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
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
Developmental Biology
Jennifer Shannon, Aishwarya Sundaresan, Orhan Bukulmez, Zexu Jiao, Kaitlin Doody, Sarah Capelouto, Bruce Carr, Laura A. Banaszynski
Summary: Understanding how gene regulatory elements influence ovarian follicle development is crucial for addressing issues such as decreased fertility with age and short-term graft function after ovarian tissue cryopreservation. The ATAC-seq technique can identify regulatory elements important for gene regulation and fertility, but challenges remain in obtaining data from frozen samples.
MOLECULAR HUMAN REPRODUCTION
(2022)
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.
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
Biochemistry & Molecular Biology
Shahd Horie, Hector Gonzalez, Jack Brady, James Devaney, Michael Scully, Daniel O'Toole, John G. Laffey
Summary: The experiments compared the efficacy of umbilical-cord-derived MSCs and bone-marrow-derived MSCs in treating ventilator-induced lung injury, with results showing that umbilical-cord-derived MSCs comparably retained their efficacy in preserving injury resolution.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Agriculture, Dairy & Animal Science
Julie Strand, Henrik Callesen, Cino Pertoldi, Stig Purup
Summary: This study successfully established a cell line from a threatened amphibian species, highlighting the importance of using fresh tissue for cell line establishment, as well as confirming the effects of different media and contamination on cell growth.
Article
Biochemical Research Methods
Gael Castel, Laurent David
Summary: The authors describe an optimized protocol for reprogramming somatic cells into human induced trophoblast stem cells and converting pluripotent stem cells into converted trophoblast stem cells. This protocol has significant implications for genome-specific placental disease modeling.
Review
Biochemistry & Molecular Biology
Qiulin Luo, Nan Wang, Hanyun Que, Erziya Mai, Yanting Hu, Rui Tan, Jian Gu, Puyang Gong
Summary: The development of regenerative medicine has brought new possibilities for treating end-stage liver diseases. Stem cells, particularly induced pluripotent stem cells (iPSCs), have shown potential as a reliable source for generating hepatocyte-like cells (HLCs) due to their unlimited multiplication capacity and ability to simulate human disease. However, efficiently and accurately inducing iPSCs to differentiate into HLCs remains a hot topic. This review discusses the methods, challenges, and parameters involved in inducing iPSC differentiation, as well as the application of iPSCs in drug screening and modeling of liver disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemical Research Methods
Diana Cadena Castaneda, Sonia Jangra, Marina Yurieva, Jan Martinek, Megan Callender, Matthew Coxe, Angela Choi, Juan Garcia-Bernalt Diego, Te-Chia Wu, Florentina Marches, Damien Chaussabel, Adolfo Garcia-Sastre, Michael Schotsaert, Adam Williams, Karolina Palucka
Summary: This protocol provides a method for establishing primary human lung organoid-derived air-liquid interface (ALI) cultures from cryopreserved human lung tissue. It describes the specific steps, quality control measures, and technical readouts for monitoring virus response. The utility of these cultures is demonstrated through an example of severe acute respiratory syndrome coronavirus 2 infection.
Article
Cardiac & Cardiovascular Systems
Marcus Ground, Young Eun Park, Steve Waqanivavalagi, Karen Callon, Robert Walker, Paget Milsom, Jillian Cornish
Summary: This study presents an optimized method for isolating hVICs from diseased human valves donated during surgery, showing that two rounds of 1000 U/mL collagenase digestion for not more than 2 hours can result in a phenotypically stable cell culture with minimal endothelial cell contamination. Additionally, it is recommended that cells be seeded at a density of 10,000 cells/cm2 for experimentation. The success of the isolation procedure is not affected by patient pathology, but is instead predicted by ensuring >500 mg valve tissue as starting material.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2022)
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
Toxicology
Yujian Wang, Yuting Chen, Yijing Chen, Wenwen Luo, Yungang Liu
Summary: In this study, molecular docking and cytogenotoxic toxicity assays were used to investigate the mutagenic effects of carbamazepine (CBZ), an antiepileptic drug. The results showed that CBZ can induce chromosome damage and gene mutations at therapeutic concentrations, mainly through the activation of human CYP2B6 enzyme.
