Article
Cell Biology
Yu Sugimoto, Daiki Endo, Yasuaki Aratani
Summary: In a zymosan-induced systemic inflammation model, CGD mice deficient in the phagocyte NADPH oxidase gp91phox subunit exhibited severe thymic atrophy and lymphopenia, along with enhanced neutrophilic inflammation, while showing increased circulating and splenic neutrophils and enhanced granulopoiesis compared with wild-type mice.
Article
Biochemistry & Molecular Biology
Stephenson B. Owusu, Elodie Hudik, Celine Ferard, Sophie Dupre-Crochet, Eric C. D. K. Addison, Kwasi Preko, Tania Bizouarn, Chantal Houee-Levin, Laura Baciou
Summary: Simulating oxidative stress with gamma irradiation leads to shortened half-lives of neutrophils but pre-activates surviving cells to produce superoxide anions. Incomplete assembly of the NADPH oxidase complex after irradiation significantly enhances neutrophil reactivity.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Microbiology
Hasnaa Maksouri, Dounia Darif, Jerome Estaquier, Myriam Riyad, Christophe Desterke, Meryem Lemrani, Pham My-Chan Dang, Khadija Akarid
Summary: This study evaluated the impact of Moroccan strains of L. major and L. tropica on PMNs. The results showed that L. tropica inhibited O-2(-) production, while L. major did not. Additionally, Leishmania soluble antigens from both species inhibited O-2(-) induction.
Review
Oncology
Hao Sun, Yingmei Li, Peng Zhang, Haizhou Xing, Song Zhao, Yongping Song, Dingming Wan, Jifeng Yu
Summary: Toll-like receptors (TLRs) are expressed in immune cells and tumors, playing roles in tumor immune surveillance and growth. Activation of TLR7/8 induces innate immune response and can be used as diagnostic and therapeutic targets in cancer.
BIOMARKER RESEARCH
(2022)
Article
Chemistry, Medicinal
Mu Yang, Peter G. Larson, Lincoln Brown, John R. Schultz, Tamara A. Kucaba, Thomas S. Griffith, David M. Ferguson
Summary: This study investigates the effect of isomeric substitutions to the C2-butyl group of imidazoquinoline agonists on Toll-like receptors (TLR) 7 and 8. The results show that the conformations of the dimeric receptor complex are highly sensitive to steric perturbations, indicating the importance of the ligand binding pocket in regulating the receptor signal. This finding has significant implications for the design of immunomodulatory agents.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Natsumi Ogawa, Shingo Nakajima, Kenya Tamada, Natsuki Yokoue, Haruki Tachibana, Miwa Okazawa, Takahiro Oyama, Hideaki Abe, Hiroaki Yamazaki, Atsushi Yoshimori, Akira Sato, Takanori Kamiya, Takehiko Yokomizo, Fumiaki Uchiumi, Takehiko Abe, Sei-ichi Tanuma
Summary: The spasmolytic drug trimebutine has shown potential as an anti-inflammatory agent in experiments, reducing the production of various proinflammatory factors and significantly decreasing mortality in a mouse model of sepsis. Studies have found that trimebutine exerts its anti-inflammatory effects by inhibiting TLR signaling pathways and NF-kappa B activity.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Chemistry, Multidisciplinary
Yanyun Hao, Hui Li, Xiaoyan Ge, Yang Liu, Xia Li, Yutong Liu, Hongfei Chen, Shiying Zhang, Jing Zou, Lingling Huang, Fabao Zhao, Dongwei Kang, Bruno G. De Geest, Zhiyue Zhang
Summary: In this study, a polymeric nano-immunomodulator was developed to selectively activate the immune system in tumors, enhancing T lymphocyte infiltration without causing immune-related adverse effects. It shows promising potential for safe systemic targeting delivery.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Medicinal
Ratna Kumar Sreekantha, Christopher P. Mussari, Dharmpal S. Dodd, Laxman Pasunoori, Subramanya Hegde, Shana L. Posy, David Critton, Stefan Ruepp, Murali Subramanian, Luisa M. Salter-Cid, Debarati Mazumder Tagore, Sanket Sarodaya, Shailesh Dudhgaonkar, Michael A. Poss, Gary L. Schieven, Percy H. Carter, John E. Macor, Alaric J. Dyckman
Summary: Toll-like receptors are crucial for activation of the innate immune system. Aberrant activation of TLR7 and TLR8 can lead to autoimmune disorders, and inhibition of their signaling holds promise for disease treatment. A study identified potent dual inhibitors of TLR7 and TLR8, which selectively targeted these receptors and showed promising in vitro and in vivo results.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Review
Pharmacology & Pharmacy
Xuan Huang, Xiaoyong Zhang, Mengji Lu
Summary: TLR7 and TLR8 signaling pathways are favorable drug candidates for the treatment of immune disorders, with agonists and antagonists being used to enhance immune responses or reduce immune overreactions. Optimizing drug safety, efficacy, and specificity, as well as conducting detailed mechanistic studies, will contribute to the development of novel TLR7/8 immunomodulators and therapeutic strategies.
