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
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
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
Gastroenterology & Hepatology
Takayuki Miyoshi, Masaaki Hidaka, Daisuke Miyamoto, Yusuke Sakai, Shunsuke Murakami, Yu Huang, Takanobu Hara, Akihiko Soyama, Kengo Kanetaka, Takahiro Ochiya, Susumu Eguchi
Summary: The study demonstrates that hepatocytes can be isolated from damaged livers, and human chemically induced liver progenitors (hCLiP) can be obtained through culture and induction. These hCLiPs can differentiate into mature hepatocytes in vitro and have the potential to remodel damaged livers.
JOURNAL OF GASTROENTEROLOGY
(2022)
Article
Pharmacology & Pharmacy
Jakub Havlasek, Jiri Vrba, Martina Zatloukalova, Barbora Papouskova, Martin Modriansky, Jan Storch, Jan Vacek
Summary: This study investigated the biotransformation of phytocannabinoids in human hepatocytes, revealing the different metabolic pathways and susceptibility of the compounds.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jianing Tian, Ruimin Wang, Xiao Yang, Jie Yang, Yifei Zhang, Xuan Li, Hangfei Liang, Shicheng Fan, Yue Gao, Simin Zhang, Xiangyang Qu, Min Huang, Huichang Bi
Summary: This study aimed to explore the features of spatial changes in hepatocytes during PXR-induced liver enlargement. The results showed that hepatocyte hypertrophy mainly occurred around the central vein, while hepatocyte proliferation mainly occurred around the portal vein. Furthermore, the spatial changes in hepatocyte hypertrophy and proliferation were closely associated with the regional expression of related proteins and the regional distribution of triglycerides.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Review
Cell Biology
Ye Xie, Jia Yao, Weilin Jin, Longfei Ren, Xun Li
Summary: The review suggests that hepatocyte-like cells (HLCs), derived from stem cells or modified adult cells, have advantages in cell source and in vitro expansion ability. However, most induced HLCs are still immature and exhibit heterogeneous differentiation, limiting their clinical application. Various methods have been developed to promote the maturation of HLCs for in vivo transplantation and in vitro model establishment.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
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
Multidisciplinary Sciences
Arnav Chhabra, H-H Greco Song, Katarzyna A. Grzelak, William J. Polacheck, Heather E. Fleming, Christopher S. Chen, Sangeeta N. Bhatia
Summary: This study developed a 3D platform for modeling human liver regeneration and found that endothelial cell secretion and cytokine stimulation can promote hepatocyte proliferation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemical Research Methods
Bing-Qing Deng, Meng-Yuan Li, Xian Fu, Ying Luo, Qing Qiao, Jun-Yan Liu
Summary: This study revealed that the cytochrome P450 (CYP) epoxygenase/epoxide hydrolase (EH) axis is activated in IgA nephropathy (IgAN) patients and may be a therapeutic target. Significant changes in CYP/EH-mediated lipid epoxides and diols were observed in the plasma of IgAN patients. The mRNA levels of CYP2C8, CYP2C18, CYP2J2, EPHX1, and EPHX2 were increased in whole blood cells, and the protein expression of these genes was upregulated in kidney tissue from IgAN patients. Cell experiments further supported the importance of the CYPs/EHs axis.
JOURNAL OF PROTEOME RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Estela Villanueva-Badenas, M. Teresa Donato, Laia Tolosa
Summary: Hepatotoxicity or drug-induced liver injury (DILI) is a significant problem in drug development, leading to drug failure and regulatory measures. The development of a co-culture system involving hepatocytes and other cell types has been shown to enhance the understanding and prediction of iDILI. In this study, a co-culture system using HepG2 cells and THP-1-derived macrophages was established and used to evaluate the effects of model iDILI compounds on viability and oxidative stress induction.
