Article
Biotechnology & Applied Microbiology
A. Romaldini, R. Spano, F. Catalano, F. Villa, A. Poggi, S. Sabella
Summary: The impact of graphene oxide on hepatic functional cells was studied. The results showed a mild activation of early apoptosis and no oxidative stress or inflammatory response. Graphene oxide inhibited the gene expression and metabolic activity of phase-I drug-metabolism enzymes, while had no effect on phase-II enzyme GST and phase-III efflux transporter ABCG2. Graphene oxide induced an acute-phase response in liver cells, which may have detrimental consequences for human health.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Eva Sanchez-Quant, Maria Lucia Richter, Maria Colome-Tatche, Celia Pilar Martinez-Jimenez
Summary: This study investigated the metabolic capacity of individual human hepatocytes in vitro and found that chronic accumulation of lipids can increase cellular heterogeneity and impair drug metabolism. Using a phenotyping five-probe cocktail, four functional subgroups of hepatocytes were identified, displaying differential gene expression profiles and xenobiotic metabolism-related specialization. Intracellular fat accumulation was shown to lead to increased transcriptional variability and diminish the drug-related metabolic capacity of hepatocytes.
Article
Multidisciplinary Sciences
Rieko Tanaka-yachi, Kazuko Aizawa, Kie Shimizu, Hidenori Akutsu, Kazuaki Nakamura
Summary: The newly established HepG2-DP cell line, created through stable double knockdown of DNMT1 and PKR, is a highly functional hepatocyte model with enhanced gene expression and drug metabolism capability. Furthermore, HepG2-DP cells can be further matured through differentiation induction.
SCIENTIFIC REPORTS
(2022)
Article
Engineering, Environmental
Ruiming Zhang, Pengfei Li, Ruiying Zhang, Xiangli Shi, Yanwei Li, Qingzhu Zhang, Wenxing Wang
Summary: This study elucidated the detoxifying mechanism of DDT metabolized by human P450 enzymes, suggesting that DDT can be metabolized through hydrogen abstraction and electrophilic addition mechanisms to form less toxic derivatives such as epoxides. The increase in solubility of these derivatives can accelerate their excretion from the body.
JOURNAL OF HAZARDOUS MATERIALS
(2021)
Article
Pharmacology & Pharmacy
Line Skute Braten, Tore Haslemo, Marin M. Jukic, Maxim Ivanov, Magnus Ingelman-Sundberg, Espen Molden, Marianne Kristiansen Kringen
Summary: Escitalopram, a commonly used antidepressant drug, shows substantial interindividual variation in clinical response, which can be attributed to the polymorphic nature of the CYP2C19 gene. A novel CYP2C-haplotype associated with ultrarapid metabolism of escitalopram was identified in this study.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Chemistry, Multidisciplinary
Gustavo Perez Ortiz, John D. Sidda, Emmanuel L. C. de los Santos, Catherine B. Hubert, Sarah M. Barry
Summary: The antimycobacterial peptides rufomycins exhibit antibiotic activity due to oxidative tailoring of the cyclic peptide. Cytochrome P450s RufS and RufM play roles in regioselective epoxidation and alkyl oxidation, creating a complex product profile dependent on redox partner availability. Additionally, in vitro one pot conversion of rufomycin B to rufomycin C has been successfully demonstrated.
CHEMICAL COMMUNICATIONS
(2021)
Article
Nutrition & Dietetics
Melisa Kozaczek, Walter Bottje, Diyana Albataineh, Reza Hakkak
Summary: Obesity can lead to chronic health complications such as NAFLD, characterized by lipid aggregation in hepatocytes and liver inflammation. Soy protein isolate (SPI) has shown potential in reducing liver steatosis, possibly through regulating CYP gene expression. Transcriptomic analysis revealed changes in CYP gene expression with SPI diet, suggesting a potential role in attenuating liver steatosis.
