First described in 2020, multi-system inflammatory syndrome in children (MIS-C) is an, initially life-threatening, disease characterised by severe inflammation and following exposure to SARS-CoV-2. The immunopathology of MIS-C involves a hyperinflammation characterised by a cytokine storm and activation of both the innate and adaptive immune system, eventually leading to multi-organ failure. Several etiological theories are described in literature. Firstly, it is suggested that the gut plays an important role in the translocation of microbial products to the systemic circulation. Additionally, the production of autoantibodies that develop after the initial infection with SARS-CoV-2 might lead to many of its broad clinical symptoms. Finally, the superantigen theory where non-specific binding of the SARS-CoV-2 spike glycoprotein to the T-cell receptor leads to a subsequent activation of T cells, generating a powerful immune response. Despite the sudden outbreak of MIS-C and alarming messages, as of 2024, cases have declined drastically and subsequently show a less severe clinical spectrum. However, subacute cases not meeting current diagnostic criteria might be overlooked even though they represent a valuable research population. In the future, research should focus on adjusting these criteria to better understand the broad pathophysiology of MIS-C, aiding early detection, therapy, and prediction.
Background: Cerebral ischemia/reperfusion injury (CIRI) is still a complicated disease with high fatality rates worldwide. Transmembrane Protein 79 (TMEM79) regulates inflammation and oxidative stress in some other diseases.
Methods: CIRI mouse model was established using C57BL/6J mice through middle cerebral artery occlusion-reperfusion (MCAO/R), and BV2 cells were subjected to oxygen and glucose deprivation/reoxygenation (OGD/R) to simulate CIRI. Brain tissue or BV2 cells were transfected or injected with lentivirus-carried TMEM79 overexpression vector. The impact of TMEM79 on CIRI-triggered oxidative stress was ascertained by dihydroethidium (DHE) staining and examination of oxidative stress indicators. Regulation of TMEM79 in neuronal apoptosis and inflammation was determined using TUNEL staining and ELISA.
Results: TMEM79 overexpression mitigated neurological deficit induced by MCAO/R and decreased the extent of cerebral infarct. TMEM79 prevented neuronal death in brain tissue of MCAO/R mouse model and suppressed inflammatory response by reducing inflammatory cytokines levels. Moreover, TMEM79 significantly attenuated inflammation and oxidative stress caused by OGD/R in BV2 cells. TMEM79 facilitated the activation of Nrf2 and inhibited NLRP3 and caspase-1 expressions. Rescue experiments indicated that the Nrf2/NLRP3 signaling pathway mediated the mitigative effect of TMEM79 on CIRI in vivo and in vitro.
Conclusion: Overall, TMEM79 was confirmed to attenuate CIRI via regulating the Nrf2/NLRP3 signaling pathway.
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