Frontiers in network physiology最新文献_第6页

Data-driven and equation-free methods for neurological disorders: analysis and control of the striatum network. 神经系统疾病的数据驱动和无方程方法：纹状体网络的分析与控制。

Frontiers in network physiology Pub Date : 2024-08-07 eCollection Date: 2024-01-01 DOI: 10.3389/fnetp.2024.1399347

Konstantinos Spiliotis, Rüdiger Köhling, Wolfram Just, Jens Starke

{"title":"Data-driven and equation-free methods for neurological disorders: analysis and control of the striatum network.","authors":"Konstantinos Spiliotis, Rüdiger Köhling, Wolfram Just, Jens Starke","doi":"10.3389/fnetp.2024.1399347","DOIUrl":"10.3389/fnetp.2024.1399347","url":null,"abstract":"The striatum as part of the basal ganglia is central to both motor, and cognitive functions. Here, we propose a large-scale biophysical network for this part of the brain, using modified Hodgkin-Huxley dynamics to model neurons, and a connectivity informed by a detailed human atlas. The model shows different spatio-temporal activity patterns corresponding to lower (presumably normal) and increased cortico-striatal activation (as found in, e.g., obsessive-compulsive disorder), depending on the intensity of the cortical inputs. By applying equation-free methods, we are able to perform a macroscopic network analysis directly from microscale simulations. We identify the mean synaptic activity as the macroscopic variable of the system, which shows similarity with local field potentials. The equation-free approach results in a numerical bifurcation and stability analysis of the macroscopic dynamics of the striatal network. The different macroscopic states can be assigned to normal/healthy and pathological conditions, as known from neurological disorders. Finally, guided by the equation-free bifurcation analysis, we propose a therapeutic close loop control scheme for the striatal network.","PeriodicalId":73092,"journal":{"name":"Frontiers in network physiology","volume":"4 ","pages":"1399347"},"PeriodicalIF":0.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic approaches targeting seizure networks. 针对癫痫发作网络的治疗方法。

Frontiers in network physiology Pub Date : 2024-08-07 eCollection Date: 2024-01-01 DOI: 10.3389/fnetp.2024.1441983

Jenna Langbein, Ujwal Boddeti, Matthew Kreinbrink, Ziam Khan, Ihika Rampalli, Muzna Bachani, Alexander Ksendzovsky

{"title":"Therapeutic approaches targeting seizure networks.","authors":"Jenna Langbein, Ujwal Boddeti, Matthew Kreinbrink, Ziam Khan, Ihika Rampalli, Muzna Bachani, Alexander Ksendzovsky","doi":"10.3389/fnetp.2024.1441983","DOIUrl":"10.3389/fnetp.2024.1441983","url":null,"abstract":"Epilepsy is one of the most common neurological disorders, affecting over 65 million people worldwide. Despite medical management with anti-seizure medications (ASMs), many patients fail to achieve seizure freedom, with over one-third of patients having drug-resistant epilepsy (DRE). Even with surgical management through resective surgery and/or neuromodulatory interventions, over 50 <math><mi>%</mi></math> of patients continue to experience refractory seizures within a year of surgery. Over the past 2 decades, studies have increasingly suggested that treatment failure is likely driven by untreated components of a pathological seizure network, a shift in the classical understanding of epilepsy as a focal disorder. However, this shift in thinking has yet to translate to improved treatments and seizure outcomes in patients. Here, we present a narrative review discussing the process of surgical epilepsy management. We explore current surgical interventions and hypothesized mechanisms behind treatment failure, highlighting evidence of pathologic seizure networks. Finally, we conclude by discussing how the network theory may inform surgical management, guiding the identification and targeting of more appropriate surgical regions. Ultimately, we believe that adapting current surgical practices and neuromodulatory interventions towards targeting seizure networks offers new therapeutic strategies that may improve seizure outcomes in patients suffering from DRE.","PeriodicalId":73092,"journal":{"name":"Frontiers in network physiology","volume":"4 ","pages":"1441983"},"PeriodicalIF":0.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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 network is more important than the node: stereo-EEG evidence of neurocognitive networks in epilepsy 网络比节点更重要：癫痫患者神经认知网络的立体电子脑电图证据