EXPERT OPINION ON DRUG DISCOVERY
(2021)
Article
Chemistry, Multidisciplinary
Guo Li, Yongxiao Xu, Xiaojie Kong, Liuwei Gu, Yuling Qin, Li Wu
Summary: An NQO1-responsive precursor called R848-QPA has been developed to induce an anti-tumor immune response. When activated by overexpressed NQO1 in the tumor microenvironment, R848-QPA can activate innate immunity, but it shows lower activity in NQO1-deprived environments. This strategy offers a new approach for the development of tumor-microenvironment-responsive prodrugs for antitumor immunotherapy.
CHEMICAL COMMUNICATIONS
(2023)
Article
Immunology
Maarit Eskuri, Niko Kemi, Olli Helminen, Heikki Huhta, Joonas H. Kauppila
Summary: The study found that high nuclear expression of TLR3 is associated with poorer 5-year survival in gastric cancer patients, while TLR7, TLR8, and TLR9 are not.
Article
Immunology
Ershun Zhou, Zhikai Wu, Xingyi Zhu, Peixuan Li, Jingjing Wang, Zhengtao Yang
Summary: This study investigated the role of histamine on bovine NET formation and its preliminary molecular mechanisms. The results showed that histamine triggered dose-dependent NET release and elevated ROS production, phosphorylated ERK and p38 proteins in PMNs. Inhibition of NADPH oxidase, ERK, and p38 pathways reduced histamine-induced NET formation, revealing potential molecular mechanisms behind this process.
VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY
(2021)
Review
Pharmacology & Pharmacy
Sachin Bhagchandani, Jeremiah A. Johnson, Darrell J. Irvine
Summary: Imidazoquinoline derivatives function as synthetic agonists of Toll-like receptors 7 and 8, with potential therapeutic utility in antitumor immunomodulation and vaccine adjuvants. However, challenges such as broad expression profiles, poor pharmacokinetic properties, and associated toxicities hinder their successful clinical translation. Strategies to enhance safety and efficacy through bioconjugates and nanoparticle formulations are being explored to address these barriers.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Article
Immunology
Melika Shafeghat, Sina Kazemian, Arya Aminorroaya, Zahra Aryan, Nima Rezaei
Summary: TLR-7 plays a crucial role in the pathogenesis and development of cardiovascular diseases by activating inflammatory responses and affecting the risk of thrombus formation. It has a two-sided effect, both increasing and decreasing the risk of cardiovascular problems.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Cell Biology
Stuart Hawtin, Cedric Andre, Geraldine Collignon-Zipfel, Simone Appenzeller, Bettina Bannert, Lea Baumgartner, Damian Beck, Claudia Betschart, Thomas Boulay, Hermine I. Brunner, Melanie Ceci, Jonatha Deane, Roland Feifel, Enrico Ferrero, Diego Kyburz, Frederique Lafossas, Pius Loetscher, Christina Merz-Stoeckle, Pierre Michellys, Barbara Nuesslein-Hildesheim, Friedrich Raulf, James S. Rush, Giulia Ruzzante, Thomas Stein, Samantha Zaharevitz, Grazyna Wieczorek, Richard Siegel, Peter Gergely, Tamas Shisha, Tobias Junt
Summary: Genetic and in vivo evidence suggests that MHV370, a selective oral TLR7/8 inhibitor, can effectively inhibit TLR7/8-dependent immune cell activity and cytokine production, particularly interferon-a. In mouse models, MHV370 shows promising results in preventing and treating TLR7 responses-related diseases, including cytokine secretion, B cell activation, and upregulation of interferon-stimulated genes. These findings support the ongoing phase 2 clinical trial of MHV370.
