Biosafety and efficacy considerations that impede clinical application of gene therapy could be addressed by nonviral ex vivo cell therapy, utilizing transgenic cells that have been comprehensively pre-evaluated for genotoxic potential and transgene expression. We evaluated the genotoxic potential of phiC31 bacteriophage integrase-mediated transgene integration in cord-lining epithelial cells (CLECs) readily cultured from the outer membrane of human umbilical cords, by sequencing and mapping integration sites, spectral karyotyping, high-resolution genome copy number, transcriptome, and transgene copy number analyses and in vivo tumorigenicity. Of 44 independent integration events, <5% were exonic and 85% of modified cells had integrated
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2911251 PMC http://dx.doi.org/10.1038/mt.2010.61 DOI Listing Publication Analysis
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Mol Ther
January 2025
Nucleic Acid Chemistry and Engineering Unit, Okinawa Institute of Science and Technology Graduate University, Onna, Okinawa 904 0495, Japan. Electronic address:
Transgene expression in stem cells is a powerful means of regulating cellular properties and differentiation into various cell types. However, existing vectors for transgene expression in stem cells suffer from limitations such as the need for genomic integration, the transient nature of gene expression, and the inability to temporally regulate transgene expression, which hinder biomedical and clinical applications. Here we report a new class of RNA virus-based vectors for scalable and integration-free transgene expression in mouse embryonic stem cells (mESCs).
View Article and Find Full Text PDFNutrients
December 2024
Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
: Endothelial peroxisome proliferator-activated receptor gamma (PPARγ) regulates adipose tissue by facilitating lipid uptake into white adipocytes, but the role of endothelial lipid transport in systemic energy balance remains unclear. Ghrelin conveys nutritional information through the central nervous system and increases adiposity, while deficiency in its receptor, growth hormone secretagogue-receptor (GHSR), suppresses adiposity on a high-fat diet. This study aims to examine the effect of ghrelin/GHSR signaling in the endothelium on lipid metabolism.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
State Key Laboratory of Tree Genetics and Breeding, Beijing Forestry University, Beijing 100083, China; National Engineering Research Center of Tree Breeding and Ecological Restoration, Beijing Forestry University, Beijing 100083, China; Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China. Electronic address:
Populus tomentosa, a deciduous tree species distinguished by its significant economic and ecological value, enjoys a wide-ranging natural distribution. However, its long juvenile period severely restricts the advancement of breeding work. The SPL gene family, a distinctive class of transcription factors exclusive to the plant kingdom, is critical in various processes of plant growth and development.
View Article and Find Full Text PDFCell Rep
January 2025
Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address:
Hepatic stellate cells (HSCs) are key drivers of local fibrosis. Adiponectin, conventionally thought of as an adipokine, is also expressed in quiescent HSCs. However, the impact of its local expression on the progression of liver fibrosis remains unclear.
View Article and Find Full Text PDFCNS Neurol Disord Drug Targets
January 2025
School of Medicine, Foshan University, Foshan, 528000, China.
Introduction: Neuroinflammation derived from the activation of the microglia is considered a vital pathogenic factor of Alzheimer's Disease (AD). T-006, a tetramethylpyrazine derivative, has been found to alleviate cognitive deficits via inhibiting tau expression and phosphorylation in AD transgenic mouse models. Recently, T-006 has been proven to dramatically decrease the levels of total Amyloid β (Aβ) peptide and Glial Fibrillary Acidic Protein (GFAP) and suppress the expression of ionized calcium binding adaptor molecule-1 (Iba-1) in APP/PS1 mice.
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