Article
Chemistry, Medicinal
Nanna Tynelius, Christoffer Bundgaard, Claudia E. Mueller
Summary: Hepatocyte cocultures like HepatoPac have advantages in enzymatic activity over time, making them more frequently used for assessing the intrinsic clearance of slowly metabolised drugs. However, the high cost and practical limitations hinder the inclusion of quality control compounds in studies, resulting in the lack of monitoring of important metabolic enzymes. This study evaluates the use of a cocktail approach of quality control compounds in the human HepatoPac system to ensure adequate activity of major metabolising enzymes.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Nuria Oliva-Vilarnau, Sabine U. Vorrink, Florian A. Buettner, Timo Heinrich, Janike Sensbach, Isabel Koscielski, Dirk Wienke, Carl Petersson, Dominique Perrin, Volker M. Lauschke
Summary: This study tested the induction potential of various YAP/TEAD inhibitors with different modes of action and TEAD isoform selectivity profiles on CYP in primary human hepatocytes. The results showed that YAP/TEAD inhibition can broadly induce CYP in 2D monolayers, but only marginally in 3D spheroids. RNA-Seq analysis revealed increased YAP/TEAD signaling in 2D culture, along with elevated activities of the interacting transcription factors LXR and ESRRA. Inhibition of YAP/TEAD hyperactivation reduced hepatocyte dedifferentiation and increased hepatic functionality.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Yoon-Jee Chae, Min-Soo Kim, Suk-Jae Chung, Mi-Kyung Lee, Kyeong-Ryoon Lee, Han-Joo Maeng
Summary: This study found that calcitriol can induce the expression of certain CYP enzymes in human liver cells in vitro. However, the induction of CYP by calcitriol treatment is considered to be clinically insignificant under typical clinical conditions.
Article
Pharmacology & Pharmacy
Matthew D. Davidson, Joshua Pickrell, Salman R. Khetani
Summary: The study developed a novel physiologically-inspired culture medium that extended the functional lifespan of primary human hepatocytes (PHHs) in vitro, maintaining their morphology, functions, and response to drugs. This culture medium is significant for modeling chronic drug exposure, disease pathogenesis, and cell-based therapies.
Article
Pharmacology & Pharmacy
Fabio Bachmann, Urs Duthaler, Stephan Krahenbuhl
Summary: This study investigated the effect of deglucuronidation on the plasma concentration of the constituents of the Basel phenotyping cocktail. The results showed that deglucuronidation of plasma samples improves the stability of phenotyping results and is necessary to reliably detect CYP induction.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Toxicology
Jing Gao, Yuanjin Zhang, Xueqin Lei, Yuan Xu, Zhenliang Sun, Xin Wang
Summary: Hydroxygenkwanin (HGK), a natural flavonoid extracted from Daphne genkwa Sieb.et Zucc., exhibits a wide range of pharmacological activities and it competitively inhibits CYP1A2 and 2C enzymes. The inhibitory effect of HGK on CYP enzymes is weaker than diosmetin, possibly due to the substitution of hydroxyl and methoxy in the A and B rings of the flavone skeleton, which may lead to potential drug-drug interactions and toxicity.
TOXICOLOGY IN VITRO
(2022)
Article
Gastroenterology & Hepatology
Alexander Laemmle, Martin Poms, Bernadette Hsu, Mariia Borsuk, Veronique Rufenacht, Joshua Robinson, Martin C. Sadowski, Jean-Marc Nuoffer, Johannes Haberle, Holger Willenbring
Summary: The study identified the critical role of AQP9 in functional urea metabolism and successfully established an in vitro liver disease model of OTCD using hiPSC-Heps. By manipulating hiPSC-Heps, OTC activity and ureagenesis could be corrected, potentially improving the therapy of OTCD through genotype/phenotype correlation and drug screens.
Article
Multidisciplinary Sciences
Yanyan Hu, Yuanyuan Yang, Pengcheng Tan, Yuxia Zhang, Mengxia Han, Jiawei Yu, Xin Zhang, Zeran Jia, Dan Wang, Ke Yao, Huanhuan Pang, Zeping Hu, Yinqing Li, Tianhua Ma, Kang Liu, Sheng Ding
Summary: Researchers have successfully induced and maintained totipotent stem cells in mice using a combination of three small molecules. These chemically induced totipotent stem cells resembled early mouse embryo cells at the transcriptome, epigenome, and metabolome levels. They were able to produce both embryonic and extraembryonic cells in vitro and in teratoma, and when injected into 8-cell embryos, they contributed to both embryonic and extraembryonic lineages with high efficiency. This study provides a defined in vitro system for manipulating and understanding the totipotent state and the development of multicellular organisms from non-germline cells.