FRONTIERS IN NUTRITION
(2021)
Review
Pharmacology & Pharmacy
Xiaokang Wang, Jiaoyu Rao, Zhiyi Tan, Tianrong Xun, Jingqian Zhao, Xixiao Yang
Summary: This article summarizes the impact of new inflammatory-response signaling pathways on the activity and expression of CYP drug-metabolizing enzymes, and provides an overview of drugs that have the potential to regulate drug-metabolizing enzyme activity. The aim of the research is to inspire the development of clinical drug treatment processes that consider the impact of the inflammatory environment on drug treatment, as well as provide research targets for those studying drug metabolism.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Sumiko Ohnami, Akane Naruoka, Mitsuhiro Isaka, Maki Mizuguchi, Sou Nakatani, Fukumi Kamada, Yuji Shimoda, Ai Sakai, Keiichi Ohshima, Keiichi Hatakeyama, Kouji Maruyama, Yasuhisa Ohde, Hirotsugu Kenmotsu, Toshiaki Takahashi, Yasuto Akiyama, Takeshi Nagashima, Kenichi Urakami, Shumpei Ohnami, Ken Yamaguchi
Summary: The differences in genetic susceptibility to lung adenocarcinoma and squamous cell carcinoma are still not clear. Researchers developed a gene sequencing panel to detect germline variants in these two types of cancer. The study found that certain gene variants were associated with an increased risk of squamous cell carcinoma, while whole-gene deletion was associated with adenocarcinoma.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Nataliia Kovalchuk, Joseph L. Jilek, Laura S. Van Winkle, Nathan J. Cherrington, Xinxin Ding
Summary: The study used a lung-Cpr-null mouse model to investigate the role of lung POR in PQ-induced pulmonary fibrosis, finding that CPR plays a critical role in this process.
Article
Pharmacology & Pharmacy
Melina Lopez, Pedro F. Malacarne, Anna Gajos-Draus, Xinxin Ding, Andreas Daiber, Jon O. Lundberg, Stefan Offermanns, Ralf P. Brandes, Flavia Rezende
Summary: The study suggests that metabolism by vascular CYPs does not contribute to the pharmacological function of organic nitrates, while ALDH2 plays an important role in activating organic nitrates.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Engineering, Environmental
Hang Yu, Meiqi Song, Keqi Hu, Yujian Wang, Ruifang Fan, Zongying Yang, Hansruedi Glatt, Albert Braeuning, Yungang Liu
Summary: Bisphenol compounds may increase the genotoxic effects of metabolically activated carcinogens by modulating the expression of nuclear receptors and xenobiotic-metabolizing enzymes in human liver cancer cells, potentially aggravating chromosome damage caused by impactful carcinogens in human cells.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2021)
Article
Cell Biology
Lukas S. Wijaya, Carina Rau, Theresa S. Braun, Serif Marangoz, Vincent Spegg, Matthijs Vlasveld, Wiebke Albrecht, Tim Brecklinghaus, Hennicke Kamp, Joost B. Beltman, Jan G. Hengstler, Bob van de Water, Marcel Leist, Stefan Schildknecht
Summary: This study found that the antibiotic NFT can transiently elevate intracellular glutathione levels by regulating the Nrf2-GCL axis, enhancing cells' resistance to various stressors.
CELL BIOLOGY AND TOXICOLOGY
(2022)
Article
Chemistry, Medicinal
Soudeh Bahramian Nasab, Ahmad Homaei, Roberto Fernandez-Lafuente, Jon Del Arco, Jesus Fernandez-Lucas
Summary: The use of marine enzymes as catalysts for biotechnological applications is a hot topic. In this study, a liver NADPH-dependent cytochrome P450 reductase (CPR) from the marine fish Liza klunzingeri (LkCPR) was isolated, purified and biochemically characterized. LkCPR showed remarkable catalytic features, such as a wide range of pH and temperature stability, high catalytic activity, and highest thermostability among reported CPRs. These findings suggest that LkCPR has great potential as a biocatalyst.
