One limit to successful receptor-mediated gene delivery is the exit of the endocytosed material from the endosome. We demonstrate here the delivery of marker genes to tissue culture cells using a modification of the receptor-mediated gene delivery technique that exploits the endosomolytic activity of defective adenovirus particles. In particular, greater than 90% of the transfected-cell population is found to express a beta-galactosidase gene, and, most importantly, this high level of expression can be obtained with psoralen-inactivated virus particles. Furthermore, because the delivered gene is not carried within the genome of the adenovirus particle, the size constraints are relieved, and we can, therefore, show the delivery of a 48-kilobase cosmid DNA molecule.
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http://dx.doi.org/10.1073/pnas.89.13.6094 | DOI Listing |
PLoS One
January 2025
Nephrological Department, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
Secondary hyperparathyroidism (sHPT) is a significant clinical complication of CKD leading to bone abnormalities and cardiovascular disease. Current treatment based on activating the parathyroid calcium-sensing receptor (CaSR) using calcimimetics such as Cinacalcet, aims to decrease plasma PTH levels and inhibit the progression of parathyroid hyperplasia. In the present study, we found significant diurnal rhythmicity of Casr, encoding the Cinacalcet drug target in hyperplastic parathyroid glands (p = 0.
View Article and Find Full Text PDFTissue Eng Part B Rev
January 2025
Department of Orthopedics, Pudong New Area Gongli Hospital, Shanghai, China.
Osteoporosis, affecting the entire skeletal system, can cause bone mass to diminish, thereby reducing bone strength and elevating fracture risk. Fracture nonunion and bone defects are common in patients with fractures, and pain and loss of function may cause serious distress. The search for a new therapeutic strategy is essential because of the limited therapeutic options available.
View Article and Find Full Text PDFRev Med Chil
May 2024
Departamento de Nefrología, Clínica Dávila, Santiago, Chile.
Unlabelled: Uremic leontiasis ossia (ULO) is a rare manifestation of renal osteodystrophy in) patients with end-stage chronic kidney disease (CKD) and secondary hyperparathyroidism (SHPTH). It occurs due to increased osteoclastic activity secondary to high plasmatic parathyroid hormone (PTH) levels. This leads to bone deformation with thickening and massive enlargement of the cranial vault, resulting in a leonine face appearance.
View Article and Find Full Text PDFFASEB J
January 2025
Department of Biochemistry and Molecular Biology, Institute of Marine and Environmental Technology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Molecular chaperones play critical roles in post-translational maintenance in protein homeostasis. Previous studies have shown that loss of Smyd1b function results in defective myofibril organization and dramatic upregulation of heat shock protein gene (hsp) expression in muscle cells of zebrafish embryos. To investigate the molecular mechanisms and functional importance of this stress response, we characterized changes of gene expression in smyd1b knockdown and knockout embryos using RNA-seq.
View Article and Find Full Text PDFBioact Mater
April 2025
Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, 210029, Nanjing, China.
Bone defect repair remains a great challenge in the field of orthopedics. Human body essential trace element such as copper is essential for bone regeneration, but how to use it in bone defects and the underlying its mechanisms of promoting bone formation need to be further explored. In this study, by doping copper into mesoporous bioactive glass nanoparticles (Cu-MBGNs), we unveil a previously unidentified role of copper in facilitating osteoblast mitophagy and mitochondrial dynamics, which enhance amorphous calcium phosphate (ACP) release and subsequent biomineralization, ultimately accelerating the process of bone regeneration.
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