Article
Clinical Neurology
Wojciech Paslawski, Per Svenningsson
Summary: This study validates previous findings that ApoE, ApoJ, and lipoprotein-bound aSN levels are significantly increased in the CSF of PD patients. Plasma levels of ApoAI and ApoJ are also decreased in PD patients.
PARKINSONISM & RELATED DISORDERS
(2023)
Article
Multidisciplinary Sciences
Mario Castro, Grant Lythe, Jolanda Smit, Carmen Molina-Paris
Summary: Endosomes play a crucial role in mediating cell communication with the extracellular environment and regulating intracellular trafficking. Viruses can hijack endosomes to replicate and evade degradation, with endosomal maturation depending on Rab proteins. The relationship between endosomal active Rab levels and pH may contribute to variability in viral escape times and ultimately regulate the viability of a viral intracellular infection.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
David Wensel, Shawn Williams, David P. Dixon, Paris Ward, Patti McCormick, Nestor Concha, Eugene Stewart, Xuan Hong, Charles Mazzucco, Shreya Pal, Bo Ding, Christoph Fellinger, Mark Krystal
Summary: GSK3732394, a multi-specific biologic inhibitor of HIV entry, binds to CD4 and inhibits downstream actions of gp160. The adnectin interacts with domains D2-D3 of CD4, stabilizing a novel T-shaped conformation. Amino acid F202 forms a key interaction with the adnectin and L151 contributes to the specificity for binding to human CD4.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Zhixiong Ying, Robin van Eenige, Rosa Beerepoot, Mariette R. Boon, Niels J. Kloosterhuis, Bart van de Sluis, Alexander Bartelt, Patrick C. N. Rensen, Sander Kooijman
Summary: Activation of brown adipose tissue (BAT) with the β3 receptor agonist mirabegron can promote fat oxidation and reduce fat accumulation, but it exacerbates atherosclerosis. However, in the APOE*3-Leiden.CETP mouse model, mirabegron treatment can reduce dyslipidemia and atherosclerosis.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Hin Chu, Bingjie Hu, Xiner Huang, Yue Chai, Dongyan Zhou, Yixin Wang, Huiping Shuai, Dong Yang, Yuxin Hou, Xi Zhang, Terrence Tsz-Tai Yuen, Jian-Piao Cai, Anna Jinxia Zhang, Jie Zhou, Shuofeng Yuan, Kelvin Kai-Wang To, Ivy Hau-Yee Chan, Ko-Yung Sit, Dominic Chi-Chung Foo, Ian Yu-Hong Wong, Ada Tsui-Lin Ng, Tan To Cheung, Simon Ying-Kit Law, Wing-Kuk Au, Melinda A. Brindley, Zhiwei Chen, Kin-Hang Kok, Jasper Fuk-Woo Chan, Kwok-Yung Yuen
Summary: Understanding the factors contributing to efficient SARS-CoV-2 infection in human cells can provide insights into the virus's transmissibility and pathogenesis. The study identifies heparan sulfate as an important attachment factor, while sialic acids on ACE2 may restrict efficient spike/ACE2 interaction in lung tissues. Moreover, the presence of a furin-like cleavage site in SARS-CoV-2 spike is crucial for efficient virus replication in human lungs.
NATURE COMMUNICATIONS
(2021)
Review
Virology
Tao Hu, Zhen Wu, Shaoxiong Wu, Shun Chen, Anchun Cheng
Summary: Flaviviruses infect hosts through envelope proteins, which mainly bind to cell attachment receptors and endocytic receptors. Key envelope protein amino acids, mainly located in specific regions of the protein structure, play important roles in the early infection process by potentially affecting interactions between different domains. Some of these amino acids are involved in conformational changes in envelope proteins during viral entry.
Article
Microbiology
Rebekka Adfeldt, Janna Schmitz, Barbara Kropff, Marco Thomas, Natalia Monakhova, Julia E. Hoelper, Barbara G. Klupp, Thomas C. Mettenleiter, Vadim Makarov, Elke Bogner
Summary: This study characterized the antiviral activity of two new diazadispiroalkane derivatives, 11826091 and 11826236, against human cytomegalovirus (HCMV) and pseudorabies virus (PrV). These small molecules demonstrated strong antiviral effects by targeting early steps of infection, mainly through inhibiting attachment to cell surface heparan sulfate mediated by glycoprotein C. The results suggest potential new treatment options for herpesvirus infections.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Cell Biology
Parikshit Bagchi, Xiaofang Liu, Woo Jung Cho, Billy Tsai
Summary: Polyomavirus SV40 reorganizes host ER membranes to form focal structures that facilitate virus escape into the cytosol. The virus preferentially localizes at multi-tubular ER junctions, exploiting vulnerable sites for membrane penetration. ER membrane protein Lunapark relocates to ER foci to support focus formation and facilitate virus escape and infection.
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.
Article
Gastroenterology & Hepatology
Antonio Saviano, Francois Habersetzer, Joachim Lupberger, Pauline Simo-Noumbissie, Catherine Schuster, Michel Doffoel, Catherine Schmidt-Mutter, Thomas F. Baumert
Summary: This study assessed the safety and antiviral activity of erlotinib in patients with chronic hepatitis C (CHC). The results showed that erlotinib is safe in noncirrhotic CHC patients, and a dose of 100 mg/d displayed antiviral activity, providing prospects for further research as a chemopreventive agent for hepatocellular carcinoma (HCC) in CHC patients.
CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY
(2022)
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)
Article
Medicine, Research & Experimental
Emilie Crouchet, Shen Li, Mozhdeh Sojoodi, Simonetta Bandiera, Naoto Fujiwara, Hussein El Saghire, Shijia Zhu, Tongqi Qian, Fahmida Akter Rasha, Fabio Del Zompo, Stephen C. Barrett, Eugenie Schaeffer, Marine A. Oudot, Clara Ponsolles, Sarah C. Durand, Sarani Ghoshal, Gunisha Arora, Fabio Giannone, Raymond T. Chung, Nevena Slovic, Nicolaas Van Renne, Emanuele Felli, Patrick Pessaux, Joachim Lupberger, Nathalie Pochet, Catherine Schuster, Kenneth K. Tanabe, Yujin Hoshida, Bryan C. Fuchs, Thomas F. Baumert
Summary: This study developed a simple human cell-based system that successfully predicted liver disease progression and HCC risk, and identified captopril as a potential drug for HCC chemoprevention. The results showed that captopril effectively reduced liver fibrosis and prevented the development of HCC in preclinical models. Mechanistic data revealed that captopril suppressed several signaling pathways related to fibrogenesis, inflammation, and carcinogenesis, including the EGFR pathway. Clinical data demonstrated that captopril could reverse the high-risk status of HCC in liver tissues with advanced fibrosis.
Article
Gastroenterology & Hepatology
Natascha Roehlen, Marion Muller, Zeina Nehme, Emilie Crouchet, Frank Juhling, Fabio Del Zompo, Sara Cherradi, Francois H. T. Duong, Nuno Almeida, Antonio Saviano, Mirian Fernandez-Vaquero, Tobias Riedl, Houssein El Saghire, Sarah C. Durand, Clara Ponsolles, Marine A. Oudot, Romain Martin, Nicolas Brignon, Emanuele Felli, Patrick Pessaux, Antonin Lallement, Irwin Davidson, Simonetta Bandiera, Christine Thumann, Patrice Marchand, Solange Moll, Brandon Nicolay, Nabeel Bardeesy, Yujin Hoshida, Mathias Heikenwaelder, Roberto Iacone, Alberto Toso, Markus Meyer, Greg Elson, Tamas Schweighoffer, Geoffrey Teixeira, Mirjam B. Zeisel, Patrice Laquerriere, Joachim Lupberger, Catherine Schuster, Laurent Mailly, Thomas F. Baumert
Summary: In this study, the role of CLDN1 as a therapeutic target for hepatocellular carcinoma (HCC) was investigated using humanized monoclonal antibodies targeting non-junctional CLDN1 and various cell and animal models. The results demonstrated that targeting non-junctional CLDN1 significantly suppressed tumor growth and invasion, and affected tumor stemness, metabolism, oncogenic signaling, and the tumor immune microenvironment. These findings provide a rationale for targeting CLDN1 in the treatment of advanced HCC and lay the foundation for the development of CLDN1-specific monoclonal antibodies for clinical use.
JOURNAL OF HEPATOLOGY
(2023)
Article
Pharmacology & Pharmacy
Charlotte Bach, Julie Lucifora, Marion Delphin, Laura Heydmann, Margaux J. Heuschkel, Caroline Pons, Kaku Goto, Els Scheers, Catherine Schuster, David Durantel, Frederik Pauwels, Thomas F. Baumert, Eloi R. Verrier
Summary: Chronic hepatitis D, caused by super-infection of hepatitis B virus (HBV)-infected hepatocytes with hepatitis D virus (HDV), is the most aggressive form of chronic viral hepatitis. Further improvement in therapy is needed to address the unmet medical need, which requires a more detailed characterization of virus-host interactions for the identification of novel therapeutic targets.
ANTIVIRAL RESEARCH
(2023)
Editorial Material
Oncology
Romain Desert, Fabio Giannone, Catherine Schuster, Thomas F. Baumert
INTERNATIONAL JOURNAL OF CANCER
(2023)
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)
Article
Cell Biology
Natascha Roehlen, Antonio Saviano, Houssein El Saghire, Emilie Crouchet, Zeina Nehme, Fabio Del Zompo, Frank Juehling, Marine A. Oudot, Sarah C. Durand, Francois H. T. Duong, Sara Cherradi, Victor Gonzalez Motos, Nuno Almeida, Clara Ponsolles, Laura Heydmann, Tessa Ostyn, Antonin Lallement, Patrick Pessaux, Emanuele Felli, Andrea Cavalli, Jacopo Sgrignani, Christine Thumann, Olga Koutsopoulos, Bryan C. Fuchs, Yujin Hoshida, Maike Hofmann, Mogens Vyberg, Birgitte Martine Viuff, Elisabeth D. Galsgaard, Greg Elson, Alberto Toso, Markus Meyer, Roberto Iacone, Tamas Schweighoffer, Geoffrey Teixeira, Solange Moll, Claudio De Vito, Tania Roskams, Irwin Davidson, Danijela Heide, Mathias Heikenwaelder, Mirjam B. Zeisel, Joachim Lupberger, Laurent Mailly, Catherine Schuster, Thomas F. Baumert
Summary: Tissue fibrosis is a major contributor to end-stage organ failure and cancer, accounting for a significant portion of deaths in developed countries. The protein CLDN1 has been identified as a mediator and therapeutic target for liver fibrosis, and its targeted treatment has shown promising results in preclinical studies.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Gastroenterology & Hepatology
Emanuele Felli, Emmanuel Boleslawski, Daniele Sommacale, Olivier Scatton, Raffaele Brustia, Lilian Schwarz, Daniel Cherqui, Thomas Zacharias, Alexis Laurent, Jean-Yves Mabrut, Catherine Schuster, Benoit Gallix, Patrick Pessaux
Summary: This study analyzed the role of preoperative 3D reconstruction models in selecting the surgical approach and modifying the established plan for hepatocellular carcinoma patients. The results showed that 3D imaging had a better prediction of the actual surgical procedure compared to conventional 2D imaging.
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.
