Article
Biochemistry & Molecular Biology
Alvaro Baeza Garcia, Edwin Siu, Xin Du, Lin Leng, Blandine Franke-Fayard, Chris J. Janse, Shanshan W. Howland, Laurent Renia, Elias Lolis, Richard Bucala
Summary: Cerebral malaria, the deadliest complication of Plasmodium parasite infection, may be caused by neuroinflammation leading to cerebral edema and blood-brain barrier dysfunction. Plasmodium MIF can enhance inflammatory response by signaling through host MIF receptor CD74, contributing to the development of cerebral malaria. Studies using CD74 deficient hosts and PMIF deficient parasites suggest a potential mechanism for the onset of experimental cerebral malaria and liver stage Plasmodium development.
Article
Immunology
Hongxia Duan, Shuai Zhao, Jianquan Xiang, Chenhui Ju, Xuehui Chen, Irene Gramaglia, Xiyun Yan
Summary: The study found that endothelial CD146 plays a crucial role in experimental cerebral malaria, with its overexpression leading to the aggregation of infected red blood cells and lymphocytes, thereby disrupting BBB integrity. Deletion of endothelial CD146 or treatment with anti-CD146 antibody can prevent severe symptoms of cerebral malaria, and combined treatment with anti-CD146 antibody and antiparasitic drugs can improve cognition and memory in patients with cerebral malaria.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Physiology
Patrick S. Hume, Jazalle McClendon, Katrina W. Kopf, Julie W. Harral, Joanna M. Poczobutt, Alexandra L. McCubbrey, Bradford J. Smith, Peter M. Henson, Susan M. Majka, Irina Petrache, William J. Janssen
Summary: This study examined the role of leukocyte HIF-1α in the development of cigarette smoke-induced lung disease using mice with conditional deletion or overexpression of HIF-1α. The results showed that overexpression of leukocyte HIF-1α did not affect the development of cigarette smoke-induced lung disease, suggesting that this signaling pathway is not involved in the development of murine lung disease.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2022)
Article
Cell Biology
Min Chen, Lei Wang, Min Li, Marietta M. Budai, Jin Wang
Summary: Mitochondrial disruption can lead to cell death through caspase-9 activation. However, cell death can also occur independently of caspase-9, suggesting the existence of caspase-9-independent cell death mechanisms. Through a genome-wide siRNA library screening, researchers identified a network of genes that mediate caspase-9-independent cell death through ROS production and Alox5-dependent membrane lipid peroxidation. The Erk1-Alox5 pathway plays a critical role in promoting membrane lipid peroxidation and nuclear translocation of cytolytic molecules, resulting in cell death.
Article
Multidisciplinary Sciences
Marcela Parra, Jiyeon Yang, Megan Weitner, Mustafa Akkoyunlu
Summary: The study found that the lack of PABA in maternal milk may provide protection against malaria infection in newborn mice, delaying and reducing the onset of parasitemia. Mice fed with a PABA-deficient diet after weaning were still able to control parasitemia and developed robust T follicular helper responses, providing protection against a second challenge with Plasmodium yoelii.
SCIENTIFIC REPORTS
(2021)
Article
Clinical Neurology
Regina T. Vontell, Juan Pablo de Rivero Vaccari, Xiaoyan Sun, Sakir Humayun Gultekin, Helen M. Bramlett, W. Dalton Dietrich, Robert W. Keane
Summary: Alzheimer's disease (AD) is a progressive neurodegenerative disease that affects memory and cognitive function. Inflammasome activation is thought to play a crucial role in the neuroinflammatory response in AD progression. This study explored the expression of inflammasome proteins in different brain regions of AD donors and observed changes in cellular pathology between early and intermediate stages of AD. The results showed increased expression of inflammasome proteins in the early pathological stages of AD, and the use of specific antibodies identified neurons and microglia involved in the disease.
Article
Multidisciplinary Sciences
Sireesh Kumar Teertam, Prakash Babu Phanithi
Summary: The study found that the expression of Sirt1, Beclin-1, Atg-3, 5, 7, 12-5, and Lc3-II/I were upregulated in stroke patients. Immunohistochemistry results showed increased immunoreactivity of Sirt1, Beclin-1, Atg-7, Lc3-I/II, and cleaved caspase-3 in stroke brains.
