Scientists discuss the possibility of using various approved drugs, or drugs currently in clinical development, to treat COVID-19. They suggest to enhance STAT1 activity and/or inhibit STAT3 functions for COVID-19 treatment.
[Cell Death & Differentiation]
MSCs were activated with LPS following a short one hour exposure or long-time exposure for 48hrs, and then, scientists evaluated the biological response in vitro, the immunosuppressive capacity of MSCs in vitro, and the therapeutic potential of MSCs in an experimental autoimmune encephalomyelitis (EAE) mouse model.
[Stem Cell Research & Therapy]
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Kurte, M., Vega-Letter, A. M., Luz-Crawford, P., Djouad, F., Noël, D., Khoury, M., & Carrión, F. (2020). Time-dependent LPS exposure commands MSC immunoplasticity through TLR4 activation leading to opposite therapeutic outcome in EAE. Stem Cell Research & Therapy, 11(1), 416. https://doi.org/10.1186/s13287-020-01840-2 Cite
Scientists identified NEDD4-binding protein 1 (N4BP1) as a suppressor of cytokine production that was cleaved and inactivated by caspase-8. N4BP1 deletion in mice increased production of select cytokines upon Toll-like receptor 1/2, TLR7, or TLR9 stimulation, but not upon TLR3 or TLR4 engagement.
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Gitlin, A. D., Heger, K., Schubert, A. F., Reja, R., Yan, D., Pham, V. C., Suto, E., Zhang, J., Kwon, Y. C., Freund, E. C., Kang, J., Pham, A., Caothien, R., Bacarro, N., Hinkle, T., Xu, M., McKenzie, B. S., Haley, B., Lee, W. P., … Dixit, V. M. (2020). Integration of innate immune signaling by caspase-8 cleavage of N4BP1. Nature, 1–9. https://doi.org/10.1038/s41586-020-2796-5 Cite
Primary amniotic mesenchymal cells (AMCs), chorion cells and decidual cells were isolated from placental membranes of women with uncomplicated pregnancies at full-term using enzymatic digestion.
Researchers characterized NOTCH signaling in macrophages activated by Toll-like receptor triggering and determined that DLL1 and DLL4 were the main ligands responsible for NOTCH signaling.
Full-thickness excisional wounds were made on the back of Il36rn−/− mice and healing was assessed by monitoring macroscopic wound sizes, numbers of infiltrated cells, and gene expression of inflammatory cytokines.
TLR4‐induced innate immune functions, including phagocytosis and iNOS expression, were attenuated in autotaxin‐deficient macrophages.
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Kim, S. J., Howe, C., Mitchell, J., Choo, J., Powers, A., Oikonomopoulos, A., Pothoulakis, C., Hommes, D. W., Im, E., & Rhee, S. H. (2020). Autotaxin loss accelerates intestinal inflammation by suppressing TLR4-mediated immune responses. EMBO Reports, n/a(n/a), e49332. https://doi.org/10.15252/embr.201949332 Cite
The authors investigated whether and how ruscogenin (RUS) exerted therapeutic effects on PM-induced acute lung injury. RUS was orally administered to mice prior to or after intratracheal instillation of particulate matter suspension.
[Acta Pharmacologica Sinica]
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Wang, Y., Wu, Y., Zhang, J., Tang, J., Fan, R., Li, F., Yu, B., Kou, J., & Zhang, Y. (2020). Ruscogenin attenuates particulate matter-induced acute lung injury in mice via protecting pulmonary endothelial barrier and inhibiting TLR4 signaling pathway. Acta Pharmacologica Sinica, 1–9. https://doi.org/10.1038/s41401-020-00502-6 Cite
Both LPS stimulation of isolated B lymphocytes in vitro and TNP-LPS challenge in vivo led to significantly higher plasma cell formation and antibodies production in β-arr2−/− mice as compared with WT mice.
[Acta Pharmacologica Sinica]
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Zhou, W., Wang, D., Tao, J., Tai, Y., Zhou, Z., Wang, Z., Guo, P., Sun, W., Chen, J., Wu, H., Yan, S., Zhang, L., Wang, Q., & Wei, W. (2020). Deficiency of β-arrestin2 exacerbates inflammatory arthritis by facilitating plasma cell formation. Acta Pharmacologica Sinica, 1–12. https://doi.org/10.1038/s41401-020-00507-1 Cite
Researchers report that mice haploinsufficient for the astrocyte-enriched α2Na+/K+-ATPase isoform had a reduced proinflammatory response to lipposacharides, accompanied by a reduced hypothermic reaction compared to wild type litter mates.
Scientists examined the regulation and function of leukocyte associated immunoglobulin like receptor 1 on monocyte, dendritic cell and macrophage subtypes, using different in vitro models.
[Frontiers in Immunology]
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Carvalheiro, T., Garcia, S., Pascoal Ramos, M. I., Giovannone, B., Radstake, T. R. D. J., Marut, W., & Meyaard, L. (2020). Leukocyte Associated Immunoglobulin Like Receptor 1 Regulation and Function on Monocytes and Dendritic Cells During Inflammation. Frontiers in Immunology, 11. https://doi.org/10.3389/fimmu.2020.01793 Cite