Frontiers in network physiology Pub Date : 2024-07-24 DOI: 10.3389/fnetp.2024.1424004

Nicholas W. G. Murray, Anthony C. Kneebone, Petra L. Graham, Chong H. Wong, Greg Savage, Lisa Gillinder, Michael W. K. Fong

{"title":"The network is more important than the node: stereo-EEG evidence of neurocognitive networks in epilepsy","authors":"Nicholas W. G. Murray, Anthony C. Kneebone, Petra L. Graham, Chong H. Wong, Greg Savage, Lisa Gillinder, Michael W. K. Fong","doi":"10.3389/fnetp.2024.1424004","DOIUrl":"https://doi.org/10.3389/fnetp.2024.1424004","url":null,"abstract":"Neuropsychological assessment forms an integral part of the presurgical evaluation for patients with medically refractory focal epilepsy. Our understanding of cognitive impairment in epilepsy is based on seminal lesional studies that have demonstrated important structure-function relationships within the brain. However, a growing body of literature demonstrating heterogeneity in the cognitive profiles of patients with focal epilepsy (e.g., temporal lobe epilepsy; TLE) has led researchers to speculate that cognition may be impacted by regions outside the seizure onset zone, such as those involved in the interictal or “irritative” network.Neuropsychological data from 48 patients who underwent stereoelectroencephalography (SEEG) monitoring between 2012 and 2023 were reviewed. Patients were categorized based on the site of seizure onset, as well as their irritative network, to determine the impact of wider network activity on cognition. Neuropsychological data were compared with normative standards (i.e., z = 0), and between groups.There were very few distinguishing cognitive features between patients when categorized based purely on the seizure onset zone (i.e., frontal lobe vs. temporal lobe epilepsy). In contrast, patients with localized irritative networks (i.e., frontal or temporal interictal epileptiform discharges [IEDs]) demonstrated more circumscribed profiles of impairment compared with those demonstrating wider irritative networks (i.e., frontotemporal IEDs). Furthermore, the directionality of propagation within the irritative network was found to influence the manifestations of cognitive impairment.The findings suggest that neuropsychological assessment is sensitive to network activity beyond the site of seizure onset. As such, an overly focal interpretation may not accurately reflect the distribution of the underlying pathology. This has important implications for presurgical work-up in epilepsy, as well as subsequent surgical outcomes.","PeriodicalId":73092,"journal":{"name":"Frontiers in network physiology","volume":"87 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141807745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Surrogate modelling of heartbeat events for improved J-peak detection in BCG using deep learning 利用深度学习建立心跳事件的替代模型，以改进卡介苗中的 J 峰检测

Frontiers in network physiology Pub Date : 2024-07-19 DOI: 10.3389/fnetp.2024.1425871

Christoph Schranz, Christina Halmich, Sebastian Mayr, Dominik P. J. Heib

{"title":"Surrogate modelling of heartbeat events for improved J-peak detection in BCG using deep learning","authors":"Christoph Schranz, Christina Halmich, Sebastian Mayr, Dominik P. J. Heib","doi":"10.3389/fnetp.2024.1425871","DOIUrl":"https://doi.org/10.3389/fnetp.2024.1425871","url":null,"abstract":"Sleep, or the lack thereof, has far-reaching consequences on many aspects of human physiology, cognitive performance, and emotional wellbeing. To ensure undisturbed sleep monitoring, unobtrusive measurements such as ballistocardiogram (BCG) are essential for sustained, real-world data acquisition. Current analysis of BCG data during sleep remains challenging, mainly due to low signal-to-noise ratio, physical movements, as well as high inter- and intra-individual variability. To overcome these challenges, this work proposes a novel approach to improve J-peak extraction from BCG measurements using a supervised deep learning setup. The proposed method consists of the modeling of the discrete reference heartbeat events with a symmetric and continuous kernel-function, referred to as surrogate signal. Deep learning models approximate this surrogate signal from which the target heartbeats are detected. The proposed method with various surrogate signals is compared and evaluated with state-of-the-art methods from both signal processing and machine learning approaches. The BCG dataset was collected over 17 nights using inertial measurement units (IMUs) embedded in a mattress, together with an ECG for reference heartbeats, for a total of 134 h. Moreover, we apply for the first time an evaluation metric specialized for the comparison of event-based time series to assess the quality of heartbeat detection. The results show that the proposed approach demonstrates superior accuracy in heartbeat estimation compared to existing approaches, with an MAE (mean absolute error) of 1.1 s in 64-s windows and 1.38 s in 8-s windows. Furthermore, it is shown that our novel approach outperforms current methods in detecting the location of heartbeats across various evaluation metrics. To the best of our knowledge, this is the first approach to encode temporal events using kernels and the first systematic comparison of various event encodings for event detection using a regression-based sequence-to-sequence model.","PeriodicalId":73092,"journal":{"name":"Frontiers in network physiology","volume":"122 21","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141820791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chaos control in cardiac dynamics: terminating chaotic states with local minima pacing. 心脏动力学中的混沌控制：用局部最小起搏终止混沌状态。