Article
Toxicology
Aafke W. F. Janssen, Loes P. M. Duivenvoorde, Deborah Rijkers, Rosalie Nijssen, Ad A. C. M. Peijnenburg, Meike van der Zande, Jochem Louisse
Summary: The study evaluated the expression of CYP enzymes and chemical-induced changes in a hiPSC-derived HIO model, showing higher gene expression levels of important intestinal CYP enzymes in HIOs compared to other models. CYP3A4 activity was induced by phenobarbital and rifampicin in HIOs, indicating the potential of hiPSC-based HIOs as a useful in vitro intestinal model for studying the biotransformation of chemicals in the intestine.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Pharmacology & Pharmacy
Na Yin, Wenjun Zhang, Runxiu Wei, Qiang Yang, Fengming He, Ling Guo, Min Feng
Summary: Acute liver failure (ALF) is a fatal and critical hepatic disease. Oxidative stress, inflammation storm, and hepatocyte death are crucial in its development. A study found that a cocktail activator could alleviate hepatocyte damage, remodel the damage microenvironment, promote hepatocyte expansion, and favor liver regeneration.
ASIAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Erkka Jarvinen, Helen S. Hammer, Oliver Poetz, Magnus Ingelman-Sundberg, Tore Bjerregaard Stage
Summary: The study assessed the usage of 3D spheroid primary human hepatocytes (PHHs) for studying the induction of important cytochrome P450 enzymes and drug transporters. The results showed that the 3D spheroid PHHs model can effectively investigate the mRNA and protein induction of hepatic drug-metabolizing enzymes and transporters, providing a solid basis for clinically relevant research.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Pharmacology & Pharmacy
Erkka Jarvinen, Ann-Cathrine Dalgard Dunvald, Martin Thomsen Ernst, Helen S. Hammer, Oliver Poetz, Anton Pottegard, Tore B. Stage
Summary: This study investigated the effect of dicloxacillin on the efficacy of warfarin and assessed its induction of cytochrome P450 enzymes. The results showed that dicloxacillin can induce CYPs and reduce the clinical efficacy of warfarin in patients. Therefore, caution is warranted for warfarin patients that initiate dicloxacillin or flucloxacillin, especially for a long-term treatment of endocarditis.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Haoqian Zhang, Furong Zhao, Yong Liu, Ying Li, Haiwen Liu, Hongzhi Sun
Summary: This research aimed to determine the inhibitory potential of eleven CPs on nine human CYP isoforms. The results showed that trichlorophenols, tetrachlorophenols, and PCP strongly inhibited CYP2C8 and CYP2C9, and clear structure-activity relationships of CPs on CYP2C8 were defined. Overall, CPs were found to cause inhibitory effects on CYP isoforms in vitro.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Dhwanil A. Dalwadi, Andrea Calabria, Amita Tiyaboonchai, Jeffrey Posey, Willscott E. Naugler, Eugenio Montini, Markus Grompe
Summary: Research found a high frequency of chromosomal integrations of recombinant adeno-associated viral vectors in liver cells, with most inserted sequences heavily rearranged and accompanied by deletions of host genomic sequences at integration sites. This indicates a certain risk associated with rAAV integration.
Article
Engineering, Environmental
Mengchao Ding, Haoyu Chen, Tianyi Wang, Lijuan Wu, Kai Shao, Lei Han, Xiaoying Kong, Jinsheng Shi
Summary: A PRDH nanosystem was prepared to attack tumor cells through photothermal therapy and chemodynamic therapy, as well as removing protection of sticky factors and triggering tumor recognition by immune cells. The nanosystem released Rg3 and catalyzed CO2 into CO, inhibiting the expression of ICAM-1 and promoting the exposure of the MUC1 antigen, leading to targeted elimination of tumor cells by immune cells.
