CYP3A5 and POR gene polymorphisms as predictors of infection and graft rejection in post-liver transplant patients treated with tacrolimus – a cohort study
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Functional assessment of autologous tissue expansion grafts for vaginal reconstruction in a rabbit model
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Clostridioides difficile infection induces a pro-inflammatory and pro-steatotic metabolic state in liver
Using a multi-omics approach, this study investigated Clostridioides difficile infection (CDI) as a direct contributor to hepatic dysmetabolism. Fifty-four C57BL/6 mice were divided into Control, Antibiotic control (Abx), and C. difficile-infected (C. diff) groups. The Abx and C. diff groups received antibiotics to induce gut dysbiosis, followed by C. difficile challenge in C. diff group. Mice were euthanized after 48 h to collect samples for multi-omics analyses. Liver metabolomics and transcriptomics pathway analyses revealed significant alterations in lipid metabolism, including dysregulation in glycerolipid, steroid, and energy metabolisms in C. difficile-infected mice. Metabolites and pathways associated with oxidative stress and inflammation were enriched. Gut metagenome-liver metabolome correlation analysis identified specific bacterial species correlating with differentially enriched liver metabolites involved in oxidative stress, amino acid, and uric acid metabolism. CDI triggers metabolic shifts that could facilitate steatosis and inflammation, suggesting that CDI could be a risk factor for metabolic liver diseases.
Correction to: A pharmacogenomic study on the pharmacokinetics of tacrolimus in healthy subjects using the DMETTM Plus platform
Introduction Although rs776746 T > C (also known as CYP3A5*3), which is a nonfunctioning allele of the CYP3A5 gene, is associated with decreased tacrolimus metabolism4, the role…
Advancements in bioengineering for descemet membrane endothelial keratoplasty (DMEK)
Corneal diseases are the third leading cause of blindness worldwide. Descemet’s Membrane Endothelial Keratoplasty (DMEK) is the preferred surgical technique for treating corneal endothelial disorders, relying heavily on high-quality donor tissue. However, the scarcity of suitable donor tissue and the sensitivity of endothelial cells remain significant challenges. This review explores the current state of DMEK, focusing on advancements in tissue engineering as a promising solution to improve outcomes and address donor limitations.
Plasma concentrations of venetoclax and Pharmacogenetics correlated with drug efficacy in treatment naive leukemia patients: a retrospective study
Venetoclax (VEN) was the only Bcl-2 inhibitor approved yet and showed large differences in clinical efficacy. The aim of the study was to explore the relationships between the plasma concentration and efficacy of VEN, and identify potential influencing factors. A retrospective cohort study was conducted and a total of 76 trough (C0h) and 91 6 h post-dose plasma concentration (C6h) blood concentrations of VEN were collected in 54 patients. C6h/D concentration of VEN was found to be significantly correlated with treatment efficacy (p = 0.006) in leukemia patients with good or intermediate prognosis stratification. A ROC curve was then established and the cut-off value was calculated as 0.2868 μg/ml (AUC = 0.7097, p = 0.1081). Besides, patients co-administered with triazoles or carrying CYP3A5 rs776746 AA/AG genotypes were prone to induce higher VEN plasma concentration regardless of whether VEN dosage was reduced or not. Through LASSO-logistic regression and nomogram analysis, chemotherapy regimens and neutrophil percentages were identified as the critical elements that may predict drug response. Above all, in addition to identify prognostic stratification, AML patients taken with VEN were suggested to test plasma concentration routinely so as to achieve desired efficacy, especially when co-administered with triazoles or carried with CYP3A5 rs776746 AA/AG.
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