Article
Biochemistry & Molecular Biology
He Liu, Zixia Hu, Ningning Han, Yi Yang, Guode Zhao, Mengdie Su, Yue Zhang, Weiwei Li, Ying Peng, Jiang Zheng
Summary: The study aimed to investigate the metabolic activation of MTX and its possible correlation with cytotoxicity. An oxidative metabolite (M1) and a GSH conjugate (M2) were observed in S9 fraction incubations and rat primary hepatocyte culture after MTX exposure. M1 and M2 were also detected in the bile of MTX-treated rats. CYP2A6 was found to be the dominant enzyme responsible for the oxidation of MTX. Inhibition of CYP2A6 and sulfotransferase significantly decreased the formation of M2. Pretreatment of primary hepatocytes with inhibitors reduced the susceptibility to MTX-induced cytotoxicity.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Toxicology
M. Teresa Donato, Nuria Jimenez, Maria Pelecha, Laia Tolosa
Summary: Drug-induced liver injury (DILI) is a common and serious adverse drug reaction that often leads to drug development failure and withdrawal. Enhanced levels of reactive oxygen species (ROS) have been identified as a major mechanism of DILI. Human-derived cell models, such as Upcyte human hepatocytes and HepaRG cells, are suitable for long-term hepatotoxicity assessments and mechanistic studies. These cell models maintain the expression and functionality of phase I and phase II enzymes, as well as antioxidant enzymes, making them suitable for routine toxicological assessments during drug preclinical testing.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Biochemical Research Methods
Marta Moreno-Torres, Manoj Kumar, Guillem Garcia-Llorens, Guillermo Quintas, Tine Tricot, Ruben Boon, Laia Tolosa, Burak Toprakhisar, Francois Chesnais, Catherine Verfaillie, Jose Castell
Summary: This article introduces a new strategy to assess the differentiation degree of iPSCs by comparing their cellular metabolome with that of primary human hepatocytes. The analysis of metabolome changes in three different iPSC progenies cultured in different differentiation media validates the feasibility of this approach and identifies the factors that promote metabolome changes.
JOURNAL OF PROTEOME RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Ruben Rodriguez-Agudo, Naroa Goikoetxea-Usandizaga, Marina Serrano-Macia, Pablo Fernandez-Tussy, David Fernandez-Ramos, Sofia Lachiondo-Ortega, Irene Gonzalez-Recio, Claudia Gil-Pitarch, Maria Mercado-Gomez, Laura Moran, Maider Bizkarguenaga, Fernando Lopitz-Otsoa, Petar Petrov, Miren Bravo, Sebastiaan Martijn Van Liempd, Juan Manuel Falcon-Perez, Amaia Zabala-Letona, Arkaitz Carracedo, Jose Vicente Castell, Ramiro Jover, Luis Alfonso Martinez-Cruz, Teresa Cardoso Delgado, Francisco Javier Cubero, Maria Isabel Lucena, Raul Jesus Andrade, Jon Mabe, Jorge Simon, Maria Luz Martinez-Chantar
Summary: The study demonstrates that anti-miR-873-5p is effective in combating APAP-induced liver injury by restoring GNMT and the methionine cycle to prevent mitochondrial dysfunction and activate hepatocyte proliferative response.
Review
Biochemistry & Molecular Biology
Marta Moreno-Torres, Guillermo Quintas, Jose Castell
Summary: Metabolomics as a tool holds great potential in DILI biomarker research, although there are limitations and inconsistencies that hinder the translation of research findings into general clinical practice, notable progress has been made in identifying promising novel metabolite biomarkers.
Article
Health Care Sciences & Services
Guillem Garcia-Llorens, Sergi Lopez-Navarro, Teresa Jaijo, Jose Castell, Roque Bort
Summary: In this study, a novel gene variant was identified, and personalized hepatocyte-like cells were generated using a direct reprogramming strategy, allowing for a clear molecular diagnosis and disease research.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
M. Teresa Donato, Gloria Gallego-Ferrer, Laia Tolosa
Summary: Drug-induced liver injury (DILI) is a significant problem in terms of patient health, healthcare costs, and drug development. Animal models are not reliable for predicting human DILI due to interspecies differences. Various cell models have been proposed to study hepatotoxicity and mimic long-term effects. This review evaluates existing cell models for DILI prediction, focusing on chronic hepatotoxicity and emphasizing the importance of better characterization and mechanistic studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Toxicology
Teresa Martinez-Sena, Erika Moro, Marta Moreno-Torres, Guillermo Quintas, Jan Hengstler, Jose V. Castell
Summary: Toxicity studies, especially hepatotoxicity, are crucial in preclinical drug development to minimize undesired toxic effects. In vitro models, particularly cultured hepatocytes, offer a reliable alternative to animal testing for predicting human risk. This study proposes an innovative strategy using mass spectrometry to analyze metabolome changes in HepG2 cells induced by hepatotoxic and non-hepatotoxic compounds. By comparing the alterations and elucidating the mechanisms, specific metabolic patterns were identified, allowing prediction of hepatotoxicity and mechanism-related toxicity.
