Mucosal transcriptomic landscape along the small and large intestines in individuals with and without type 2 diabetes
Background & aim: A detailed mapping of functional differences among intestinal regions in healthy individuals remains incomplete. Identifying regional alterations in individuals with type 2 diabetes (T2D) could enhance our understanding of disease-related intestinal changes. Aim: To characterise the transcriptomic…
Reproducible and clinically translatable hepatoprotective effects of tirzepatide in the GAN diet-induced obese and biopsy-confirmed mouse model of MASH
Background & aim: The glucagon-like peptide-1 receptor (GLP-1R) and gastric inhibitory polypeptide receptor (GIPR) dual agonist tirzepatide is currently approved for the treatment of obesity and type 2 diabetes. In a recent phase 2b trial (SYNERGY-NASH) in patients with metabolic-dysfunction…
Proof-of-concept testing of semaglutide in the GAN diet-induced obese and biopsy-confirmed mouse model of MASH
Background & aim: The long-acting glucagon-like peptide-1 (GLP-1) analogue semaglutide is approved for the treatment of type 2 diabetes and obesity. Recently, semaglutide has been reported to improve liver histopathological outcomes in patients with metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis…
Superior Hepatoprotective Effects of OPK-88006, a Novel GLP-1/Glucagon receptor dual agonist, to Semaglutide and Survodutide in the GAN Diet-Induced Obese and Biopsy-Confirmed Mouse Model of MASH
Background & aim: OPK-88006 is a novel peptide-based, long-acting glucagon-like peptide-1 receptor (GLP1R)/glucagon receptor (GCGR) dual agonist in current preclinical development for metabolic diseases, including obesity and metabolic dysfunction-associated steatohepatitis (MASH). The present study aimed to compare the therapeutic profile…
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…
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…
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…