Ntau qhov kev tshawb fawb qhia tias kev ua kom NLRP3 inflammasome yog lub luag haujlwm rau kev mob ua pa nyuaj thiab / lossis mob ntsws mob (ARDS/ALI) pom hauv cov neeg mob hnyav COVID-19 uas feem ntau ua rau tuag vim muaj ntau lub cev tsis ua haujlwm. Qhov no qhia tias NLRP3 tuaj yeem ua lub luag haujlwm tseem ceeb hauv chav kho mob. Yog li, nws yog qhov yuav tsum tau ua sai sai los muab qhov kev xav no los sim rau kev tshawb nrhiav NLRP3 raws li lub hom phiaj siv tshuaj los tawm tsam COVID-19.
Tus kab mob COVID-19 tau ua rau muaj kev puas tsuaj thoob ntiaj teb cuam tshuam rau ntau lab tus tib neeg lub neej thiab cuam tshuam rau tag nrho lub ntiaj teb kev lag luam. Cov kws tshawb fawb hauv ntau lub teb chaws tab tom ua haujlwm tawm tsam lub sijhawm los nrhiav kev kho mob los tiv thaiv COVID-19 kom tib neeg tuaj yeem kho tau sai thiab zoo li qub tuaj yeem rov qab los. Cov tswv yim tseem ceeb uas tau siv tam sim no suav nrog kev tsim kho tshiab thiab rov tsim cov tshuaj uas twb muaj lawm1,2 uas yog raws li, cov hom phiaj tshuaj tau txheeb xyuas los ntawm kev kawm txog kev sib cuam tshuam ntawm tus kab mob sib kis, tsom rau cov kab mob sib kis kom ntes tus kab mob sib kis thiab kev tsim tshuaj tiv thaiv. Nkag siab txog kab mob ntawm tus kab mob COVID-19 kom nthuav dav ntxiv los ntawm kev nkag siab txog nws cov txheej txheem ntawm kev ua, tuaj yeem ua rau kev txheeb xyuas cov hom phiaj tshuaj tshiab uas tuaj yeem siv los tsim kho tshiab thiab rov ua dua tshiab. tshuaj tawm tsam cov hom phiaj no.
Thaum feem ntau (~ 80%) ntawm cov neeg mob COVID-19 mob ua npaws me me, hnoos, hnov mob nqaij thiab rov zoo nyob rau lub sijhawm 14-38 hnub, feem ntau loj heev Cov neeg mob thiab cov neeg uas tsis rov qab muaj mob ua pa nyuaj thiab / lossis mob ntsws raug mob (ARDS/ALI), ua rau ntau lub cev tsis ua haujlwm ua rau tuag taus.3. Cytokine cua daj cua dub tau cuam tshuam rau txoj kev loj hlob ntawm ARDS/ALI4. Qhov no cytokine cua daj cua dub yog tshwm sim los ntawm kev ua kom NLRP3 inflammasome (ib tug multimeric protein complex uas pib inflammatory teb thaum ua kom muaj ntau yam stimuli.5) by SARS-CoV-2 proteins6-9 uas implicates NLRP3 raws li ib tug loj pathophysiological tivthaiv nyob rau hauv txoj kev loj hlob ntawm ARDS/ALI10-14, uas ua rau ua pa tsis ua haujlwm hauv cov neeg mob.
NLRP3 plays lub luag haujlwm tseem ceeb hauv lub cev tiv thaiv kab mob. Nyob rau hauv ib qho kev mob ntawm lub cev, NLRP3 muaj nyob rau hauv lub xeev tsis muaj zog khi los ntawm cov proteins tshwj xeeb hauv cytoplasm. Thaum ua kom los ntawm stimuli, nws ua rau cov lus teb inflammatory uas thaum kawg ua rau tuag ntawm cov kab mob uas raug tshem tawm ntawm lub cev, thiab NLRP3 rov qab mus rau nws lub xeev tsis ua haujlwm. NLRP3 inflammasome kuj tseem txhawb nqa platelet activation, aggregation thiab thrombus tsim hauv vitro.15. Txawm li cas los xij, hauv cov kab mob pathophysiological xws li COVID-19 kev kis tus kab mob, dysregulated activation ntawm NLRP3 tshwm sim ua rau muaj cua daj cua dub cytokine. Kev tso tawm ntawm proinflammatory cytokines ua rau infiltration ntawm alveoli nyob rau hauv lub ntsws ua rau fulminant pulmonary o thiab tom qab ua pa tsis ua hauj lwm tab sis kuj yuav ua rau thrombosis los ntawm rupturing ntawm plaques nyob rau hauv cov hlab ntsha vim o. Kev mob ntawm cov leeg nqaij hauv plawv tau nyob rau feem ntau ntawm cov neeg mob pw hauv tsev kho mob nrog COVID-1916.
