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Hepatic conditioning results in better lung endothelial cell preservation under hypoxic environment in vitro.
Int J Artif Organs
January 2025
Departments of Surgery and Bioengineering, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Background: as we look to extend lung perfusion times (EVLP) to improve preservation, the metabolic activity of the lungs will require support from other organ functions. Active functional liver support, including detoxification, synthesis, and regulation, can improve lung preservation during EVLP. This study aimed to demonstrate the effects of hepatic conditioning of the EVLP perfusate on lung endothelium, via the receptor of advanced glycation end-products (RAGE)-nuclear-factor-κB (NF-κB) signaling in vitro.
View Article and Find Full Text PDFHepatocyte-derived liver progenitor-like cells attenuate liver cirrhosis via induction of apoptosis in hepatic stellate cells.
Hepatol Commun
February 2025
Department of Anesthesiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Background: Cell therapy demonstrates promising potential as a substitute therapeutic approach for liver cirrhosis. We have developed a strategy to effectively expand murine and human hepatocyte-derived liver progenitor-like cells (HepLPCs) in vitro. The primary objective of the present study was to apply HepLPCs to the treatment of liver cirrhosis and to elucidate the underlying mechanisms responsible for their therapeutic efficacy.
View Article and Find Full Text PDFMulti-omics analysis reveals distinct gene regulatory mechanisms between primary and organoid-derived human hepatocytes.
Dis Model Mech
January 2025
Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Science, Radboud University, Nijmegen 6525GA, The Netherlands.
Hepatic organoid cultures are a powerful model to study liver development and diseases in vitro. However, hepatocyte-like cells differentiated from these organoids remain immature compared to primary human hepatocytes (PHHs), which are the benchmark in the field. Here, we applied integrative single-cell transcriptome and chromatin accessibility analysis to reveal gene regulatory mechanisms underlying these differences.
View Article and Find Full Text PDFFatty acid oxidation-induced HIF-1α activation facilitates hepatic urate synthesis through upregulating NT5C2 and XDH.
Life Metab
October 2024
CAS Key Laboratory of Nutrition, Metabolism, and Food Safety, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences (CAS), Shanghai 200031, China.
Dyslipidemia affects approximately half of all people with gout, and prior Mendelian randomization analysis suggested a causal role for elevated triglycerides in hyperuricemia (HU), but the underlying mechanisms remain elusive. We hypothesize that dyslipidemia promotes hepatic urate biosynthesis in HU and gout and fatty acid (FA) oxidation (FAO) drives this process. Here we developed a targeted metabolomics to quantify major metabolites in purine metabolic pathway in the sera of a human cohort with HU, gout, and normaluricemic controls.
View Article and Find Full Text PDFSurvival Analysis of Liver Transplants in Patients with Acute Liver Failure from Acetaminophen and Mushroom Toxicity.
Ann Transplant
January 2025
Department of General Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
BACKGROUND Acute liver failure (ALF) remains a critical concern, accounting for about 8% of all liver transplants, with acetaminophen overdose contributing to nearly half of these cases. Besides synthetic toxins, natural toxins such as phallotoxin from Amanita phalloides mushrooms also lead to severe hepatocyte damage. This study investigates the outcomes of liver transplantation (LT) as a life-saving intervention in patients suffering from ALF due to acetaminophen and Amanita phalloides poisoning.
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