Severe COVID cases present extensive lung damage and the presence of infected multinucleated syncytial pneumocytes.
Sars-CoV2 infected cells fuse with healthy neighboring cells to form syncytia through the peak protein activating calcium-activated chlorine channel TMEM16 proteins
This process is accelerated by the TMPRSS2 protease, but can be restricted by the interferon-induced transmembrane protein IFITM1.
TMEM16A activates NFKB and IL6 👉 inflammation and vasoconstriction👉 Pulmonary Hypertension or Cystic Fibrosis.
@Parsifaler Protective effects of Epo and derivatives against lung injuries. In normal alveolus: intact cellular component (AEC I, AEC II, fibroblast) and pulmonary capillary.
@Parsifaler In injured alveoli: Treatment with epo protect the lung from injury-induced cell and tissue damage by reducing apoptosis, oxidative stress,and pulmonary fibrosis.Prevent pulmonary edema and inflammatory lesions and,therefore,maintain cell integrity @drakchaurasia@DrLBoominathan
✅The severity of COVID-19 disease, especially in the elderly and patients with comorbidities, is characterized by hypercytokinemia, an exaggerated immune response associated with an uncontrolled and excessive release of pro-inflammatory cytokine mediators (cytokine storm).
1. The immunomodulatory capacity of flavonoids, carried out by the regulation of inflammatory mediators, the inhibition of endothelial activation, the NLRP3 inflammasome, the toll-like receptors (TLR)
2. Or the bromodomain-containing protein 4 (BRD4), and the activation erythroid-derived nuclear factor 2 (Nrf2), could be beneficial in regulating cytokine storm during SARS-CoV-2 infection.
The general course of events during infections (Sars-CoV2) leading to "cytokine storm" can look like this:
1. Cells undergo damage, senescence, or become infected with a virus.
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2. Those cells release damage-associated molecular patterns (DAMPs) or pathogen-associated molecular patterns (PAMPs), which activate receptors in the immune system.
⬇️ 3. DAMPs, like HBGM1, signal the production of the inflammatory response.
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4. HBGM1 binds to TLR2 / TLR4 / RAGE receptors to begin mobilizing pro-inflammatory cytokines.
⬇️ 5. Activation of the NF-kB / NLRP3 inflammasomes ensues.
⬇️ 6. Release of pro-inflammatory cytokines IL-1, IL-6, IL-1B, IL-18, IL-17, IL-22, and others occurs.
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# Mechanistic therapy on Notch-3 signaling, N-acetyl-cysteine prophylaxis and treatment in pulmonary fibrosis (# sequelacovid19) and other complications. #Immunometabolic
Proteins of the Notch family are cell surface receptors that TRANSDUCE SIGNALS BETWEEN NEIGHBORING CELLS. The Notch signaling pathway is evolutionarily highly conserved, including many aspects of vascular development.
The interaction of Notch receptors with ligands leads to the cleavage of the Notch intracellular domain (NICD) which then translocates to the nucleus and activates the transcription factor CBF1 / JBP-Jkappa, regulating downstream gene expression.