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Species-specific in vivo exposure assessment and in vivo-in vitro correlation of the carboxylate esters prodrug HD56 targeting FK506 binding proteins: The pivotal role of humanized mice.
Drug Metab Dispos
February 2025
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China. Electronic address:
HD561, which was designed to enhance nerve growth, was re-engineered into HD56, a carboxylic acid ester prodrug. The goal of this study was to compare the druggability, species differences, and the correlation between in vitro and in vivo transformation of HD56 to HD561 from a pharmacokinetic (PK) perspective, offering a scientific basis for HD56's clinical research. The bidirectional transmembrane transport of HD56 and HD561 was investigated using Caco-2 cells and LLC-PK1 cells overexpressing MDR1 monolayer cells.
View Article and Find Full Text PDFHGF-DPSCs ameliorate asthma by regulating CCR1 Th2 cells responses in mice pulmonary mucosa.
Cytotherapy
February 2025
Health Management Institute, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China. Electronic address:
Asthma, a prevalent allergic disease affecting approximately 300 million individuals globally, remains a significant public health challenge. Mesenchymal stromal cells (MSCs) and hepatocyte growth factor (HGF), both recognized for their immunomodulatory properties, hold therapeutic potential for asthma. However, their precise mechanisms remain underexplored.
View Article and Find Full Text PDFEffects and potential pathways of goose astrovirus infection on gosling hepatic lipid metabolism.
Front Microbiol
February 2025
Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, Jiangxi, China.
Introduction: The adverse effects of goose astrovirus (GoAstV) on avian growth and health have been widely reported previously, while the stress reactions and corresponding mechanism of gosling liver responding to GoAstV infection remain not entirely clear.
Methods: One-day-old goslings inoculated subcutaneously with 2 × 10 TCID of GoAstV were employed as an experimental model, and the potential effects and pathways of GoAstV infection on gosling liver functions were investigated by combining the morphological, biochemical and RNA sequencing (RNA-seq) techniques.
Results: Structural and functional impairments were found in gosling livers post the virus infection, as characterized by the histological alterations in liver index and morphology of hepatic cord and sinuses, as well as the abnormal expression patterns of the cellular antioxidant, inflammation and apoptosis-related genes.
Melatonin, also known as the pineal hormone, is secreted by the pineal gland and primarily regulates circadian rhythms. Additionally, it possesses immunomodulatory properties and anticancer effects. However, its specific mechanism in hepatocellular carcinoma (HCC) remains unclear, particularly regarding its effect on HCC-mediated immune escape through PD-L1 expression.
View Article and Find Full Text PDFVDAC2 and Bak scarcity in liver mitochondria enables targeting hepatocarcinoma while sparing hepatocytes.
Nat Commun
March 2025
MitoCare Center, Department of Pathology and Genomic Medicine and Thomas Jefferson University, Philadelphia, PA, USA.
Differences between normal tissues and invading tumors that allow tumor targeting while saving normal tissue are much sought after. Here we show that scarcity of VDAC2, and the consequent lack of Bak recruitment to mitochondria, renders hepatocyte mitochondria resistant to permeabilization by truncated Bid (tBid), a Bcl-2 Homology 3 (BH3)-only, Bcl-2 family protein. Increased VDAC2 and Bak is found in most human liver cancers and mitochondria from tumors and hepatic cancer cell lines exhibit VDAC2- and Bak-dependent tBid sensitivity.
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