Pflugers Archiv : European journal of physiology最新文献

{"title":"The obesity pandemic and its impact on non-communicable disease burden.","authors":"Staffan Hildebrand, Alexander Pfeifer","doi":"10.1007/s00424-025-03066-8","DOIUrl":"10.1007/s00424-025-03066-8","url":null,"abstract":"<p><p>The rising prevalence of overweight and obesity across the globe is a major threat both to public health and economic development. This is mainly due to the link of obesity with the development and outcomes of non-communicable diseases (NCDs). NCDs are a leading cause of global death and disability, and reducing the burden of NCDs on patients and healthcare systems is of critical importance to improve public health. Obesity is projected to be the number one preventable risk factor for NCDs by 2035, and there is an urgent need to tackle the growing obesity rates in order to reduce NCD incidence and severity. Here, we review the current understanding of the impact of obesity on NCD burden in general, as well as the epidemiological and mechanistic relationship between obesity and some of the most common classes of NCDs. By literature review, we found that over 70% of NCDs have a documented association with obesity, highlighting the importance of a better understanding of the pathophysiologies underlying obesity/overweight as well as the interaction between obesity and NCDs in order to reduce global disease burden.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"657-668"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrinsic responses to hypoxia and hypercapnia of neurons in the cardiorespiratory center of the ventral medulla of newborn rats.","authors":"Hiroshi Onimaru, Yui Koyanagi, Kamon Iigaya, Keiko Ikeda, Masahiko Izumizaki","doi":"10.1007/s00424-025-03077-5","DOIUrl":"10.1007/s00424-025-03077-5","url":null,"abstract":"<p><p>The rostral ventrolateral medulla (RVLM) includes a variety of neurons essential for cardiorespiratory control. Although some of these neurons are thought to be intrinsically sensitive to hypercapnia and/or hypoxia, relationships between types of neurons and responses to hypoxia and/or hypercapnia are not well understood. Tyrosine hydroxylase (TH) is one of the cell-type markers of the RVLM neurons. Here, we report effects of hypoxia and hypercapnia on TH-positive or -negative neurons in the RVLM of newborn rats. Brainstem-spinal cord preparations were isolated from 0-3-day-old Wistar rats and superfused with artificial cerebrospinal fluid equilibrated with 95% O₂ and 5% CO₂, pH 7.4 at 25-26 °C. Membrane potential responses to hypoxia (95% → 0% O₂) and/or hypercapnia (2% → 8% CO₂) were examined in the presence of tetrodotoxin (TTX) after identification of the firing pattern. We found that TH-positive C1 neurons in the RVLM were sensitive to hypoxia with membrane depolarization but less sensitive to hypercapnia. TH-negative neurons in the C1 area showed responses similar to those of C1 neurons. Moreover, C1 area neurons remained depolarized by hypoxia in the presence of TTX plus gliotransmitter blockers. In contrast, Phox2b-positive and TH-negative neurons in the parafacial respiratory group were intrinsically sensitive to CO₂ but not sensitive to hypoxia. Respiratory-related neurons (Phox2b and TH negative) showed a variable response to hypoxia: unchanging, depolarizing, or hyperpolarizing. Our findings suggest that C1 area neurons in the RVLM are intrinsically sensitive to hypoxia and belong to one of the elements constituting central hypoxic sensors.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"685-705"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuronal subtype-dependent kinetics of EPSCs induced by thalamocortical projections from the ventroposteromedial thalamic nucleus to the insular cortex in rats.","authors":"Yuko Koyanagi, Kiyofumi Yamamoto, Kouhei Kitano, Mie Kajiwara, Masayuki Kobayashi","doi":"10.1007/s00424-025-03074-8","DOIUrl":"10.1007/s00424-025-03074-8","url":null,"abstract":"<p><p>Cerebrocortical neurons receive glutamatergic inputs via thalamocortical projections, and their activities are simultaneously controlled by GABAergic interneurons. Few studies have demonstrated the difference in the amplitude of evoked excitatory postsynaptic currents (EPSCs) via thalamocortical projections onto glutamatergic excitatory (ENs) and GABAergic inhibitory neurons (INs); the strength of excitation among neural subtypes varies among sensory cortices. The present study aimed to reveal the profile of thalamocortical inputs to ENs and inhibitory neurons in the insular cortex (IC) by evaluating the amplitude and latency of EPSCs evoked in the connection from the ventroposteromedial (VPM) thalamic nucleus to the IC. Whole-cell patch-clamp recordings were prepared from ENs, fast-spiking neurons (FSNs), and non-fast-spiking neurons (NFSNs) in the middle layers (layer 4 and adjacent layers) of the IC. Photostimulation-induced EPSCs (pEPSCs) were evoked via the selective activation of thalamocortical axons via optogenetics. All the neuronal subtypes received direct excitatory inputs from the VPM, and pEPSCs recorded from FSNs had the greatest amplitude and shortest latency compared with those recorded from ENs and NFSNs. Under current-clamp conditions, FSNs almost invariably exhibited action potentials responding to photostimulation, whereas ENs and NFSNs often showed the failure of action potential induction. In addition to excitatory inputs, some neurons exhibited pEPSCs followed by outward GABA_A receptor-mediated currents, which curtailed the pEPSC peak and aligned the timing of the action potential to photostimulation. These results suggested that FSNs play a role in the feedforward inhibition of EN activity in the upper layer of the IC. (244 words).