Comprehensive Physiology最新文献

{"title":"Digital Twinning of Interorgan Communications.","authors":"Lance Fortnow","doi":"10.1002/cph4.70002","DOIUrl":"10.1002/cph4.70002","url":null,"abstract":"<p><p>Recent advances in our ability to collect and process information, particularly through artificial intelligence, opens up some exciting possibilities for understanding interorgan communication and treating conditions that arise from that communication breaking down. We describe a vision of a digital twin of interorgan communication that will give us a testbed for virtually researching, teaching and searching treatments, greatly increasing our capabilities to understand and manage the complex interactions in our bodies.</p>","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"15 1","pages":"e70002"},"PeriodicalIF":4.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381752","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}

{"title":"Leptin and Associated Neural Pathways Underlying Obesity-Induced Hypertension.","authors":"Connor Laule, Kamal Rahmouni","doi":"10.1002/cph4.8","DOIUrl":"https://doi.org/10.1002/cph4.8","url":null,"abstract":"<p><p>Obesity rates have surged to pandemic levels, placing tremendous burden on our society. This chronic and complex disease is related to the development of many life-threatening illnesses including cardiovascular diseases. Hypertension caused by obesity increases the risk for cardiovascular mortality and morbidity by promoting stroke, myocardial infarction, congestive heart failure, and end-stage renal disease. Overwhelming evidence supports neural origins for obesity-induced hypertension and pinpoints the adipose-derived hormone, leptin, and the sympathetic nervous system as major causal factors. Hyperleptinemia in obesity is associated with selective leptin resistance where leptin's renal sympathoexcitatory and pressor effects are preserved while the metabolic actions are impaired. Understanding the mechanisms driving this phenomenon is critical for developing effective therapeutics. This review describes the neural mechanisms of obesity-induced hypertension with a focus on the molecular and neuronal substrates of leptin action.</p>","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"15 1","pages":"e8"},"PeriodicalIF":4.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981622","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}

{"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":"<p><p>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.</p>","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}

{"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":"<p><p>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.</p>","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}

{"title":"Neuromechanical Circuits of the Spinal Motor Apparatus.","authors":"T Richard Nichols","doi":"10.1002/cphy.c240002","DOIUrl":"https://doi.org/10.1002/cphy.c240002","url":null,"abstract":"<p><p>The evolution of mechanisms for terrestrial locomotion has resulted in multi-segmented limbs that allow navigation on irregular terrains, changing of direction, manipulation of external objects, and control over the mechanical properties of limbs important for interaction with the environment, with corresponding changes in neural pathways in the spinal cord. This article is focused on the organization of these pathways, their interactions with the musculoskeletal system, and the integration of these neuromechanical circuits with supraspinal mechanisms to control limb impedance. It is argued that neural pathways from muscle spindles and Golgi tendon organs form a distributive impedance controller in the spinal cord that controls limb impedance and coordination during responses to external disturbances. These pathways include both monosynaptic and polysynaptic components. Autogenic, monosynaptic pathways serve to control the spring-like properties of muscles preserving the nonlinear relationship between stiffness and force. Intermuscular monosynaptic pathways compensate for inertial disparities between the inertial properties of limb segments and help to control inertial coupling between joints and axes of rotation. Reciprocal inhibition controls joint stiffness in conjunction with feedforward cocontraction commands. Excitatory force feedback becomes operational during locomotion and increases muscular stiffness to accommodate the higher inertial loads. Inhibitory force feedback is widely distributed among muscles. It is integrated with excitatory pathways from muscle spindles and Golgi tendon organs to determine limb stiffness and interjoint coordination during interactions with the environment. The intermuscular distribution of force feedback is variable and serves to modulate limb stiffness to meet the physical demands of different motor tasks. © 2024 American Physiological Society. Compr Physiol 14:5789-5838, 2024.</p>","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"14 5","pages":"5789-5838"},"PeriodicalIF":4.2,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853295","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}

{"title":"Exploring the Lifeline: Unpacking the Complexities of Placental Vascular Function in Normal and Preeclamptic Pregnancies.","authors":"Carolin Schliefsteiner, Christian Wadsack, Hanna H Allerkamp","doi":"10.1002/cphy.c230020","DOIUrl":"https://doi.org/10.1002/cphy.c230020","url":null,"abstract":"<p><p>The proper development and function of the placenta are essential for the success of pregnancy and the well-being of both the fetus and the mother. Placental vascular function facilitates efficient fetal development during pregnancy by ensuring adequate gas exchange with low vascular resistance. This review focuses on how placental vascular function can be compromised in the pregnancy pathology preeclampsia, and conversely, how placental vascular dysfunction might contribute to this condition. While the maternal endothelium is widely recognized as a key focus in preeclampsia research, this review emphasizes the importance of understanding how this condition affects the development and function of the fetal placental vasculature. The placental vascular bed, consisting of microvasculature and macrovasculature, is discussed in detail, as well as structural and functional changes associated with preeclampsia. The complexity of placental vascular reactivity and function, its mediators, its impact on placental exchange and blood distribution, and how these factors are most affected in early-onset preeclampsia are further explored. These factors include foremost lipoproteins and their cargo, oxygen levels and oxidative stress, biomechanics, and shear stress. Challenges in studying placental pathophysiology are discussed, highlighting the necessity of innovative research methodologies, including ex vivo experiments, in vivo imaging tools, and computational modeling. Finally, an outlook on the potential of drug interventions targeting the placental endothelium to improve placental vascular function in preeclampsia is provided. Overall, this review highlights the need for further research and the development of models and tools to better understand and address the challenges posed by preeclampsia and its effects on placental vascular function to improve short- and long-term outcomes for the offspring of preeclamptic pregnancies. © 2024 American Physiological Society. Compr Physiol 14:5763-5787, 2024.</p>","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"14 5","pages":"5763-5787"},"PeriodicalIF":4.2,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853286","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}