Article
Endocrinology & Metabolism
Kyoko Kamoshita, Hirohiko Tsugane, Kiyo-Aki Ishii, Hiroaki Takayama, Xingyu Yao, Halimulati Abuduwaili, Ryota Tanida, Yasumasa Taniguchi, Hein Ko Oo, Guzel Gafiyatullina, Shuichi Kaneko, Seiichi Matsugo, Toshinari Takamura
Summary: Lauric acid induces hepatic insulin resistance by upregulating Selenop. These findings caution the metabolic risk of excessive lauric acid intake, especially in people with hepatic insulin resistance associated with type 2 diabetes.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2022)
Article
Chemistry, Medicinal
Natthaporn Kuendee, Alisa Naladta, Thitianan Kulsirirat, Thunyatorn Yimsoo, Werayut Yingmema, Kanoktip Pansuksan, Korbtham Sathirakul, Sophida Sukprasert
Summary: This study investigated the effects of Lysiphyllum strychnifolium extracts on the gene expression of drug-metabolizing enzymes in rats. The results showed that different doses of the extracts can modulate the mRNA expression levels of clinically relevant CYP genes, and gender also plays a role in gene expression. These findings provide valuable information for the practical use of Lysiphyllum strychnifolium extracts in humans.
Article
Cell Biology
Zhaoliang Peng, Jiaying Wu, Shijun Hu, Aijin Ma, Lei Wang, Nan Cao, Yu Zhang, Qiyuan Li, Junying Yu, Shufang Meng, Tao Na, Xiaolei Shi, Mei Li, Huadong Liu, Linguang Qian, E. Tian, Feng Lin, Jiani Cao, Yaojin Peng, Huanxin Zhu, Lingmin Liang, Jie Hao, Tongbiao Zhao, Xin Cheng, Guoyu Pan
Summary: The 'Requirements for Primary Human Hepatocyte' is the first set of guidelines in China that specifies technical requirements, test methods, regulations, and storage for Primary Human Hepatocyte. These guidelines were originally released by the China Society for Cell Biology on January 9, 2021, with the aim of promoting institutional establishment, acceptance, and execution of proper protocols and accelerating international standardization of Primary Human Hepatocyte applications.
CELL PROLIFERATION
(2022)
Article
Biochemistry & Molecular Biology
Go Sugahara, Yuji Ishida, Jae Jin Lee, Meng Li, Yasuhito Tanaka, Hyungjin Eoh, Yusuke Higuchi, Takeshi Saito
Summary: This study aimed to define the environmental requirements necessary for maintaining the homeostasis of terminally differentiated hepatocytes. The supplementation of dimethyl sulfoxide (DMSO) was found to be indispensable for mitigating fate deterioration and promoting adaptation to the in vitro environment. Dimethyl sulfone (DMSO2) was identified as a substitute for DMSO, supporting the long-term maintenance of hepatocyte morphology, marker gene expression, and functionality.
Article
Toxicology
Amelie Tsoutsoulopoulos, Katrin Gohlsch, Niklas Moehle, Andreas Breit, Sebastian Hoffmann, Olaf Krischenowski, Harald Mueckter, Thomas Gudermann, Horst Thiermann, Michaela Aufderheide, Dirk Steinritz
TOXICOLOGY IN VITRO
(2019)
Review
Toxicology
Martin L. Stephens, Sevcan Gul Akgun-Olmez, Sebastian Hoffmann, Rob de Vries, Burkhard Flick, Thomas Hartung, Manoj Lalu, Alexandra Maertens, Hilda Witters, Robert Wright, Katya Tsaioun
TOXICOLOGICAL SCIENCES
(2019)
Review
Environmental Sciences
Judith A. K. R. van Luijk, Madalina Popa, Janne Swinkels, Julia M. L. Menon, Wynand Alkema, Nel Roeleveld, Sebastian E. Hoffman, Vivi Schlunssen, Daniele Mandrioli, Merel Ritskes-Hoitinga, Paul T. J. Scheepers
ENVIRONMENTAL RESEARCH
(2019)
Article
Toxicology
Katrin Gohlsch, Harald Mueckter, Dirk Steinritz, Michaela Aufderheide, Sebastian Hoffmann, Thomas Gudermann, Andreas Breit
TOXICOLOGY LETTERS
(2019)
Article
Multidisciplinary Sciences
Amelie Tsoutsoulopoulos, Katrin Gohlsch, Niklas Moehle, Andreas Breit, Sebastian Hoffmann, O. Krischenowski, Harald Mueckter, Thomas Gudermann, Horst Thiermann, Michaela Aufderheide, Dirk Steinritz
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2020)
Review
Biochemistry & Molecular Biology
