Article
Biochemistry & Molecular Biology
Floris Haijer, Shiva Koets-Shajari, Janette Heegsma, Sandra Serna-Salas, Tjasso Blokzijl, Manon Buist-Homan, Han Moshage, Klaas Nico Faber
Summary: Liver fibrosis is caused by excessive proliferation and collagen production by hepatic stellate cells (HSCs) due to chronic liver injury. Hydroxyurea, an anti-proliferative drug, showed inhibitory effects on HSC proliferation and fibrosis development in both in vitro and in vivo experiments. This study provides evidence for the therapeutic potential of hydroxyurea in treating liver fibrosis.
Review
Biochemistry & Molecular Biology
Yufei Yan, Jiefei Zeng, Linhao Xing, Changyong Li
Summary: Hepatic fibrosis is characterized by the accumulation of extracellular matrix in the liver due to persistent injury. Understanding the cellular and molecular mechanisms controlling the fibrotic response is crucial for developing clinical strategies to prevent fibrosis progression. Activation of hepatic stellate cells plays a key role in promoting ECM synthesis, and various external signals contribute to this process.
Article
Gastroenterology & Hepatology
Chen-Ting Hung, Tung-Hung Su, Yen-Ting Chen, Yueh-Feng Wu, You-Tzung Chen, Sung-Jan Lin, Shuei-Liong Lin, Kai-Chien Yang
Summary: The study identified TXNDC5 as a critical mediator of liver fibrosis, showing that its upregulation is associated with the activation of HSCs and the production of excessive extracellular matrix. Targeting TXNDC5 could potentially be a novel therapeutic strategy to ameliorate liver fibrosis.
Article
Biochemistry & Molecular Biology
Hanglu Ying, Long Li, Yufen Zhao, Feng Ni
Summary: This study evaluated the function of ivermectin in regulating liver fibrosis. The results showed that ivermectin alleviated histopathological changes, improved liver function, reduced collagen deposition, and downregulated the expression of profibrotic genes. Mechanistically, it inhibited intrahepatic macrophage accumulation and suppressed the production of proinflammatory factors. Importantly, it also promoted HSC deactivation by reducing the protein levels of alpha-smooth muscle actin (alpha-SMA).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Hiroyuki Ogawa, Kosuke Kaji, Norihisa Nishimura, Hirotetsu Takagi, Koji Ishida, Hiroaki Takaya, Hideto Kawaratani, Kei Moriya, Tadashi Namisaki, Takemi Akahane, Hitoshi Yoshiji
Summary: Lenvatinib shows potential as a novel therapeutic strategy for liver fibrosis by inhibiting hepatic stellate cell proliferation and promoting apoptosis, as well as reducing protein expression levels and intrahepatic neovascularization.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Immunology
Ting-Ting Li, Xiao-Wei Su, Lin-Lin Chen, Wan-Nian Zhang, Jun-Ping Zhang, Yan Wang, Wei-Heng Xu
Summary: Hepatic fibrosis is a stage of chronic liver disease that can lead to cirrhosis or liver cancer. The activation of hepatic stellate cells (HSCs) is a crucial event in fibrosis development and inhibiting this activation has been shown to alleviate fibrosis. Roxarsone, an organoarsenic additive used in livestock production, has been found to inhibit HSC activation and improve liver function in a mouse model of fibrosis. These findings suggest that Roxarsone could be a potential treatment for liver fibrosis.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yang You, Chongqing Gao, Junru Wu, Hengdong Qu, Yang Xiao, Ziwei Kang, Jinying Li, Jian Hong
Summary: ARK5 plays a critical role in liver fibrosis by maintaining the continuous transduction of the TGF-beta signaling pathway in HSCs and inducing epithelial-mesenchymal transition and inflammatory factor secretion in hepatocytes, thereby promoting liver fibrosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Medicine, General & Internal
Mariana Yazmin Medina Pizano, Maria de Jesus Loera Arias, Roberto Montes de Oca Luna, Odila Saucedo Cardenas, Javier Ventura Juarez, Martin Humberto Munoz Ortega
Summary: The sympathetic nervous system and the immune system communicate through neurotransmitters and cytokines. Liver immune cells and nerve fibers overlap, facilitating interactions. Neurotransmitters from the sympathetic nervous system activate hepatic stellate cells, contributing to fibrosis. Regulation of the hepatic nervous system and neurotransmitters may be important for treating hepatic fibrosis and cirrhosis. Strategies using alpha-adrenoblockers have shown promise in reducing fibrosis.