</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"707-717"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intracellular pH regulates the strength of the intrinsic inward rectification of Kir4.1/Kir5.1 channels.","authors":"Iván A Aréchiga-Figueroa, Leticia G Marmolejo-Murillo, Mayra Delgado-Ramírez, Rodrigo Zamora-Cárdenas, Eloy G Moreno-Galindo, Tania Ferrer, Ricardo A Navarro-Polanco, José A Sánchez-Chapula, Aldo A Rodríguez-Menchaca","doi":"10.1007/s00424-025-03079-3","DOIUrl":"10.1007/s00424-025-03079-3","url":null,"abstract":"<p><p>Kir4.1/Kir5.1 channels play a crucial role in important physiological functions, notably in the kidneys and brain. A hallmark of these channels is the coexistence of two mechanisms of inward rectification: the classical \"extrinsic\" inward rectification induced by polyamines and Mg²⁺ blocking the pore, and a novel \"intrinsic\" voltage-dependent mechanism driven by K⁺ flux. Previous studies have shown that Kir4.1/Kir5.1 channels are modulated by the intracellular pH in the physiological range. Here, we investigated the influence of the intracellular pH on the extent of the intrinsic inward rectification of Kir4.1/Kir5.1 channels expressed in HEK-293 cells and recorded using the inside-out configuration of the patch-clamp technique. We found that mutations that are known to modulate the pH sensitivity of Kir4.1/Kir5.1 channels attenuated inward rectification. The combination of these mutations in the triple mutant channel Kir4.1(K67M)/Kir5.1(N161E-R230E) virtually abolished inward rectification at pH 7.4; however, this property was re-established at acidic pH values. Consistently, the strong inward rectification of wild-type Kir4.1/Kir5.1 channels was reduced by intracellular alkalinization and further enhanced by acidification. Altogether, these experiments indicate that the intracellular pH strongly regulates the strength of the intrinsic inward rectification. Furthermore, triple mutant channels retained the extrinsic mechanism of inward rectification at pH 7.4, as can be blocked by spermine, but lost the ability to respond to elevated levels of PIP_2, unlike wild-type channels. Interestingly, whole-cell recordings of wild-type and triple mutant channels imply that the mechanism of intrinsic inward rectification is an important contributor to the overall rectification of Kir4.1/Kir5.1 channels in basal conditions.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"741-752"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reproducibility of smooth muscle mechanical properties in consecutive stretch and activation protocols.","authors":"Simon Kiem, Stefan Papenkort, Mischa Borsdorf, Markus Böl, Tobias Siebert","doi":"10.1007/s00424-025-03075-7","DOIUrl":"10.1007/s00424-025-03075-7","url":null,"abstract":"<p><p>Mechanical organ models are crucial for understanding organ function and clinical applications. These models rely on input data regarding smooth muscle properties, typically gathered from experiments involving stimulations at different muscle lengths. However, reproducibility of these experimental results is a major challenge due to rapid changes in active and passive smooth muscle properties during the measurement period. Usually, preconditioning of the tissue is employed to ensure reproducible behavior in subsequent experiments, but this process itself alters the tissue's mechanical properties. To address this issue, three protocols (P1, P2, P3) without preconditioning were developed and compared to preserve the initial mechanical properties of smooth muscle tissue. Each protocol included five repetitive experimental cycles with stimulations at a long muscle length, varying in the number of stimulations at a short muscle length (P1: 0, P2: 1, P3: 2 stimulations). Results showed that P2 and P3 successfully reproduced the initial active force at a long length over five cycles, but failed to maintain the initial passive forces. Conversely, P1 was most effective in maintaining constant passive forces over the cycles. These findings are supported by existing adaptation models. Active force changes are primarily due to the addition or removal of contractile units in the contractile apparatus, while passive force changes mainly result from actin polymerization induced by contractions, leading to cytoskeletal stiffening. This study introduces a new method for obtaining reproducible smooth muscle parameters, offering a foundation for future research to replicate the mechanical properties of smooth muscle tissue without preconditioning.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"729-739"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding pathology: the role of computational pathology in research and diagnostics.","authors":"David L Hölscher, Roman D Bülow","doi":"10.1007/s00424-024-03002-2","DOIUrl":"10.1007/s00424-024-03002-2","url":null,"abstract":"<p><p>Traditional histopathology, characterized by manual quantifications and assessments, faces challenges such as low-throughput and inter-observer variability that hinder the introduction of precision medicine in pathology diagnostics and research. The advent of digital pathology allowed the introduction of computational pathology, a discipline that leverages computational methods, especially based on deep learning (DL) techniques, to analyze histopathology specimens. A growing body of research shows impressive performances of DL-based models in pathology for a multitude of tasks, such as mutation prediction, large-scale pathomics analyses, or prognosis prediction. New approaches integrate multimodal data sources and increasingly rely on multi-purpose foundation models. This review provides an introductory overview of advancements in computational pathology and discusses their implications for the future of histopathology in research and diagnostics.