Review
Chemistry, Inorganic & Nuclear
Shin A. Yoon, Yujin Cha, Maxine Mambo Fortibui, Song Yi Yoo, Eun-Young Jo, Chulhun Kang, Min Hee Lee
Summary: This tutorial review summarizes recent advances in chemosensors that fluoresce in response to the enzyme systems involved in Phase I xenobiotic metabolism. It discusses both in vitro and in vivo imaging applications on biomedical models, highlighting enzyme systems such as cytochrome P450, monoamine oxidase, nitroreductases, aldehyde dehydrogenases, esterases, and amidases. These enzymatic activities play a role in the metabolism of diverse chemicals and have potential implications in various pathophysiological processes. Enzyme-directed imaging techniques, particularly those utilizing fluorescent chemosensors activated through xenobiotic metabolism, are promising diagnostic modalities with high sensitivity, selectivity, and rapidity in monitoring live biosystems.
COORDINATION CHEMISTRY REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Sandra Doss, Corinne Blessing, Katharina Haller, Georg Richter, Martin Sauer
Summary: Antibiotics are crucial in fighting bacterial infections, but some of them can cause hepatotoxicity.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2022)
Article
Medicine, Research & Experimental
Yu Sun, Hadrien Demagny, Adrien Faure, Francesca Pontanari, Antoine Jalil, Nadia Bresciani, Ece Yildiz, Melanie Korbelius, Alessia Perino, Kristina Schoonjans
Summary: The enzyme asparagine synthetase (ASNS) is responsible for the de novo synthesis of the nonessential amino acid asparagine. The expression of ASNS in pericentral hepatocytes, specialized liver cells in xenobiotic detoxification, is significantly increased in models of acute liver injury. Mice with hepatocyte-specific Asns deletion are more susceptible to pericentral liver damage, which can be reversed by intravenous administration of asparagine. The upregulation of ASNS in response to stress is mediated by the nuclear receptor, liver receptor homolog 1 (LRH-1; NR5A2) through an ATF4-independent, noncanonical pathway.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Biochemistry & Molecular Biology
Yixiang Zhong, Jun Sang Yu, Xiaoqiong Wang, Bert Binas, Hye Hyun Yoo
Summary: Our comparison between 5C and 3D PHHs showed that the 5C PHH monolayers perform at least as well as the 3D PHHs in terms of functionality and maintainability, suggesting that the 5C PHH monolayer format combines the advantages of traditional monolayer and spheroid formats.
Review
Biochemistry & Molecular Biology
Sabine Weber, Alexander L. Gerbes
Summary: Drug-induced liver injury (DILI) is a rare but potentially severe adverse drug event, which poses a major challenge for diagnosis in clinical practice and pharmacovigilance. Efforts have been made to establish diagnostic testing methods and biomarkers for safe diagnosis and differentiation from other liver diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Csilla Temesszentandrasi-Ambrus, Gabor Nagy, Annamaria Bui, Zsuzsanna Gaborik
Summary: ABCB4 is primarily found in the liver and is responsible for transporting phospholipids into bile for bile formation. Polymorphisms and deficiencies in ABCB4 have been linked to various hepatobiliary disorders, highlighting its importance in physiological function. Inhibiting ABCB4 with drugs can result in cholestasis and drug-induced liver injury (DILI), and although there are limited identified substrates and inhibitors, its similarity with ABCB1 suggests potential overlap. This study aimed to develop a cell line expressing ABCB4 to specifically investigate drug interactions and identify potential inhibitors and substrates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Engineering, Biomedical
Siming Lu, Jingwei Zhang, Sha Lin, Danfeng Zheng, Yan Shen, Jiale Qin, Yangyang Li, Shuqi Wang
Summary: Liver injury is a common cause of drug approval withdrawal, emphasizing the importance of in vitro hepatotoxicity assessment models for early detection. Biomaterials and bioengineering technologies have been utilized for the development of these models with the goal of clinical translation.
