Results 41 to 50 of about 95,693 (243)

Quantitative Systems Pharmacology: A Case for Disease Models

Clinical Pharmacology & Therapeutics, 2016
Quantitative systems pharmacology (QSP) has emerged as an innovative approach in model‐informed drug discovery and development, supporting program decisions from exploratory research through late‐stage clinical trials. In this commentary, we discuss the unique value of disease‐scale “platform” QSP models that are amenable to reuse and repurposing to ...
Musante, CJ, Ramanujan, S, Schmidt, BJ, Ghobrial, OG, Lu, J, Heatherington, AC   +5 more
openaire   +2 more sources

Residual tail twisting in ascidian larvae is stabilized by asymmetric myofibrils that resist bilateral symmetry restoration

FEBS Letters, EarlyView.
Ascidian Ciona larvae initially show strong clockwise tail twisting, which is largely corrected during development. However, a small residual twist remains. This study shows that organized helical myofibrils in tail muscles mechanically stabilize this residual asymmetry, preventing complete restoration of bilateral symmetry and revealing how embryos ...
Yuki S. Kogure, Misaki K. Nishio, Satoru Okuda, Kohji Hotta   +3 more
wiley   +1 more source

Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies [PDF]

Scientific Reports, 2018
AbstractMicrophysiological systems (MPSs) are in vitro models that capture facets of in vivo organ function through use of specialized culture microenvironments, including 3D matrices and microperfusion. Here, we report an approach to co-culture multiple different MPSs linked together physiologically on re-useable, open-system microfluidic platforms ...
Collin D. Edington, Wen Li Kelly Chen, Emily Geishecker, Timothy Kassis, Luis R. Soenksen, Brij M. Bhushan, Duncan Freake, Jared Kirschner, Christian Maass, Nikolaos Tsamandouras, Jorge Valdez, Christi D. Cook, Tom Parent, Stephen Snyder, Jiajie Yu, Emily Suter, Michael Shockley, Jason Velazquez, Jeremy J. Velazquez, Linda Stockdale, Julia P. Papps, Iris Lee, Nicholas Vann, Mario Gamboa, Matthew E. LaBarge, Zhe Zhong, Xin Wang, Laurie A. Boyer, Douglas A. Lauffenburger, Rebecca L. Carrier, Catherine Communal, Steven R. Tannenbaum, Cynthia L. Stokes, David J. Hughes, Gaurav Rohatgi, David L. Trumper, Murat Cirit, Linda G. Griffith   +37 more
openaire   +3 more sources

An Integrative Mechanistic Model of Type 1 IFN‐Mediated Inflammation in Systemic Lupus Erythematosus

CPT: Pharmacometrics & Systems Pharmacology
Type I interferon (IFN1) pathway–targeting therapies represent a highly promising class of remedies for the treatment of systemic lupus erythematosus. However, the overall clinical benefit of these compounds is afflicted by marked variability.
Alina Volkova, Victor Sokolov, Florencia Tettamanti, Meghna Verma, Yaroslav Ugolkov, Kirill Peskov, Weifeng Tang, Holly Kimko   +7 more
doaj   +1 more source

Septin 9 PB domains coordinate centrosome positioning and microtubule acetylation to control epithelial polarity

FEBS Letters, EarlyView.
Septin 9 polybasic domains couple phosphoinositide‐rich membrane binding to centrosome positioning, Golgi organization, and microtubule acetylation to control epithelial polarity. Their loss disrupts this axis, causing centrosome mispositioning, Golgi fragmentation, reduced microtubule acetylation, and polarity inversion via upregulation of the ...
Ting ting Cai, Mohyeddine Omrane, Nassima Benzoubir, Didier Samuel, Ama Gassama‐Diagne   +4 more
wiley   +1 more source

Degradation mechanism of the von Willebrand factor A2 domain by nattokinase

FEBS Letters, EarlyView.
Nattokinase, a natto‐derived protease, exhibits potent antithrombotic effects. This study demonstrates that nattokinase directly cleaves the von Willebrand factor (vWF) A2 domain in vitro. Unlike the native regulator ADAMTS13, nattokinase degrades folded vWF independently of shear stress.
Ryuichi Hyakumoto, Masatomo So, Ayako Furukawa, Kenji Sugase   +3 more
wiley   +1 more source

Leveraging In Silico and Artificial Intelligence Models to Advance Drug Disposition and Response Predictions Across the Lifespan

Clinical and Translational Science
Incorporating inter‐individual differences in drug disposition and responses is essential for ensuring the safe and effective use of drugs in real‐world patients.
Kyunghee Yang, Daniel Gonzalez, Jeffrey L. Woodhead, Pallavi Bhargava, Murali Ramanathan   +4 more
doaj   +1 more source

A Quantitative Systems Pharmacology Platform Reveals NAFLD Pathophysiological States and Targeting Strategies

Metabolites, 2022
Non-alcoholic fatty liver disease (NAFLD) has a high global prevalence with a heterogeneous and complex pathophysiology that presents barriers to traditional targeted therapeutic approaches.
Daniel E. Lefever, Mark T. Miedel, Fen Pei, Johanna K. DiStefano, Richard Debiasio, Tong Ying Shun, Manush Saydmohammed, Maria Chikina, Lawrence A. Vernetti, Alejandro Soto-Gutierrez, Satdarshan P. Monga, Ramon Bataller, Jaideep Behari, Vijay K. Yechoor, Ivet Bahar, Albert Gough, Andrew M. Stern, D. Lansing Taylor   +17 more
doaj   +1 more source

α‐Synuclein aggregation landscape from phase separation to neurotoxic intermediates

FEBS Letters, EarlyView.
Alpha‐synuclein aggregation in Parkinson's disease involves a complex landscape of transient intermediates, including oligomers, fibrils and liquid–liquid phase separation (LLPS). A view is emerging in which LLPS maturation into solid‐like condensates may contribute to the formation of neurotoxic species.
Silvia Arino, Giuliana Fusco, Alfonso De Simone   +2 more
wiley   +1 more source

Dimethyl fumarate combined with cisplatin at subcytotoxic doses sensitizes cervical cancer toward ferroptosis and apoptosis through GSH restriction and p53 (re)activation

Molecular Oncology, EarlyView.
Dimethyl fumarate (DMF) reduces growth of HPV‐positive cervical cancer spheroids and induces ferroptosis in cervical cancer cells via blocking SLC7A11/Glutathione (GSH) axis. Combination of subcytotoxic doses of DMF and cisplatin (CDDP) further suppresses spheroid growth and drives cell death in 2D culture models.
Carolina Punziano, Giuseppina Minopoli, Simona Romano, Laura Marrone, Katia Aquilano, Maria Lina Tornesello, Raffaella Faraonio   +6 more
wiley   +1 more source