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AI and Immunology Considerations in Pandemics and SARS-CoV-2 COVID-19
Published in Louis J. Catania, AI for Immunology, 2021
As discussed above and in detail in Chapter 4, chronic inflammatory organ injury (e.g., heart, lungs, kidneys) may occur in severe COVID-19, with a subgroup of patients having markedly elevated levels of inflammatory markers. Several therapeutic interventions have been proposed to mitigate inflammatory organ injury in viral pneumonia including glucocorticoids (i.e., dexamethasone). Glucocorticoids have been widely used in syndromes closely related to COVID-19, including SARS, Middle East respiratory syndrome (MERS), severe influenza, and community-acquired pneumonia. However, the evidence to support or discourage the use of glucocorticoids under these conditions has been weak.58 In patients hospitalized with COVID-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support.59 Other steroids are also beginning to show some promising results.60
Microbial Transformation of Steroids and Sterols
Published in Nduka Okafor, Benedict C. Okeke, Modern Industrial Microbiology and Biotechnology, 2017
Nduka Okafor, Benedict C. Okeke
The greatest portion of steroid drug production is aimed at the synthesis of glucocorticoids which are highly effective agents for the treatment of chronic inflammation. Glucocorticoids exert their effects by binding to the cytoplasmic glucocorticoid receptor within the target cell and thus either increase or decrease transcription of a number of genes involved in the inflammatory process. Specifically, glucocorticoids down-regulate potential mediators of inflammation such as cytokines. Typical oral glucocorticoids used to treat rheumatoid arthritis are prednisone and 6-α-methylprednisolone. Corticosteroids are the most efficacious treatment available for the long-term treatment of asthma, and inhaled corticosteroids are considered to be a first-line therapy for asthma. They are also used to treat rhinitis, nasal congestion, and inflammations of the skin.
Anti-Inflammatory Dendrimers
Published in Delphine Felder-Flesch, Dendrimers in Nanomedicine, 2016
Cédric-Olivier Turrin, Anne-Marie Caminade
Treatment of inflammation is often a gradual response involving a wide range of drugs. Non-steroidal anti-inflammatory (NSAI) drugs are widely used and inhibit the prostaglandin synthase, also name cyclooxygenase (COX) involved in the first step of synthesis of some inflammation mediators. Glucocorticoid derivatives are steroidal hormone analogous to endogenous cortisol, which affect several physiological processes, including immune response, regulation of inflammation, carbohydrate and protein metabolisms. Biologics or biological products refer to as blood components, cells tissues and recombinant proteins, and contrarily to synthetic drugs, these complex mixtures produced by living organisms are not easily identified or characterized. Biologics like soluble receptors or monoclonal antibodies (MoAbs) that target a specific cell-derived or plasma protein-derived chemical mediators of inflammatory processes are widely used in firstline treatments for CIDs.
Phthalate esters and dexamethasone synergistically activate glucocorticoid receptor
Published in Journal of Environmental Science and Health, Part A, 2020
Yue Leng, Yonghai Sun, Wei Huang, Chengyu Lv, Jingyan Cui, Tiezhu Li, Yongjun Wang
Glucocorticoids (GCs), owing to their immunomodulatory and anti-inflammatory activities, are steroid hormones successfully used in therapeutic administration.[12,13] GCs regulated by the hypothalamic-pituitary-adrenal axis play key roles in the regulation of homeostasis, central nervous system function, glucose and lipid metabolism and immune response.[14–16] For this reason, GCs become the mainstay in the treatment of various typical disorders, such as rheumatoid arthritis, asthma, systemic lupus erythematosus and other inflammatory diseases.[17,18] In target cells, GCs exert their major actions via activating GR. On binding glucocorticoid, the receptor undergoes several conformational changes, which result in nuclear translocation.[19] The GR complex (GRC) interacts with specific target DNA sequences as a homodimer and regulates transcriptional activation or repression.[20,21] Recently, a few studies suggest that several of the PAEs have the potential to disturb GR and regulate downstream genes. DEHP reportedly possesses glucocorticoid-like activity.[22] In addition, dicyclohexyl phthalate and mono-cyclohexyl phthalate can also stimulate GR activity.[23,24] However, the detailed mechanisms how PAEs bind to GR have not been clarified.