Frontiers in network physiology Pub Date : 2024-07-03 eCollection Date: 2024-01-01 DOI: 10.3389/fnetp.2024.1401661

Daniel Suth, Stefan Luther, Thomas Lilienkamp

{"title":"Chaos control in cardiac dynamics: terminating chaotic states with local minima pacing.","authors":"Daniel Suth, Stefan Luther, Thomas Lilienkamp","doi":"10.3389/fnetp.2024.1401661","DOIUrl":"10.3389/fnetp.2024.1401661","url":null,"abstract":"Current treatments of cardiac arrhythmias like ventricular fibrillation involve the application of a high-energy electric shock, that induces significant electrical currents in the myocardium and therefore involves severe side effects like possible tissue damage and post-traumatic stress. Using numerical simulations on four different models of 2D excitable media, this study demonstrates that low energy pulses applied shortly after local minima in the mean value of the transmembrane potential provide high success rates. We evaluate the performance of this approach for ten initial conditions of each model, ten spatially different stimuli, and different shock amplitudes. The investigated models of 2D excitable media cover a broad range of dominant frequencies and number of phase singularities, which demonstrates, that our findings are not limited to a specific kind of model or parameterization of it. Thus, we propose a method that incorporates the dynamics of the underlying system, even during pacing, and solely relies on a scalar observable, which is easily measurable in numerical simulations.","PeriodicalId":73092,"journal":{"name":"Frontiers in network physiology","volume":"4 ","pages":"1401661"},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Treatment effects in epilepsy: a mathematical framework for understanding response over time. 癫痫的治疗效果：了解随时间变化的反应的数学框架。

Frontiers in network physiology Pub Date : 2024-06-26 eCollection Date: 2024-01-01 DOI: 10.3389/fnetp.2024.1308501

Elanor G Harrington, Peter Kissack, John R Terry, Wessel Woldman, Leandro Junges

{"title":"Treatment effects in epilepsy: a mathematical framework for understanding response over time.","authors":"Elanor G Harrington, Peter Kissack, John R Terry, Wessel Woldman, Leandro Junges","doi":"10.3389/fnetp.2024.1308501","DOIUrl":"10.3389/fnetp.2024.1308501","url":null,"abstract":"Epilepsy is a neurological disorder characterized by recurrent seizures, affecting over 65 million people worldwide. Treatment typically commences with the use of anti-seizure medications, including both mono- and poly-therapy. Should these fail, more invasive therapies such as surgery, electrical stimulation and focal drug delivery are often considered in an attempt to render the person seizure free. Although a significant portion ultimately benefit from these treatment options, treatment responses often fluctuate over time. The physiological mechanisms underlying these temporal variations are poorly understood, making prognosis a significant challenge when treating epilepsy. Here we use a dynamic network model of seizure transition to understand how seizure propensity may vary over time as a consequence of changes in excitability. Through computer simulations, we explore the relationship between the impact of treatment on dynamic network properties and their vulnerability over time that permit a return to states of high seizure propensity. For small networks we show vulnerability can be fully characterised by the size of the first transitive component (FTC). For larger networks, we find measures of network efficiency, incoherence and heterogeneity (degree variance) correlate with robustness of networks to increasing excitability. These results provide a set of potential prognostic markers for therapeutic interventions in epilepsy. Such markers could be used to support the development of personalized treatment strategies, ultimately contributing to understanding of long-term seizure freedom.","PeriodicalId":73092,"journal":{"name":"Frontiers in network physiology","volume":"4 ","pages":"1308501"},"PeriodicalIF":0.0,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11233745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pairing cellular and synaptic dynamics into building blocks of rhythmic neural circuits. A tutorial. 将细胞和突触动力学配对成节律神经回路的构建模块。教程。

