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Exceptional Uptake, Limited Protein Expression: Liver Macrophages Lost in Translation of Synthetic mRNA.
Adv Sci (Weinh)
January 2025
Department of Internal Medicine III, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany.
Most gene therapies exert their actions via manipulation of hepatocytes (parenchymal cells) and the reasons behind the suboptimal performance of synthetic mRNA in non-parenchymal cells (NPC) such as Kupffer cells (KC), and liver macrophages, remain unclear. Here, the spatio-temporal distribution of mRNA encoding enhanced green fluorescent protein (Egfp), siRNA, or both co-encapsulated into lipid nanoparticles (LNP) in the liver in vivo using real-time intravital imaging is investigated. Although both KC and hepatocytes demonstrate comparable high and rapid uptake of mRNA-LNP and siRNA-LNP in vivo, the translation of Egfp mRNA occurs exclusively in hepatocytes during intravital imaging.
View Article and Find Full Text PDFThe crucial quality marker of Panax ginseng: Glycosylated modified ribonuclease-like storage protein.
Int J Biol Macromol
December 2024
State Key Laboratory of Organometallic Chemistry and National Center for Organic Mass Spectrometry in Shanghai, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, PR China. Electronic address:
Panax ginseng C.A.Mey is a famous natural herbal medicine worldwide.
View Article and Find Full Text PDFAn arabinan from Citrus grandis fruits alleviates ischemia/reperfusion-induced myocardial cell apoptosis via the Nrf2/Keap1 and IRE1/GRP78 signaling pathways.
Carbohydr Polym
January 2025
Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, The Affiliated Dongguan Songshan Lake Central Hospital, School of Pharmacy, Guangdong Medical University, Dongguan 523808, China. Electronic address:
Citrus grandis fruit is a famous traditional Chinese medicine with various bioactivities, including cardioprotective effects. Polysaccharides are one of the key active ingredients responsible for its cardioprotective effects. This study aimed to investigate the structure and cardioprotective effect of a homogeneous polysaccharide from C.
View Article and Find Full Text PDFEstablishment and Characterization of a Novel Pleuropulmonary Blastoma Cell Line.
Genes Chromosomes Cancer
October 2024
Division of Pathology, Kanagawa Children's Medical Center, Yokohama, Japan.
Purpose: Pleuropulmonary blastoma (PPB) is an infrequently encountered childhood malignant intrathoracic neoplasm associated with unfavorable clinical behavior. Since a well-characterized preclinical model is essential for developing competent agents for PPB, we aim to establish and characterize the world's first cell line of PPB, and attempt to perform the cytotoxicity assay on the PPB cell line.
Experimental Design: The index case is a 2-year-old female who developed a right thoracic tumor that was surgically removed and treated with multi-agent chemotherapy.
Discovery of Substituted 5-(2-Hydroxybenzoyl)-2-Pyridone Analogues as Inhibitors of the Human Caf1/CNOT7 Ribonuclease.
Molecules
September 2024
School of Pharmacy and Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK.
The Caf1/CNOT7 nuclease is a catalytic component of the Ccr4-Not deadenylase complex, which is a key regulator of post-transcriptional gene regulation. In addition to providing catalytic activity, Caf1/CNOT7 and its paralogue Caf1/CNOT8 also contribute a structural function by mediating interactions between the large, non-catalytic subunit CNOT1, which forms the backbone of the Ccr4-Not complex and the second nuclease subunit Ccr4 (CNOT6/CNOT6L). To facilitate investigations into the role of Caf1/CNOT7 in gene regulation, we aimed to discover and develop non-nucleoside inhibitors of the enzyme.
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