TY  - JOUR
AU  - Dong, Jia-nan
AU  - Zhao, Zhi-kun
AU  - Wang, Zhan-qing
AU  - Li, Song-ze
AU  - Zhang, Yong-peng
AU  - Sun, Zhe
AU  - Qin, Gui-xin
AU  - Zhang, Xue-feng
AU  - Zhao, Wei
AU  - Aschalew, Natnael Demelash
AU  - Wang, Tao
AU  - Zhen, Yu-guo
TI  - Impact of deoxynivalenol on rumen function, production, and health of dairy cows: Insights from metabolomics and microbiota analysis
JF  - JOURNAL OF HAZARDOUS MATERIALS
J2  - J HAZARD MATER
VL  - 465
PY  - 2024
SN  - 0304-3894
DO  - 10.1016/j.jhazmat.2023.133376
UR  - https://m2.mtmt.hu/api/publication/34470059
ID  - 34470059
N1  - College of Animal Science and Technology, JLAU-Borui Dairy Science and Technology R&D Center, Key Laboratory of Animal Nutrition and Feed Science of Jilin Province, Key Laboratory of Animal Production Product Quality and Security Ministry of Education, Jilin Agricultural University, Changchun, 130118, China            
            Postdoctoral Scientific Research Workstation, Feed Engineering Technology Research Center of Jilin Province, Changchun Borui Science & Technology Co., Ltd, Changchun, 130118, China            
            College of Life Science, Jilin Agricultural University, Changchun, 130118, China            
            Export Date: 9 February 2024            
            CODEN: JHMAD            
            Correspondence Address: Wang, T.; College of Animal Science and Technology, China; email: cagewang@163.com
LA  - English
DB  - MTMT
ER  - 

TY  - GEN
AU  - Bakos, Tamás
AU  - Mészáros, Tamás
AU  - Kozma, Gergely Tibor
AU  - Petra, Berényi
AU  - Facskó, Réka
AU  - Henriette, Farkas
AU  - Dézsi, László
AU  - Carlo, Heirman
AU  - Stefaan, de Koker
AU  - Raymond, Schiffelers
AU  - Kathryn, Anne Glatter
AU  - Radovits, Tamás
AU  - Szénási, Gábor
AU  - Szebeni, János
TI  - mRNA-LNP COVID-19 vaccine lipids induce low level complement activation and production of proinflammatory cytokines: Mechanisms, effects of complement inhibitors, and relevance to adverse reactions
PY  - 2024
UR  - https://m2.mtmt.hu/api/publication/34521339
ID  - 34521339
AB  - Messenger RNA-containing lipid nanoparticles (mRNA-LNPs) enabled widespread COVID-19 vaccination with a small fraction of vaccine recipients displaying acute or sub-acute inflammatory symptoms. The molecular mechanism of these adverse events (AEs) remains undetermined. Here we report that the mRNA-LNP vaccine, Comirnaty, triggers low-level complement (C) activation and production of inflammatory cytokines, which may be key underlying processes of inflammatory AEs. In serum, Comirnaty and the control PEGylated liposome (Doxebo) caused different rises of C split products, C5a, sC5b-9, Bb and C4d, indicating stimulation of the classical pathway of C activation mainly by the liposomes, while a stronger stimulation of the alternative pathway was equal with the vaccine and the liposomes. Spikevax had similar C activation as Comirnaty, but viral or synthetic mRNAs had no such effect. In autologous serum-supplemented peripheral blood mononuclear cell (PBMC) cultures, Comirnaty caused increases in the levels of sC5b-9 and proinflammatory cytokines in the following order: IL-1α < IFN-γ < IL-1β < TNF-α < IL-6 < IL-8, whereas heatinactivation of serum prevented the rises of IL-1α, IL-1β, and TNF-α. Clinical C inhibitors, Soliris and Berinert, suppressed vaccine-induced C activation in serum but did not affect cytokine production when applied individually. These findings suggest that the PEGylated lipid coating of mRNA-LNP nanoparticles can trigger C activation mainly via the alternative pathway, which may be causally related to the induction of some, but not all inflammatory cytokines. While innate immune stimulation is essential for the vaccine’s efficacy, concurrent production of C- and PBMC-derived inflammatory mediators may contribute to some of the AEs. Pharmacological attenuation of harmful cytokine production using C inhibitors likely requires blocking the C cascade at multiple points.
LA  - English
DB  - MTMT
ER  -