Article
Pharmacology & Pharmacy
Seok Hwee Koo, Gaik Hong Soon, Alain Pruvost, Henri Benech, Tiing Leong Ang, Edmund Jon Deoon Lee, Daphne Shih Wen Ang
Summary: The primary objectives of this study were to investigate the suitability of a 6-probe cocktail for assessing drug metabolizing enzymes and transporters, and examine differences in drug handling among groups with different genetic regulation. The study involved 20 young, healthy Chinese volunteers and found that the 6-probe cocktail was safe and effective for assessing drug metabolizing activities. Genetic variations were also identified and correlated with phenotypic status, which will contribute to the implementation of personalized medicine.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2022)
Article
Environmental Sciences
Jinpeng Tang, Chencheng Zhang, Jinhua Zhang, Yanyan Jia, Ji Fang
Summary: The increasing concentration of endocrine disrupting compounds (EDCs) in the aquatic environment has irreversible effects on biota's endocrine and reproductive systems. This study measured the concentrations of seven common EDCs in fish, invertebrate species, and plankton collected from South China. The results showed that fish had the highest EDC concentrations, with 4-nonylphenol and bisphenol S being the predominant components. Trophic magnification factors (TMFs) were negatively correlated with in vitro biotransformation clearance rates (CL in vitro) and CYP450 enzymes activities, indicating that metabolism plays a significant role in the trophic transfer of EDCs.
SCIENCE OF THE TOTAL ENVIRONMENT
(2023)
Review
Health Care Sciences & Services
Navid Neyshaburinezhad, Hengameh Ghasim, Mohammadreza Rouini, Youssef Daali, Yalda H. Ardakani
Summary: Genetic polymorphisms in cytochrome P450 genes can affect the metabolic activity of clinically important drugs, serving as pharmacogenetic biomarkers for drug dosing, efficacy, and safety. Variations in the distribution of cytochrome P450 alleles among populations have implications for personalized drug therapy and healthcare programs.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Review
Pharmacology & Pharmacy
Xiaoyan Pang, Chongzhuang Tang, Runcong Guo, Xiaoyan Chen
Summary: This review focuses on the role of oxidative metabolism in regulating the exposure and effects of xenobiotics and their metabolites. It discusses the involvement of non-CYP450 enzymes in the metabolism of drugs and summarizes the common reaction mechanisms, factors affecting enzyme expression and activity, and species differences. The review highlights the potential impact of xenobiotic factors on the gene expression levels and activities of non-CYP450 enzymes.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Pharmacology & Pharmacy
Arunsajee Sae-be, Teerawat Wiwatpanit, Thaveechai Varatthan, Thanaphon Namporn, Sasiwat Laungkulldej, Ratthiya Thiabma, Atchara Jaiboonma, Khanit Sa-ngiamsuntorn, Daniel Elson, Alexandra E. Porter, Korbtham Sathirakul, Suradej Hongeng, Pakatip Ruenraroengsak
Summary: Liver spheroids serve as ideal alternative models for assessing the efficacy and toxicity of new anticancer drugs and diagnostic methods for hepatocellular carcinoma. These 3D models accurately evaluate cellular morphology, metabolic activity, and drug penetration. Different types of spheroid models exhibit variations in gene expression and drug metabolism, and the presence of hepatic stellate cells enhances the biological barrier for drug penetration.
ADVANCED THERAPEUTICS
(2023)
Article
Pharmacology & Pharmacy
Sylwia Szelag-Pieniek, Stefan Oswald, Mariola Post, Joanna Lapczuk-Romanska, Marek Drozdzik, Mateusz Kurzawski
Summary: The study revealed downregulation of drug-metabolizing enzymes and drug transporters in the livers of Wilson's disease patients, which may result in alterations in drug metabolism and efficacy in this group of patients.