CELL REPORTS MEDICINE
(2023)
Article
Gastroenterology & Hepatology
Shantha Ram Valainathan, Riccardo Sartoris, Laure Elkrief, Marta Magaz, Fabian Betancourt, Silvia Pellegrino, Arianna Nivolli, Marco Dioguardi Burgio, Yves Flattet, Sylvain Terraz, Nicolas Drilhon, Marie Lazareth, Julia Herrou, Onorina Bruno, Audrey Payance, Aurelie Plessier, Francois Durand, Maxime Ronot, Dominique-Charles Valla, Valerie Paradis, Juan Carlos Garcia-Pagan, Valerie Vilgrain, Pierre-Emmanuel Rautou
Summary: This study demonstrates that liver surface nodularity (LSN) and CT features are highly correlated with the diagnosis of Porto-sinusoidal vascular disorder (PSVD). A combination of LSN < 2.5 and normal-sized or enlarged segment IV strongly suggests PSVD in patients with signs of portal hypertension.
Article
Gastroenterology & Hepatology
Dimitri Loureiro, Issam Tout, Stephanie Narguet, Cheikh Mohamed Bed, Morgane Roinard, Ahmad Sleiman, Nathalie Boyer, Nathalie Pons-Kerjean, Corinne Castelnau, Nathalie Giuly, Dorothy Tonui, Vassili Soumelis, Jamel El Benna, Patrick Soussan, Richard Moreau, Valerie Paradis, Abdellah Mansouri, Tarik Asselah
Summary: This study found that hepatitis B virus (HBV) infection can alter liver mitochondria and lead to changes in mitochondrial function and DNA damage associated with cirrhosis and fibrosis. In vitro experiments showed that HBV replication or expression of HBV X protein can induce the production of reactive oxygen species and nitric oxide, as well as mitochondrial DNA damage and impairment of mitochondrial function. These findings suggest that mitochondria may be a new target for drug development to prevent fibrosis progression.
Article
Gastroenterology & Hepatology
Jiri Reinis, Oleksandr Petrenko, Benedikt Simbrunner, Benedikt S. Hofer, Filippo Schepis, Marco Scoppettuolo, Dario Saltini, Federica Indulti, Tomas Guasconi, Agustin Albillos, Luis Tellez, Candid Villanueva, Anna Brujats, Juan Carlos Garcia-Pagan, Valeria Perez-Campuzano, Virginia Hernandez-Gea, Pierre-Emmanuel Rautou, Lucile Moga, Thomas Vanwolleghem, Wihelmus J. Kwanten, Sven Francque, Jonel Trebicka, Wenyi Gu, Philip G. Ferstl, Lise Lotte Gluud, Flemming Bendtsen, Soren Moller, Stefan Kubicek, Mattias Mandorfer, Thomas Reiberger
Summary: Machine learning models based on standard laboratory parameters can predict the severity of portal hypertension in individuals with compensated advanced chronic liver disease (cACLD). The models performed well in the Vienna cohort but had heterogeneous results in external validation.
