Article
Oncology
Dana El-Chami, Maria Al Haddad, Ralph Abi-Habib, Mirvat El-Sibai
Summary: Breast cancer is a major cause of death in women worldwide, with targeting breast cancer cell metastasis being an important therapeutic approach. The MAPK pathway has been identified as a key player in cellular invasion and migration. In this study, treatment with anthrax lethal toxin (LeTx) inhibited breast cancer cell migration by affecting the activation of RhoA and Cdc42, leading to decreased invasion and increased adhesion.
Article
Microbiology
Kenneth Smith, Lori Garman, Kathleen Norris, Jennifer Muther, Angie Duke, Renata J. M. Engler, Michael R. Nelson, Limone C. Collins, Christina Spooner, Carla Guthridge, Judith A. James
Summary: Research has found that some individuals vaccinated with anthrax vaccine may produce antibodies with poor neutralizing capabilities, potentially due to increased IgG4 to IgG1 ratios, low antibody avidity, and insufficient antibody targeting specific regions. Future vaccine formulations and vaccination schedules should aim to improve these deficiencies.
Article
Biochemistry & Molecular Biology
Rongfeng Li, Huahua Yu, Aoyu Li, Chunlin Yu, Pengcheng Li
Summary: In this study, a key lethal toxin (Letoxcn) was isolated from the jellyfish Cyanea nozakii. Its molecular weight is about 50 kDa and the N-terminal sequence is QADAEKVNLPVGVCV. Peptide mass fingerprinting analysis suggests that Letoxcn may have motifs of phospholipase, metalloprotease, thrombin-like enzyme, potassium channel inhibitor, etc. However, in vitro toxicity analysis only showed metalloprotease activity and no hemolytic, PLA2, or blood coagulation activity.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biophysics
Minghan Li, Shanchuan Chen, Yunjiao Wang, Shaoxia Zhang, Dandan Song, Rong Tian, Jia Geng, Liang Wang
Summary: In this study, a nanopore platform was fabricated to monitor intercellular protein transport and detect the activity of anthrax lethal factor (aLF) at a single molecule level. The aLF activity was successfully inhibited using screening approaches of protein-metal ion acquisition and other condition controlment. Ca2+, Mg2+, Mn2+, Ni2+ in collaboration with Zn2+ were found to promote aLF activity, while Cd2+, Co2+, Cu2+ showed inhibitory effects. The results also revealed that the speed of aLF endopeptidase activity with different ions functions as the nanopore signal frequency in a linear manner. In addition, the strength of the proton or hydroxide, as well as adapted temperature and gamma-ray, played integral roles in inhibiting aLF activity.
BIOSENSORS & BIOELECTRONICS
(2023)
Article
Multidisciplinary Sciences
Zehua Zuo, Jie Liu, Zhihao Sun, Yu-Wei Cheng, Michael Ewing, Thomas H. Bugge, Toren Finkel, Stephen H. Leppla, Shihui Liu
Summary: The current antitumor microenvironment strategies have limited efficacy due to poor understanding of the roles and contributions of tumor stromal cells in tumor development. Researchers have developed a versatile in vivo delivery system for an anthrax toxin protein, which allows for clear genetic evaluation of individual tumor stromal elements. The findings reveal the specific contribution of tumor endothelial cells (ECs) to the antitumor activity of the toxin, highlighting the importance of the MEK-ERK-c-Myc central metabolic axis in tumor ECs for tumor progression.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Medicine, Research & Experimental
Maryam Eskandari Mehrabadi, Roohullah Hemmati, Amin Tashakor, Ahmad Homaei, Masoumeh Yousefzadeh, Karim Hemati, Saman Hosseinkhani
Summary: This article discusses the impact of the novel coronavirus on ACE2 substrates and products, pointing out that this imbalance exacerbates the severity of COVID-19. It proposes multiple therapeutic strategies to rebalance ACE2 products and alleviate the symptoms of the disease.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Cell Biology
Idil Orhon, Cecilia Rocchi, Beatriz Villarejo-Zori, Paola Serrano Martinez, Mirjam Baanstra, Uilke Brouwer, Patricia Boya, Rob Coppes, Fulvio Reggiori
Summary: In dormant salivary gland stem cells, autophagy has a slower flux compared to self-renewing cells; however, enhancement of autophagy upon activation promotes self-renewal and tissue regeneration. Autophagy is a key pathway in activating self-renewal in low proliferative adult tissues, with potential for promoting tissue regeneration through pharmacological manipulation.
