ABSTRACT
Introduction: Increased Vascular Endothelial Growth Factor A (VEGF-A) levels are associated with Severe Acute Respiratory (SARS) infection. The aim was to investigate in vivo VEGF-A and VEGF-B (VEGF-A/B) gene expression (GE) in severe pulmonary disease pathogenesis. Method: Twelve temporal Mus musculus Wildtype (WT) C57BL/6 SARS-CoV MA15 lung studies were selected from the NCBI GEO database for GE profiling. Results: In murine dataset (GSE68820) Day 2 was compared to Day 7 demonstrating a downregulation trend in VEGF-A GE, with an opposite effect on VEGF-B GE (p=4.147e-03, p=7.580e-07, respectively). A v-shaped VEGF-B gene expression trajectory was noteworthy across certain datasets and after dORF6 stimulation. In addition, MA15 dose stimulation studies showed that a higher antigenic load caused more profound effects on VEGF-A resulting in a steeper fall in GE compared to other antigens. Conclusions: Distinct temporal trajectory patterns of VEGF-A and VEGF-B gene expression were associated with SARS-CoV MA15 stimulation. Unraveling the importance of VEG-A/B dynamics offers exciting prospects for improved bio-marking and therapeutic precision.
Subject(s)
Severe Acute Respiratory Syndrome , Lung DiseasesABSTRACT
Background and Aim Coronary involvement in Kawasaki Disease (KD), whether its after SARS-CoV2 infection or not, can result in significant complications. There is the risk of aneurysm formation associated with inflammation and an unremitting fever. We wished to study the Vasoactive Endothelial Growth Factor (VEGF) and Heat Shock Response from a gene-expression perspective. Thereby aiming to furnish to insights that might be useful in the treatment of Kawasaki Disease. Method KD datasets based on previous work, were selected including microarray studies KD1 (GSE63881), KD2 (GSE73461), KD3 (GSE68004) and the RNAseq dataset KD4 (GSE64486) from the NCBI online repository. Based on clinical literature. HSP genes shown to be associated with angiogenesis were chosen for analysis as well as gene expression for VEFGA and VEGFB. Further in order to gain an impression of inflammatory patterns, gene expression for NFKB1 and TNF were also chosen. Tools for analysis included Gene Set Expression Analysis (GSEA). A KEGG pathway, outlining a relationship between VEGF and endothelial migration and proliferation was assumed. Results A KD dataset showed increased VEGFA and decreased VEGFB in acute versus convalescent samples. In all three KD datasets, HSPA1A and HSBAP1 genes were upregulated in acute versus convalescent samples. In KD4, cases of KD versus controls, VEGFB was down-regulated (p = 4.932e-02) and HSPBAP1 up-regulated (p = 1.202e-03). GSEA of KD1, KD2 and KD3, using Hallmark gene sets, suggested an inflammatory response with TNFA signaling via NFKB, IL6 JAK STAT 3 signaling, apoptosis, angiogenesis, and unfolded protein response. Conclusions A novel application of a model of VEGF and HSP to KD was presented. Coronary pathogenesis based on VEGF and HSP was explored. The ability to follow angiogenesis at the molecular level using a VEGF-HSP model may have therapeutic implications. Further, the significance of gene expression between VEGFA, VEGFB in KD and the relationship of HSP gene expression to angiogenesis in KD requires further study.
Subject(s)
Mucocutaneous Lymph Node Syndrome , Fever , Coronary Aneurysm , Inflammation , AneurysmABSTRACT
The COVID-19 pandemic has recently emerged as a worldwide health emergency that necessitates coordinated international measures. To contain the virus's spread, governments and health organisations raced to develop vaccines that would lower Covid-19 morbidity, relieve pressure on healthcare systems, and allow economies to open. As a way forward after the COVID-19 vaccination, the Vaccination certificate has been adopted to help the authorities formulate policies by controlling cross-border travelling. To resolve significant privacy concerns and remove the need for relying on third parties to maintain trust and control the user's data, in this paper, we leverage blockchain technologies in developing a secure and verifiable vaccination certificate. Our approach has the advantage of utilising a hybrid architecture that implements different advanced technologies, such as smart contracts, interPlanetary File System (IPFS), and Self-sovereign Identity (SSI). We will rely on verifiable credentials paired with smart contracts to implement on-chain access control decisions and provide on-chain verification and validation of the user and issuer DIDs. The usability of this approach was further analysed, particularly concerning performance and security. Our analysis proved that our approach satisfies vaccination certificate security requirements.