Single-cell Transcriptomic Profiling of MASH-HCC Development
Background & aim: Cellular-level insights into metabolic associated steatohepatitis (MASH) and its progression to hepatocellular carcinoma (HCC) have been limited by bulk RNA-sequencing, which masks rare or tumor-relevant populations. Here, we applied single-cell transcriptomics to characterize liver cell-specific transcriptome changes…
Molecular Hallmarks of Lung Cellular Senescence in the Repetitive Bleomycin-induced and Spirometry-confirmed Mouse Model of IPF
Background & aim: Growing evidence suggests that senescent cells contribute to the development and progression of idiopathic pulmonary fibrosis (IPF). This study aimed to identify and characterize key markers of lung senescence using a repetitive bleomycin-induced (BLEO), spirometry-confirmed mouse model…
Automated AI-assisted Ashcroft scoring of lung fibrosis in spirometry-confirmed and bleomycin-induced mouse model of IPF
Background & aim: The Ashcroft scoring system, originally developed for clinical assessment of pulmonary fibrosis, is widely applied in preclinical models of idiopathic pulmonary fibrosis (IPF). Like other manual, semiquantitative histopathological methods, Ashcroft scoring it subject to inter- and intra-observer…
Metabolic Effects of Tirzepatide and Semaglutide: Energy Expenditure and Adaptations During and After Treatment
Background & aim: Obesity pharmacotherapy has significantly improved weight management, with semaglutide (GLP-1 receptor agonist) and tirzepatide (dual GLP-1 and GIP receptor agonist) demonstrating substantial efficacy in reducing body weight. These drugs primarily act by suppressing appetite and improving glucose…
Comparative anti-fibrotic efficacy of resmetirom, semaglutide, tirzepatide and efruxifermin in the GAN diet-induced obese and biopsy-confirmed mouse model of MASH
Background & aim: Resmetirom (RES, THR-βR agonist) has recently been FDA-approved for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). Other drug concepts are in late-stage clinical development for MASH, including semaglutide (SEMA, GLP1R agonist), tirzepatide (TZP, GLP1R-GIPR co-agonist) and efruxifermin…
3D whole-brain imaging of parenchymal/vascular amyloid plaque architecture during disease progression in a transgenic mouse model of Alzheimer’s disease
Background & Aim: Alzheimer’s disease (AD) is histologically defined by accumulation of Abeta (Aβ) plaques in the brain. Age and gender are important factors in AD pathology. To develop more effective interventions, preclinical studies should therefore consider these factors in…
Advances in Extracellular Matrix-Associated Diagnostics and Therapeutics
Abstract: The extracellular matrix (ECM) is the common denominator of more than 50 chronic diseases. Some of these chronic pathologies lead to enhanced tissue formation and deposition, whereas others are associated with increased tissue degradation, and some exhibit a combination…
Transferrin receptor-binding blood-brain barrier shuttle enhances brain delivery and efficacy of a therapeutic anti-Aβ antibody
Background & Aim: Improved CNS access of amyloid β (Aβ)-directed antibodies may increase therapeutic benefits while also reducing dose-dependent adverse effects of this drug class. Using light sheet fluorescence microscopy (LSFM), we 3D mapped and quantified brain delivery, distribution and…