Review
Biochemistry & Molecular Biology
Jing Zhang, Xianxin Zheng, Peiyan Wang, Jianxun Wang, Wei Ding
Summary: ARC is a highly effective and multifunctional inhibitor of apoptosis expressed in postmitotic cells like cardiomyocytes and skeletal muscle cells. It has a cardioprotective role by inhibiting cardiomyocyte death in various ways, such as reducing apoptotic response to stresses like extrinsic apoptosis induced by death receptor ligands, Ca2+ homeostasis, ER stress, oxidative stress, and hypoxia.ARC also plays a regulatory role in other types of cell death and can cause physiological and pathological changes in the heart.
Article
Environmental Sciences
Zhuanxu Ouyang, Bijing Yang, Jiangnan Yi, Shanshan Zhu, Suge Lu, Yingwei Liu, Yangwei Li, Yuanliang Li, Khalid Mehmood, Riaz Hussain, Muhammad Ijaz, Jianying Guo, Zhaoxin Tang, Ying Li, Hui Zhang
Summary: This study revealed the harmful effects of sodium fluoride on liver tissues of ducks, including promoting apoptosis and altering the expression levels of key genes.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Article
Gastroenterology & Hepatology
Jing Wang, Jun Tian, Lin Wang, Zhi-Wen Yang, Ping Xu
Summary: This study found that mesenchymal stem cells (MSCs) regulate M1 polarization of macrophages through the CARD9-NF-kappa B signaling pathway in severe acute pancreatitis. This provides an effective treatment option for SAP.
JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Xiali Qin, Yu Gu, Tianyu Liu, Chen Wang, Weilong Zhong, Bangmao Wang, Hailong Cao
Summary: This review summarizes the current research progress on fungal dysbiosis in CRC, discusses the potential mechanisms of fungi in CRC development, and explores potential therapeutic strategies for CRC treatment. This contributes to a better understanding of the correlation between fungal community and CRC, with modulating fungal community being a promising target against CRC.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2021)
Article
Biochemistry & Molecular Biology
Jinsu An, So Yeon Kim, Eun Gyeong Yang, Hak Suk Chung
Summary: Recognition of intracellular lipopolysaccharide (LPS) by Caspase-4 is critical for host defense. In this study, a high-throughput screening system was devised to identify inhibitors of the LPS and Casp-4 interaction. Inhibition of LPS-Casp-4 interaction may be a promising strategy for treating infectious diseases and sepsis induced by LPS.
Article
Medicine, Research & Experimental
Yuxin Chen, Xiaohuan Li, Qian Xiong, Yehong Du, Man Luo, Lilin Yi, Yayan Pang, Xiuyu Shi, Yu Tian Wang, Zhifang Dong
Summary: The activation of the NLRP3 inflammasome signaling pathway plays a role in neuroinflammation and brain injury in neonates with HIE. Inhibiting this pathway increases p97-mediated surface GluA1 expression and promotes neurological recovery, providing new insights for HIE therapy.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Craig M. Brackett, Kellee F. Greene, Alyssa R. Aldrich, Nicholas H. Trageser, Srabani Pal, Ivan Molodtsov, Bojidar M. Kandar, Lyudmila G. Burdelya, Scott Abrams, Andrei Gudkov
Summary: Contrary to radioprotection, this study found that neutrophils are essential for the radiomitigative activity of entolimod in a mouse model of lethal ARS. Neutrophils express functional TLR5, exit the bone marrow rapidly following TLR5 stimulation, accumulate in solid tissues, and release MMP-9, which in turn increases the number of active hematopoietic pluripotent precursors in the BM.
CELL DEATH DISCOVERY
(2021)
Article
Chemistry, Medicinal
Karolina Vankova, Dianne T. Keough, Dana Hockova, Luke W. Guddat, Zlatko Janeba
Summary: Twelve N2'-branched acyclic nucleoside phosphonates and bisphosphonates were synthesized as potential inhibitors of Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase (PfHGXPRT). The compounds showed low to modest selectivity for the parasite enzyme over human HGPRT. The effect of different chemical groups/linkers attached to N2' atom on inhibition constants and selectivity was discussed.