ARCHIVES OF TOXICOLOGY
(2023)
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
Nutrition & Dietetics
Alvaro Perez-Rubio, Polina Soluyanova, Erika Moro, Guillermo Quintas, Ivan Rienda, Maria Dolores Perianez, Andres Painel, Jose Vizuete, Judith Perez-Rojas, Jose V. Castell, Ramon Trullenque-Juan, Eugenia Pareja, Ramiro Jover
Summary: Bariatric surgery can resolve non-alcoholic fatty liver disease, but not all patients experience this benefit. This study found that specific changes in gut microbiota and plasma bile acids are associated with resolution of fatty liver after bariatric surgery. The results provide valuable insights for interventions using prebiotics and/or probiotics to promote a gut microbiome that favors fatty liver resolution in bariatric surgery patients.
Article
Chemistry, Analytical
Julia Kuligowski, Alvaro Perez-Rubio, Marta Moreno-Torres, Polina Soluyanova, Judith Perez-Rojas, Ivan Rienda, David Perez-Guaita, Eugenia Pareja, Ramon Trullenque-Juan, Jose Castell, Marcha Verheijen, Florian Caiment, Ramiro Jover, Guillermo Quintas
Summary: This study introduces a novel variable selection approach called cluster PLS (c-PLS) to assess the joint impact of variable groups selected based on biological characteristics on the predictive performance of a multivariate model. The usefulness of c-PLS is shown using miRNomic and metabolomic datasets obtained from the analysis of liver tissue biopsies.
ANALYTICA CHIMICA ACTA
(2024)
Article
Polymer Science
Maria Guillot-Ferriols, Maria Inmaculada Garcia-Briega, Laia Tolosa, Carlos M. Costa, Senentxu Lanceros-Mendez, Jose Luis Gomez Ribelles, Gloria Gallego Ferrer
Summary: Piezoelectric stimulation promotes pre-differentiation of MSCs, and PVDF-CFO cell culture supports offer a wireless stimulation strategy. MSCs embedded in electroactive microspheres can be locally stimulated. This magnetically activated 3D electroactive cell culture support can be used for pre-differentiation of MSCs before transplantation.
Meeting Abstract
Cell & Tissue Engineering
Gloria Gallego-Ferrer, Julio Rodriguez-Fernandez, Emma Garcia-Legler, Sandra Clara-Trujillo, M. Teresa Donato, Manuel Salmeron-Sanchez, Laia Tolosa
TISSUE ENGINEERING PART A
(2022)
Meeting Abstract
Cell & Tissue Engineering
Gloria Gallego-Ferrer, Maria Guillot-Ferriols, Maria Inmaculada Garcia-Briega, Laia Tolosa, Senentxu Lanceros-Mendez, Jose Luis Gomez-Ribelles
TISSUE ENGINEERING PART A
(2022)
Article
Materials Science, Biomaterials
Sandra Clara-Trujillo, Laia Tolosa, Lourdes Cordon, Amparo Sempere, Gloria Gallego Ferrer, Jose Luis Gomez Ribelles
Summary: This study presents a novel 3D platform for modeling multiple myeloma (MM), a hematological malignancy. The platform allows suspension culture of non-adherent MM cells and can be easily tuned with different functionalizations. The results demonstrate the platform's suitability for studying MM cell proliferation and drug resistance.
BIOMATERIALS ADVANCES
(2022)