JOURNAL OF HEPATOLOGY
(2023)
Letter
Gastroenterology & Hepatology
Shantha Ram Valainathan, Maxime Ronot, Valerie Vilgrain, Pierre-Emmanuel Rautou
Article
Immunology
Marta Magaz, Heloise Giudicelli-Lett, Oana Nicoara-Farcau, Neil Rajoriya, Ashish Goel, Karlien Raymenants, Sophie Hillaire, Gonzalo Crespo, Luis Tellez, Laure Elkrief, Constantino Fondevila, Lara Orts, Filipe Nery, Akash Shukla, Helene Larrue, Yiliam Fundora, Helena Degroote, Victoria Aguilera, Elba LLop, Laura Turco, Federica Indulti, Stefania Gioia, Giulia Tosetti, Niccolo Bitto, Chiara Becchetti, Edilmar Alvarado, Cristina Roig, Raquel Diaz, Michael Praktiknjo, Anna-Lena Konicek, Guillem Soy, Pol Olivas, Jose Ignacio Fortea, Helena Masnou, Angela Puente, Alba Ardevol, Carmen Alvarez-Navascues, Marta Romero, Bernhard Scheiner, Georg Semmler, Mattias Mandorfer, Filipe Damiao, Anna Baiges, Fanny Turon, Macarena Simon-Talero, Carlos Gonzalez-Alayon, Alba Diaz, Angeles Garcia-Criado, Andrea de Gottardi, Enric Reverter, Annabel Blasi, Joan Genesca, Olivier Roux, Claire Francoz, Carlos Noronha Ferreira, Thomas Reiberger, Manuel Rodriguez, Rosa Maria Morillas, Javier Crespo, Jonel Trebicka, Rafael Banares, Candid Villanueva, Annalisa Berzigotti, Massimo Primignani, Vincenzo La Mura, Oliviero Riggio, Filippo Schepis, Bogdan Procopet, Xavier Verhelst, Jose Luis Calleja, Christophe Bureau, Agustin Albillos, Frederik Nevens, Virginia Hernandez-Gea, Dhiraj Tripathi, Pierre-Emmanuel Rautou, Francois Durand, Juan Carlos Garcia-Pagan
Summary: This study aimed to identify features associated with post-LT outcomes in PSVD. The results showed that patients without associated severe conditions had better survival rates after LT, while pre-LT high bilirubin levels and creatinine >100 μmol/L were associated with poor survival.
Article
Gastroenterology & Hepatology
Alberto Queiroz Farias, Anna Curto Vilalta, Patricia Momoyo Zitelli, Gustavo Pereira, Luciana L. Goncalves, Aldo Torre, Juan Manuel Diaz, Adrian C. Gadano, Angelo Z. Mattos, Liliana S. C. Mendes, Mario R. Alvares-da-Silva, Paulo L. Bittencourt, Carlos Benitez, Claudia Alves Couto, Manuel Mendizabal, Claudio L. Toledo, Daniel F. C. Mazo, Mauricio Castillo Barradas, Eva M. Uson Raposo, P. Martin Padilla-Machaca, Adelina Zarela Lozano Miranda, Rene Male-Velazquez, Andre Castro Lyra, Milagros B. Davalos-Moscol, Jose L. Perez Hernandez, Rafael O. Ximenes, Giovanni Faria Silva, Oscar A. Beltran-Galvis, Maria S. Gonzalez Huezo, Fernando Bessone, Tarciso D. S. Rocha, Eduardo Fassio, Carlos Terra, Juan I. Marin, Patricia Sierra Casas, Carlos de la Pena-Ramirez, Ferran Aguilar Parera, Flavia Fernandes, Maria da Penha Zago-Gomes, Osvely Mendez-Guerrero, Sebastian Marciano, Angelo A. Mattos, Joao C. Oliveira, Gabriel T. S. Guerreiro, Liana Codes, Marco Arrese, Mateus J. Nardelli, Marcelo O. Silva, Renato Palma-Fernandez, Camila Alcantara, Cristina Sanchez Garrido, Jonel Trebicka, Thierry Gustot, Javier Fernandez, Joan Claria, Rajiv Jalan, Paolo Angeli, Vicente Arroyo, Richard Moreau, ACLARA Study Collaborators
Summary: This study investigated the association of genetic ancestry and race with acute-on chronic liver failure (ACLF). The results showed that Latin American patients with higher Native American genetic ancestry and Native American race were more likely to develop ACLF. This suggests that genetic ancestry and race may be associated with the risk of ACLF.