Article
Immunology
Emma Morrish, Tim Wartewig, Andreas Kratzert, Marc Rosenbaum, Katja Steiger, Juergen Ruland
Summary: VAV1-MYO1F is a newly identified fusion protein that is frequently detected in T-cell non-Hodgkin's lymphoma (T-NHL) patients. The pathophysiological functions of VAV1-MYO1F in lymphomagenesis are not well defined. In this study, transgenic mouse models were generated to conditionally express VAV1-MYO1F in T-cells. The results demonstrate that VAV1-MYO1F triggers cell autonomous activation of T-cell signaling and induces aberrant T-cell differentiation, proliferation, and neoplastic transformation.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Cell Biology
Julian Rapp, Malte Jung, Rhena F. U. Klar, Julian Wolf, Jakob Arnold, Oliver Gorka, Olaf Gross, Clemen Lange, Hansjurgen Agostini, Guenther Schlunck, Felicitas Bucher
Summary: Aberrant angiogenesis is a hallmark of cardiovascular and retinal neovascular disease. The STAT3 signaling pathway represents a potential pharmacological target for these diseases due to its impact on angiogenesis. However, the effects of STAT3 activation on angiogenesis vary depending on the specific cytokine.
JOURNAL OF CELL SCIENCE
(2023)
Article
Immunology
Ying-Yin Chao, Alisa Puhach, David Frieser, Mahima Arunkumar, Laurens Lehner, Thomas Seeholzer, Albert Garcia-Lopez, Marlot van der Wal, Silvia Fibi-Smetana, Axel Dietschmann, Thomas Sommermann, Tamara Cikovic, Leila Taher, Mark S. Gresnigt, Sebastiaan J. Vastert, Femke van Wijk, Gianni Panagiotou, Daniel Krappmann, Olaf Gross, Christina E. Zielinski
Summary: In this study, it was discovered that human T cells express GSDME, which is associated with durable viability and the release of IL-1 alpha. This property is only present in a subset of human helper type 17 T cells with specificity for Candida albicans, regulated by the T cell-intrinsic NLRP3 inflammasome. The release of IL-1 alpha is mediated by a proteolytic cascade involving caspase-8, caspase-3, and GSDME cleavage, as well as T cell receptor stimulation and calcium-licensed calpain maturation of pro-IL-1 alpha form. This finding expands our understanding of the functional diversity and mechanism of T cells and has implications for antifungal immunity.
Editorial Material
Parasitology
Franziska Hildebrandt, Johan Ankarklev, Kai Matuschewski
Summary: The researchers conducted a high-resolution transcriptomic analysis of Plasmodium berghei liver-stage maturation and identified molecular signatures of heterogeneity during the pre-erythrocytic development of malarial parasites.
TRENDS IN PARASITOLOGY
(2023)
Article
Cell Biology
Laura Griewahn, Madeleine Mueller-Foxworth, Lukas Peintner, Manuela Wissler, Martina Weiss, Prisca Brauns-Schubert, Ramin Massoumi, Christoph Borner, Olaf Gross, Monica Yabal, Celine Charvet, Ulrich Maurer
Summary: SPATA2 bridges the interaction between CYLD and HOIP, a component of the LUBAC, thereby mediating the recruitment of CYLD to immune receptor complexes. In addition, SPATA2 competes with OTULIN for binding to HOIP, promoting autoubiquitylation of LUBAC and attenuating pro-inflammatory signaling. These findings highlight the independent functions of SPATA2 and CYLD in immune regulation.
