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The histamine pathway is a target to treat hepatic experimental erythropoietic protoporphyria.
Cell Mol Gastroenterol Hepatol
January 2025
Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ, USA. Electronic address:
Background & Aims: Erythropoietic protoporphyria (EPP) is caused by mutations in ferrochelatase which inserts iron into protoporphyrin-IX (PP-IX) to generate heme. EPP is characterized by PP-IX accumulation, skin photosensitivity, cholestasis, and end-stage liver disease. Despite available drugs that address photosensitivity, treatment of EPP-related liver disease remains an unmet need.
View Article and Find Full Text PDFA 3D Model of the Human Lung Airway for Evaluating Permeability of Inhaled Drugs.
ACS Pharmacol Transl Sci
January 2025
Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, United States Food and Drug Administration (FDA), Silver Spring, Maryland 20993, United States.
Current in vitro cell-based methods, relying on single cell types, have structural and functional limitations in determining lung drug permeability, which is a contributing factor affecting both local and systemic drug levels. To address this issue, we investigated a 3D human lung airway model generated using a cell culture insert, wherein primary human lung epithelial and endothelial cells were cocultured at an air-liquid interface (ALI). To ensure that the cell culture mimics the physiological and functional characteristics of airway tissue, the model was characterized by evaluating several parameters such as cellular confluency, ciliation, tight junctions, mucus-layer formation, transepithelial electrical resistance, and barrier function through assaying fluorescein isothiocyanate-dextran permeability.
View Article and Find Full Text PDFIn silico analysis of -derived peptides and plasmid construction for recombinant anti-aging therapies.
Narra J
December 2024
Department of Medicine, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia.
Skin aging is one of the degenerative processes influenced by tyrosinase, elastase, collagenase, hyaluronidase, and matrix metalloproteinase-9 (MMP9) activity. One promising avenue for discovering antiaging therapeutics is the peptides from the spine. The aim of this study was to explore the potential of peptides from spine as a multitarget inhibitor for recombinant antiaging therapies through in silico approaches.
View Article and Find Full Text PDFA Drug-Drug Interaction Study of Mobocertinib and Midazolam, a Cytochrome P450 3A Substrate, in Patients With Advanced Non-Small Cell Lung Cancer.
Clin Pharmacol Drug Dev
January 2025
Takeda Development Center Americas, Inc., Cambridge, MA, USA.
Mobocertinib is a kinase inhibitor designed to selectively target epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations in non-small cell lung cancer. This drug-drug interaction study assessed the effect of multiple-dose administration of mobocertinib on the pharmacokinetics (PK) of midazolam, a sensitive cytochrome P450 3A substrate. Patients with locally advanced or metastatic non-small cell lung cancer refractory/intolerant to standard available therapy were enrolled.
View Article and Find Full Text PDFIn vitro NIH3T3 mouse embryonic fibroblast cell model does not predict AAV2 or AAVdj-mediated cell transformation.
Toxicol Appl Pharmacol
January 2025
Drug Safety Research & Development, Pfizer, Inc., Groton, CT 06340, USA.
One of the potential risk factors of recombinant adeno-associated virus (rAAV)-based gene therapy is insertional mutagenesis, which has been associated with the development of hepatocellular carcinoma (HCC) in rAAV-treated neonatal mice. The objective of this study was to investigate if well-established in vitro cell transformation assays (CTA) in mouse cell lines can detect AAV2 or AAVdj-mediated cell transformation. Since AAV integration at the Rian locus in neonatal mice has been implicated in AAV-mediated HCC, an rAAV vector specifically targeting the mouse Rian locus and an additional rAAV vector previously shown to cause HCC in neonatal mice were both tested for the induction of cell transformation in NIH3T3 cells.
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