MAP kinase phosphatase-1, a gatekeeper of the acute innate immune response

Kirk, Sean G.; Samavati, Lobelia; Liu, Yusen

doi:10.1016/j.lfs.2019.117157

Cited by 29 publications

(23 citation statements)

References 122 publications

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“…However, no differences were seen in the bone phenotype between female MKP-1 deficient and wild type mice. MKP-1 is an important negative regulator of the MAPK pathways of the innate immune system [ 36 ]. In contrast to these models of inflammatory osteolysis, we found that in mice in homeostasis bone marrow-derived osteoclastogenesis was greater in cells from female than from males [ 14 ].…”

Section: Inflammationmentioning

confidence: 99%

Sexual Dimorphism in Osteoclasts

Lorenzo

2020

Cells

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Osteoclasts are the principal mediators of bone resorption. They form through the fusion of mononuclear precursor cells under the principal influence of the cytokines macrophage colony stimulating factor (M-CSF, aka CSF-1) and receptor activator of NF-κB ligand (RANKL, aka TNFSF11). Sexual dimorphism in the development of the skeleton and in the incidence of skeletal diseases is well described. In general, females, at any given age, have a lower bone mass than males. The reasons for the differences in the bone mass of the skeleton between women and men at various ages, and the incidence of certain metabolic bone diseases, are multitude, and include the actions of sex steroids, genetics, age, environment and behavior. All of these influence the rate that osteoclasts form, resorb and die, and frequently produce different effects in females and males. Hence, a variety of factors are responsible for the sexual dimorphism of the skeleton and the activity of osteoclasts in bone. This review will provide an overview of what is currently known about these factors and their effects on osteoclasts.

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Section: Inflammationmentioning

confidence: 99%

Sexual Dimorphism in Osteoclasts

Lorenzo

2020

Cells

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“…Our data implicated MAPK signaling as part of the mechanisms underlying VC + GA antiviral function. MAPK cascades are crucial signaling pathways in the regulation of host immune response to infection [ 60 ]. Specifically, MAPK signaling induces pro-inflammatory mediators and activation of anti-inflammatory pathways through controlling many downstream effectors [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

Integrative pharmacological mechanism of vitamin C combined with glycyrrhizic acid against COVID-19: findings of bioinformatics analyses

et al. 2020

Briefings in Bioinformatics

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Objective Coronavirus disease 2019 (COVID-19) is a fatal and fast-spreading viral infection. To date, the number of COVID-19 patients worldwide has crossed over six million with over three hundred and seventy thousand deaths (according to the data from World Health Organization; updated on 2 June 2020). Although COVID-19 can be rapidly diagnosed, efficient clinical treatment of COVID-19 remains unavailable, resulting in high fatality. Some clinical trials have identified vitamin C (VC) as a potent compound pneumonia management. In addition, glycyrrhizic acid (GA) is clinically as an anti-inflammatory medicine against pneumonia-induced inflammatory stress. We hypothesized that the combination of VC and GA is a potential option for treating COVID-19. Methods The aim of this study was to determine pharmacological targets and molecular mechanisms of VC + GA treatment for COVID-19, using bioinformational network pharmacology. Results We uncovered optimal targets, biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of VC + GA against COVID-19. Our findings suggested that combinatorial VC and GA treatment for COVID-19 was associated with elevation of immunity and suppression of inflammatory stress, including activation of the T cell receptor signaling pathway, regulation of Fc gamma R-mediated phagocytosis, ErbB signaling pathway and vascular endothelial growth factor signaling pathway. We also identified 17 core targets of VC + GA, which suggest as antimicrobial function. Conclusions For the first time, our study uncovered the pharmacological mechanism underlying combined VC and GA treatment for COVID-19. These results should benefit efforts to address the most pressing problem currently facing the world.

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“…This study implicated MAPK signaling as part of the potential mechanisms underlying TJQW antiviral function. MAPK cascades are crucial signaling pathways in the regulation of host immune response to infection [ 56 ]. MAPK phosphatase 1 regulates pro- and anti-inflammatory cytokines dynamically in innate immune responses [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic mechanism of Toujie Quwen granules in COVID-19 based on network pharmacology

Huang

Zheng

et al. 2020

BioData Mining

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Background Chinese medicine Toujie Quwen granule (TJQW) has proven to be effective in the treatment of mild coronavirus disease 2019 (COVID-19) cases by relieving symptoms, slowing the progression of the disease, and boosting the recovery of patients. But the bioactive compounds and potential mechanisms of TJQW for COVID-19 prevention and treatment are unclear. This study aimed to explore the potential therapeutic mechanism of TJQW in coronavirus disease 2019 (COVID-19) based on an integrated network pharmacology approach. Methods TCMSP were used to search and screen the active ingredients in TJQW. The Swiss TargetPrediction was used to predict the potential targets of active ingredients. Genes co-expressed with ACE2 were considered potential therapeutic targets on COVID-19. Venn diagram was created to show correlative targets of TJQW against COVID-19. Cytoscape was used to construct a “drug-active ingredient-potential target” network, STRING were used to construct protein-protein interaction network, and cytoHubba performed network topology analysis. Enrichment of biological functions and signaling pathways of core targets was performed by using the clusterProfiler package in R software and ClueGO with CluePedia plugins in Cytoscape. Results A total of 156 active ingredients were obtained through oral bioavailability and drug-likeness screenings. Two hundred twenty-seven potential targets of TJQW were related to COVID-19. The top ten core targets are EGFR, CASP3, STAT3, ESR1, FPR2, F2, BCL2L1, BDKRB2, MPO, and ACE. Based on that, we obtained 19 key active ingredients: umbelliprenin, quercetin, kaempferol, luteolin, praeruptorin E, stigmasterol, and oroxylin A. And the enrichment analysis obtained multiple related gene ontology functions and signaling pathways. Lastly, we constructed a key network of “drug-component-target-biological process-signaling pathway”. Our findings suggested that TJQW treatment for COVID-19 was associated with elevation of immunity and suppression of inflammatory stress, including regulation of inflammatory response, viral process, neutrophil mediated immunity, PI3K-Akt signaling pathway, MAPK signaling pathway, Jak-STAT signaling pathway, Complement and coagulation cascades, and HIF-1 signaling pathway. Conclusions Our study uncovered the pharmacological mechanism underlying TJQW treatment for COVID-19. These results should benefit efforts for people around the world to gain more knowledge about Chinese medicine TJQW in the treatment of this vicious epidemic COVID-19, and help to address this pressing problem currently facing the world.

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MAP kinase phosphatase-1, a gatekeeper of the acute innate immune response

Cited by 29 publications

References 122 publications

Sexual Dimorphism in Osteoclasts

Sexual Dimorphism in Osteoclasts

Integrative pharmacological mechanism of vitamin C combined with glycyrrhizic acid against COVID-19: findings of bioinformatics analyses

Therapeutic mechanism of Toujie Quwen granules in COVID-19 based on network pharmacology

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