Background: Many complications following liver transplantation are linked to ischemia-reperfusion injury. Activation of the pregnane X receptor (PXR) has been shown to alleviate this process in animal models. The aim of this retrospective study was to investigate the effect of early activation of human PXR (hPXR) on postoperative complications and survival following liver transplantation.
Methods: The study included deceased donor liver transplants at a single center over 6 years. Estimated hPXR activation value on day 7 (EPAV ) was calculated per patient based on potency/total dose of known hPXR-activating drugs administered in the first week post-transplantation. Patients were divided into low and high hPXR activation groups based on EPAV .
Results: Overall, 240 liver transplants were included. Average EPAV was significantly lower in patients who developed anastomotic biliary strictures (17.7 ± 5.5 vs 35.1 ± 5.7 in stricture-free patients; P = .03) and sepsis (16.4 ± 7.1 vs 34.9 ± 5.5; P = .04). Patient survival was significantly improved in the high hPXR group (5-year survival: 88.7% ± 3.8% versus 70.7% ± 5.8% [low hPXR]; P = .023). Regression analysis identified EPAV as a significant independent predictor of patient survival.
Conclusion: hPXR activation within the first week of liver transplantation is a prognostic indicator of patient survival, possibly due to the associated lower biliary stricture and infection rates.
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http://dx.doi.org/10.1111/ctr.13734 | DOI Listing |
Front Pharmacol
October 2024
National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, United States.
Pregnane X receptor (PXR) is a xenobiotic-sensing nuclear receptor with a well-established role in regulating drug metabolism and clearance. Recent studies have shown that PXR is involved in cell proliferation, apoptosis, immune response, and energy homeostasis. It is important to identify compounds that may modulate PXR activity to prevent drug-drug interactions, distinguish chemicals which could potentially generate toxicity, and identify compounds for further development towards therapeutic usage.
View Article and Find Full Text PDFJ Nat Prod
October 2024
School of Pharmacy, Lanzhou University, Lanzhou 730000, Gansu, P. R. China.
We report here the orchestration of molecular ion networking (MoIN) and a set of computationally assisted structural elucidation approaches in the discovery and assignment of a new class of rearranged 4,5--abietane diterpenoids including serra A (), which possesses an unusual 6/6/5/5 fused-ring skeleton system, together with two previously unreported diterpenoids serras B-C (-) and five known compounds were isolated from (). The structures were elucidated by spectroscopic analysis in conjunction with computationally assisted structure elucidation tools. , serras A-C (-) bind well to PXR, suggesting their potential role in reducing inflammation.
View Article and Find Full Text PDFBiochem J
September 2024
Laboratory of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526 Japan.
Pregnane X receptor (PXR) is a xenobiotic-sensing nuclear receptor that plays a key role in drug metabolism. Recently, PXR was found to attenuate the development of liver cancer by suppressing epithelial-mesenchymal transition (EMT) in liver cancer cells in a mouse model of two-stage chemical carcinogenesis. To elucidate the role of PXR in the EMT of liver cancer cells, we focused on its role in hepatic stellate cells (HSCs), which are components of the tumor microenvironment in hepatocellular carcinoma (HCC).
View Article and Find Full Text PDFEnviron Int
August 2024
College of Chemistry and Chemical Engineering, Qiqihar University, Qiqihar, 161006, China. Electronic address:
Acta Pharmacol Sin
October 2023
Health Science Center, East China Normal University, Shanghai, 200241, China.
Renal fibrosis is a common pathological feature of chronic kidney disease (CKD) with various etiologies, which seriously affects the structure and function of the kidney. Pregnane X receptor (PXR) is a member of the nuclear receptor superfamily and plays a critical role in regulating the genes related to xenobiotic and endobiotic metabolism in mammals. Previous studies show that PXR is expressed in the kidney and has protective effect against acute kidney injury (AKI).
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