ARCHIVES OF TOXICOLOGY
(2023)
Article
Engineering, Biomedical
Gyunggyu Lee, Hyemin Kim, Ji Young Park, Gyeongmin Kim, Jiyou Han, Seok Chung, Ji Hun Yang, Jang Su Jeon, Dong-Hun Woo, Choongseong Han, Sang Kyum Kim, Han-Jin Park, Jong-Hoon Kim
Summary: Advances in pluripotent stem cell technology have led to the efficient and reproducible generation of hepatocyte-like cell spheroids in various sizes using microwell culture platforms. These spheroids show high expressions of hepatic marker genes, enhanced drug-metabolizing activity, and increased sensitivity to hepatotoxicants compared to traditional hepatocytes. This imaging-based toxicity screening system holds promise for predicting drug-induced hepatotoxicity in the early stages of drug discovery.
Article
Chemistry, Medicinal
Dorian Dupommier, Claire Muller, Corinne Comoy, Sabine Mazerbourg, Andrea Bordessa, Eline Piquard, Manon Pawlak, Flavian Piquard, Helene Martin, Elia De Fays, Stephanie Grandemange, Stephane Flament, Michel Boisbrun
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Review
Pharmacology & Pharmacy
Raphael Cornu, Arnaud Beduneau, Helene Martin
Article
Toxicology
Raphael Cornu, Claire Chretien, Yann Pellequer, Helene Martin, Arnaud Beduneau
ARCHIVES OF TOXICOLOGY
(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
Correction
Chemistry, Medicinal
Dorian Dupommier, Claire Muller, Corinne Comoy, Sabine Mazerbourg, Andrea Bordessa, Eline Piquard, Manon Pawlak, Flavian Piquard, Helene Martin, Elia De Fays, Stephanie Grandemange, Stephane Flament, Michel Boisbrun
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Review
Rheumatology
Sophie Hecquet, Perle Totoson, Helene Martin, Clement Prati, Daniel Wendling, Celine Demougeot, Frank Verhoeven
Summary: Intestinal permeability is increased in patients with spondyloarthritis, while its impact on rheumatoid arthritis patients is more controversial. NSAID treatment does not seem to affect intestinal permeability in spondyloarthritis patients, but it appears to increase permeability in rheumatoid arthritis patients.
SEMINARS IN ARTHRITIS AND RHEUMATISM
(2021)
Article
Chemistry, Medicinal
Irene Pachon-Angona, Maciej Maj, Artur Wnorowski, Helene Martin, Krzysztof Jozwiak, Lhassane Ismaili
Summary: This study synthesized twelve new compounds and evaluated their Ca2+ channel blockade capacity, cholinesterase inhibition, and antioxidant power. Results showed that one of the compounds has the potential for Alzheimer's disease therapy.
FUTURE MEDICINAL CHEMISTRY
(2021)
Article
Nanoscience & Nanotechnology
Taghrid Zaiter, Raphael Cornu, Nadine Millot, Michaele Herbst, Yann Pellequer, Georges Moarbess, Helene Martin, Mona Diab-Assaf, Arnaud Beduneau
Summary: The E551 additive is made up of synthetic amorphous silica particles. The current regulation does not specify their size and distribution, allowing the presence of silica nanoparticles despite their potential toxicity. Research found that a size cutoff of 70nm limits the interaction of the E551 additive with intestinal cells.
Review
Toxicology
Raphael Cornu, Arnaud Beduneau, Helene Martin
Summary: Titanium dioxide nanoparticles, commonly used in the food industry, may pose potential health risks when ingested, leading to chronic intestinal inflammation and increased risk of carcinogenesis. Children are particularly vulnerable to exposure, and maternal-foetal transfer during pregnancy and breastfeeding further contribute to offspring exposure. France has suspended the use of E171 as a precautionary measure. Further research is needed to understand the effects of oral exposure to titanium dioxide nanoparticles, especially on the gastrointestinal tract.