Article
Plant Sciences
Da-chuan Zhang, Ling-long Luo, Zhi-rong Wang, Wen-juan Xu, Jun-ling Li, Shu-ting Tan, Jia-hui Wu, Yan Li, Chi Zhang, Chen Liang, Xue-yong Wang
Summary: This study reveals that the SmDXS5 gene plays a significant role in increasing the content of tanshinones in Salvia miltiorrhiza. It regulates the distribution of tanshinones in primary and secondary metabolism and affects the transcription level and secondary metabolome profile of hairy roots in S. miltiorrhiza. The overexpression of SmDXS5 leads to the upregulation of the mevalonate and methylerythritol phosphate pathways, resulting in a significant increase in tanshinone components and a decrease in the accumulation of another secondary metabolite.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Xiaoyan Li, Hailang Fan, Xiantao Song, Bangrong Song, Wenxian Liu, Ran Dong, Haikun Zhang, Shicheng Guo, Hao Liang, Steven J. Schrodi, Xuebin Fu, Sunjay Kaushal, Yanlong Ren, Dake Zhang
Summary: Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease. Our study found aberrant DNA methylation patterns in HCM myocardium compared to normal myocardium, even though the transcription of methylation-related genes did not significantly differ. Functional enrichment analysis revealed immune cell function and muscle system processes as key clusters associated with DNA methylation alteration. The protein-protein interaction network highlighted the involvement of immune response and cardiac electrophysiology-related genes. A combination of DNA methylation and transcriptome profiles could potentially lead to the identification of new therapeutic targets for HCM.
Article
Chemistry, Medicinal
Madhulata Kumari, Naidu Subbarao
Summary: The aim of this study was to develop a one-dimensional convolutional neural network-based quantitative structure-activity relationship (1D-CNN-QSAR) model for identifying novel anthrax inhibitors and analyzing chemical space. The 1D-CNN-QSAR model showed a mean square error of 0.045 and a predicted correlation coefficient of 0.79 for the test set. Chemical space analysis revealed high fragment pair similarity and identified specific fragments associated with activity cliffs. These findings provide a basis for developing potent novel drug candidates for anthrax using the proposed model and fingerprint analysis.
FUTURE MEDICINAL CHEMISTRY
(2023)
Article
Plant Sciences
Conghui Li, Yadi Liu, Xiatong Liu, Keith Ka Ki Mai, Jiaxin Li, Xiaorui Guo, Chong Zhang, Hui Li, Byung-Ho Kang, Inhwan Hwang, Hai Lu
Summary: This study uncovered the process of chloroplast development in Populus tomentosa and identified the crucial role of PtotAPX in light-induced chloroplast development. These findings provide important insights into the mechanism of chloroplast development in woody plants.
JOURNAL OF EXPERIMENTAL BOTANY
(2021)
Review
Biochemistry & Molecular Biology
Melvin R. Hayden, William A. Banks
Summary: Obesity, metabolic syndrome, type 2 diabetes, and aging are global societal problems with potential complications, causing economic burdens to individuals and families. This review focuses on the role of leptin hormone from white adipose tissue in brain remodeling in female mice with hyperphagia, obesity, or hyperglycemia, examining structural changes in various brain components.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Food Science & Technology
Chenfan Dong, Haiyan Wu, Guanchao Zheng, Jixing Peng, Mengmeng Guo, Zhijun Tan
Summary: The study found that Mytilus galloprovincialis has a more efficient inflammatory balance mechanism compared to Argopecten irradians when exposed to PSTs, while A. irradians bears a higher risk of death due to the lack of a balance system.
