Post COVID-19 vaccine deaths - Singapore's early experience.

Singapore has been using mRNA vaccines developed by Pfizer-BioNTech and Moderna as part of the nation's COVID vaccination program since 30 December 2020. From 1 February 2021-30 June 2021, a total of 34 deaths that occurred within 72 h of the deceased receiving their COVID-19 vaccination were referred to the Forensic Medicine Division of the Health Sciences Authority of Singapore. Autopsies, histological sampling and ancillary investigations consisting of total tryptase level, Immunoglobulin E (IgE), and C-reactive Protein (CRP), were performed on 29 of these cases. Our study has shown no definite causative relationship between the mRNA vaccination and deaths of individuals who died within 72 h after receiving the vaccination, in particular with regards to anaphylactic reactions, myocarditis and pericarditis, and thrombotic complications. Further studies may consider increasing the incident time frame from 72 h to seven days post-vaccination or longer to include any potential delayed presentation of adverse effects.

Mechanism of chlorogenic acid in alveolar macrophage polarization in Klebsiella pneumoniae-induced pneumonia.

Chlorogenic acid (CA) has been discovered to regulate macrophage polarization in pneumonia. This study aims to analyze the functional mechanism of CA in alveolar macrophage (AM) polarization and provide a theoretical basis for treatment of Klebsiella pneumoniae (Kp)-induced pneumonia. Mice were infected with Kp, and treated with CA and silent information regulator 1 (SIRT1) inhibitor (Selisistat). Mouse survival rate was recorded and bacterial burden was detected. AM polarization and pathologic change of lung tissues were evaluated. Expressions of SIRT1 and HMGB1 and cytokine levels were detected. MH-S cells were infected with Kp to establish the pneumonia cell model, followed by transfection of si-SIRT1 and HMGB1 overexpression vector. The HMGB1 expression in the nucleus and cytoplasm was detected. HMGB1 subcellular localization and HMGB1 acetylation level were detected. Kp led to high death rates, SIRT down-regulation and increases in inflammatory factor level and bacterial burden, and promoted M1 polarization. CA treatment improved mouse survival rate and promoted M2 polarization and SIRT1 expression. SIRT1 decreased HMGB1 acetylation level to inhibit nuclear to the cytoplasm translocation. Silencing SIRT1 or HMGB1 overexpression reversed the effect of CA on Kp-induced pneumonia. Overall, CA activated SIRT1 to inhibit HMGB1 acetylation level and nuclear translocation, thereby promoting M2 polarization in AMs and alleviating Kp-induced pneumonia.

MicroRNA-124 alleviates hyperoxia-induced inflammatory response in pulmonary epithelial cell by inhibiting TLR4/NF-κB/CCL2.

BACKGROUND: Lung epithelial cell dysfunction induced by hyperoxia-associated oxidative stress is a prominent feature involved in the development of acute lung injury (ALI). How the underlying molecular mechanisms contributed to this process are poorly defined. In the present study, we sought to identify the role of miR-124 in hyperoxia-induced cell apoptosis and excessive inflammatory response in pulmonary epithelial cell. METHODS: The miR-124 levels in pulmonary epithelial cell were assayed by qRT-PCR. MiR-124 mimics and inhibitors were transfected to gain or loss of miR-124 function. Cell proliferation was analyzed by CCK8 assay. Cell apoptosis was analyzed by flow cytometry. The targeted genes were predicted by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. The protein levels were assayed by western blotting. RESULTS: The results showed that miR-124 was significantly down-regulated in Beas2B cells and primary LECs upon hyperoxia exposure conditions. However, overexpression of miR-124 dramatically attenuated hyperoxia-provoked TLR4, NF-κB and pro-inflammatory cytokines production. In vitro, the cell viability and apoptosis was significantly reversed following transfection with miR-124 mimics in the presence of hyperoxia. Furthermore, the 3'-untranslated region (3'-UTR) of CCL2 was bound by miR-124. CONCLUSION: It was concluded that miR-124 inhibited hyperoxia-induced apoptosis and excessive inflammatory response in Beas2B cells and primary LECs, at least partially, through the inhibition of TLR4/NF-κB/CCL2 signaling cascades.