PHARMACOLOGICAL REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Serena Calamaio, Marialaura Serzanti, Jennifer Boniotti, Annamaria Fra, Emirena Garrafa, Manuela Cominelli, Rosanna Verardi, Pietro Luigi Poliani, Silvia Dotti, Riccardo Villa, Giovanna Mazzoleni, Patrizia Dell'Era, Nathalie Steimberg
Summary: The process of developing a new drug is time-consuming and expensive, and hepatotoxicity is a major concern. Animal models have limitations due to interspecies differences, but human induced pluripotent stem cells (hiPSCs) offer new possibilities for drug testing. We miniaturized the process of generating hepatic organoids using hiPSC-derived mesenchymal stem cells, hepatocytes, and endothelial cells. These organoids were cultivated in vitro using static and dynamic cultures, and could be maintained for up to 1 week. This hiPSC-derived liver organoid model could potentially replace animal testing in pharmacological and toxicological studies.
Review
Biochemistry & Molecular Biology
Anna Laura Voigt, Shiama Thiageswaran, Nathalia de Lima e Martins Lara, Ina Dobrinski
Summary: Spermatogonial stem cells are unique adult stem cells that play a crucial role in treating infertility. Understanding the factors necessary for their lifelong maintenance and in vitro expansion is essential for successful clinical applications. Metabolism is discussed as vital for cell biology, stem cell integrity, and decision-making in the context of SSC maintenance, differentiation, and expansion.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Jereme G. Spiers, Li Si Tan, Stephen T. Anderson, Andrew F. Hill, Nickolas A. Lavidis, Hsiao-Jou Cortina Chen
Summary: This study investigated the changes in essential metal homeostasis following exposure to short-term repeated stress in rats, revealing that stress can lead to hepatic redox imbalance and metal redistribution. Additionally, stress was found to modulate the mRNA levels of key metal transporters.
Article
Chemistry, Analytical
Robert Knitsch, Mohammad AlWahsh, Hannes Raschke, Joerg Lambert, Roland Hergenroeder
Summary: Three-dimensional cell cultures are becoming increasingly important in biochemical research, requiring adaptations of established analytical techniques for more accurate representation of tissue features. This study presents an NMR-based approach to obtain dynamically radial metabolite profiles for cell spheroids, one of the most frequently used 3D models, using spatially selective NMR pulse sequences and a commercially available cryogenic NMR probe.
ANALYTICAL CHEMISTRY
(2021)
Article
Environmental Sciences
You Weng, Zhuizui Huang, Anyi Wu, Qianxuan Yu, Huahui Lu, Ze Lou, Longxi Lu, Zhiwei Bao, Yuanxiang Jin
Summary: The study found that EPX has toxic effects on zebrafish embryos and larvae, affecting development, biochemical parameters, and gene transcription, especially glucose and lipid metabolism. This indicates that triazole fungicides have toxic effects on non-target organisms.
SCIENCE OF THE TOTAL ENVIRONMENT
(2021)
Article
Pharmacology & Pharmacy
Kyoko Ondo, Motoki Isono, Masataka Nakano, Shiori Hashiba, Tatsuki Fukami, Miki Nakajima
Summary: This study identified that m(6)A modification posttranscriptionally regulates the expression of UGT2B7 by affecting its mRNA stability and transactivity.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Environmental Sciences
Hu Zhang, Xiaofang Wang, Mingrong Qian, Yuanxiang Jin
Summary: The study found that exposure to ATZ caused hepatic metabolism disorder in zebrafish, resulting in decreased triglyceride levels and increased pyruvate and total cholesterol levels in the liver. Metabolomic analysis showed that ATZ affected the arginine, proline, and glutathione metabolic pathways in zebrafish.
Article
Cell Biology
Jia Guo, Yuanyuan Li, Zili Gao, Jiawei Lyu, Wenli Liu, Yongchao Duan, Lixun Zhou, Qi Gu
Summary: In this study, 3D printed anisotropic microporous scaffolds were used to culture embryos, and the results showed the critical role of 3D architecture for embryo implantation.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Endocrinology & Metabolism
Brecht Attema, Aafke W. F. Janssen, Deborah Rijkers, Evert M. van Schothorst, Guido J. E. J. Hooiveld, Sander Kersten
Summary: The study found that long-term low-dose exposure to PFOA and GenX disrupts hepatic lipid metabolism in mice, particularly having adverse effects on the liver. The effects of PFOA and GenX differ in pathways, with PFOA being regulated by multiple nuclear receptors and GenX being entirely mediated by PPARa.
