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Modeling early pathophysiological phenotypes of diabetic retinopathy in a human inner blood-retinal barrier-on-a-chip.
Nat Commun
February 2024
Roche Pharma Research and Early Development, Cardiovascular, Metabolism, Immunology, Infectious Diseases and Ophthalmology, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Diabetic retinopathy (DR) is a microvascular disorder characterized by inner blood-retinal barrier (iBRB) breakdown and irreversible vision loss. While the symptoms of DR are known, disease mechanisms including basement membrane thickening, pericyte dropout and capillary damage remain poorly understood and interventions to repair diseased iBRB microvascular networks have not been developed. In addition, current approaches using animal models and in vitro systems lack translatability and predictivity to finding new target pathways.
View Article and Find Full Text PDFBiomarkers of Type IV Collagen Turnover Reflect Disease Activity in Patients with Early-Stage Non-Alcoholic Fatty Liver (NAFL).
Biology (Basel)
August 2023
NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham NG7 2UH, UK.
Background: Identification of progressive liver disease necessitates the finding of novel non-invasive methods to identify and monitor patients in need of early intervention. Investigating patients with early-liver injury may help identify unique biomarkers. Early-liver injury is characterized by remodeling of the hepatocyte basement membrane (BM) of the extracellular matrix.
View Article and Find Full Text PDFElephant TP53-RETROGENE 9 induces transcription-independent apoptosis at the mitochondria.
Cell Death Discov
February 2023
Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Approximately 20 TP53 retrogenes exist in the African and Asian elephant genomes (Loxodonta Africana, Elephas Maximus) in addition to a conserved TP53 gene that encodes a full-length protein. Elephant TP53-RETROGENE 9 (TP53-R9) encodes a p53 protein (p53-R9) that is truncated in the middle of the canonical DNA binding domain. This C-terminally truncated p53 retrogene protein lacks the nuclear localization signals and oligomerization domain of its full-length counterpart.
View Article and Find Full Text PDFDanger signals released during cold ischemia storage activate NLRP3 inflammasome in myeloid cells and influence early allograft function in liver transplantation.
EBioMedicine
January 2023
Molecular Inflammation Group, University Clinical Hospital Virgen de la Arrixaca, Biomedical Research Institute of Murcia (IMIB-Pascual Parrilla), 30120, Murcia, Spain. Electronic address:
Background: Innate immunity plays a fundamental role in solid organ transplantation. Myeloid cells can sense danger signals or DAMPs released after tissue or cell damage, such as during ischemia processes. This study aimed to identify DAMPs released during cold ischemia storage of human liver and analyze their ability to activate the inflammasome in myeloid cells and the possible implications in terms of short-term outcomes of liver transplantation.
View Article and Find Full Text PDFPlasma Kallikrein-Activated TGF-β Is Prognostic for Poor Overall Survival in Patients with Pancreatic Ductal Adenocarcinoma and Associates with Increased Fibrogenesis.
Biomolecules
September 2022
Nordic Bioscience, 2730 Herlev, Denmark.
Pancreatic ductal adenocarcinoma (PDAC) is a hard-to-treat cancer due to the collagen-rich (fibrotic) and immune-suppressed microenvironment. A major driver of this phenomenon is transforming growth factor beta (TGF-β). TGF-β is produced in an inactive complex with a latency-associated protein (LAP) that can be cleaved by plasma kallikrein (PLK), hereby releasing active TGF-β.
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