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Background: We have previously reported the neuroprotective effects of fosgonimeton in amyloid-β (Aβ)-driven preclinical models of Alzheimer's disease (AD). Fosgonimeton is an investigational small-molecule positive modulator of the neurotrophic hepatocyte growth factor (HGF) system, currently under investigation for mild-to-moderate AD (LIFT-AD; NCT04488419). Given the recent approvals of Aβ-targeting monoclonal antibodies (Aβ-mAbs) for the treatment of AD, and growing recognition that combination therapies may improve treatment outcomes, we sought to investigate the preclinical activity of fosgonimeton in the presence of Aβ-mAbs.
View Article and Find Full Text PDFTubulointerstitial nephritis antigen-like 1 promotes the progression of liver fibrosis after HCV eradication with direct-acting antivirals.
Int J Biol Sci
January 2025
CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.
Although therapies based on direct-acting antivirals (DAAs) effectively eradicate hepatitis C virus (HCV) in patients, there is still a high risk of liver fibrosis even after a sustained virological response. Therefore, it is of great clinical importance to understand the mechanism of potential factors that promote liver fibrosis after virological cure by treatment with DAAs. Here, we found that tubulointerstitial nephritis antigen-like 1 (TINAGL1) is significantly increased in HCV-infected hepatocytes and in the liver of patients with liver fibrosis, and that higher TINAGL1 expression persists in HCV-eradicated hepatocytes after treatment with DAAs.
View Article and Find Full Text PDFDevelopment of genetically tailored orthotopic implantation hepatocellular carcinoma model in oncopigs by somatic cell CRISPR editing.
Dis Model Mech
January 2025
Department of Radiology, University of Illinois at Chicago, Chicago, IL, USA.
Hepatocellular carcinoma (HCC) is an aggressive disease with poor prognosis, necessitating preclinical models for evaluating novel therapies. Large animal models are particularly valuable for assessing locoregional therapies, which are widely employed across HCC stages. This study aimed to develop a large animal HCC model with tailored tumor mutations.
View Article and Find Full Text PDFMorphological Features Influence the Drug Loading and Delivery Efficacy of Photoactivatable Gold Nanocarriers for Antitumor Photo/Chemotherapy.
ACS Appl Mater Interfaces
January 2025
Institute of Optical Functional Materials for Biomedical Imaging, School of Chemistry and Pharmaceutical Engineering, Shandong First Medical University & Shandong Academy of Medical Science, Taian, Shandong 271016, PR China.
Photoactivatable gold nanocarriers are transforming antitumor therapies by leveraging their distinctive physicochemical properties, enabling targeted drug delivery and enhanced therapeutic efficacy in cancer treatment. This study systematically investigates how surface topography and morphology of gold nanocarriers influence drug loading capacity, light-to-heat conversion efficiency, and overall therapeutic performance in photo/chemotherapy. We synthesized four distinct morphologies of gold nanoparticles: porous gold nanocups (PAuNCs), porous gold nanospheres (PAuNSs), solid gold nanocups (SAuNCs), and solid gold nanospheres (SAuNSs).
View Article and Find Full Text PDFSilibinin alleviates acute liver failure by modulating AKT/GSK3β/Nrf2/GPX4 pathway.
Naunyn Schmiedebergs Arch Pharmacol
January 2025
Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, P. R. China.
Silibinin (Sil) is a major bioactive component of silymarin, extracted from the fruit and seeds of Silybum marianum. Silibinin meglumine (SM) is a water-soluble derivative of silibinin that has shown significant potential in liver fibrosis. However, the potential effects and underlying mechanisms of SM on acute liver failure (ALF) are still not fully understood.
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