Article
Biochemistry & Molecular Biology
Julia Figl, Heike Koehler, Nadine Wedlich, Elisabeth M. Liebler-Tenorio, Leander Grode, Gerald Parzmair, Gopinath Krishnamoorthy, Natalie E. Nieuwenhuizen, Stefan H. E. Kaufmann, Christian Menge
Summary: A more effective vaccine against tuberculosis is urgently needed. The recombinant vaccine VPM1002 has been found to be safer and more efficacious than the existing vaccine BCG in mice models. In this study, the safety and immunogenicity of VPM1002 and its derivatives, PDX and NUOG, were assessed in juvenile goats. The results showed that VPM1002 and NUOG induced anti-tuberculous immunity with a comparable safety profile to BCG.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Ann-Brit Klatt, Christina Diersing, Juliane Lippmann, Sabine Mayer-Lambertz, Felix Stegmann, Swantje Fischer, Sandra Caesar, Facundo Fiocca Vernengo, Katja Hoenzke, Andreas C. Hocke, Juergen Ruland, Martin Witzenrath, Bernd Lepenies, Bastian Opitz
Summary: CLEC12A can bind to Legionella pneumophila-derived ligands, but it does not play a major role in the innate defense against the bacterium.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Jana Zecha, Florian P. Bayer, Svenja Wiechmann, Julia Woortman, Nicola Berner, Julian Mueller, Annika Schneider, Karl Kramer, Mar Abril-Gil, Thomas Hopf, Leonie Reichart, Lin Chen, Fynn M. Hansen, Severin Lechner, Patroklos Samaras, Stephan Eckert, Ludwig Lautenbacher, Maria Reinecke, Firas Hamood, Polina Prokofeva, Larsen Vornholz, Chiara Falcomata, Madeleine Dorsch, Ayla Schroeder, Anton Venhuizen, Stephanie Wilhelm, Guillaume Medard, Gabriele Stoehr, Juergen Ruland, Barbara M. Gruener, Dieter Saur, Maike Buchner, Benjamin Ruprecht, Hannes Hahne, Matthew The, Mathias Wilhelm, Bernhard Kuster
Summary: A proteomic assay called decryptM is introduced to quantify drug-regulated posttranslational modifications (PTMs) for thousands of PTMs in cells, providing insights into target engagement and drug mechanisms. The approach is shown to be applicable across 31 cancer drugs and 13 cell lines. The resulting 1.8 million dose-response curves are provided as an interactive molecular resource in ProteomicsDB, expanding the utility of the research.
Article
Multidisciplinary Sciences
Anke Schumann, Marion Brutsche, Monique Havermans, Sarah C. Gruenert, Stefan Koelker, Olaf Gross, Luciana Hannibal, Ute Spiekerkoetter
Summary: Methylmalonic aciduria (MMA-uria) is a condition caused by a lack of the enzyme methylmalonyl-CoA mutase (MUT) in mitochondria. It affects energy generation from certain amino acids, fatty acids, and cholesterol. Chronic kidney disease (CKD) is a known complication of MMA-uria. Research has shown that MMA-uria cells have increased creatinine levels and decreased antioxidant defense. Mitochondrial homeostasis is disrupted, with changes in metabolites and impaired energy generation from fatty acid oxidation. Potentially toxic metabolite methylcitrate is increased under high protein and isoleucine/valine conditions. Mitophagy is disabled, while autophagy is active, especially under high protein and isoleucine/valine conditions. Mitochondrial dynamics shift towards fission and the stress-resistance protein Sirtuin1 is down-regulated. Overall, these findings highlight the role of protein toxicity and provide insight into how accumulating toxic organic acids may contribute to CKD in MMA-uria.
SCIENTIFIC REPORTS
(2023)
Article
Gastroenterology & Hepatology
Frances Winkler, Anna Hipp, Carlos Ramirez, Bianca Martin, Matteo Villa, Emilia Neuwirt, Oliver Gorka, Jeroen Aerssens, Susanne E. Johansson, Nisha Rana, Sian Llewellyn-Lacey, David A. Price, Marcus Panning, Olaf Gross, Erika L. Pearce, Carl M. Hermann, Kathrin Schumann, Luciana Hannibal, Christoph Neumann-Haefelin, Tobias Boettler, Percy Knolle, Maike Hofmann, Dirk Wohlleber, Robert Thimme, Bertram Bengsch
Summary: Exhausted T cells with limited function are common in chronic HBV and HCV infection, but the relationship between metabolism and exhaustion states, the impact of antiviral therapy, and the role of metabolic checkpoints in dysfunction are not fully understood.
Article
Cell Biology
Kunjan Harit, Rituparna Bhattacharjee, Kai Matuschewski, Jennifer Becker, Ulrich Kalinke, Dirk Schlueter, Gopala Nishanth
Summary: This study reveals that the deubiquitinating enzyme OTUD7b prevents TNF-induced apoptosis of dendritic cells (DCs) during infection, resulting in efficient immune response. OTUD7b stabilizes the E3 ligase TNF-receptor-associated factor 2 (TRAF2) by counteracting its K48-ubiquitination, facilitating the activation of NF-κB and MAP kinases, IL-12 production, and expression of anti-apoptotic cFLIP and Bcl-xL. Mice with DC-specific OTUD7b-deficiency showed DC apoptosis and failure to induce CD8(+) T cell-mediated brain pathology in a murine malaria infection model. These findings highlight the importance of OTUD7b as a central molecular switch for DC survival and provide insights for manipulating DC responses.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Veronika Ecker, Lisa Brandmeier, Martina Stumpf, Piero Giansanti, Aida Varela Moreira, Lisa Pfeuffer, Marcel H. . A. M. Fens, Junyan Lu, Bernhard Kuster, Thomas Engleitner, Simon Heidegger, Roland Rad, Ingo Ringshausen, Thorsten Zenz, Clemens-Martin Wendtner, Markus Muschen, Julia Jellusova, Jurgen Ruland, Maike Buchner
Summary: Inhibition of the phosphatases DUSP1 and DUSP6 reduces cell survival and induces cell death in chronic lymphocytic leukemia. Transient inhibition of DUSP1/6 shows promise as a treatment concept for drug-resistant CLL.