ARCHIVES OF TOXICOLOGY
(2022)
Review
Chemistry, Multidisciplinary
Taghrid Zaiter, Raphael Cornu, Wassim El Basset, Helene Martin, Mona Diab, Arnaud Beduneau
Summary: Engineered nanoparticles used in skin products can potentially cause cytotoxicity, oxidative stress, inflammatory response, and genotoxicity. However, the toxicity of nanoparticles applied to healthy skin is still debated due to their inability to reach the viable epidermis.
JOURNAL OF NANOPARTICLE RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Thomas Stalder, Taghrid Zaiter, Wassim El -Basset, Raphael Cornu, Helene Martin, Mona Diab-Assaf, Arnaud Beduneau
Summary: The gastrointestinal tract serves as a primary entry route for many nanomaterials, which are commonly used as food additives and are present in food packaging. Humans can also be orally exposed to nanoparticles in the air or drinking water. Ingested nanoparticles can interact with gastrointestinal fluids, microbiota, mucus layers, and the epithelial barrier, potentially leading to translocation and toxic effects. However, the toxicological profile of ingested nanoparticles remains unclear due to their diverse composition and physicochemical properties, as well as limited research. Understanding the fate and toxicity of ingested nanoparticles in the intestinal lumen is therefore of great importance.
Review
Medicine, Research & Experimental
Celian Peyronnel, Perle Totoson, Helene Martin, Celine Demougeot
Summary: Rheumatoid arthritis (RA) is associated with excessive cardiovascular mortality due to premature atherosclerosis, with endothelial activation (EA) playing a key role. EA involves loss of vascular integrity, expression of leucocyte adhesion molecules, transition to a prothrombotic phenotype, cytokine production, shedding of membrane microparticles, and recruitment of endothelial progenitor cells. Circulating markers of EA may serve as potential biomarkers for vascular pathology and cardiovascular (CV) risk. This review presents the biology of EA, analyzes available data on EA markers in RA in relation to vascular pathology and CV events, discusses their relevance as biomarkers of CV risk, and proposes future directions.
Article
Biochemistry & Molecular Biology
Rim Malek, Alexey Simakov, Audrey Davis, Maciej Maj, Paul J. Bernard, Artur Wnorowski, Helene Martin, Jose Marco-Contelles, Fakher Chabchoub, Patrick Dallemagne, Christophe Rochais, Krzysztof Jozwiak, Lhassane Ismaili
Summary: New multitarget-directed ligands BIGI 4a-d and BIGI 5a-d were designed and synthesized through a one-pot three-component Biginelli reaction, targeting acetyl-/butyrylcholinesterases inhibition, calcium channel antagonism, and antioxidant ability. Promising hit compounds BIGI 4b, BIGI 4d, and BIGI 5b showed in vitro balanced activities toward recognized AD targets. Additionally, these compounds exhibited suitable physicochemical properties and a good druglikeness score predicted by Data Warrior software.
Article
Pharmacology & Pharmacy
Usana Chatturong, Helene Martin, Perle Totoson, Kornkanok Ingkaninan, Prapapan Temkitthawon, Saharat Sermsenaphorn, Thanachon Somarin, Adchatawut Konsue, M. Paul Gleeson, Celine Demougeot, Krongkarn Chootip
Summary: Phosphodiesterase 5 (PDE5) inhibitors have good selectivity and vasorelaxant effects in the treatment of pulmonary arterial hypertension (PAH). This study identified two quinazoline analogues with potential as new drugs for PAH, as they showed good PDE5 inhibitory activity and selectivity for the pulmonary vasculature. These compounds enhance nitric oxide-sGC-cGMP pathway and inhibit calcium, leading to a relaxant effect on the pulmonary arteries.
VASCULAR PHARMACOLOGY
(2022)
Article
Rheumatology
C. Peyronnel, P. Totoson, V Petitcolin, F. Bonnefoy, X. Guillot, P. Saas, F. Verhoeven, H. Martin, C. Demougeot
Summary: This study found that local cryotherapy can reduce systemic endothelial activation, immune cell infiltration, and endothelial dysfunction in rats with adjuvant-induced arthritis. This effect may be achieved by reducing circulating levels of IL-17A.
ARTHRITIS RESEARCH & THERAPY
(2022)
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)