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"555-570"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pioneering new paths: the role of generative modelling in neurological disease research.","authors":"Moritz Seiler, Kerstin Ritter","doi":"10.1007/s00424-024-03016-w","DOIUrl":"10.1007/s00424-024-03016-w","url":null,"abstract":"<p><p>Recently, deep generative modelling has become an increasingly powerful tool with seminal work in a myriad of disciplines. This powerful modelling approach is supposed to not only have the potential to solve current problems in the medical field but also to enable personalised precision medicine and revolutionise healthcare through applications such as digital twins of patients. Here, the core concepts of generative modelling and popular modelling approaches are first introduced to consider the potential based on methodological concepts for the generation of synthetic data and the ability to learn a representation of observed data. These potentials will be reviewed using current applications in neuroimaging for data synthesis and disease decomposition in Alzheimer's disease and multiple sclerosis. Finally, challenges for further research and applications will be discussed, including computational and data requirements, model evaluation, and potential privacy risks.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"571-589"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Explainable artificial intelligence for spectroscopy data: a review.","authors":"Jhonatan Contreras, Thomas Bocklitz","doi":"10.1007/s00424-024-02997-y","DOIUrl":"10.1007/s00424-024-02997-y","url":null,"abstract":"<p><p>Explainable artificial intelligence (XAI) has gained significant attention in various domains, including natural and medical image analysis. However, its application in spectroscopy remains relatively unexplored. This systematic review aims to fill this gap by providing a comprehensive overview of the current landscape of XAI in spectroscopy and identifying potential benefits and challenges associated with its implementation. Following the PRISMA guideline 2020, we conducted a systematic search across major journal databases, resulting in 259 initial search results. After removing duplicates and applying inclusion and exclusion criteria, 21 scientific studies were included in this review. Notably, most of the studies focused on using XAI methods for spectral data analysis, emphasizing identifying significant spectral bands rather than specific intensity peaks. Among the most utilized AI techniques were SHapley Additive exPlanations (SHAP), masking methods inspired by Local Interpretable Model-agnostic Explanations (LIME), and Class Activation Mapping (CAM). These methods were favored due to their model-agnostic nature and ease of use, enabling interpretable explanations without modifying the original models. Future research should propose new methods and explore the adaptation of other XAI employed in other domains to better suit the unique characteristics of spectroscopic data.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"603-615"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current methods in explainable artificial intelligence and future prospects for integrative physiology.","authors":"Bettina Finzel","doi":"10.1007/s00424-025-03067-7","DOIUrl":"10.1007/s00424-025-03067-7","url":null,"abstract":"<p><p>Explainable artificial intelligence (XAI) is gaining importance in physiological research, where artificial intelligence is now used as an analytical and predictive tool for many medical research questions. The primary goal of XAI is to make AI models understandable for human decision-makers. This can be achieved in particular through providing inherently interpretable AI methods or by making opaque models and their outputs transparent using post hoc explanations. This review introduces XAI core topics and provides a selective overview of current XAI methods in physiology. It further illustrates solved and discusses open challenges in XAI research using existing practical examples from the medical field. The article gives an outlook on two possible future prospects: (1) using XAI methods to provide trustworthy AI for integrative physiological research and (2) integrating physiological expertise about human explanation into XAI method development for useful and beneficial human-AI partnerships.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"513-529"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Special issue European Journal of Physiology: Artificial intelligence in the field of physiology and medicine.","authors":"Anika Westphal, Ralf Mrowka","doi":"10.1007/s00424-025-03071-x","DOIUrl":"10.1007/s00424-025-03071-x","url":null,"abstract":"<p><p>This special issue presents a collection of reviews on the recent advancements and applications of artificial intelligence (AI) in medicine and physiology. The topics covered include digital histopathology, generative AI, explainable AI (XAI), and ethical considerations in AI development and implementation. The reviews highlight the potential of AI to transform medical diagnostics, personalized medicine, and clinical decision making, while also addressing challenges such as data quality, interpretability, and trustworthiness. The contributions demonstrate the growing importance of AI in physiological research and medicine, the need for multi-level ethics approaches in AI development, and the potential benefits of generative AI in medical applications. Overall, this special issue showcases some of the the pioneering aspects of AI in medicine and physiology, covering technical, applicative, and ethical viewpoints, and underlines the remarkable impact of AI on these fields.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"509-512"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}