Tsis tas li ntawd, NLRP3 inflammasome tau tshwm sim, raws li qhov tshwj xeeb stimulation, koom nrog cov txiv neej infertility pathogenesis ntawm inflammatory cytokine induction hauv Sertoli hlwb.17.
Yog li ntawd, nyob rau hauv kev pom ntawm lub luag hauj lwm uas tau hais los saum toj no, NLRP3 inflammasome zoo li tau ua lub luag haujlwm tseem ceeb hauv kev kho mob ntawm cov neeg mob hnyav COVID-19. Yog li ntawd, muaj qhov yuav tsum tau ceev nrooj los muab qhov kev xav no los sim rau kev tshawb nrhiav NLRP3 inflammasome ua lub hom phiaj tshuaj los tawm tsam COVID-19. Qhov kev xav no tau raug muab tso rau kev sim los ntawm cov kws tshawb fawb Greek uas tau npaj ib qho kev tshawb fawb soj ntsuam kuaj mob hu ua GRECCO-19 los tshawb xyuas cov teebmeem inhibitory ntawm colchicine ntawm NLRP3 inflammasome.18.
Tsis tas li ntawd, kev tshawb fawb txog lub luag haujlwm ntawm NLRP3 inflammasome tseem yuav muab kev nkag siab ntxiv txog cov kab mob thiab kev loj hlob ntawm tus kab mob COVID-19. Qhov no yuav pab tau cov kws kho mob zoo tswj cov neeg mob tshwj xeeb tshaj yog cov neeg uas muaj cov kab mob sib kis xws li kab mob plawv thiab cov neeg laus. Hauv cov neeg mob laus, cov hnub nyoog muaj feem cuam tshuam rau T thiab B-hlwb ua rau muaj kev nthuav qhia ntau ntxiv ntawm cytokines, ua rau cov lus teb ntev ntev, uas ua rau cov txiaj ntsig tsis zoo.16.
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References:
1. Soni R., 2020. A Novel Approach to 'Repurpose' Existing Drugs For COVID-19. Kev tshawb fawb European. Tshaj tawm rau lub Ob Hlis 07, 2020. Muaj nyob online ntawm https://www.scientificeuropean.co.uk/covid-19/a-novel-approach-to-repurpose-existing-drugs-for-covid-19/ Tau txais los ntawm 08 May 2020.
2. Soni R., 2020. Tshuaj tiv thaiv COVID-19: Kev Sib Tw Tawm Tsam Sijhawm. Kev tshawb fawb European. Tshaj tawm rau lub Plaub Hlis 14, 2020. Muaj nyob online ntawm https://www.scientificeuropean.co.uk/covid-19/vaccines-for-covid-19-race-against-time/ Tau txais los ntawm 07 May 2020.
3. Liming L., Xiaofeng L., et al 2020. Ib qho kev hloov tshiab ntawm cov yam ntxwv ntawm kev kis tus kabmob tshiab (COVID-19). Suav Journal of Epidemiology, 2020,41, XNUMX: Online pre-publishing. DOI:10.3760/cma.j.issn.0254-6450.2020.02.002
4. Chousterman BG, Swirski FK, Weber GF. 2017. Cytokine cua daj cua dub thiab kab mob sepsis pathogenesis. Seminars hauv Immunopathology. 2017 Lub Xya Hli; 39(5): 517-528. DOI: https://doi.org/10.1007/s00281-017-0639-8
5. Yang Y, Wang H, Kouadir M, thiab al., 2019. Tsis ntev los no kev nce qib hauv cov txheej txheem ntawm NLRP3 inflammasome activation thiab nws cov inhibitors. Cell Tuag thiab Kab Mob 10, Tshooj xov tooj: 128 (2019). DOI: https://doi.org/10.1038/s41419-019-1413-8
6. Nieto-Torres JL, Verdiá-Báguena, C., Jimenez-Guardeño JM et al. 2015. Mob hnyav ua pa mob coronavirus E protein thauj calcium ions thiab activates NLRP3 inflammasome. Virology, 485 (2015), pp. 330-339, DOI: https://doi.org/10.1016/j.virol.2015.08.010