Article
Gastroenterology & Hepatology
Emmanuel Weiss, Carlos de la Pena-Ramirez, Ferran Aguilar, Juan-Jose Lozano, Cristina Sanchez-Garrido, Patricia Sierra, Pedro Izquierdo-Bueno Martin, Juan Manuel Diaz, Francois Fenaille, Florence A. Castelli, Thierry Gustot, Wim Laleman, Agustin Albillos, Carlo Alessandria, Marco Domenicali, Paolo Caraceni, Salvatore Piano, Faouzi Saliba, Stefan Zeuzem, Alexander L. Gerbes, Julia A. Wendon, Christian Jansen, Wenyi Gu, Maria Papp, Raj Mookerjee, Carmine Gabriele Gambino, Cesar Jimenez, Ilaria Giovo, Giacomo Zaccherini, Manuela Merli, Antonella Putignano, Frank Erhard Uschner, Thomas Berg, Tony Bruns, Christian Trautwein, Alexander Zipprich, Rafael Banares, Jose Presa, Joan Genesca, Victor Vargas, Javier Fernandez, Mauro Bernardi, Paolo Angeli, Rajiv Jalan, Joan Claria, Christophe Junot, Richard Moreau, Jonel Trebicka, Vicente Arroyo
Summary: This study aimed to identify metabolites associated with short-term death in patients with acutely decompensated cirrhosis and design metabolomic prognostic models. Three prognostic metabolites strongly associated with death were selected and two models were built, which were found to be more accurate in predicting death within 7, 14, and 28 days compared to traditional scoring systems.
Article
Gastroenterology & Hepatology
European Assoc Study Liver, Richard Moreau, Marta Tonon, Aleksander Krag, Paolo Angeli, Marina Berenguer, Annalisa Berzigotti, Javier Fernandez, Claire Francoz, Thierry Gustot, Rajiv Jalan, Maria Papp, Jonel Trebicka
Summary: Acute-on-chronic liver failure (ACLF) is a severe form of acutely decompensated cirrhosis characterized by organ system failure(s) and high short-term mortality. Patients with ACLF may benefit from liver transplantation and should be promptly stabilized for transplantation by treating identified precipitants and providing intensive care support. These guidelines aim to help clinicians recognize ACLF, make triage decisions, manage acute precipitants, support organ systems, determine futility of intensive care, and identify potential indications for liver transplantation.
JOURNAL OF HEPATOLOGY
(2023)
Review
Gastroenterology & Hepatology
Laure Elkrief, Audrey Payance, Aurelie Plessier, Louis d'Alteroche, Maxime Ronot, Valerie Paradis, Dominique Valla, Pierre-Emmanuel Rautou
Summary: The article discusses splanchnic vein thrombosis, including Budd-Chiari syndrome and portal vein thrombosis. These rare diseases can cause portal hypertension and its complications. Risk factors for thrombosis in these patients include myeloproliferative neoplasms, and a thorough work-up is needed. Long-term anticoagulation is typically recommended. The presence and nature of underlying liver disease affect the management of portal vein thrombosis, with indications for anticoagulation in cirrhosis patients growing. Collaborative studies have provided new insights into the management of these diseases.
Review
Gastroenterology & Hepatology
Joan Claria, Vicente Arroyo, Richard Moreau
Summary: Acute-on-chronic liver failure (ACLF) is the most severe form of acutely decompensated cirrhosis and is characterized by intense systemic inflammation and various mechanisms that lead to organ failures, including vasodilation, neutrophil migration, microthrombi formation, hepatic encephalopathy, and energy competition.
Article
Gastroenterology & Hepatology
Pierre-Emmanuel Rautou, Stephen H. Caldwell, Erica Villa
Summary: Our understanding of the coagulopathy of liver disease has significantly evolved over the past 25 years. Despite the common impression of hemorrhagic tendency, this form of coagulopathy is actually hypercoagulability. The use of INR as a measure in this situation is not meaningful and may worsen pressure-driven bleeding.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Review
Gastroenterology & Hepatology
Ruben Hernaez, Hai Li, Richard Moreau, Minneke J. Coenraad
Summary: This narrative review discusses the definition of acute-on-chronic liver failure, its association with high short-term mortality in patients with chronic liver disease and/or cirrhosis, and the differences in definitions between the East and the West. Despite the variations, all definitions have clinical utility and serve different purposes. The review also provides epidemiological data to illustrate how these definitions apply in different regions.