Article
Biochemistry & Molecular Biology
Maxim Sinitsky, Anna Sinitskaya, Daria Shishkova, Alexey Tupikin, Maxim Asanov, Maria Khutornaya, Marsel Kabilov, Anastasia Ponasenko
Summary: Atherosclerosis, a leading cause of cardiovascular diseases, is linked to genotoxic stress-induced endothelial dysfunction. Transcriptome sequencing of endothelial cells exposed to mitomycin C revealed differentially expressed genes and identified functional groups involved in the development of atherosclerosis. This study contributes to a better understanding of the underlying mechanisms.
Review
Oncology
Ke-Ran Sun, Hui-Fang Lv, Bei-Bei Chen, Cai-Yun Nie, Jing Zhao, Xiao-Bing Chen
Summary: ANTXR1, also known as tumor endothelial marker 8, is a highly conserved cell surface protein overexpressed in tumor-infiltrating vessels. It promotes migration of endothelial cells, and plays an important role in tumor angiogenesis as well as in the growth and metastasis of many kinds of tumors. Previous studies have shown that ANTXR1 is necessary for tumor rather than physiological angiogenesis.
WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY
(2021)
Article
Cell Biology
Meng-Chen Tsai, Lucile Fleuriot, Sebastien Janel, David Gonzalez-Rodriguez, Camille Morel, Amel Mettouchi, Delphine Debayle, Stephane Dallongeville, Jean-Christophe Olivo-Marin, Bruno Antonny, Frank Lafont, Emmanuel Lemichez, Helene Barelli
Summary: This study investigated the impact of DHA-PLs on cell biomechanical properties and found that enrichment of DHA-PLs reduces cell thickness and promotes membrane fusion, while low DHA-PL levels lead to the formation of unstable and wider cell channels.
JOURNAL OF CELL SCIENCE
(2022)
Editorial Material
Genetics & Heredity
Marina Lusic, Musa M. Mhlanga
Summary: This article reveals that LINE1-containing transcripts play a crucial role in regulating T cell effector function and exhaustion, while the function of transposable elements in mammalian genomes remains unknown.
Article
Cell Biology
Adrien Grenier, Laury Poulain, Johanna Mondesir, Arnaud Jacquel, Claudie Bosc, Lucille Stuani, Sarah Mouche, Clement Larrue, Ambrine Sahal, Rudy Birsen, Victoria Ghesquier, Justine Decroocq, Fetta Mazed, Mireille Lambert, Mamy Andrianteranagna, Benoit Viollet, Patrick Auberger, Andrew A. Lane, Pierre Sujobert, Didier Bouscary, Jean-Emmanuel Sarry, Jerome Tamburini
Summary: AMPK activation in AML cells triggers the unfolded protein response, leading to repression of oxidative phosphorylation, TCA cycle, and pyrimidine biosynthesis, as well as enhanced mitochondrial apoptotic signaling. Combination therapy with the AMPK activator GSK621 and the Bcl-2 inhibitor venetoclax shows synergistic effects, suggesting therapeutic potential in AML.
Article
Oncology
Paul Chaintreuil, Lucie Laplane, Florian Esnault, Victoria Ghesquier, Coline Savy, Nathan Furstoss, Marie-Laure Arcangeli, Thomas Cluzeau, Guillaume Robert, Nathalie Droin, Eric Solary, Patrick Auberger, Arnaud Jacquel
Summary: Macrophages are innate immune cells that play crucial roles in various physiological and pathological processes. Caspases, previously known for their involvement in programmed cell death, are found to have non-apoptotic functions in macrophage differentiation and inflammation. Emricasan, a pan-caspase inhibitor, has shown potential in reprogramming monocyte-derived macrophages and could be an alternative therapy for diseases driven by these macrophages.