Frontiers in network physiology Pub Date : 2024-06-25 eCollection Date: 2024-01-01 DOI: 10.3389/fnetp.2024.1397151

James Scully, Jassem Bourahmah, David Bloom, Andrey L Shilnikov

{"title":"Pairing cellular and synaptic dynamics into building blocks of rhythmic neural circuits. A tutorial.","authors":"James Scully, Jassem Bourahmah, David Bloom, Andrey L Shilnikov","doi":"10.3389/fnetp.2024.1397151","DOIUrl":"10.3389/fnetp.2024.1397151","url":null,"abstract":"In this study we focus on two subnetworks common in the circuitry of swim central pattern generators (CPGs) in the sea slugs, Melibe leonina and Dendronotus iris and show that they are independently capable of stably producing emergent network bursting. This observation raises the question of whether the coordination of redundant bursting mechanisms plays a role in the generation of rhythm and its regulation in the given swim CPGs. To address this question, we investigate two pairwise rhythm-generating networks and examine the properties of their fundamental components: cellular and synaptic, which are crucial for proper network assembly and its stable function. We perform a slow-fast decomposition analysis of cellular dynamics and highlight its significant bifurcations occurring in isolated and coupled neurons. A novel model for slow synapses with high filtering efficiency and temporal delay is also introduced and examined. Our findings demonstrate the existence of two modes of oscillation in bicellular rhythm-generating networks with network hysteresis: i) a half-center oscillator and ii) an excitatory-inhibitory pair. These 2-cell networks offer potential as common building blocks combined in modular organization of larger neural circuits preserving robust network hysteresis.","PeriodicalId":73092,"journal":{"name":"Frontiers in network physiology","volume":"4 ","pages":"1397151"},"PeriodicalIF":0.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Network approach reveals preferential T-cell and macrophage association with α-linked β-cells in early stage of insulitis in NOD mice. 网络方法揭示了在 NOD 小鼠胰岛炎早期，T 细胞和巨噬细胞优先与 α 链接的 β 细胞结合。

Frontiers in network physiology Pub Date : 2024-06-24 eCollection Date: 2024-01-01 DOI: 10.3389/fnetp.2024.1393397

Nirmala V Balasenthilkumaran, Jennifer C Whitesell, Laura Pyle, Rachel S Friedman, Vira Kravets

{"title":"Network approach reveals preferential T-cell and macrophage association with α-linked β-cells in early stage of insulitis in NOD mice.","authors":"Nirmala V Balasenthilkumaran, Jennifer C Whitesell, Laura Pyle, Rachel S Friedman, Vira Kravets","doi":"10.3389/fnetp.2024.1393397","DOIUrl":"10.3389/fnetp.2024.1393397","url":null,"abstract":"One of the challenges in studying islet inflammation-insulitis-is that it is a transient phenomenon. Traditional reporting of the insulitis progression is based on cumulative, donor-averaged values of leucocyte density in the vicinity of pancreatic islets, that hinder intra- and inter-islet heterogeneity of disease progression. Here, we aimed to understand why insulitis is non-uniform, often with peri-insulitis lesions formed on one side of an islet. To achieve this, we demonstrated the applicability of network theory in detangling intra-islet multi-cellular interactions during insulitis. Specifically, we asked the question \"What is unique about regions of the islet that interact with immune cells first\". This study utilized the non-obese diabetic mouse model of type one diabetes and examined the interplay among α-, β-, T-cells, myeloid cells, and macrophages in pancreatic islets during the progression of insulitis. Disease evolution was tracked based on the T/β cell ratio in individual islets. In the early stage, we found that immune cells are preferentially interacting with α-cell-rich regions of an islet. At the islet periphery α-linked β-cells were found to be targeted significantly more compared to those without α-cell neighbors. Additionally, network analysis revealed increased T-myeloid, and T-macrophage interactions with all β-cells.","PeriodicalId":73092,"journal":{"name":"Frontiers in network physiology","volume":"4 ","pages":"1393397"},"PeriodicalIF":0.0,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11228247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Resilience of the slow component in timescale-separated synchronized oscillators. 时标分离同步振荡器中慢速分量的恢复能力

