Kawasaki Disease (KD) is an acute and self-limiting vasculitis of unknown etiology that mainly occurs in infancy and can lead to vascular endothelial injury. Hesperidin (HES) is an economical dietary biological flavonoid with anti-oxidant, anti-inflammatory, and anti-apoptotic pharmacological effects. The main objective of this study was to investigate the protective effects of HES on KD, and try to elucidate the underlying mechanism. The Candida albicans water-soluble fraction (CAWS) was used to induce coronary arteritis of KD mouse model in vivo, and tumor necrosis factor α (TNF-α) was employed to induce human umbilical vein endothelial cell (HUVEC) injury of KD cell model in vitro to investigate the anti-inflammatory and anti-apoptotic effects of HES on KD. Our in vivo results showed that HES significantly reduced coronary artery injury in KD mice by alleviating pericoronary inflammatory infiltration and tissue fibrosis, inhibiting inflammatory cytokines and chemokines expressions, and decreasing vascular endothelial cell apoptosis. Our in vitro study confirmed that HES had the opposite ability of the NF-κB agonist NF-ĸB activator 1 (ACT1) to significantly alleviate the inflammatory response, CellROX level, and apoptosis by decreasing BAX/BCL-2 and Cleaved Caspase-3 levels as well as reducing TUNEL positive cells and the ratio of flow cytometry apoptotic cells in TNF-α induced HUVECs. The further mechanism study based on bioinformatics analysis and western blot demonstrated that HES could protect against vascular inflammation and cell apoptosis of KD through inhibiting the TLR4/IĸBα/NF-ĸB pathway, suggesting that HES may be a promising therapeutic candidate for KD.

Background: To identify alarming symptoms that could potentially lead to severe form of COVID-19 pneumonia (i.e. novel coronavirus pneumonia: NCP), a disease that is now having pandemic spread. Methods: Articles from PubMed, Embase, Cochrane database and Google up to 24 February 2020 were systematically reviewed. 18 publications that had documented cases of COVID-19 pneumonia were identified. The relevant data were extracted, systematically reviewed and further evaluated using meta-analysis. We define severe COVID-19 pneumonia as the disease status that requires admission to the intensive care unit (ICU) and respiratory/circulatory support, which is in align with the guideline from the World Health Organization (WHO). Results: 14 studies including 1,424 patients were considered eligible and analyzed. Symptoms such as fever (89.2%), cough (67.2%), fatigue (43.6%) were quite common; but dizziness, hemoptysis, abdominal pain and conjunctival congestion/conjunctivitis were relatively rare. The incidence of dyspnea was significantly higher in patients with severe than non-severe COVID-19 pneumonia (42.7% vs.16.3%, p<0.0001). Similarly, fever and diarrhea were also drastically more common in patients with severe form (p=0.0374 and 0.0267). Further meta-analysis using three high-quality China-based studies confirmed such findings and showed that dyspnea, fever and diarrhea were 3.53 (OR: 3.53, 95%CI: 1.95-6.38), 1.70 (OR: 1.70, 95%CI: 1.01-2.87), and 1.80 (OR: 1.80, 95%CI: 1.06-3.03) folds higher respectively in patients with severe COVID-19 pneumonia. Conclusion: Dyspnea, fever and diarrhea are significantly more prevalent in patients with severe COVID-19 pneumonia, suggesting they are alarming symptoms that warrant close attention and timely management.