7. Shi CS, Nabar NR, et al 2019. SARS-Coronavirus Open Reading Frame-8b ua rau txoj kev ntxhov siab hauv lub cev thiab ua rau NLRP3 inflammasomes. Cell Death Discovery, 5 (1) (2019) p. 101, TSI: https://doi.org/10.1038/s41420-019-0181-7
8. Siu KL, Yuen KS, et al 2019. Mob hnyav ua pa mob coronavirus ORF3a protein activates NLRP3 inflammasome los ntawm kev txhawb TRAF3-dependent ubiquitination ntawm ASC. FASEB J, 33 (8) (2019), pp. 8865-8877, DOI: https://doi.org/10.1096/fj.201802418R
9. Chen LY, Moriyama, M., et al 2019. Mob hnyav ua pa mob Coronavirus Viroporin 3a Ua rau NLRP3 Inflammasome. Frontier Microbiology, 10 (Lub Ib Hlis) (2019), p. 50, TSI: https://doi.org/10.3389/fmicb.2019.00050
10. Grailer JJ, Canning BA, et al. 2014. Lub luag haujlwm tseem ceeb rau NLRP3 Inflammasome thaum mob ntsws mob. J Immunol, 192 (12) (2014), pp. 5974-5983. DOI: https://doi.org/10.4049/jimmunol.1400368
11. Li D, Ren W, et al, 2018. Regulation of the NLRP3 inflammasome and macrophage pyroptosis by p38 MAPK signaling pathway in a mouse model of mob ntsws mob. Mol Med Rep, 18 (5) (2018), pp. 4399-4409. DOI: https://doi.org/10.3892/mmr.2018.9427
12. Jones HD, Crother TR, et al 2014.The NLRP3 inflammasome yog xav tau rau kev loj hlob ntawm hypoxemia hauv LPS/mechanical ventilation mob ntsws mob. Am J Respir Cell Mol Biol, 50 (2) (2014), pp. 270-280. DOI: https://doi.org/10.1165/rcmb.2013-0087OC
13. Dolinay T, Kim YS, et al 2012. Inflammasome-regulated cytokines yog cov kws kho mob tseem ceeb ntawm kev mob ntsws ntsws. Am J Respir Crit Care Med, 185 (11) (2012), pp. 1225-1234. DOI: https://doi.org/10.1164/rccm.201201-0003OC
14. Bulgarian Academy of Sciences 2020. Xov Xwm - Cov ntaub ntawv pov thawj tshiab tau lees paub qhov kev xav ntawm cov kws tshawb fawb ntawm BAS rau lub luag haujlwm ntawm NLRP3 inflammasome hauv cov kab mob ntawm cov teeb meem hauv COVID-19. Tshaj tawm rau lub Plaub Hlis 29, 2020. Muaj nyob online ntawm https://www.bas.bg/?p=29866&lang=en Tau txais los ntawm 06 May 2020.
15. Qiao J, Wu X, et al. 2018. NLRP3 Regulates Platelet Integrin ΑIIbβ3 Outside- InSignaling, Hemostasis Thiab Arterial Thrombosis. Haematologica Cuaj hlis 2018 103: 1568-1576; DOI: https://doi.org/10.3324/haematol.2018.191700
16. Zhou F, Yu T, et al. 2020. Cov chav kho mob thiab cov xwm txheej txaus ntshai rau kev tuag ntawm cov neeg laus hauv tsev kho mob nrog COVID-19 hauv Wuhan, Tuam Tshoj: kev tshawb fawb rov qab. Lancet (Lub Peb Hlis 2020). DOI: https://doi.org/10.1016/s0140-6736(20)30566-3
17. Hayrabedyan S, Toodorova K, Jabeen A, et al. 2016. Sertoli hlwb muaj kev ua haujlwm NALP3 inflammasome uas tuaj yeem hloov kho autophagy thiab cytokine ntau lawm. Nature Scientific Reports ntim 6, Tshooj xov tooj: 18896 (2016). DOI: https://doi.org/10.1038/srep18896
18. Deftereos SG, Siasos G, Giannopoulos G, Vrachatis DA, et al. 2020. Txoj kev tshawb fawb Greek hauv qhov cuam tshuam ntawm colchicine hauv COVID-19 kev tiv thaiv kev nyuaj siab (GRECCO-19 txoj kev tshawb fawb): Kev tsim nyog thiab kev kawm tsim. ClinicalTrials.gov Identifier: NCT04326790. Hellenic Journal of Cardiology (hauv xovxwm). DOI: https://doi.org/10.1016/j.hjc.2020.03.002
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