Letter
Oncology
Vilma Barroca, Elia Henry, Nathalie Dechamps, Laurent Renou, Paul Chaintreuil, Rohan Kulkarni, Saiyirami Devanand, Arnaud Jacquel, Guillaume Robert, Patrick Auberger, Francoise Pflumio, Marie-Laure Arcangeli
Article
Multidisciplinary Sciences
Shivalika Tanwar, Patrick Auberger, Germain Gillet, Mario DiPaola, Katya Tsaioun, Bruno O. Villoutreix
Summary: Identification of off-targets is crucial in drug discovery, and FastTargetPred is a method that predicts putative macromolecular targets for small molecule compounds based on chemical similarity search approaches. This study provides a new dataset for target prediction of peptides and includes links to ChEMBL, UniProt, and Reactome databases.
Article
Biotechnology & Applied Microbiology
Emmanuelle Boix, Louis Coroller, Olivier Couvert, Stella Planchon, Arnoud H. M. van Vliet, Jason Brunt, Michael W. Peck, Christine Rasetti-Escargueil, Emmanuel Lemichez, Michel R. Popoff, Stephane Andre
Summary: This study investigates the physiological characteristics of C. sporogenes and Group I C. botulinum isolates. It found that the combination of pH, NaCl, and heat treatment can help prevent or minimize foodborne botulism outbreaks.
Article
Food Science & Technology
Grazia Cottone, Letizia Chiodo, Luca Maragliano, Michel-Robert Popoff, Christine Rasetti-Escargueil, Emmanuel Lemichez, Therese E. Malliavin
Summary: Combined homology modeling and atomistic simulations are used to investigate the internal dynamics of botulinum neurotoxins (BoNTs). The study reveals that the conformational variations of BoNTs are influenced by pH and protein structure, and the mobility of the belt alpha-helix may interact with the core translocation domain during the translocation process, providing important insights into the molecular mechanism of BoNTs.
Article
Hematology
Lorric Delage, Mireille Lambert, Cindy Kundlacz, Dimitri Chartoire, Axel Conchon, Lucas Gorka, Patrick Auberger, Arnaud Jacquel, Carole Soussain, Olivier Destaing, Henri -Jacques Delecluse, Susanne Delecluse, Samir Merabet, Alexandra Traverse-Glehen, Gilles Salles, Emmanuel Bachy, Marc Billaud, Herve Ghesqueres, Jean-Pierre Rouaut, Pierre Sujobert
Summary: Understanding the role of mutated genes is crucial for improving cancer treatment. This study focuses on the BTG1 gene, which is frequently mutated in DLBCL. The researchers found that BTG1 deletion accelerates the development of lymphoproliferative disease driven by Bcl2 overexpression. They also discovered that BCAR1 is a partner of BTG1 and that overactivation of the BCAR1-RAC1 pathway increases cell migration ability. The SRC inhibitor dasatinib can target these modifications, providing new therapeutic opportunities for BTG1 mutated DLBCL.
Article
Oncology
Zakia Aid, Elie Robert, Cecile K. Lopez, Maxence Bourgoin, Fabien Boudia, Melchior Le Mene, Julie Riviere, Marie Baille, Salima Benbarche, Laurent Renou, Alexandre Fagnan, Cecile Thirant, Laetitia Federici, Laure Touchard, Yann Lecluse, Anton Jetten, Birgit Geoerger, Helene Lapillonne, Eric Solary, Muriel Gaudry, Soheil Meshinchi, Francoise Pflumio, Patrick Auberger, Camille Lobry, Arnaud Petit, Arnaud Jacquel, Thomas Mercher
Summary: Pediatric acute myeloid leukemia expressing the ETO2::GLIS2 fusion oncogene has a poor prognosis. The expression of ETO2::GLIS2 leads to activation of CASP3 and increased cell death. Inhibiting both BCL2 and MCL1 is necessary to prevent disease progression in vivo, suggesting a potential therapeutic strategy for this aggressive pediatric AML subgroup.