BIO-DESIGN AND MANUFACTURING
(2021)
Article
Medicine, General & Internal
Dina Halegoua-DeMarzio, Victor Navarro, Jawad Ahmad, Bharathi Avula, Huiman Barnhart, A. Sidney Barritt, Herbert L. Bonkovsky, Robert J. Fontana, Marwan S. Ghabril, Jay H. Hoofnagle, Ikhlas A. Khan, David E. Kleiner, Elizabeth Phillips, Andrew Stolz, Raj Vuppalanchi
Summary: This case series study describes the clinical, histological, and HLA associations of turmeric-associated liver injury cases in the US Drug-Induced Liver Injury Network (DILIN). Ten cases of turmeric-associated liver injury were found, predominantly in women and with a strong linkage to HLA-B*35:01. Chemical analysis confirmed the presence of turmeric in all tested products. The study suggests an increasing trend of liver injury due to turmeric in the United States.
AMERICAN JOURNAL OF MEDICINE
(2023)
Review
Gastroenterology & Hepatology
Xiaoyun Li, Jieting Tang, Yimin Mao
Summary: The epidemiology and aetiology of drug-induced liver injury (DILI) vary across different countries and populations. Antibiotics are the leading cause of DILI in Western countries, while traditional Chinese medicine is the primary cause in Eastern countries. The incidence of hepatotoxicity induced by herbal and dietary supplements is increasing globally. Although several risk factors for DILI have been described, there are no confirmed risk factors for all-cause DILI.
LIVER INTERNATIONAL
(2022)
Article
Biochemical Research Methods
Jingyu Lee, Myeong-sang Yu, Dokyun Na
Summary: The study developed an ensemble model consisting of three high-performance DILI prediction models, which showed high predictive performance and is expected to provide a more reliable prediction model for drug discovery, reducing the rate of drug withdrawal.
CURRENT BIOINFORMATICS
(2022)
Article
Toxicology
Guillermo Quintas, Teresa Martinez-Sena, Isabel Conde, Eugenia Pareja Ibars, Jos Kleinjans, Jose Castell
Summary: DILI, an adverse toxic reaction associated with drug administration, is currently classified based on ALT and ALP values, but lacks accuracy. By integrating metabolomic information, a more accurate evaluation of DILI phenotypes can be achieved.
ARCHIVES OF TOXICOLOGY
(2021)
Review
Pharmacology & Pharmacy
Magnus Ingelman-Sundberg, Volker M. Lauschke
Summary: Drug development is a challenging and failure-prone process, with liver toxicity being a major cause of safety failures. The current preclinical systems for compound selection are inadequate, necessitating the development of new strategies to increase clinical success rates. Human liver spheroids are becoming increasingly utilized for various analyses and drug development, showing promise as a new standard in translational pharmacology and toxicology.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2022)
Review
Oncology
Camille Houron, Marie Danielou, Olivier Mir, Bernard Fromenty, Gabriel Perlemuter, Cosmin Sebastian Voican
Summary: Multikinase inhibitors (MKI) have revolutionized cancer management, but there is a lack of data on MKI-related liver injury risk and clinical guidelines. Liver toxicity from MKI typically occurs one to two months after treatment initiation, with hepatocellular toxicity being more common. Early detection and monitoring of liver function are crucial for managing MKI-induced liver injury.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2021)
Review
Pharmacology & Pharmacy
Mirjana Stanic Benic, Lana Nezic, Vesna Vujic-Aleksic, Liliana Mititelu-Tartau
Summary: Many drugs can cause hepatotoxicity, and the treatment of drug-induced liver injury (DILI) is challenging. This study searched various databases to summarize the mechanisms, potential benefits, and adverse reactions of novel therapies for managing DILI. The evidence suggests that MgIG treatment may be effective in normalizing ALT levels, while bicyclol treatment may reduce ALT levels.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Plant Sciences
