Lymphopenia-by-SARSCov2-and-ClO2.plantuml

@startuml
' License: CC0
title リンパ球減少の原因へのウイルス及び二酸化塩素の関与の可能性\n(Determination of the Effectiveness of Chlorine Dioxide in the Treatment of COVID 19, \nISSN1747-0862 Molecular and Genetic Medicine を元にライター作成)\n
skinparam defaultFontSize 18
skinparam monochrome true

storage "**二酸化塩素**" as clo2
storage "**SARS-CoV-2**" as ncov

card "ほとんどの患者に見られる\n**リンパ球減少**" as lymphopenia
card "カスパーゼ-8複合体の合成" as casp8
card "・細胞骨格の乱れ\n\
・クロマチンと細胞質の凝縮\n\
・ミトコンドリア機能の喪失\n\
・DNAの断片化" as cytoCorruption
card "破れた膜・アポトーシス小体の形成" as apoptoticBody
card "マクロファージによる貪食" as phagocytosis
storage "・インターフェロン\n・プロテインキナーゼR" as interf
storage "対応する受容体" as receptor
card "ウイルスへの免疫応答反応" as immuResp
card "抗ウイルス的炎症反応" as antvInflammation
storage "プロアポトーシス遺伝子" as proap
storage "病原性ペプチドPB1-F2" as pb1F2
card "**白血球の細胞死**" as wbcDeath

card "NLRP3の脱ユビキチン化" as desubiqOfNLRP3
card "NLRP3インフラマソームの活性化" as nlrp3Inflammasome

' The lymphopenia observed in most patients could be due to a process that begins with disorganization of the cytoskeleton, condensation of chromatin and cytoplasm, loss of mitochondrial function, DNA fragmentation and terminal formation of ruptured membranes or apoptotic bodies, finally eliminated by macrophages.

cytoCorruption --> apoptoticBody
apoptoticBody --> phagocytosis

' This phenomenon is mediated by the synthesis of the caspase-8 complex, which we consider could be activated by non-canonical means.

casp8 --> wbcDeath
wbcDeath --> cytoCorruption

' The complex is favored by protein kinase-R, also accelerated by interferon generated in the presence of the virus.

immuResp --> interf : 生成

' The signaling pathways that are activated by these receptors initiate an inflammatory response, with antiviral effects,

interf --> casp8
interf --> receptor
receptor --> antvInflammation : シグナル伝達を活性化

' The virus also activates the transforming growth factor-b through neuraminidase, thus generating another cascade that ends with c-Jun-N-kinase and triggers transcription followed by the expression of pro apoptosis genes.

ncov --> immuResp
ncov --> proap : 発現

' The virus could synthesize the virulence peptide PB1-F2, a small fragment responsible for destroying lymphocytes, a circumstance that could explain the lymphopenia observed in COVID19.

ncov --> pb1F2 : 合成
pb1F2 --> wbcDeath

' The action could also be mediated by action on inflammasomes, where the signaling (redox) by ATP can induce the desubiquitination of NLRP3, possibly induced by chlorine dioxide.

clo2 ----> desubiqOfNLRP3 : ATPシグナル伝達を誘導
desubiqOfNLRP3 --> nlrp3Inflammasome
nlrp3Inflammasome --> wbcDeath

' 以下ライターによる補足

proap --> wbcDeath
antvInflammation --> wbcDeath
wbcDeath -----> lymphopenia

@enduml