ANNALS OF MEDICINE
(2023)
Article
Cell Biology
Wenjun Zhang, Simon J. Conway, Ying Liu, Paige Snider, Hanying Chen, Hongyu Gao, Yunlong Liu, Kadir Isidan, Kevin J. Lopez, Gonzalo Campana, Ping Li, Burcin Ekser, Heather Francis, Weinian Shou, Chandrashekhar Kubal
Summary: This study identified multiple subpopulations of HSCs and characterized their unique roles and characteristics during liver injury, including differentiating into myofibroblasts and potential involvement in liver regeneration, immune reaction, and vascular remodeling. The scRNA-seq data provided insight into the dynamic transition from HSCs to myofibroblasts in response to liver injury, highlighting the heterogeneity and functional diversity of HSCs. The findings also suggest similarities between the heterogeneity of HSCs in injured mouse livers and cirrhotic human livers.
Article
Biochemistry & Molecular Biology
Hye-Young Seo, So-Hee Lee, Eugene Han, Jae Seok Hwang, Sol Han, Mi Kyung Kim, Byoung Kuk Jang
Summary: In this study, we found that evogliptin can inhibit inflammatory and fibrotic signaling in liver cells and induce autophagy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Zhiman Li, Lijuan Zhao, Yunshi Xia, Jianbo Chen, Mei Hua, Yinshi Sun
Summary: The study demonstrates that Schisandrin B inhibits the activity of hepatic stellate cells induced by TGF-beta 1 by promoting apoptosis.
Article
Food Science & Technology
Liyan Shi, Xiuli Zhang, Xin Liu, Yunyao Jiang, Yongyan Deng, Junzhi Liu
Summary: Cranberry phytochemicals (CPS) can inhibit HSC activation and liver fibrosis by reducing the expression of inflammatory cytokines and inhibiting the TGF beta/Smad signaling pathway. In vitro studies have shown significant effects of CPS on HSCs, with promising therapeutic effects in a rat model of liver fibrosis.
Article
Pharmacology & Pharmacy
Chen Shuai, Guo-qing Xia, Fei Yuan, Sheng Wang, Xiong-wen Lv
Summary: CD39 plays a role in alcoholic liver disease by regulating HSC activation and fibrosis development, and its blockade can prevent these processes. The findings suggest that ATP-adenosine signaling is a novel therapeutic target for alcoholic liver disease.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Gastroenterology & Hepatology
Taixiong Xue, Lin Yue, Guonian Zhu, Zui Tan, Hongyao Liu, Cailing Gan, Chen Fan, Xingping Su, Yuting Xie, Tinghong Ye
Summary: In this study, a phenylacrylic acid derivative, FA11, was synthesized and found to have excellent antifibrotic activity, making it a potential candidate for the treatment of liver fibrosis.
LIVER INTERNATIONAL
(2023)
Article
Engineering, Biomedical
Pengkai Wu, Xinping Luo, Meiling Sun, Beicheng Sun, Minjie Sun
Summary: A versatile nanocomplex was developed that improved liver fibrosis therapy by overcoming biological barriers and co-regulating Kupffer cells, extracellular matrix, and hepatic stellate cells.