Zhichao Yu, Zhe Feng, Ling Fu, Jing Wang, Changqing Li, Huaxu Zhu, Tong Xie, Jie Zhou, Lingling Zhou, Xueping Zhou
Summary: This study found that Tripterygium wilfordii can cause liver injury by interfering with lipid metabolism, and Qingluotongbi can protect against this toxic effect. Tripterygium wilfordii upregulates LXR alpha to activate endoplasmic reticulum stress (ERS) and increase lipid synthesis, while Qingluotongbi inhibits the LXR alpha-ERS-SREBP-1c pathway to reduce abnormal lipid synthesis and liver toxicity.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Toxicology
Stefan O. Mueller, Wolfgang Dekant, Paul Jennings, Emanuela Testai, Frederic Bois
TOXICOLOGY IN VITRO
(2015)
Article
Toxicology
Stefan O. Mueller, Andre Guillouzo, Philip G. Hewitt, Lysiane Richert
TOXICOLOGY IN VITRO
(2015)
Article
Toxicology
Jessica J. W. Broeders, Celine Parmentier, Germaine L. Truisi, Rozenn Josse, Eliane Alexandre, Camille C. Savary, Philip G. Hewitt, Stefan O. Mueller, Andre Guillouzo, Lysiane Richert, Jan C. H. van Eijkeren, Joop L. M. Hermens, Bas J. Blaauboer
TOXICOLOGY IN VITRO
(2015)
Article
Toxicology
Alice Limonciel, Konrad Moenks, Sven Stanzel, Germaine L. Truisi, Celine Parmentier, Lydia Aschauer, Anja Wilmes, Lysiane Richert, Philip Hewitt, Stefan O. Mueller, Arno Lukas, Annette Kopp-Schneider, Martin O. Leonard, Paul Jennings
TOXICOLOGY IN VITRO
(2015)
Article
Toxicology
Germaine L. Truisi, Emma Di Consiglio, Celine Parmentier, Camille C. Savary, Giuliana Pomponio, Frederic Bois, Birthe Lauer, Rozenn Josse, Philip G. Hewitt, Stefan O. Mueller, Lysiane Richert, Andre Guillouzo, Emanuela Testai
TOXICOLOGY LETTERS
(2015)
Article
Biochemical Research Methods
Anja Wilmes, Alice Limonciel, Lydia Aschauer, Konrad Moenks, Chris Bielow, Martin O. Leonard, Jeremy Hamon, Donatella Carpi, Silke Ruzek, Andreas Handler, Olga Schmal, Karin Herrgen, Patricia Bellwon, Christof Burek, Germaine L. Truisi, Philip Hewitt, Emma Di Consiglio, Emanuela Testai, Bas J. Blaauboer, Claude Guillou, Christian G. Huber, Arno Lukas, Walter Pfaller, Stefan O. Mueller, Frederic Y. Bois, Wolfgang Dekant, Paul Jennings
JOURNAL OF PROTEOMICS
(2013)
Article
Biochemical Research Methods
Joris Vandeputte, Melanie Saville, Marco Cavaleri, Martin Friede, Adam Hacker, Stefan O. Mueller, Ruben Rizzi, Dean Smith, Steffen Thirstrup, Ralf Wagner, Marc Baay, Pieter Neels
Summary: The use of platform technologies for vaccine development is crucial in tackling emerging infectious diseases like SARS-CoV-2, with the need for continuous development and improvement. The webinar discussed techniques used in COVID-19 vaccine development and the experiences and expectations of regulatory authorities in this field.
Article
Immunology
Susanne Rauch, Nicole Roth, Kim Schwendt, Mariola Fotin-Mleczek, Stefan O. Mueller, Benjamin Petsch
Summary: mRNA technologies have shown clinical efficacy against COVID-19, with the CVnCoV vaccine demonstrating strong immune responses and protection against SARS-CoV-2 in preclinical studies. Overall, CVnCoV represents a potent and safe candidate for a COVID-19 vaccine.
Article
Medicine, General & Internal
Peter G. Kremsner, Philipp Mann, Arne Kroidl, Isabel Leroux-Roels, Christoph Schindler, Julian J. Gabor, Mirjam Schunk, Geert Leroux-Roels, Jacobus J. Bosch, Rolf Fendel, Andrea Kreidenweiss, Thirumalaisamy P. Velavan, Mariola Fotin-Mleczek, Stefan O. Mueller, Gianluca Quintini, Oliver Schoenborn-Kellenberger, Dominik Vahrenhorst, Thomas Verstraeten, Margarida Alves de Mesquita, Lisa Walz, Olaf-Oliver Wolz, Lidia Oostvogels
Summary: The RNActive technology platform was used to prepare CVnCoV, a COVID-19 vaccine containing optimized mRNA encoding for a stabilized form of SARS-CoV-2 spike protein. The dosage escalation phase 1 study showed that 12 µg of CVnCoV vaccine elicited immune responses comparable to those seen in convalescent sera from COVID-19 patients, with acceptable safety and reactogenicity.