MOLECULAR METABOLISM
(2022)
Article
Cell Biology
Jinwook Choi, Yu Jin Jang, Catherine Dabrowska, Elhadi Iich, Kelly Evans, Helen Hall, Sam M. Janes, Benjamin D. Simons, Bon-Kyoung Koo, Jonghwan Kim, Joo-Hyeon Lee
Summary: The study reveals a crucial role of the IL-1 beta-Notch-Fosl2 signaling axis in regulating the conversion of airway secretory cells into alveolar type 2 cells. It demonstrates the coordination of airway progenitor differentiation plasticity by inflammatory signals during alveolar regeneration. The findings propose a potential therapeutic target for guiding the fate decision of secretory cells during lung injury repair.
NATURE CELL BIOLOGY
(2021)
Article
Engineering, Biomedical
Chul-Yong Park, Gyunggyu Lee, Gyeongmin Kim, Dong-Hun Woo, Choongseong Han, Han-Jin Park, Dong-Wook Kim, Jong-Hoon Kim, Jeong Sang Son, Ji Young Park, Hyo Jin Kim, Kyun Yoo Chi, Sang Kyum Kim
Summary: This study successfully used genome engineering and induced pluripotent stem cell (iPSC) technologies to create endothelial cells that can increase the level of coagulation factor VIII, showing promising results in treating hemophilia A in animal models. This research opens up new possibilities for gene therapy in hemophilia.
Review
Cell & Tissue Engineering
Hyo Jin Kim, Gyeongmin Kim, Jihun Lee, Youngseok Lee, Jong-Hoon Kim
Summary: Stem cells or stem cell-derived cells may assist tissue repair by delivering secretory molecules, while extracellular vesicles (EVs) play crucial roles in intercellular communication.
TISSUE ENGINEERING AND REGENERATIVE MEDICINE
(2022)
Article
Multidisciplinary Sciences
Sung-Mi Shim, Young Ho Koh, Jong-Hoon Kim, Jae-Pil Jeon
Summary: This study analyzed the role of autoantibodies in the diagnosis of Alzheimer's disease and found that anti-ATCAY and anti-PAIP2 autoantibodies could be potential diagnostic biomarkers of AD.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Seung-Cheol Choi, Ha-Rim Seo, Long-Hui Cui, Myeong-Hwa Song, Ji-Min Noh, Kyung-Seob Kim, Ji-Hyun Choi, Jong-Ho Kim, Chi-Yeon Park, Hyung Joon Joo, Soon Jun Hong, Tae Hee Ko, Jong-Il Choi, Hyo Jin Kim, Jong-Hoon Kim, Se-Hwan Paek, Ji-Na Park, Dong-Hyung Kim, Yongjun Jang, Yongdoo Park, Do-Sun Lim
Summary: The study demonstrates that FGF4 and ascorbic acid can induce differentiation of human embryonic stem cell-cardiogenic mesoderm cells into mature cardiomyocytes, providing a model for adult-onset cardiac disease and drug discovery. These mature cardiomyocytes release acute myocardial infarction biomarkers in response to hypoxic injury, with potential for diagnosis and prognosis in coronary artery diseases based on transcriptome analyses.
Article
Biochemistry & Molecular Biology
Geun Ho An, Jaehun Lee, Xiong Jin, Jinwoo Chung, Joon-Chul Kim, Jung-Hyuck Park, Minkyung Kim, Choongseong Han, Jong-Hoon Kim, Dong-Hun Woo
Summary: This study introduced a truncated form of MFG-E8 that demonstrated advanced therapeutic benefits in treating liver fibrosis. The modified MFG-E8 more efficiently suppressed TGF-beta signaling, inhibiting hepatic stellate cell proliferation in the liver disease environment, and showed safety profiles in rat models.
Article
Multidisciplinary Sciences
Yu Jin Jang, Mijeong Kim, Bum-Kyu Lee, Jonghwan Kim
Summary: The authors developed a simple procedure to convert human primed pluripotent stem cells into trophoblast stem-like cells using bone morphogenetic protein 4, providing an important opportunity to study human placenta development and pathology.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Gastroenterology & Hepatology
Youngseok Lee, Jong-Hoon Kim
Summary: Extracellular vesicles (EVs) play crucial roles in mediating intercellular and interorgan communication, regulating and maintaining hepatic homeostasis. EVs released by liver cells can modulate distant organs, while liver also integrates EVs from other organs for pathophysiological processes. EVs have potential therapeutic applications in liver diseases.