LIVER INTERNATIONAL
(2023)
Editorial Material
Radiology, Nuclear Medicine & Medical Imaging
Alessandro M. Bozzato, Onorina Bruno, Audrey Payance, Aurelie Plessier, Amelie Chouard, Pierre -Emmanuel Rautou, Valerie Vilgrain, Maxime Ronot
Article
Gastroenterology & Hepatology
Gautam Mehta, Antonio Riva, Maria Pilar Ballester, Eva Uson, Montserrat Pujadas, Angela Carvalho-Gomes, Ivan Sahuco, Ariadna Bono, Federico D'Amico, Raffaela Vigano, Elena Diago, Beatriz Tormo Lanseros, Elvira Inglese, Dani Martinez Vazquez, Rajni Sharma, Hio Lam Phoebe Tsou, Nicola Harris, Annelotte Broekhoven, Marjolein Kikkert, Shessy P. Torres Morales, Sebenzile K. Myeni, Mar Riveiro-Barciela, Adriana Palom, Nicola Zeni, Alessandra Brocca, Annarosa Cussigh, Sara Cmet, Desamparados Escudero-Garcia, Matteo Stocco, Leonardo Antonio Natola, Donatella Ieluzzi, Veronica Paon, Angelo Sangiovanni, Elisa Farina, Clara di Benedetto, Yolanda Sanchez-Torrijos, Ana Lucena-Varela, Eva Roman, Elisabet Sanchez, Ruben Sanchez-Aldehuelo, Julia Lopez-Cardona, Itzel Canas-Perez, Christine Eastgate, Dhaarica Jeyanesan, Alejandro Esquivel Morocho, Simone Di Cola, Lucia Lapenna, Giacomo Zaccherini, Deborah Bongiovanni, Paola Zanaga, Katia Sayaf, Sabir Hossain, Javier Crespo, Mercedes Robles-Diaz, Antonio Madejon, Helena Degroote, Javier Fernandez, Marko Korenjak, Xavier Verhelst, Javier Garcia-Samaniego, Raul J. Andrade, Paula Iruzubieta, Gavin Wright, Paolo Caraceni, Manuela Merli, Vishal C. Patel, Amir Gander, Agustin Albillos, German Soriano, Maria Francesca Donato, David Sacerdoti, Pierluigi Toniutto, Maria Buti, Christophe Duvoux, Paolo Antonio Grossi, Thomas Berg, Wojciech G. Polak, Massimo Puoti, Anna Bosch-Comas, Luca Belli, Patrizia Burra, Francesco Paolo Russo, Minneke Coenraad, Jose Luis Calleja, Giovanni Perricone, Marina Berenguer, Joan Claria, Richard Moreau, Vicente Arroyo, Paolo Angeli, Cristina Sanchez, Javier Ampuero, Salvatore Piano, Shilpa Chokshi, Rajiv Jalan
Summary: This study aimed to measure humoral responses to COVID-19 vaccine among liver patients and determine the factors predicting breakthrough infection. The results showed that liver transplant patients had the lowest response to the vaccine, while reduced response in cirrhosis patients was associated with age, stage of liver disease, and systemic inflammation.
HEPATOLOGY COMMUNICATIONS
(2023)
Review
Critical Care Medicine
Jinjin Luo, Jiaqi Li, Peng Li, Xi Liang, Hozeifa Mohamed Hassan, Richard Moreau, Jun Li
Summary: Acute-on-chronic liver failure (ACLF) is a severe clinical syndrome characterized by acute deterioration of chronic liver disease, organ failure, and high short-term mortality. Different definitions and diagnostic criteria have been proposed in different geographic regions due to varied causes and trigger events. Predictive and prognostic scores have been developed and validated to guide clinical management. The specific pathophysiology of ACLF is uncertain but is believed to be associated with intense systemic inflammation and immune-metabolism disorder.