WIENER KLINISCHE WOCHENSCHRIFT
(2021)
Article
Multidisciplinary Sciences
Donata Hoffmann, Bjorn Corleis, Susanne Rauch, Nicole Roth, Janine Muhe, Nico Joel Halwe, Lorenz Ulrich, Charlie Fricke, Jacob Schon, Anna Kraft, Angele Breithaupt, Kerstin Wernike, Anna Michelitsch, Franziska Sick, Claudia Wylezich, Bernd Hoffmann, Moritz Thran, Andreas Thess, Stefan O. Mueller, Thomas C. Mettenleiter, Benjamin Petsch, Anca Dorhoi, Martin Beer
Summary: The study demonstrates that two spike encoding mRNA vaccines provide effective protection against the variants of concern B.1.351 and the ancestral strain BavPat1 of SARS-CoV-2, despite lower neutralizing antibody titers against B.1.351.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Makda S. Gebre, Susanne Rauch, Nicole Roth, Jingyou Yu, Abishek Chandrashekar, Noe B. Mercado, Xuan He, Jinyan Liu, Katherine McMahan, Amanda Martinot, David R. Martinez, Victoria Giffin, David Hope, Shivani Patel, Daniel Sellers, Owen Sanborn, Julia Barrett, Xiaowen Liu, Andrew C. Cole, Laurent Pessaint, Daniel Valentin, Zack Flinchbaugh, Jake Yalley-Ogunro, Jeanne Muench, Renita Brown, Anthony Cook, Elyse Teow, Hanne Andersen, Mark G. Lewis, Adrianus C. M. Boon, Ralph S. Baric, Stefan O. Mueller, Benjamin Petsch, Dan H. Barouch
Summary: In non-human primates, the second-generation mRNA vaccine CV2CoV was found to induce higher levels of immune responses and provide stronger protection against SARS-CoV-2 variants compared to CVnCoV. The optimization of non-coding regions greatly improved the immunogenicity and protective efficacy of the non-modified mRNA vaccine in non-human primates.
Article
Immunology
Makda S. Gebre, Susanne Rauch, Nicole Roth, Janina Gergen, Jingyou Yu, Xiaowen Liu, Andrew C. Cole, Stefan O. Mueller, Benjamin Petsch, Dan H. Barouch
Summary: mRNA vaccines can be developed and produced quickly, and clinical trials have shown that they can rapidly induce antibody responses. Compared to other vaccine modalities, mRNA vaccines can elicit protective antibodies more quickly and stimulate rapid humoral immune responses, which is a unique and advantageous property for controlling infectious disease outbreaks.
Article
Immunology
Nicole Roth, Jacob Schoen, Donata Hoffmann, Moritz Thran, Andreas Thess, Stefan O. Mueller, Benjamin Petsch, Susanne Rauch
Summary: This study compares the immunogenicity of a first-generation mRNA vaccine candidate, CVnCoV, with a second-generation mRNA vaccine candidate, CV2CoV, in rats. The results show that CV2CoV expresses higher levels of S protein and induces higher titres of neutralising antibodies with faster kinetics compared to CVnCoV. Additionally, CV2CoV demonstrates significant cross-neutralisation against circulating SARS-CoV-2 variants and induces higher antibody levels at lower doses, suggesting the possibility of dose-sparing and improving worldwide vaccine supply.
Article
Medicine, Research & Experimental
Klara Lenart, Fredrika Hellgren, Sebastian Ols, Xianglei Yan, Alberto Cagigi, Rodrigo Arcoverde Cerveira, Inga Winge, Jakub Hanczak, Stefan O. Mueller, Edith Jasny, Kim Schwendt, Susanne Rauch, Benjamin Petsch, Karin Lore
Summary: A study on rhesus macaques investigated the immune response to three doses of CureVac's CVnCoV vaccine. The results showed that the third dose significantly increased the levels of S-specific binding and neutralizing antibodies, and enhanced immune responses against various SARS-CoV-2 variants. The improved binding affinity of serum antibodies correlated with higher somatic hypermutation in S-specific B cells, indicating that the third dose can enhance antibody affinity and breadth.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Pharmacology & Pharmacy
Celine Parmentier, Germaine L. Truisi, Konrad Moenks, Sven Stanzel, Arno Lukas, Annette Kopp-Schneider, Eliane Alexandre, Philip G. Hewitt, Stefan O. Mueller, Lysiane Richert
DRUG METABOLISM AND DISPOSITION
(2013)