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Advanced In Vitro Models for Preclinical Drug Safety: Recent Progress and Prospects.
Curr Issues Mol Biol
December 2024
Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), University Hospital Aachen, D-52074 Aachen, Germany.
The majority of drugs are typically orally administered. The journey from drug discovery to approval is often long and expensive, involving multiple stages. A major challenge in the drug development process is drug-induced liver injury (DILI), a condition that affects the liver, the organ responsible for metabolizing most drugs.
View Article and Find Full Text PDFTopic "Signaling Pathways in Liver Disease".
Cells
January 2025
Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), University Hospital Aachen, D-52074 Aachen, Germany.
Liver diseases pose a significant global health challenge, affecting millions of individuals and resulting in substantial morbidity and mortality [...
View Article and Find Full Text PDFSingle-cell analysis identifies the CNP/GC-B/cGMP axis as marker and regulator of modulated VSMCs in atherosclerosis.
Nat Commun
January 2025
Interfakultäres Institut für Biochemie, University of Tübingen, Tübingen, Germany.
A balanced activity of cGMP signaling contributes to the maintenance of cardiovascular homeostasis. Vascular smooth muscle cells (VSMCs) can generate cGMP via three ligand-activated guanylyl cyclases, the NO-sensitive guanylyl cyclase, the atrial natriuretic peptide (ANP)-activated GC-A, and the C-type natriuretic peptide (CNP)-stimulated GC-B. Here, we study natriuretic peptide signaling in murine VSMCs and atherosclerotic lesions.
View Article and Find Full Text PDFExploring Molecular Mechanisms of Liver Fibrosis.
Int J Mol Sci
January 2025
Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), University Hospital Aachen, D-52074 Aachen, Germany.
Liver diseases, particularly metabolic dysfunction-associated steatotic liver disease (MASLD), have emerged as a major global health concern, affecting millions of individuals and leading to increased morbidity and mortality [...
View Article and Find Full Text PDFGlucosylceramide Synthase Inhibition in Combination with Aripiprazole Sensitizes Hepatocellular Cancer Cells to Sorafenib and Doxorubicin.
Int J Mol Sci
December 2024
Lipid Pathobiochemistry Group, German Cancer Research Center, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
Hepatocellular carcinoma () is one of the leading causes of cancer deaths due to its late diagnosis and restricted therapeutic options. Therefore, the search for appropriate alternatives to commonly applied therapies remains an area of high clinical need. Here we investigated the therapeutic potential of the glucosylceramide synthase (GCS) inhibitor Genz-123346 and the cationic amphiphilic drug aripiprazole on the inhibition of Huh7 and Hepa 1-6 hepatocellular cancer cell and tumor microsphere growth.
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