A Quantitative Systems Pharmacology Model That Describes Neurofilament Light Dynamics During Alzheimer's Disease Progression. [PDF]
Maliukova P, Karelina T.
europepmc +1 more source
This study identifies the HDAC6/GATA4/HtrA1 axis as a critical driver of cellular senescence in the inner ear. GATA4 nuclear translocation, facilitated by HDAC6 downregulation, transcriptionally activates HtrA1, promoting hair cell senescence, SASP, and audio‐vestibular dysfunction in models of Ménière's disease and age‐related audio‐vestibular ...
Na Zhang +16 more
wiley +1 more source
We report a new thiolate‐reactive α,α‐gem‐dibromo lactam warhead that activates transcription factor Nrf2 and demonstrates anti‐inflammatory activities, which have implications in cancer, neurodegeneration, and cardiovascular diseases. RNA‐seq illuminated detailed transcriptional profiles, and chemical reactions with cysteine‐containing compounds ...
Beau R. Brummel +16 more
wiley +1 more source
TRMT6‐mediated m1A modification in CDK9 mRNA enhances its mRNA stability and translation efficiency, thereby increasing the protein levels of CDK9. Upregulated CDK9 promotes the progression of HCC by elevating the levels of oncogenic factors including p‐STAT3, MCL1, and BCL‐2. On the other hand, CDK9 phosphorylates TARDBP at Ser254 to activate HBV core
Rui Zhang +12 more
wiley +1 more source
Mechanistic data-informed multiscale quantitative systems pharmacology modeling framework enables the clinical translation and efficacy assessment of CAR-T therapy in solid tumors. [PDF]
Yang S +11 more
europepmc +1 more source
A Central Somatic Transmission Mediates Proprioceptive Facilitation of Muscle Pain
Zhang et al. uncover a novel central mechanism for persistent muscle pain, in which TRPA1 sensitization in MeV proprioceptive neurons enhances somatic secretion. This, in turn, disinhibits descending pain control from neighboring noradrenergic locus coeruleus neurons via local GABAergic circuits, thereby promoting inflammatory muscle pain.
Xiaoyu Zhang +15 more
wiley +1 more source
In Silico Hypothesis Testing in Drug Discovery: Using Quantitative Systems Pharmacology Modeling to Evaluate the Therapeutic Value of Proinsulin Conversion to Insulin Therapy for Type 2 Diabetes Mellitus. [PDF]
Trujillo ME +7 more
europepmc +1 more source
Quantitative Systems Pharmacology (QSP) Modeling of efficacy and nausea of GLP-1 mono and dual (GLP-1/GIP) receptor agonists (RA) to support weight management and glycemic control in obese patients [PDF]
E Shivaani +6 more
openalex +1 more source
A flexible, ultrathin multi‐channel microelectrode array (MEA) conformally integrated onto a curved slide‐well enables stable electrical interfacing with 3D cardiac organoids. The geometry‐guided self‐alignment allows simultaneous recording of extracellular field potentials and contractile motion from irregular, beating tissues.
Ye Seul Kim +12 more
wiley +1 more source
Material‐Induced Nuclear Deformation Controls Chromatin Architecture in Adipose Stem Cells
Tuning cell and cytoskeleton mechanics modulated nuclear shape and heterochromatin organization in ASCs. Distinct cytoskeletal architectures induced nuclear morphologies from oblate to prolate ellipsoids. Large elongated cells with a structured actin cap exhibited high nuclear strain, driving nuclear envelope deformation and heterochromatin ...
Carlo F. Natale +6 more
wiley +1 more source