{"title":"Familial Hyperkalemic Hypertension.","authors":"Ryan J Cornelius, Yujiro Maeoka, Ujwal Shinde, James A McCormick","doi":"10.1002/cphy.c240004","DOIUrl":"https://doi.org/10.1002/cphy.c240004","url":null,"abstract":"<p><p>The rare disease Familial Hyperkalemic Hypertension (FHHt) is caused by mutations in the genes encoding Cullin 3 (CUL3), Kelch-Like 3 (KLHL3), and two members of the With-No-Lysine [K] (WNK) kinase family, WNK1 and WNK4. In the kidney, these mutations ultimately cause hyperactivation of NCC along the renal distal convoluted tubule. Hypertension results from increased NaCl retention, and hyperkalemia by impaired K ⁺ secretion by downstream nephron segments. CUL3 and KLHL3 are now known to form a ubiquitin ligase complex that promotes proteasomal degradation of WNK kinases, which activate downstream kinases that phosphorylate and thus activate NCC. For CUL3, potent effects on the vasculature that contribute to the more severe hypertensive phenotype have also been identified. Here we outline the in vitro and in vivo studies that led to the discovery of the molecular pathways regulating NCC and vascular tone, and how FHHt-causing mutations disrupt these pathways. Potential mechanisms for variability in disease severity related to differential effects of each mutation on the kidney and vasculature are described, and other possible effects of the mutant proteins beyond the kidney and vasculature are explored. © 2024 American Physiological Society. Compr Physiol 14:5839-5874, 2024.</p>","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"14 5","pages":"5839-5874"},"PeriodicalIF":4.2,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853292","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}

{"title":"Issue Information.","authors":"","doi":"10.1002/cphy.cv14i05","DOIUrl":"https://doi.org/10.1002/cphy.cv14i05","url":null,"abstract":"","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"14 5","pages":"1-2"},"PeriodicalIF":4.2,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853294","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}

{"title":"Prenatal Origins of Obstructive Airway Disease: Starting on the Wrong Trajectory?","authors":"Kimberley C W Wang, Alan L James, Graham M Donovan, Peter B Noble","doi":"10.1002/cphy.c230019","DOIUrl":"https://doi.org/10.1002/cphy.c230019","url":null,"abstract":"<p><p>From the results of well-performed population health studies, we now have excellent data demonstrating that deficits in adult lung function may be present early in life, possibly as a result of developmental disorders, incurring a lifelong risk of obstructive airway diseases such as asthma and chronic obstructive pulmonary disease. Suboptimal fetal development results in intrauterine growth restriction and low birth weight at term (an outcome distinct from preterm complications), which are associated with subsequent obstructive disease. Numerous prenatal exposures and disorders compromise fetal development and these are summarized herein. Various physiological, structural, and mechanical abnormalities may result from prenatal disruption, including changes to airway smooth muscle structure-function, goblet cell biology, airway stiffness, geometry of the bronchial tree, lung parenchymal structure and mechanics, respiratory skeletal muscle contraction, and pulmonary inflammation. The literature therefore supports the need for early life intervention to prevent or correct growth defects, which may include simple nutritional or antioxidant therapy. © 2024 American Physiological Society. Compr Physiol 14:5729-5762, 2024.</p>","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"14 5","pages":"5729-5762"},"PeriodicalIF":4.2,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853349","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}

{"title":"Mitochondrial Function and Dysfunction in White Adipocytes and Therapeutic Implications.","authors":"Fenfen Wang, Phu M Huynh, Yu A An","doi":"10.1002/cphy.c230009","DOIUrl":"https://doi.org/10.1002/cphy.c230009","url":null,"abstract":"<p><p>For a long time, white adipocytes were thought to function as lipid storages due to the sizeable unilocular lipid droplet that occupies most of their space. However, recent discoveries have highlighted the critical role of white adipocytes in maintaining energy homeostasis and contributing to obesity and related metabolic diseases. These physiological and pathological functions depend heavily on the mitochondria that reside in white adipocytes. This article aims to provide an up-to-date overview of the recent research on the function and dysfunction of white adipocyte mitochondria. After briefly summarizing the fundamental aspects of mitochondrial biology, the article describes the protective role of functional mitochondria in white adipocyte and white adipose tissue health and various roles of dysfunctional mitochondria in unhealthy white adipocytes and obesity. Finally, the article emphasizes the importance of enhancing mitochondrial quantity and quality as a therapeutic avenue to correct mitochondrial dysfunction, promote white adipocyte browning, and ultimately improve obesity and its associated metabolic diseases. © 2024 American Physiological Society. Compr Physiol 14:5581-5640, 2024.</p>","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"14 4","pages":"5581-5640"},"PeriodicalIF":4.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388696","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}