Review
Gastroenterology & Hepatology
Antonio Saviano, Florian Wrensch, Marc G. Ghany, Thomas F. Baumert
Summary: COVID-19 infection caused by SARS-CoV-2 poses a diverse range of liver damage, from asymptomatic abnormalities to hepatic decompensation, which are correlated with disease severity and mortality rates. Although SARS-CoV-2 RNA has been detected in the liver of patients, the specific mechanism of infection and replication in liver cells remains unclear.
Review
Microbiology
Stephen J. Polyak, I. Nicholas Crispe, Thomas F. Baumert
Summary: Chronic hepatitis C is a major cause of hepatocellular carcinoma worldwide, and even though DAA drugs can cure all HCV infections, patients with advanced liver disease may still develop HCC. Studies have shown that HCV infection induces epigenetic, signaling, and gene expression changes in the liver related to altered hepatic innate immunity and liver cancer risk.
Editorial Material
Gastroenterology & Hepatology
Julie Lucifora, Thomas F. Baumert
JOURNAL OF HEPATOLOGY
(2021)
Article
Multidisciplinary Sciences
Xiaodong Zhuang, Donall Forde, Senko Tsukuda, Valentina D'Arienzo, Laurent Mailly, James M. Harris, Peter A. C. Wing, Helene Borrmann, Mirjam Schilling, Andrea Magri, Claudia Orbegozo Rubio, Robert J. Maidstone, Mudassar Iqbal, Miguel Garzon, Rosalba Minisini, Mario Pirisi, Sam Butterworth, Peter Balfe, David W. Ray, Koichi Watashi, Thomas F. Baumert, Jane A. McKeating
Summary: The study shows that REV-ERB regulates hepatitis B virus entry and BMAL1 directly binds HBV DNA and activates viral genome transcription.
NATURE COMMUNICATIONS
(2021)
Article
Virology
Clotilde Muller, Sophie Alain, Claire Gourin, Thomas F. Baumert, Gaetan Ligat, Sebastien Hantz
Summary: Researchers analyzed the terminase complex of human cytomegalovirus and identified conserved regions and potential functional motifs within pUL52. These findings reveal the importance of these regions in viral replication and provide potential targets for the development of new antiviral drugs.
Editorial Material
Medicine, General & Internal
Joachim Lupberger, Thomas F. Baumert
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Zakaria Boulahtouf, Alessia Virzi, Thomas F. Baumert, Eloi R. Verrier, Joachim Lupberger
Summary: Chronic viral hepatitis is a major cause of liver disease and hepatocellular carcinoma. Despite being caused by different viruses, hepatitis B, C, and D have striking similarities in pathological impact. The advancements in omics and bioinformatics have revealed the important role of signaling networks in viral pathogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Virology
Andrea Magri, James M. Harris, Valentina D'Arienzo, Rosalba Minisini, Frank Juhling, Peter A. C. Wing, Rachele Rapetti, Monica Leutner, Barbara Testoni, Thomas F. Baumert, Fabien Zoulim, Peter Balfe, Mario Pirisi, Jane A. McKeating
Summary: Chronic hepatitis B virus (HBV) infection is a global health problem that is characterized by interactions between the virus and the host immune system, leading to a spectrum of liver disease. The study investigates the contribution of HBV genomes, including episomal covalently closed circular DNA (cccDNA) and chromosomal integrants, to viral transcripts in chronic hepatitis B (CHB). The results demonstrate that cccDNA-derived transcripts are associated with liver inflammation markers, while integrant-derived transcripts are significantly associated with increasing age but not with inflammatory status.