Article
Multidisciplinary Sciences
Arthur Louche, Amandine Blanco, Thais Lourdes Santos Lacerda, Lison Cancade-Veyre, Claire Lionnet, Celia Berge, Monica Rolando, Frederique Lembo, Jean-Paul Borg, Carmen Buchrieser, Masami Nagahama, Francine C. A. Gerard, Jean-Pierre Gorvel, Virginie Gueguen-Chaignon, Laurent Terradot, Suzana P. P. Salcedo
Summary: The cell nucleus is a primary target for intracellular bacterial pathogens. Two Brucella abortus effectors, NyxA and NyxB, interfere with host protease SENP3, promoting intracellular replication of the pathogen.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Anne Calleja, Michael Loschi, Laurent Bailly, Adeline Morisot, Alice Marceau, Lionel Mannone, Guillaume Robert, Patrick Auberger, Claude Preudhomme, Sophie Raynaud, Fabien Subtil, Pierre Sujobert, Thomas Cluzeau
Summary: Personalized medicine is a significant challenge for patients with acute myeloid leukemia (AML). This study evaluated the prognostic value of a personalized prognostic scoring algorithm known as Knowledge Bank (KB) on a cohort of 167 real-life AML patients. The results showed that the KB algorithm accurately predicted outcomes for younger patients in favorable and intermediate ELN risk categories but failed to predict survival for younger patients in the adverse ELN risk category and older patients in the favorable ELN risk category. The discrepancies may be attributed to the emergence of new therapeutic options and improvements in allogeneic stem cell transplantation (aHSCT) outcomes and supportive cares. Therefore, prospective validation of these scoring systems is necessary to incorporate recent therapeutic innovations.
Article
Multidisciplinary Sciences
Daniel Schator, Sonia Mondino, Jeremy Berthelet, Cristina Di Silvestre, Mathilde Ben Assaya, Christophe Rusniok, Fernando Rodrigues-Lima, Annemarie Wehenkel, Carmen Buchrieser, Monica Rolando
Summary: Legionella pneumophilia secretes more than 300 effectors, including RomA and LphD, via a type IV secretion system. RomA methylates histone H3 at K14 to counteract host immune responses, while LphD deacetylates H3K14 to work synergistically with RomA. The two effectors target host chromatin and bind the HBO1 histone acetyltransferase complex to regulate histone modifications.
NATURE COMMUNICATIONS
(2023)
Meeting Abstract
Hematology
Coen van Solingen, Yannick Cyr, Kaitlyn Scacalossi, Maren de Vries, Tessa Barrett, Annika De Jong, Morgane Gourvest, Tracy Zhang, Raadhika Kher, Macintosh Cornwell, Michael Gildea, Emily Brown, Stephanie Fanucchi, Musa Mhlanga, Jeffrey Berger, Meike Dittmann, Kathryn J. Moore
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Article
Oncology
Kevin H. Lin, Justine C. Rutter, Abigail Xie, Shane T. Killarney, Camille Vaganay, Chaima Benaksas, Frank Ling, Gaetano Sodaro, Paul-Arthur Meslin, Christopher F. Bassil, Nina Fenouille, Jacob Hoj, Rachel Washart, Hazel X. Ang, Christian Cerda-Smith, Paul Chaintreuil, Arnaud Jacquel, Patrick Auberger, Antoine Forget, Raphael Itzykson, Min Lu, Jiaxing Lin, Mariaelena Pierobon, Zhecheng Sheng, Xinghai Li, Ashutosh Chilkoti, Kouros Owzar, David A. Rizzieri, Timothy S. Pardee, Lina Benajiba, Emanuel Petricoin, Alexandre Puissant, Kris C. Wood
Summary: The XPO1 inhibitor Selinexor activates PI3Ky-dependent AKT signaling in AML via upregulation of P2RY2, leading to positive antileukemic effects. Inhibiting this signaling pathway enhances the efficacy of Selinexor in AML.