A forum investigating the similarities between COVID-19 and fluoride poisoning, thyroid dysfunction and Gq/11 pathways.
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COVID 19 involves virus activation of the NF-κB pathway. (NF-κB is essential for SARS-CoV-2 replication.)

"The NF-κB pathway is often targeted by viral pathogens to enhance viral replication, host cell survival and host immune evasion. Viruses may activate or suppress NF-kB. (5). There have been many studies on SARS-COV since 2002-2003 SARS epidemic. SARS-COV2 (COVID-19) belongs to the same family of corona viruses and shares many similarities (3)...COVID 19 activates NF-kB pathway, like MERS and SARS-COV (3). SARS-COV virus has been studied in vitro and in mice and was shown to promote inflammatory mediators in vitro and in vivo through actions on NF-kB. Levels of NF-kB were higher in lungs of (recombinant SARS (rSARS)-infected mice. Inhibitors of NF-kB improved survival of BALB/c mice and reduced rSARS-COV-induced inflammation, without influencing viral titers (6) . NF-kB is specifically induced by SARS-COV S protein to produce inflammatory mediators that are associated with ARDS in SARS in vitro (7)." (Karadsheh, 2020)

Karadsheh AJ - "Rapid Response:Re: Covid-19: what treatments are being investigated?" BMJ 2020;368:m1252

Alharbi KS, Fuloria NK, Fuloria S, Rahman SB, Al-Malki WH, Javed Shaikh MA, Thangavelu L, Singh SK, Rama Raju Allam VS, Jha NK, Chellappan DK, Dua K, Gupta G - "Nuclear factor-kappa B and its role in inflammatory lung disease" Chem Biol Interact 345:109568 (2021) ... 21)00206-4

Martínez-Sánchez G, Schwartz A, Donna VD - "Potential Cytoprotective Activity of Ozone Therapy in SARS-CoV-2/COVID-19" Antioxidants (Basel) 9(5):E389 (2020)
doi: 10.3390/antiox9050389

Rex DAB, Dagamajalu S, Kandasamy RK, Raju R, Prasad TSK - "SARS-CoV-2 signaling pathway map: A functional landscape of molecular mechanisms in COVID-19" J Cell Commun Signal. 2021 Jun 28:1–8. doi: 10.1007/s12079-021-00632-4

Su CM, Wang L, Yoo D - "Activation of NF-κB and induction of proinflammatory cytokine expressions mediated by ORF7a protein of SARS-CoV-2" Sci Rep 11(1):13464 (2021) doi: 10.1038/s41598-021-92941-2. PMID: 34188167; PMCID: PMC8242070.

Wu YH, Chiu DT, Lin HR, Tang HY, Cheng ML, Ho HY - "Glucose-6-Phosphate Dehydrogenase Enhances Antiviral Response through
Downregulation of NADPH Sensor HSCARG and Upregulation of NF-κB Signaling" Viruses 7(12):6689-706 (2015) doi: 10.3390/v7122966.

Nilsson-Payant BE, Uhl S, Grimont A, Doane AS, Cohen P, Patel RS, Higgins CA, Acklin JA, Bram Y, Chandar V, Blanco-Melo D, Panis M, Lim JK, Elemento O, Schwartz RE, Rosenberg BR, Chandwani R, tenOever BR - "The NF-κB transcriptional footprint is essential for SARS-CoV-2 replication" J Virol JVI0125721 (2021) doi: 10.1128/JVI.01257-21. Epub ahead of print. PMID: 34523966.

"The use of sodium fluoride (NaF) as a major ingredient for tooth paste, mouth wash, and mouth rinse has become inevitable in our day-to-day life.....Immunohistochemistry revealed that NaF caused increase expressions of Kidney injury marker 1 (Kim-1), nuclear factor kappa bet (NF-κB), nuclear factor erythroid 2-related factors 2 (Nrf2), and cardiac troponin I (CTnI)." (Oyagbemi et al, 2018)
Oyagbemi AA, Omobowale TO, Ola-Davies OE, Asenuga ER, Ajibade TO, Adejumobi OA, Afolabi JM, Ogunpolu BS, Falayi OO, Saba AB, Adedapo AA, Yakubu MA - "Luteolin-mediated Kim-1/NF-kB/Nrf2 signaling pathways protects sodium fluoride-induced hypertension and cardiovascular complications" Biofactors 44(6):518-531 (2018)
doi: 10.1002/biof.1449. Epub 2018 Nov 26. PMID: 30474894.

Zhao Y, Pu G, Li Y, Jiang H, Zhang Q, Chen P, Lu Q, Wang M, Yang R - "Serum Levels of CXCR4, SDF-1, MCP-1, NF-κB and ERK1/2 in Patients with Skeletal Fluorosis" Int J Environ Res Public Health 19(24):16555 (2022) doi: 10.3390/ijerph192416555

Luo Q, Cui H, Deng H, Kuang P, Liu H, Lu Y, Fang J, Zuo Z, Deng J, Li Y, Wang X, Zhao L - "Sodium fluoride induces renal inflammatory responses by activating NF-κB signaling pathway and reducing anti-inflammatory cytokine expression in mice" Oncotarget 8(46):80192-80207 (2017) doi: 10.18632/oncotarget.19006. PMID: 29113295; PMCID: PMC5655190.

