The HIV Protease Inhibitor Saquinavir Attenuates Sepsis-Induced Acute Lung Injury and Promotes M2 Macrophage Polarization via Targeting Matrix Metalloproteinase-9

Scientists focused on the important role of macrophage polarization in cecal ligation puncture-mediated acute lung injury and determined the ability of saquinavir to maintain M2 over M1 phenotype partially through the inhibition of matrix metalloproteinase-9.
[Cell Death & Disease]
Tong, Y., Yu, Z., Chen, Z., Zhang, R., Ding, X., Yang, X., Niu, X., Li, M., Zhang, L., Billiar, T. R., Pitt, B. R., & Li, Q. (2021). The HIV protease inhibitor Saquinavir attenuates sepsis-induced acute lung injury and promotes M2 macrophage polarization via targeting matrix metalloproteinase-9. Cell Death & Disease, 12(1), 1–14. https://doi.org/10.1038/s41419-020-03320-0 Cite
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Circulating BMP9 Protects the Pulmonary Endothelium During Inflammation-induced Lung Injury in Mice

A bone morphogeneic protein 9 (BMP9)-neutralizing antibody was administrated to healthy adult mice and lung vasculature was examined. Potential mechanisms were delineated by transcript analysis in human lung endothelial cells.
[American Journal of Respiratory and Critical Care Medicine]
Li, W., Long, L., Yang, X., Tong, Z., Southwood, M., King, R., Caruso, P., Upton, P. D., Yang, P., Bocobo, G. A., Nikolic, I., Higuera, A., Salmon, R. M., Jiang, H., Lodge, K. M., Hoenderdos, K., Baron, R. M., Yu, P. B., Condliffe, A. M., … Morrell, N. W. (2020). Circulating BMP9 Protects the Pulmonary Endothelium During Inflammation-induced Lung Injury in Mice. American Journal of Respiratory and Critical Care Medicine. https://doi.org/10.1164/rccm.202005-1761OC Cite
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K2P2.1 (TREK-1) Potassium Channel Activation Protects against Hyperoxia-Induced Lung Injury

Investigators treated hyperoxia-exposed mice and primary alveolar epithelial cells with the novel TREK-1 activators ML335 and BL1249, and quantified physiological, histological, and biochemical lung injury markers.
[Scientific Reports]
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Salidroside Regulates Inflammatory Pathway of Alveolar Macrophages by Influencing the Secretion of miRNA-146a Exosomes by Lung Epithelial Cells

Scientists explored the investigative mechanism of salidroside on LPS-induced acute lung injury/acute respiratory distress syndrome.
[Scientific Reports]
Zheng, L., Su, J., Zhang, Z., Jiang, L., Wei, J., Xu, X., & Lv, S. (2020). Salidroside regulates inflammatory pathway of alveolar macrophages by influencing the secretion of miRNA-146a exosomes by lung epithelial cells. Scientific Reports, 10(1), 20750. https://doi.org/10.1038/s41598-020-77448-6 Cite
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A High Content Screen for Mucin-1-Reducing Compounds Identifies Fostamatinib as a Candidate for Rapid Repurposing for Acute Lung Injury

In vivo, Fostamatinib reduces Mucin-1 (MUC1) abundance in lung epithelial cells in a mouse model of acute lung injury. In vitro, SYK inhibition by the active metabolite R406 promotes MUC1 removal from the cell surface.
[Cell Reports Medicine]
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Potential Application of Mesenchymal Stem Cells and Their Exosomes in Lung Injury: An Emerging Therapeutic Option for COVID-19 Patients

The authors shed light on the mechanistic view of MSC therapeutic role based on preclinical and clinical studies on acute lung injury and ARDS; therefore, offering a unique correlation and applicability in COVID-19 patients. They further highlight the challenges and opportunities in the use of MSC-based therapy.
[Stem Cell Research & Therapy]
Al-Khawaga, S., & Abdelalim, E. M. (2020). Potential application of mesenchymal stem cells and their exosomes in lung injury: an emerging therapeutic option for COVID-19 patients. Stem Cell Research & Therapy, 11(1), 437. https://doi.org/10.1186/s13287-020-01963-6 Cite
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First Patient Dosed in Phase II Trial to Treat Complications in COVID-19

Arch Biopartners, Inc. announced it has dosed the first patient in the Phase II trial of its lead drug LSALT peptide, targeting prevention of acute lung injury, acute kidney injury and other complications caused by inflammation in hospitalized patients with moderate to severe cases of COVID-19.
[Arch Biopartners, Inc.]
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Mesenchymal Stem Cells Reverse EMT Process through Blocking the Activation of NF-κB and Hedgehog Pathways in LPS-Induced Acute Lung Injury

Researchers investigated the mechanism underneath MSC-reversed lung injury and fibrosis. They determined that coculture with MSC led to the inactivation of NF-κB signaling and therefore suppressed the hedgehog pathway in LPS-treated MLE-12 cells.
[Cell Death & Disease]
Xiao, K., He, W., Guan, W., Hou, F., Yan, P., Xu, J., Zhou, T., Liu, Y., & Xie, L. (2020). Mesenchymal stem cells reverse EMT process through blocking the activation of NF-κB and Hedgehog pathways in LPS-induced acute lung injury. Cell Death & Disease, 11(10), 1–17. https://doi.org/10.1038/s41419-020-03034-3 Cite
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An Aberrant STAT Pathway Is Central to COVID-19

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]
Matsuyama, T., Kubli, S. P., Yoshinaga, S. K., Pfeffer, K., & Mak, T. W. (2020). An aberrant STAT pathway is central to COVID-19. Cell Death & Differentiation, 1–17. https://doi.org/10.1038/s41418-020-00633-7 Cite
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Mesenchymal Stem Cells Alleviate LPS-Induced Acute Lung Injury by Inhibiting the Proinflammatory Function of Ly6C+ CD8+ T Cells

Investigators showed that CD8+ T cells played an important role in MSC-mediated acute lung injury remission, and both infiltration quantity and proinflammatory function were inhibited by MSCs, indicating a potential mechanism for therapeutic intervention.
[Cell Death & Disease]
Zhu, J., Feng, B., Xu, Y., Chen, W., Sheng, X., Feng, X., Shi, X., Liu, J., Pan, Q., Yu, J., Li, L., & Cao, H. (2020). Mesenchymal stem cells alleviate LPS-induced acute lung injury by inhibiting the proinflammatory function of Ly6C + CD8 + T cells. Cell Death & Disease, 11(10), 1–11. https://doi.org/10.1038/s41419-020-03036-1 Cite
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STAT3–BDNF–TrkB Signaling Promotes Alveolar Epithelial Regeneration after Lung Injury

Single-cell transcriptome analysis identified brain-derived neurotrophic factor as a STAT3 target gene with newly accessible chromatin in a unique population of regenerating AT2 cells.
[Nature Cell Biology]
Paris, A. J., Hayer, K. E., Oved, J. H., Avgousti, D. C., Toulmin, S. A., Zepp, J. A., Zacharias, W. J., Katzen, J. B., Basil, M. C., Kremp, M. M., Slamowitz, A. R., Jayachandran, S., Sivakumar, A., Dai, N., Wang, P., Frank, D. B., Eisenlohr, L. C., Cantu, E., Beers, M. F., … Worthen, G. S. (2020). STAT3–BDNF–TrkB signalling promotes alveolar epithelial regeneration after lung injury. Nature Cell Biology, 1–14. https://doi.org/10.1038/s41556-020-0569-x Cite
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