Mapping CircRNA-miRNA-mRNA regulatory axis identifies hsa_circ_0080942 and hsa_circ_0080135 as a potential theranostic agents for SARS-CoV-2 infection.

Non-coding RNAs (ncRNAs) can control the flux of genetic information; affect RNA stability and play crucial roles in mediating epigenetic modifications. A number of studies have highlighted the potential roles of both virus-encoded and host-encoded ncRNAs in viral infections, transmission and therapeutics. However, the role of an emerging type of non-coding transcript, circular RNA (circRNA) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has not been fully elucidated so far. Moreover, the potential pathogenic role of circRNA-miRNA-mRNA regulatory axis has not been fully explored as yet. The current study aimed to holistically map the regulatory networks driven by SARS-CoV-2 related circRNAs, miRNAs and mRNAs to uncover plausible interactions and interplay amongst them in order to explore possible therapeutic options in SARS-CoV-2 infection. Patient datasets were analyzed systematically in a unified approach to explore circRNA, miRNA, and mRNA expression profiles. CircRNA-miRNA-mRNA network was constructed based on cytokine storm related circRNAs forming a total of 165 circRNA-miRNA-mRNA pairs. This study implies the potential regulatory role of the obtained circRNA-miRNA-mRNA network and proposes that two differentially expressed circRNAs hsa_circ_0080942 and hsa_circ_0080135 might serve as a potential theranostic agents for SARS-CoV-2 infection. Collectively, the results shed light on the functional role of circRNAs as ceRNAs to sponge miRNA and regulate mRNA expression during SARS-CoV-2 infection.

Blocking Toll-like receptor 9 attenuates bleomycin-induced pulmonary injury.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is one of the most common complications in coronavirus disease 2019 patients suffering from acute lung injury (ALI). In ARDS, marked distortion of pulmonary architecture has been reported. The pulmonary lesions in ARDS include hemodynamic derangements (such as alveolar edema and hemorrhage), vascular and bronchiolar damage, interstitial inflammatory cellular aggregations, and eventually fibrosis. Bleomycin induces ARDS-representative pulmonary damage in mice and rats; therefore, we used bleomycin model mice in our study. Recently, Toll-like receptor 9 (TLR9) was implicated in the development of ARDS and ALI. METHODS: In this study, we evaluated the efficiency of a TLR9 blocker (ODN2088) on bleomycin-induced pulmonary damage. We measured the apoptosis rate, inflammatory reaction, and fibroplasia in bleomycin- and bleomycin + ODN2088-treated mice. RESULTS: Our results showed a significant amelioration in bleomycin-induced damage to pulmonary architecture following ODN2088 treatment. A marked decrease in pulmonary epithelial and endothelial apoptosis rate as measured by cleaved caspase-3 expression, inflammatory reaction as indicated by tumor necrosis factor α expression, and pulmonary fibrosis as demonstrated by Van Gieson staining and α-smooth muscle actin immunohistochemistry were observed following ODN2088 treatment. CONCLUSIONS: All these findings indicate that blocking downstream TLR9 signaling could be beneficial in prevention or mitigation of ARDS through hemodynamic derangements, inflammation, apoptosis, and fibrosis.

STEMI and COVID-19 Pandemic in Saudi Arabia.

The COVID-19 pandemic had significant impact on health care worldwide which has led to a reduction in all elective admissions and management of patients through virtual care. The purpose of this study is to assess changes in STEMI volumes, door to reperfusion, and the time from the onset of symptoms until reperfusion therapy, and in-hospital events between the pre-COVID-19 (PC) and after COVID-19 (AC) period. All acute ST-segment elevation myocardial infarction (STEMI) cases were retrospectively identified from 16 centers in the Kingdom of Saudi Arabia during the COVID-19 period from January 01 to April 30, 2020. These cases were compared to a pre-COVID period from January 01 to April 30, 2018 and 2019. One thousand seven hundred and eighty-five patients with a mean age 56.3 (SD ± 12.4) years, 88.3% were male. During COVID-19 Pandemic the total STEMI volumes was reduced (28%, n = 500), STEMI volumes for those treated with reperfusion therapy was reduced too (27.6%, n= 450). Door to balloon time < 90 minutes was achieved in (73.1%, no = 307) during 2020. Timing from the onset of symptoms to the balloon of more than 12 hours was higher during 2020 comparing to pre-COVID 19 years (17.2% vs <3%, respectively). There were no differences between the AC and PC period with respect to in-hospital events and the length of hospital stay. There was a reduction in the STEMI volumes during 2020. Our data reflected the standard of care for STEMI patients continued during the COVID-19 pandemic while demonstrating patients delayed presenting to the hospital.