Article
Medicine, General & Internal
Laura Joachim, Sascha Goettert, Anna Sax, Katja Steiger, Klaus Neuhaus, Paul Heinrich, Kaiji Fan, Erik Thiele Orberg, Karin Kleigrewe, Juergen Ruland, Florian Bassermann, Wolfgang Herr, Christian Posch, Simon Heidegger, Hendrik Poeck
Summary: The composition of the gut microbiome is associated with the response to immune checkpoint inhibitors (ICI). In this study, the researchers found that oral supplementation of a bacterial metabolite called desaminotyrosine (DAT) delays tumor growth and enhances ICI immunotherapy. This enhanced antitumor immunity is dependent on host IFN-I signaling and is associated with increased activation of T cells and natural killer cells in the tumor environment. DAT supplementation also compensates for the negative effects of broad-spectrum antibiotics on ICI immunotherapy by altering the gut microbial composition.
Article
Oncology
Tim Wartewig, Jay Daniels, Miriam Schulz, Erik Hameister, Abhinav Joshi, Joonhee Park, Emma Morrish, Anuroop V. Venkatasubramani, Filippo M. Cernilogar, Frits H. A. van Heijster, Christian Hundshammer, Heike Schneider, Filippos Konstantinidis, Judith V. Gabler, Christine Klement, Henry Kurniawan, Calvin Law, Yujin Lee, Sara Choi, Joan Guitart, Ignasi Forne, Jerome Giustinani, Markus Mueschen, Salvia Jain, David M. Weinstock, Roland Rad, Nicolas Ortonne, Franz Schilling, Gunnar Schotta, Axel Imhof, Dirk Brenner, Jaehyuk Choi, Juergen Ruland
Summary: PD-1 signaling suppresses T cell malignancy by restricting glycolytic energy and acetyl coenzyme A production. Inactivation of PD-1 strengthens ATP citrate lyase activity, leading to extramitochondrial acetyl-CoA production for hyperactivation of AP-1. Pharmacological inhibition of ATP citrate lyase impedes aberrant AP-1 signaling and is toxic to PD-1-deficient T-NHLs.
Article
Cell Biology
Simon Heidegger, Florian Stritzke, Sarah Dahl, Juliane Dassler-Plenker, Laura Joachim, Dominik Buschmann, Kaiji Fan, Carolin M. Sauer, Nils Ludwig, Christof Winter, Stefan Enssle, Suqi Li, Markus Perl, Andre Goergens, Tobias Haas, Erik Thiele Orberg, Sascha Goettert, Catherine Woelfel, Thomas Engleitner, Isidro Cortes-Ciriano, Roland Rad, Wolfgang Herr, Bernd Giebel, Jurgen Ruland, Florian Bassermann, Christoph Coch, Gunther Hartmann, Hendrik Poeck
Summary: Tumor-derived extracellular vesicles (EVs) play a role in immune evasion and tumor progression through the RNA-sensing receptor RIG-I. Activation of RIG-I releases EVs that promote dendritic cell maturation and T cell antitumor immunity, synergizing with immune checkpoint blockade. Intact RIG-I, autocrine interferon signaling, and the GTPase Rab27a are necessary for the generation of immunostimulatory EVs. The composition of the EV RNA cargo, including small non-coding stimulatory RNAs, is regulated by active intrinsic RIG-I signaling. Increased transcriptional activity of EV pathway genes and RIG-I in melanoma samples is associated with prolonged patient survival and positive response to immunotherapy. EVs generated from human melanoma after RIG-I stimulation induce potent antigen-specific T cell responses.
CELL REPORTS MEDICINE
(2023)