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Protein overexpression by adeno-associated virus-based gene therapy products in cardiomyocytes induces endoplasmic reticulum stress and myocardial degeneration in mice.
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Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., 1-16-13 Kita-Kasai, Edogawa-ku, Tokyo 134-8630, Japan.
Article Synopsis
- Gene therapy using adeno-associated virus (AAV) vectors can lead to cardiotoxicity, which may stem from immune reactions and other poorly understood mechanisms.
- In a study with male mice treated with an AAV-based gene therapy product (product X), significant heart damage was observed, including cardiomyocyte hypertrophy and fibrosis, 14 days after treatment.
- The analysis indicated that the cardiac damage might be linked to endoplasmic reticulum (ER) stress due to the overexpression of a transgenic protein, activating cellular stress responses that could contribute to the toxicity of AAV-based gene therapies.
Human salivary histatin 1 regulating IP3R1/GRP75/VDAC1 mediated mitochondrial-associated endoplasmic reticulum membranes (MAMs) inhibits cell senescence for diabetic wound repair.
Free Radic Biol Med
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Department of Orthopaedics, The First Affiliated Hospital of Jinan University, No. 613 11 West Huangpu Avenue, Tianhe District, Guangzhou, Guangdong, 510630, China.
Rationale: Difficulty in skin wound healing is a concern for diabetic patients across the world. Impaired mitochondrial dysfunction and aging-related vascular dysfunction in human umbilical vein endothelial cells (HUVECs) caused by oxidative stress are major impediments to diabetic wound healing. However, research on skin repair at the mechanistic level by improving mitochondrial function and inhibiting oxidative stress-induced HUVEC senescence remains lacking.
View Article and Find Full Text PDFImmunoexpression Pattern of Autophagy-Related Proteins in Human Congenital Anomalies of the Kidney and Urinary Tract.
Int J Mol Sci
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Department of Anatomy, School of Medicine, University of Mostar, 88000 Mostar, Bosnia and Herzegovina.
The purpose of this study was to evaluate the spatiotemporal immunoexpression pattern of microtubule-associated protein 1 light chain 3 beta (LC3B), glucose-regulated protein 78 (GRP78), heat shock protein 70 (HSP70), and lysosomal-associated membrane protein 2A (LAMP2A) in normal human fetal kidney development (CTRL) and kidneys affected with congenital anomalies of the kidney and urinary tract (CAKUT). Human fetal kidneys (control, horseshoe, dysplastic, duplex, and hypoplastic) from the 18th to the 38th developmental week underwent epifluorescence microscopy analysis after being stained with antibodies. Immunoreactivity was quantified in various kidney structures, and expression dynamics were examined using linear and nonlinear regression modeling.
View Article and Find Full Text PDFRNA-binding protein PCBP2 regulates pancreatic β cell function and adaptation to glucose.
J Clin Invest
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Institute for Diabetes, Obesity, and Metabolism and Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Article Synopsis
- Glucose is crucial for pancreatic β cell function and understanding how it influences these cells could lead to new treatments for type 2 diabetes (T2D).
- The RNA-binding protein PCBP2 is essential for β cell function, especially during high glucose conditions, as it helps regulate insulin secretion and the expression of related genes.
- Research shows that PCBP2 levels increase in response to glucose but decrease in T2D patients, linking it to gene changes that are important for β cell activity and overall insulin regulation.
Borax affects cellular viability by inducing ER stress in hepatocellular carcinoma cells by targeting SLC12A5.
J Cell Mol Med
May 2024
Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Düzce University, Düzce, Turkey.
Hepatocellular carcinoma (HCC) presents a persistent challenge to conventional therapeutic approaches. SLC12A5 is implicated in an oncogenic capacity and facilitates the progression of cancer. The objective of this investigation is to scrutinize the inhibitory effects of borax on endoplasmic reticulum (ER)-stress and apoptosis mediated by SLC12A5 in HepG2 cells.
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