Results 41 to 50 of about 96,194 (242)

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

Valosin‐containing protein counteracts ATP‐driven dissolution of FUS condensates through its ATPase activity in vitro

FEBS Letters, EarlyView.
Biomolecular condensates formed by fused in sarcoma (FUS) are dissolved by high ATP concentrations yet persist in cells. Using a reconstituted system, we demonstrate that valosin‐containing protein (VCP), an AAA+ ATPase, counteracts ATP‐driven dissolution of FUS condensates through its D2 ATPase activity.
Hitomi Kimura, Shin‐ichi Tate, Kyota Yasuda   +2 more
wiley   +1 more source

In vitro to clinical translation of combinatorial effects of doxorubicin and dexrazoxane in breast cancer: a mechanism-based pharmacokinetic/pharmacodynamic modeling approach

Frontiers in Pharmacology, 2023
Dexrazoxane (DEX) is the only drug clinically approved to treat Doxorubicin-induced cardiotoxicity (DIC), however its impact on the anticancer efficacy of DOX is not extensively studied.
Hardik Mody, Tanaya R. Vaidya, Jovin Lezeau, Kareem Taha, Sihem Ait-Oudhia   +4 more
doaj   +1 more source

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

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

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

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

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

An epithelial GPR35 isoform supports tumor‐associated transcriptional and metabolic phenotypes

FEBS Letters, EarlyView.
GPR35 generates two functionally distinct isoforms with previously unresolved roles. GPR35‐short mediates immune‐cell chemotaxis, while GPR35‐long is enriched in colorectal cancer epithelium, where it supports increased metabolism, proliferation, and tumor‐associated transcriptional programs.
Jørgen D. Rønneberg, Martine Hjeltnes, Josephine Krieger, Joshua E. Elias, Maria Stensland, Kristian Holm, Xiaojun Jiang, Chuki Khangsar, Tuula A. Nyman, Arthur Kaser, Johannes R. Hov, Tom H. Karlsen, Nicole C. Kaneider, Frode L. Jahnsen, Georg Schneditz   +14 more
wiley   +1 more source