dietary intake patterns.Results: South Asia and sub-Saharan Africa have high carbohydrate but low protein and fat intake; North America and Western Europe display a \"Western diet,\" showing regional nutritional differences. Nutrient intake varies by age, gender, and region, especially for carbohydrates, protein, fat, and Omega-3 s. In 2018, NAFLD burden was highest in the Middle East and North Africa. Higher SDI linked to increased animal protein and cholesterol intake, and greater NAFLD risk. GAM analysis revealed complex nonlinear nutrient-NAFLD relationships: carbohydrate intake had peak NAFLD risk at intermediate levels (p < 0.01); dietary cholesterol showed dose-dependent risk plateauing at higher intakes (p < 0.001). Protein intake correlated positively with disease burden. Most nutrient-NAFLD associations in NHANES data supported global findings.Conclusions: This study uses a global database to analyze 10 nutrients' relation to NAFLD, showing nonlinear effects and regional differences. It suggests focusing on nutrient-specific interventions over broad dietary patterns.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 2","pages":"e70135"},"PeriodicalIF":6.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147520289","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

Loss of Y Chromosome Associates With Lung and Cardiac Dysfunction in COPD. 慢性阻塞性肺病患者Y染色体缺失与心肺功能障碍相关。

IF 6.3 2区医学

Comprehensive Physiology Pub Date : 2026-04-01 DOI: 10.1002/cph4.70142

Chanil Valasarajan, Tina Rasper, Jochen Wilhelm, Deepesh Dhakad, Stefan Kuhnert, Werner Seeger, Stefanie Dimmeler, Robert Bals, Rajkumar Savai, Ali Önder Yildirim, Andreas Zeiher, Soni Savai Pullamsetti

引用次数: 0

Functional Segregation of Pancreatic Microcirculation Reveals Sex-Dependent Microhemodynamic Signatures. 胰腺微循环功能分离揭示性别依赖的微血流动力学特征。

IF 6.3 2区医学

Comprehensive Physiology Pub Date : 2026-04-01 DOI: 10.1002/cph4.70130

Yuan Li, Yingyu Wang, Bing Wang, Qin Ouyang, Weiqi Liu, Xiang Xu, Xu Zhang, Mingming Liu, Ruijuan Xiu

{"title":"Functional Segregation of Pancreatic Microcirculation Reveals Sex-Dependent Microhemodynamic Signatures.","authors":"Yuan Li, Yingyu Wang, Bing Wang, Qin Ouyang, Weiqi Liu, Xiang Xu, Xu Zhang, Mingming Liu, Ruijuan Xiu","doi":"10.1002/cph4.70130","DOIUrl":"10.1002/cph4.70130","url":null,"abstract":"The microcirculation is a determinant of organ function, translating systemic signals into local physiological responses. However, whether the regulation of microhemodynamics is sexually dimorphic within the pancreas has remained unknown. Here, using a multi-scale approach in healthy mice, we report a sexual dimorphism in pancreatic microhemodynamics that is anatomically restricted to the exocrine compartment, defined by divergent expression of the endothelial marker CD31 and estrogen receptor ERβ, whereas the endocrine islet microvasculature remains conserved between sexes. We demonstrate that microhemodynamic dimorphism is functionally coupled to divergent systemic steroid hormone profiles, a male signature characterized by elevated androgens and steroidogenic precursors, and a female signature dominated by glucocorticoids and estrogen metabolites. The distinction manifests as fundamentally different regulatory principles for vascular control, where pancreatic blood flow in males is directly coupled to systemic blood pressure, whereas in females, the relationship is defined by correlations between blood pressure and the oscillatory components of microhemodynamics. Collectively, our data identify the pancreatic microcirculation as a primary site of physiological sexual dimorphism and establish its role as a fundamental conduit for translating the systemic hormonal milieu into sex-specific organ homeostasis.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 2","pages":"e70130"},"PeriodicalIF":6.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12997022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147472912","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

The Importance of Liver-Lung Communication in Pulmonary Vascular Diseases. 肝-肺通讯在肺血管疾病中的重要性。

IF 6.3 2区医学

Comprehensive Physiology Pub Date : 2026-04-01 DOI: 10.1002/cph4.70140

Navneet Singh, Hilary M DuBrock, Sasha Z Prisco, Zhiyu Dai, Qi Zheng, Michael B Fallon, Thenappan Thenappan, Corey E Ventetuolo, Arun Jose

{"title":"The Importance of Liver-Lung Communication in Pulmonary Vascular Diseases.","authors":"Navneet Singh, Hilary M DuBrock, Sasha Z Prisco, Zhiyu Dai, Qi Zheng, Michael B Fallon, Thenappan Thenappan, Corey E Ventetuolo, Arun Jose","doi":"10.1002/cph4.70140","DOIUrl":"10.1002/cph4.70140","url":null,"abstract":"In normal health, the liver and lungs enjoy a close anatomic, physiologic, and functional relationship. In the context of pulmonary vascular disease, however, there is accumulating evidence that the interplay between the gut microbiome, hepatic system, and pulmonary vasculature (so-called \"gut-liver-lung\" axis) plays an important role in driving disease pathogenesis and determining clinical outcomes. Despite recognizing the importance of the gut-liver-lung axis in pulmonary vascular disease however, little is known about the clinical characteristics, circulating factors, and physiologic pathways that mediate this important axis of communication. In this clinical and translationally focused review, we provide an overview of liver-lung communication in normal physiology, and contrast this with gut-liver-lung derangements in pulmonary arterial hypertension, portopulmonary hypertension, and hepatopulmonary syndrome. We conclude with identifying key gaps in knowledge that will need to be addressed in order to manipulate the gut-liver-lung axis to prevent worsening pulmonary vascular disease, develop novel therapeutics, and improve patient outcomes.","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"16 2","pages":"e70140"},"PeriodicalIF":6.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13039249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590755","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

Heart-Lung Interactions in Gas Exchange: From Physiology to Pathophysiology. 气体交换中的心肺相互作用：从生理学到病理生理学。

IF 6.3 2区医学

Comprehensive Physiology Pub Date : 2026-04-01 DOI: 10.1002/cph4.70149

Giuseppe Miserocchi, Egidio Beretta

引用次数: 0