Juliette Legler, Daniel Zalko, Fabien Jourdan, Miriam Jacobs, Bernard Fromenty, Patrick Balaguer, William Bourguet, Vesna Munic Kos, Angel Nadal, Claire Beausoleil, Susana Cristobal, Sylvie Remy, Sibylle Ermler, Luigi Margiotta-Casaluci, Julian L. Griffin, Bruce Blumberg, Christophe Chesne, Sebastian Hoffmann, Patrik L. Andersson, Jorke H. Kamstra
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Irene Pachon Angona, Solene Daniel, Helene Martin, Alexandre Bonet, Artur Wnorowski, Maciej Maj, Krzysztof Jozwiak, Tiago Barros Silva, Bernard Refouvelet, Fernanda Borges, Jose Marco-Contelles, Lhassane Ismaili
Article
Environmental Sciences
Paul Whaley, Elisa Aiassa, Claire Beausoleil, Anna Beronius, Gary Bilotta, Alan Boobis, Rob de Vries, Annika Hanberg, Sebastian Hoffmann, Neil Hunt, Crispin Halsall, Carol F. Kwiatkowski, Juleen Lam, Steven Lipworth, Olwenn Martin, Nicola Randall, Lorenz Rhomberg, Andrew A. Rooney, Holger J. Schunemann, Daniele Wikoff, Taylor Wolffe, Crispin Halsall
ENVIRONMENT INTERNATIONAL
(2020)
Article
Biochemistry & Molecular Biology
Irene Pachon Angona, Helene Martin, Solene Daniel, Ignacio Moraleda, Alexandre Bonet, Artur Wnorowski, Maciej Maj, Krzysztof Jozwiak, Isabel Iriepa, Bernard Refouvelet, Jose Marco-Contelles, Lhassane Ismaili
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Engineering, Biomedical
Michael F. Wolf, Gaurav Girdhar, Arielle A. Anderson, Samantha R. Ubl, Sinduja Thinamany, Hannah N. Jeffers, Courtney E. DeRusha, Jenny Rodriguez-Fernandez, Sebastian Hoffmann, Carrie A. Strief
Summary: In vitro thrombogenicity assessment using fresh human blood showed strong dependence on material, heparin, and time, and variable dependence on model, surface modification, and blood donor. This method is scientifically sound and cost effective compared to in vivo methods for screening intravascular materials and devices for thrombogenicity.
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
(2021)
Article
Medicine, Legal
Nicola Gilmour, Petra S. Kern, Nathalie Alepee, Fanny Boisleve, Dagmar Bury, Elodie Clouet, Morihiko Hirota, Sebastian Hoffmann, Jochen Kuehnl, Jon F. Lalko, Karsten Mewes, Masaaki Miyazawa, Hayato Nishida, Anne Osmani, Dirk Petersohn, Shuichi Sekine, Erwin van Vliet, Martina Klaric
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2020)
Article
Genetics & Heredity
Stefan Pfuhler, Thomas R. Downs, Nicola J. Hewitt, Sebastian Hoffmann, Greg C. Mun, Gladys Ouedraogo, Shambhu Roy, Rodger D. Curren, Marilyn J. Aardema
Summary: In vitro test batteries have become the standard approach for assessing the genotoxic potential of substances, but 2D cell culture assays may not accurately predict in vivo outcomes, leading to unnecessary animal studies. To address this, a 3D in vitro human skin-based genotoxicity assay was developed and validated, showing high accuracy and reproducibility.
Review
Toxicology
Sebastian Hoffmann, Bianca Marigliani, Sevcan Gul Akgun-Olmez, Danielle Ireland, Rebecca Cruz, Francois Busquet, Burkhard Flick, Manoj Lalu, Elizabeth C. Ghandakly, Rob B. M. de Vries, Hilda Witters, Robert A. Wright, Metin Olmez, Catherine Willett, Thomas Hartung, Martin L. Stephens, Katya Tsaioun
Summary: ZET has been proposed as a potential replacement for mammalian studies, but further standardization is needed; systematic review studies suggest that ZET has the potential to identify prenatal developmental toxicants, but there is a tendency for overprediction; there is a need to raise awareness in the toxicological community of the necessity and benefits of more evidence-based approaches.
TOXICOLOGICAL SCIENCES
(2021)
Review
Environmental Sciences
Julia M. L. Menon, Judith A. K. R. van Luijk, Janne Swinkels, Eva Lukas, Merel Ritskes-Hoitinga, Nel Roeleveld, Vivi Schlunssen, Daniele Mandrioli, Sebastian Hoffmann, Madalina Popa, Paul T. J. Scheepers
Summary: This review assessed available animal evidence on reproductive and developmental outcomes related to N2O inhalation to inform a health-based recommended occupational exposure limit. The study derived an OEL recommendation of 20 mg/m(3) based on the evidence gathered from animal studies.