Review
Medicine, General & Internal
Valerio Taverniti, Gaetan Ligat, Yannick Debing, Dieudonne Buh Kum, Thomas F. Baumert, Eloi R. Verrier
Summary: Despite the availability of a preventive vaccine, over 250 million people are still affected by chronic hepatitis B virus (HBV) infection, which is a major cause of liver disease and hepatocellular carcinoma. The core protein of HBV plays a crucial role in the virus's life cycle and represents a promising target for the development of new antiviral therapies. Capsid assembly modulators (CAM) have shown potent antiviral activity in cell-based and in vivo models, and several CAMs are currently being developed for clinical use.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Gastroenterology & Hepatology
Seng Gee Lim, Thomas F. Baumert, Carolina Boni, Ed Gane, Massimo Levrero, Anna S. Lok, Mala K. Maini, Norah A. Terrault, Fabien Zoulim
Summary: Functional cure of chronic hepatitis B (CHB), achieved through hepatitis B surface antigen (HBsAg) loss after 24 weeks off therapy, is the goal of current treatment. However, the rarity of achieving this cure with current therapy highlights the need for novel approaches. The three categories of treatment include reducing viral replication, reducing antigen load, and immunotherapies. Combination therapy of nucleos(t)ide analogues and immunotherapy shows promise in reducing HBsAg levels and inducing HBsAg loss in some patients, particularly those with low baseline HBsAg levels. Monitoring during therapy using viral and immunological biomarkers is important to predict HBsAg loss and understand its mechanisms.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2023)
Review
Cell Biology
Zeina Nehme, Natascha Roehlen, Punita Dhawan, Thomas F. F. Baumert
Summary: Tight junctions (TJs) are intercellular protein complexes that control paracellular permeability and cell polarity, and recent studies have shown their functional role beyond these classic functions. TJ proteins play crucial roles in cancer pathogenesis by modulating key signaling pathways that regulate cell proliferation, migration, and differentiation, as well as promoting stem cell phenotypes in cancer cells. Additionally, TJ proteins have been used as therapeutic targets and prognostic markers in preclinical and clinical studies. This review summarizes the functional role of TJ proteins in cancer biology and their potential for novel cancer prevention and treatment strategies.
Editorial Material
Gastroenterology & Hepatology
Nikolaus Jilg, Thomas F. Baumert
Article
Gastroenterology & Hepatology
Dieudonne Buh Kum, Hannah Vanrusselt, Abel Acosta Sanchez, Valerio Taverniti, Eloi R. Verrier, Thomas F. Baumert, Cheng Liu, Jerome Deval, Nikky Corthout, Sebastian Munck, Leonid Beigelman, Lawrence M. Blatt, Julian A. Symons, Pierre Raboisson, Andreas Jekle, Sandrine Vendeville, Yannick Debing
Summary: This study uncovers a novel mechanism of action for CAM-As in the treatment of chronic hepatitis B, where HBc aggregation induces cell death, leading to hepatocyte proliferation and loss of covalently closed circular DNA or its equivalent, possibly assisted by an induced innate immune response.
Meeting Abstract
Gastroenterology & Hepatology
Gaetan Ligat, Eloi Verrier, Laura Heydmann, Katharina Doernbrack, Julija Miller, Anne Maglott-Roth, Frank Juhling, Hussein El Saghire, Naoto Fujiwara, Sen-Yung Hsieh, Yujin Hoshida, David E. Root, Patrick Pessaux, Atish Mukherji, Catherine Schuster, Laurent Brino, Michael Nassal, Thomas Baumert
JOURNAL OF HEPATOLOGY
(2021)
Article
Medicine, Research & Experimental
Naoto Fujiwara, Masahiro Kobayashi, Austin J. Fobar, Ayaka Hoshida, Cesia A. Marquez, Bhuvaneswari Koneru, Gayatri Panda, Masataka Taguri, Tongqi Qian, Indu Raman, Quan-Zhen Li, Hiroki Hoshida, Hitomi Sezaki, Hiromitsu Kumada, Ryosuke Tateishi, Takeshi Yokoo, Adam C. Yopp, Raymond T. Chung, Bryan C. Fuchs, Thomas F. Baumert, Jorge A. Marrero, Neehar D. Parikh, Shijia Zhu, Amit G. Singal, Yujin Hoshida
Summary: The blood-based PLSec-AFP can accurately stratify patients with advanced liver fibrosis for long-term HCC risk and thereby guide risk-based tailored HCC screening.