Multiscale computational model predicts how environmental changes and treatments affect microvascular remodeling in fibrotic disease DOI Creative Commons
Julie Leonard‐Duke,

Samuel M. J. Agro,

David Csordas

и другие.

PNAS Nexus, Год журнала: 2024, Номер 4(1)

Опубликована: Дек. 7, 2024

Abstract Investigating the molecular, cellular, and tissue-level changes caused by disease, effects of pharmacological treatments across these biological scales, necessitates use multiscale computational modeling in combination with experimentation. Many diseases dynamically alter tissue microenvironment ways that trigger microvascular network remodeling, which leads to expansion or regression microvessel networks. When microvessels undergo remodeling idiopathic pulmonary fibrosis (IPF), functional gas exchange is impaired lung function declines. We integrated a model independent experiments investigate how combinations biomechanical biochemical cues IPF cell fate decisions leading remodeling. Our predicted extracellular matrix (ECM) stiffening reduced area, was accompanied physical uncoupling endothelial (EC) pericytes, cells comprise microvessels. Nintedanib, an Food Drug Administration-approved drug for treating IPF, further potentiate decreasing percentage quiescent pericytes while increasing undergoing pericyte-myofibroblast transition high ECM stiffnesses. Importantly, suggested YAP/TAZ inhibition may overcome deleterious nintedanib promoting EC-pericyte coupling maintaining homeostasis. Overall, our experimental can predict explain affect during disease response treatments.

Язык: Английский

Physiological network approach to prognosis in cirrhosis: A shifting paradigm DOI Creative Commons
Tope Oyelade,

Kevin P. Moore,

Ali R. Mani

и другие.

Physiological Reports, Год журнала: 2024, Номер 12(13)

Опубликована: Июль 1, 2024

Abstract Decompensated liver disease is complicated by multi‐organ failure and poor prognosis. The prognosis of patients with often dictates clinical management. Current prognostic models have focused on biomarkers considered as individual isolated units. Network physiology assesses the interactions among multiple physiological systems in health irrespective anatomical connectivity defines influence or dependence one organ system another. Indeed, recent applications network mapping methods to patient data shown improved prediction response therapy cirrhosis. Initially, different physical markers been used assess coupling cirrhosis including heart rate variability, turbulence, skin temperature variability measures. Further, parenclitic analysis was recently applied showing that impaired decompensated can predict mortality independent current while also providing valuable insights into associated pathological pathways. Moreover, predicts intravenous albumin hospitalized Thus, this review highlights importance evaluating through physiologic prism. It emphasizes limitations values techniques

Язык: Английский

Процитировано

4
What is personalized lung poromechanical modeling and how can it improve the understanding and management of fibrotic interstitial lung diseases? DOI Creative Commons
Pierre‐Yves Brillet,

Alice Peyraut,

Jean‐François Bernaudin

и другие.

Expert Review of Respiratory Medicine, Год журнала: 2025, Номер unknown, С. 1 - 4

Опубликована: Фев. 7, 2025

Keywords: Computed tomographyDigital twinExtracellular MatrixInterstitial lung diseasesIdiopathic Pulmonary FibrosisMathematical modelingMechanotransduction

Язык: Английский

Процитировано

0
The Fibrotic Phenotype of Human Precision-Cut Lung Slices Is Maintained after Cryopreservation DOI Creative Commons

Méry Marimoutou,

Vivek Patel, Jae Hun Kim

и другие.

Toxics, Год журнала: 2024, Номер 12(9), С. 637 - 637

Опубликована: Авг. 30, 2024

Human precision-cut lung slices (hPCLS) prepared from fibrotic lungs recapitulate the pathophysiological hallmarks of fibrosis. These hallmark features can also be induced by treating non-fibrotic hPCLS with a cocktail (FC). As result, and fibrosis-induced are rapidly emerging as preferred models for disease modeling drug discovery. However, current limited tissue viability in culture, they usually only viable one week after harvesting. Here, we demonstrate that cryopreserved, stored months, then thawed on demand without loss or protein content 14 days post-thawing. Cryopreservation preserves pro-fibrotic potential hPCLS. Specifically, when treated an FC, observed significant cytokine secretion elevated stiffness. changes were inhibited small-molecule tyrosine kinase inhibitor, Nintedanib. Taken together, our work indicates feasible solution to prolong pre-clinical utility is cryopreservation. We anticipate cryopreserved will serve advantageous predictive model evaluation pathways during acute chronic toxicity testing.

Язык: Английский

Процитировано

3
Digital twins for chronic lung diseases DOI Creative Commons
Apolline Gonsard, Martin Genet, David Drummond

и другие.

European Respiratory Review, Год журнала: 2024, Номер 33(174), С. 240159 - 240159

Опубликована: Окт. 1, 2024

Digital twins have recently emerged in healthcare. They combine advances cyber–physical systems, modelling and computation techniques, enable a bidirectional flow of information between the physical virtual entities. In respiratory medicine, progress connected devices artificial intelligence make it technically possible to obtain digital that allow real-time visualisation patient's health. Advances system also development could be used predict effectiveness different therapeutic approaches for patient. For researchers, lead better understanding gene–environment–time interactions involved chronic diseases. clinicians patients, they facilitate personalised timely by enabling adaptations specific each patient early detection disease progression. The objective this review is reader explore concept twins, their feasibility potential benefits challenges implementation.

Язык: Английский

Процитировано

1
Multiscale computational model predicts how environmental changes and treatments affect microvascular remodeling in fibrotic disease DOI Creative Commons
Julie Leonard‐Duke,

Samuel M. J. Agro,

David Csordas

и другие.

PNAS Nexus, Год журнала: 2024, Номер 4(1)

Опубликована: Дек. 7, 2024

Abstract Investigating the molecular, cellular, and tissue-level changes caused by disease, effects of pharmacological treatments across these biological scales, necessitates use multiscale computational modeling in combination with experimentation. Many diseases dynamically alter tissue microenvironment ways that trigger microvascular network remodeling, which leads to expansion or regression microvessel networks. When microvessels undergo remodeling idiopathic pulmonary fibrosis (IPF), functional gas exchange is impaired lung function declines. We integrated a model independent experiments investigate how combinations biomechanical biochemical cues IPF cell fate decisions leading remodeling. Our predicted extracellular matrix (ECM) stiffening reduced area, was accompanied physical uncoupling endothelial (EC) pericytes, cells comprise microvessels. Nintedanib, an Food Drug Administration-approved drug for treating IPF, further potentiate decreasing percentage quiescent pericytes while increasing undergoing pericyte-myofibroblast transition high ECM stiffnesses. Importantly, suggested YAP/TAZ inhibition may overcome deleterious nintedanib promoting EC-pericyte coupling maintaining homeostasis. Overall, our experimental can predict explain affect during disease response treatments.

Язык: Английский

Процитировано

0