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Dexamethasone is a synthetic corticosteroid that has historically been used to treat inflammation, such as from osteoarthritis, spinal cord injury and, more recently, COVID-19. The mechanism of action of dexamethasone is generally known to include attenuation of pro-inflammatory responses as well as upregulation of anti-inflammatory elements. A major issue with the use of dexamethasone is its delivery, as it is normally administered in large quantities via methods like bolus injection to attempt to maintain sufficient concentrations days or weeks after administration. In this review, we examine the mechanism of action of dexamethasone and its effects on three major cell types in the context of specific diseases: macrophages in the context of COVID, chondrocytes in the context of osteoarthritis, and astrocytes in the context of neuro-inflammatory disease. From this, we identify the key proinflammatory cytokines interleukin-1 (IL-1) and Tumor Necrosis Factor alpha (TNF-a) as universal effectors of inflammation that should be targeted alongside dexamethasone administration. Additionally, we review current extended release dosing mechanisms for dexamethasone to act over periods of weeks and months. We suggest that dual treatment of dexamethasone with IL-1 and/or TNF-a monoclonal antibodies will be an effective immediate treatment for inflammation, while the addition of fully developed dexamethasone extended release mechanisms will allow for effective long-term control of inflammatory disease.
Dexamethasone is a synthetic corticosteroid that has historically been used to treat inflammation, such as from osteoarthritis, spinal cord injury and, more recently, COVID-19. The mechanism of action of dexamethasone is generally known to include attenuation of pro-inflammatory responses as well as upregulation of anti-inflammatory elements. A major issue with the use of dexamethasone is its delivery, as it is normally administered in large quantities via methods like bolus injection to attempt to maintain sufficient concentrations days or weeks after administration. In this review, we examine the mechanism of action of dexamethasone and its effects on three major cell types in the context of specific diseases: macrophages in the context of COVID, chondrocytes in the context of osteoarthritis, and astrocytes in the context of neuro-inflammatory disease. From this, we identify the key proinflammatory cytokines interleukin-1 (IL-1) and Tumor Necrosis Factor alpha (TNF-a) as universal effectors of inflammation that should be targeted alongside dexamethasone administration. Additionally, we review current extended release dosing mechanisms for dexamethasone to act over periods of weeks and months. We suggest that dual treatment of dexamethasone with IL-1 and/or TNF-a monoclonal antibodies will be an effective immediate treatment for inflammation, while the addition of fully developed dexamethasone extended release mechanisms will allow for effective long-term control of inflammatory disease.
Autoantibody profiling with a systems medicine approach can help identify critical dysregulated signaling pathways (SPs) in cancers. In this way, immunoglobulins G (IgG) purified from the serum samples of 92 healthy controls, 10 pre-treated (PR) non-Hodgkin lymphoma (NHL) patients, and 20 NHL patients who underwent chemotherapy (PS) were screened with a phage-displayed random peptide library. Protein-protein interaction networks of the PR and PS groups were analyzed and visualized by Gephi. The results indicated AXIN2, SENP2, TOP2A, FZD6, NLK, HDAC2, HDAC1, and EHMT2, in addition to CAMK2A, PLCG1, PLCG2, GRM5, GRIN2B, GRIN2D, CACNA2D3, and SPTAN1 as hubs in 11 and 7 modules of PR and PS networks, respectively. PR- and PS-specific hubs were evaluated in the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases. The PR-specific hubs were involved in Wnt SP, signaling by Notch1 in cancer, telomere maintenance, and transcriptional misregulation. In contrast, glutamate receptor SP, Fc receptor-related pathways, growth factors-related SPs, and Wnt SP were statistically significant enriched pathways, based on the pathway analysis of PS hubs. The results revealed that the most PR-specific proteins were associated with events involved in tumor development, while chemotherapy in the PS group was associated with side effects of drugs and/or cancer recurrence. As the findings demonstrated, PR- and PS-specific proteins in this study can be promising therapeutic targets in future studies.
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