Chen L, Kuang P, Liu H, Wei Q, Cui H, Fang J, Zuo Z, Deng J, Li Y, Wang X, Zhao L - "Sodium Fluoride (NaF) Induces Inflammatory Responses Via Activating MAPKs/NF-κB Signaling Pathway and Reducing Anti-inflammatory Cytokine Expression in the Mouse Liver" Biol Trace Elem Res 189(1):157-171 (2019)

Refsnes M, Skuland T, Låg M, Schwarze PE, Øvrevik J - "Differential NF-κB and MAPK activation underlies fluoride- and TPA-mediated CXCL8 (IL-8) induction in lung epithelial cells" J Inflamm Res 7:169-85 (2014)

Chen Q, Wang Z, Xiong Y, Zou X, Liu Z - "Comparative study of p38 MAPK signal transduction pathway of peripheral blood mononuclear cells from patients with coal-combustion-type fluorosis with and without high hair selenium levels" Int J Hyg Environ Health 213(5):381-6 (2010)

Zhang M, Wang A, Xia T, He P - "Effects of fluoride on DNA damage, S-phase cell-cycle arrest and the expression of NF-kappaB in primary cultured rat hippocampal neurons" Toxicol Lett 179(1):1-5 (2008)

G q/11

NF-Kappa B is downstream from Gq/11 activation.
"Endothelial cells can sense different flow patterns and convert the mechanical signal of laminar flow into atheroprotective signals, including eNOS activation, whereas disturbed flow in atheroprone areas induces inflammatory signaling, including NF-κB activation. How endothelial cells distinguish different flow patterns is poorly understood. Here we show that both laminar and disturbed flow activate the same initial pathway involving the mechanosensitive cation channel Piezo1, the purinergic P2Y2 receptor, and Gq/G11-mediated signaling. However, only disturbed flow leads to Piezo1- and Gq/G11-mediated integrin activation resulting in focal adhesion kinase-dependent NF-κB activation." (Albarrán-Juárez et al., 2018)

Albarrán-Juárez J, Iring A, Wang S, Joseph S, Grimm M, Strilic B, Wettschureck N, Althoff TF, Offermanns S - "Piezo1 and Gq/G11 promote endothelial inflammation depending on flow pattern and integrin activation" J Exp Med 215(10):2655-2672 (2018) doi: 10.1084/jem.20180483. Epub 2018 Sep 7. PMID: 30194266; PMCID: PMC6170174.

Meng Y, Yu CH, Li W, Li T, Luo W, Huang S, Wu PS, Cai SX, Li X - "Angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis protects against lung fibrosis by inhibiting the MAPK/NF-κB pathway" Am J Respir Cell Mol Biol 50(4):723-36 (2014) doi: 10.1165/rcmb.2012-0451OC. PMID: 24168260.

NOTE: AT1 increases, Aniotensin (1-7)/Mas inhibits.

SEE ALSO: ERK/MAPK viewtopic.php?f=66&t=1914
Tumor Necrosis Factor: viewtopic.php?f=66&t=1895

"THs induced nongenomically the rapid translocation of protein kinase C (PKC) ζ isoform to cell membranes, extracellular-signal-regulated kinases (ERK1/2) phosphorylation and nuclear factor-κB (NF-κB) activation. The signaling cascade include sphingomyelinases acting up-stream the activation of PKCζ isoform, while ERK and NF-κB are activated downstream this PKC isoenzyme." (Barreiro et al., 2011)
Barreiro Arcos ML, Sterle HA, Paulazo MA, Valli E, Klecha AJ, Isse B, Pellizas CG, Farias RN, Cremaschi GA - "Cooperative nongenomic and genomic actions on thyroid hormone mediated-modulation of T cell proliferation involve up-regulation of thyroid hormone receptor and inducible nitric oxide synthase expression" J Cell Physiol 226(12):3208-18 (2011) doi: 10.1002/jcp.22681. PMID: 21344381. ... /jcp.22681
"In thyroid, NF-κB signaling is crucial for thyrocytes survival and expression of critical thyroid markers, including Nis, Ttf1, Pax8, Tpo, and thyroglobulin, making this transcription factor essential for maintenance of normal thyroid function."(Reale et al., 2018)

Reale C, Zotti T, Scudiero I, Vito P, Stilo R - "The NF-κB Family of Transcription Factors and Its Role in Thyroid Physiology" Vitam Horm 106:195-210 (2018) doi: 10.1016/bs.vh.2017.05.003. Epub 2017 Sep 4. PMID: 29407436.
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