ENVIRONMENTAL RESEARCH
(2021)
Review
Medicine, Legal
Carolina Di Paolo, Sebastian Hoffmann, Hilda Witters, Juan-Carlos Carrillo
Summary: Reproductive toxicity chemical safety assessment involves extensive use of vertebrate animals for regulatory testing purposes. Alternative methods like the zebrafish embryo teratogenicity assay (ZETA) show promise in replacing tests with mammals, but challenges to regulatory application include lack of standardization and incomplete validation.
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2021)
Article
Toxicology
Kathryn Page, Walter Westerink, Kristie Sullivan, Thomas McDonald, Clive Roper
Summary: This study developed a new method to assess the skin irritation of antimicrobial cleaning products. The method utilized a more human-like model and demonstrated its effectiveness through comparison with in vivo rabbit skin irritation data.
TOXICOLOGY IN VITRO
(2024)
Article
Toxicology
Arupam Patra, Thirukumaran Kandasamy, Siddhartha Sankar Ghosh, Gurvinder Kaur Saini
Summary: This study successfully produced recombinant anisoplin and demonstrated its significant anti-cancer effect and ability to induce apoptosis in breast cancer cells. The activation of related signaling pathways may be the key to cell death.
TOXICOLOGY IN VITRO
(2024)
Article
Toxicology
Thomas Haller, Alexander Jesacher, Alberto Hidalgo, Christina Schmidt
Summary: This study used live cell imaging to observe the accumulation of amiodarone in primary rat alveolar type II cells, and found that it specifically accumulates in lamellar bodies. The uptake is rapid, while storage is persistent. The main mechanisms for intracellular bioaccumulation of amiodarone are proposed to be passive diffusion, ion-trapping, and lipophilic interactions.
TOXICOLOGY IN VITRO
(2024)
Article
Toxicology
Filiz Bakar-Ates, Erva Ozkan
Summary: This study investigated the ferroptotic effect of CuB in breast cancer cells and evaluated its combination with erastin, a ferroptosis inducer. The results showed that the combination treatment significantly activated the ferroptotic pathways and altered the expression of iron-related proteins in breast cancer cells.
TOXICOLOGY IN VITRO
(2024)
Article
Toxicology
Rachel Z. Bennie, Ian C. Shaw
Summary: Estrogen mimics are synthetic and naturally occurring compounds that can interact with estrogen receptors in animals. In vitro transactivation reporter gene assay and in silico molecular modelling can be used to predict the mimicry of these compounds, reducing reliance on animal studies.
TOXICOLOGY IN VITRO
(2024)
Article
Toxicology
Sevda Isik, Semra Cicek
Summary: This study found that high doses of riboflavin can cause cytotoxicity in rainbow trout gonad cells and affect the transcriptional expressions of antioxidant enzymes and growth and reproductive genes, potentially leading to DNA damage and cell death.
TOXICOLOGY IN VITRO
(2024)
Article
Toxicology
Ying Wang, Jie Wu, Mengqi Wan, Dou Yang, Fasheng Liu, Kehao Li, Manxin Hu, Yuanyuan Tang, Huiqiang Lu, Shouhua Zhang, Yuanzhen Xiong
Summary: m-Cresol is commonly used as an intermediate for pesticides and other industrial applications. This study investigated the hepatotoxicity of m-cresol using zebrafish larvae and explored its molecular mechanisms. The results suggest that m-cresol may induce liver damage in zebrafish larvae through oxidative stress and cell apoptosis pathways.
TOXICOLOGY IN VITRO
(2024)
Article
Toxicology
Vincent J. Manna, Shannon Dwyer, Vanessa Pizutelli, Salvatore J. Caradonna
Summary: The widespread use of electronic cigarettes and the emergence of a new illness have raised concerns about the effects of e-cigarette vapor on respiratory tissues. Researchers have developed a simple device to mimic the response of human airway tissue after long-term exposure to e-cigarette vapor, and have identified differences in the effects of different vapor compositions on airway tissue.
TOXICOLOGY IN VITRO
(2024)