CLINICAL AND MOLECULAR HEPATOLOGY
(2022)
Article
Engineering, Biomedical
Hyemin Kim, Ilkyun Im, Jang Su Jeon, Eun-Hye Kang, Hyang-Ae Lee, Seongyea Jo, Ji-Woo Kim, Dong-Hun Woo, Young Jae Choi, Hyo Jin Kim, Ji-Seok Han, Byoung-Seok Lee, Jong-Hoon Kim, Sang Kyum Kim, Han-Jin Park
Summary: This study aims to generate liver organoids with high drug metabolic ability using human pluripotent stem cells. The fully differentiated organoids exhibit cellular polarity, hepatobiliary structures, and remarkable drug metabolic function. They can also successfully model Wilson's disease and provide an advanced tool for studying hepatic drug metabolism and diseases.
Article
Reproductive Biology
Ji Eun Kim, Min Young Lee, Min-Ji Kang, Jihyun Byun, Jeong Bin Jo, Hye-Yeong Yang, Jong-Hoon Kim, Kyung-Ah Lee, Yong-Pil Cheon
Summary: This study developed a promising in vitro model for mimicking uterine endometrial differentiation. The model showed physiological competence and flexibility for triggering induction, making it a convenient tool for studying embryo implantation mechanisms.
BIOLOGY OF REPRODUCTION
(2022)
Article
Cell & Tissue Engineering
Jaehun Lee, Gyeongmin Kim, Kyun Yoo Chi, Choongseong Han, Jong-Hoon Kim
Summary: Cytochrome P450 (CYP) reaction phenotyping is crucial for predicting drug reactions and side effects. Single nucleotide polymorphisms (SNPs) in CYP genes alter drug metabolism capacity and cause unexpected drug-related reactions. In this study, two human induced pluripotent stem cell (hiPSC) lines with pharmacologically important SNPs in CYP2D6 in conjunction with CYP2C19 or CYP3A5 genes were established. These hiPSC lines serve as valuable resources for expanding our understanding of the relationships between genotypes and drug reactions.
STEM CELL RESEARCH
(2022)
Article
Cell & Tissue Engineering
Hyo Jin Kim, Gyeongmin Kim, Kyun Yoo Chi, Hyemin Kim, Yu Jin Jang, Seongyea Jo, Jihun Lee, Youngseok Lee, Dong-Hun Woo, Choongseong Han, Sang Kyum Kim, Han-Jin Park, Jong-Hoon Kim
Summary: Multilineage liver organoids (mLOs) generated from human pluripotent stem cells (hPSCs) can recapitulate the interactions between parenchymal and non-parenchymal cells, offering a precise in vitro model for liver diseases. This study demonstrates that the assembly of hepatic endoderm, hepatic stellate cell-like cells (HscLCs), and endothelial cells derived from hPSCs can generate mLOs with luminal blood vessels and bile ducts. Notch signaling modulation plays a critical role in the formation of both bile ducts and vasculature in mLOs.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Cell & Tissue Engineering
Seongyea Jo, Ji-Woo Kim, Haneul Noh, Hyemin Kim, Jong-Hoon Kim, Han-Jin Park
Summary: PDGFRB encodes PDGFR-beta, a cell surface receptor for platelet-derived growth factors. It plays important roles in the development of vascular and nervous systems, as well as actin cytoskeleton rearrangement. In liver diseases, particularly liver fibrosis, PDGFR-beta is essential. The generated iPSC line, KITi001-A-1, provides a useful tool for studying PDGFR-beta-expressing cells and screening liver fibrosis-inducing compounds.
STEM CELL RESEARCH
(2023)
Review
Cell & Tissue Engineering
Hyo Jin Kim, Gyeongmin Kim, Kyun Yoo Chi, Jong-Hoon Kim
Summary: Liver organoids have potential applications in liver disease modeling and drug screening, but generating organoids with perfusable luminal vasculature remains challenging. Some studies have successfully generated organoids with endothelial cell networks, but usually require transplantation to host animals to form luminal structures. Achieving perfusable luminal vasculature generation is an unmet need in liver organoid research.
INTERNATIONAL JOURNAL OF STEM CELLS
(2022)