Frontiers in network physiology Pub Date : 2024-06-19 eCollection Date: 2024-01-01 DOI: 10.3389/fnetp.2024.1399352

Melvyn Tyloo

{"title":"Resilience of the slow component in timescale-separated synchronized oscillators.","authors":"Melvyn Tyloo","doi":"10.3389/fnetp.2024.1399352","DOIUrl":"10.3389/fnetp.2024.1399352","url":null,"abstract":"Physiological networks are usually made of a large number of biological oscillators evolving on a multitude of different timescales. Phase oscillators are particularly useful in the modelling of the synchronization dynamics of such systems. If the coupling is strong enough compared to the heterogeneity of the internal parameters, synchronized states might emerge where phase oscillators start to behave coherently. Here, we focus on the case where synchronized oscillators are divided into a fast and a slow component so that the two subsets evolve on separated timescales. We assess the resilience of the slow component by, first, reducing the dynamics of the fast one using Mori-Zwanzig formalism. Second, we evaluate the variance of the phase deviations when the oscillators in the two components are subject to noise with possibly distinct correlation times. From the general expression for the variance, we consider specific network structures and show how the noise transmission between the fast and slow components is affected. Interestingly, we find that oscillators that are among the most robust when there is only a single timescale, might become the most vulnerable when the system undergoes a timescale separation. We also find that layered networks seem to be insensitive to such timescale separations.","PeriodicalId":73092,"journal":{"name":"Frontiers in network physiology","volume":"4 ","pages":"1399352"},"PeriodicalIF":0.0,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dynamics of a network mediated by IL-36 and involved in the pathogenesis of psoriasis. 由 IL-36 介导并参与银屑病发病机制的网络动态。

Frontiers in network physiology Pub Date : 2024-05-31 eCollection Date: 2024-01-01 DOI: 10.3389/fnetp.2024.1363791

Sneha Pandey, Syona Tiwari, Sulagna Basu, Rajiv Kumar Mishra, Rakesh Pandey

{"title":"Dynamics of a network mediated by IL-36 and involved in the pathogenesis of psoriasis.","authors":"Sneha Pandey, Syona Tiwari, Sulagna Basu, Rajiv Kumar Mishra, Rakesh Pandey","doi":"10.3389/fnetp.2024.1363791","DOIUrl":"10.3389/fnetp.2024.1363791","url":null,"abstract":"The pathogenesis of the inflammatory, chronic, and common skin disease psoriasis involves immune cells, skin cells (keratinocytes), and the cytokines they secrete. Hyperproliferation and abnormal differentiation of keratinocytes are hallmarks of the disease. The roles of cytokines such as TNFα, IL-15, IL-17, and IL-23 in psoriasis have been studied through mathematical/computational models as well as experiments. However, the role of proinflammatory cytokine IL-36 in the onset and progression of psoriasis is still elusive. To explore the role of IL-36, we construct a network embodying indirect cell-cell interactions of a few immune and skin cells mediated by IL-36 based on existing knowledge. We also develop a mathematical model for the network and perform a global sensitivity analysis. Our results suggest that the model is most sensitive to a parameter that represents the level of cytokine IL-36. In addition, a steady-state analysis of the model suggests that an increase in the level of IL-36 could lead to the hyperproliferation of keratinocytes and, thus, psoriasis. Our analysis also highlights that the plaque formation and progression of psoriasis could occur through either a gradual or a switch-like increase in the keratinocyte population. We propose that the switch-like increase would be due to a bistable behavior of the network toward either a psoriatic or healthy state and could be used as a novel treatment strategy.","PeriodicalId":73092,"journal":{"name":"Frontiers in network physiology","volume":"4 ","pages":"1363791"},"PeriodicalIF":0.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11176455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141332586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0