CHEMICAL ENGINEERING JOURNAL
(2023)
Article
Clinical Neurology
Jean-Marie Nicolas, Jonas Hannestad, Daniel Holden, Sophie Kervyn, Nabeel Nabulsi, Dominique Tytgat, Yiyun Huang, Hugues Chanteux, Ludovicus Staelens, Alain Matagne, Francois-Xavier Mathy, Joel Mercier, Armel Stockis, Richard E. Carson, Henrik Klitgaard
Article
Clinical Neurology
Armel Stockis, Hugues Chanteux, Maria Rosa, Paul Rolan
Article
Pharmacology & Pharmacy
Maria Rosa, Pierre Bonnaillie, Hugues Chanteux
Article
Pharmacology & Pharmacy
Eric Helmer, Jean-Marie Nicolas, Jeff Long, Ad F. Roffel, Emma Jones, Hugues Chanteux, Nieves Diaz, Holly Garratt, Tjerk Bosje
JOURNAL OF CLINICAL PHARMACOLOGY
(2017)
Article
Chemistry, Multidisciplinary
Johan Nicolai, Louise Thevelin, Qi Bing, Bruno Stieger, Hugues Chanteux, Patrick Augustijns, Pieter Annaert
PHARMACEUTICAL RESEARCH
(2017)
Article
Biochemical Research Methods
Emmanuel Bourgogne, Benoit Culot, Sylvie Dell'Aiera, Hugues Chanteux, Armel Stockis, Jean-Marie Nicolas
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2018)
Article
Pharmacology & Pharmacy
Jean-Marie Nicolas, Hugues Chanteux, Johan Nicolai, Frederic Brouta, Delphine Viot, Marie-Luce Rosseels, Eric Gillent, Pierre Bonnaillie, Francois-Xavier Mathy, Jeff Long, Eric Helmer
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2020)
Article
Pharmacology & Pharmacy
Hugues Chanteux, Maria Rosa, Claude Delatour, Johan Nicolai, Eric Gillent, Sylvie Dell'Aiera, Anna-Lena Ungell
DRUG METABOLISM AND DISPOSITION
(2020)
Review
Clinical Neurology
Brian D. Moseley, Hugues Chanteux, Jean-Marie Nicolas, Cedric Laloyaux, Barry Gidal, Armel Stockis
Article
Pharmacology & Pharmacy
Trevor N. Johnson, Khaled Abduljalil, Jean-Marie Nicolas, Pierandrea Muglia, Hugues Chanteux, Johan Nicolai, Eric Gillent, Miranda Cornet, David Sciberras
Summary: This study developed a PBPK model for radiprodil in adults and successfully applied it to guide individualized dosing in a clinical trial for infants. The predicted doses for infants were in good agreement with observed concentration-time data.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Marie-Lynn Cuypers, Hugues Chanteux, Eric Gillent, Pierre Bonnaillie, Kenneth Saunders, Claire Beckers, Claude Delatour, Sylvie Dell'Aiera, Anna-Lena Ungell, Johan Nicolai
DRUG METABOLISM AND DISPOSITION
(2020)
Article
Chemistry, Multidisciplinary
Johan Nicolai, Helene Chapy, Eric Gillent, Kenneth Saunders, Anna-Lena Ungell, Jean-Marie Nicolas, Hugues Chanteux
PHARMACEUTICAL RESEARCH
(2020)
Article
Pharmacology & Pharmacy
Francesca Toselli, Melanie Golding, Johan Nicolai, Eric Gillent, Hugues Chanteux
Summary: Despite the challenges in predicting the pharmacokinetics of substrates metabolized by aldehyde oxidase (AO), this study successfully built a simple, semi-quantitative model to correlate in vitro and in vivo data and predict blood clearance. This model is particularly valuable for high-clearance compounds.
Review
Pharmacology & Pharmacy
Jean-Marie Nicolas, Francois Bouzom, Chanteux Hugues, Anna-Lena Ungell
BIOPHARMACEUTICS & DRUG DISPOSITION
(2017)
Article
Pharmacology & Pharmacy
Armel Stockis, Shikiko Watanabe, Andre J. Scheen, Dominique Tytgat, Brigitte Gerin, Maria Rosa, Hugues Chanteux, Jean-Marie Nicolas
DRUG METABOLISM AND DISPOSITION
(2016)