The effect of histone deacetylase inhibitors on AHSP expression - Table 1

<p>The effect of histone deacetylase inhibitors on AHSP expression</p> - Table

Comparison of the effect of sodium phenylbutyrate and sodium valproate on the expression of AHSP, BCL11A, γ-globin genes (HBG 1/2) and erythroid transcription factors after six days of treatment.

<p>Sodium valproate was significantly more efficient on the down-regulation of BCL11A and the up-regulation of AHSP, γ-globin genes (HBG 1/2), and erythroid transcription factors compared with sodium phenylbutyrate (<i>p</i> < 0.0005). NB, sodium phenylbutyrate; NV, sodium valproate.</p

Protein expression analysis by western blotting.

<p>K562 cells were cultured with or without sodium phenylbutyrate 1 mM (NB), sodium valproate 1 mM (NV) and hemin 50 μM. After 6 days, the cells were examined for STAT3, AHSP, γ-globin and BCL11A protein expression by Western blot analysis. To normalize protein loading, the blot was hybridized with β-actin antibody.</p

The effect of sodium phenylbutyrate and sodium valproate on the expression of AHSP, BCL11A, γ-globin genes (HBG 1/2) and erythroid transcription factors.

<p>Both compounds led to significant induction of AHSP, γ-globin genes (HBG1/2) and erythroid transcription factors in K562 cells (<i>p</i> < 0.05). However, BCL11A was significantly repressed due to treatment with them (<i>p</i> < 0.05). Higher concentrations of the studied HDIs and longer treatment times led to significantly greater repression of BCL11A and higher expression of other target genes (<i>p</i> < 0.0005). NB, sodium phenylbutyrate; NV, sodium valproate; 2D, two days of treatment; 4D, four days of treatment; 6D, six days of treatment.</p

A universal SARS‐CoV DNA vaccine inducing highly cross‐reactive neutralizing antibodies and T cells

Abstract New variants in the SARS‐CoV‐2 pandemic are more contagious (Alpha/Delta), evade neutralizing antibodies (Beta), or both (Omicron). This poses a challenge in vaccine development according to WHO. We designed a more universal SARS‐CoV‐2 DNA vaccine containing receptor‐binding domain loops from the huCoV‐19/WH01, the Alpha, and the Beta variants, combined with the membrane and nucleoproteins. The vaccine induced spike antibodies crossreactive between huCoV‐19/WH01, Beta, and Delta spike proteins that neutralized huCoV‐19/WH01, Beta, Delta, and Omicron virus in vitro. The vaccine primed nucleoprotein‐specific T cells, unlike spike‐specific T cells, recognized Bat‐CoV sequences. The vaccine protected mice carrying the human ACE2 receptor against lethal infection with the SARS‐CoV‐2 Beta variant. Interestingly, priming of cross‐reactive nucleoprotein‐specific T cells alone was 60% protective, verifying observations from humans that T cells protect against lethal disease. This SARS‐CoV vaccine induces a uniquely broad and functional immunity that adds to currently used vaccines

Metabolic perturbation associated with COVID-19 disease severity and SARS-CoV-2 replication

Viruses hijack host metabolic pathways for their replicative advantage. In this study, using patient-derived multiomics data and in vitro infection assays, we aimed to understand the role of key metabolic pathways that can regulate severe acute respiratory syndrome coronavirus-2 reproduction and their association with disease severity. We used multiomics platforms (targeted and untargeted proteomics and untargeted metabolomics) on patient samples and cell-line models along with immune phenotyping of metabolite transporters in patient blood cells to understand viral-induced metabolic modulations. We also modulated key metabolic pathways that were identified using multiomics data to regulate the viral reproduction in vitro. Coronavirus disease 2019 disease severity was characterized by increased plasma glucose and mannose levels. Immune phenotyping identified altered expression patterns of carbohydrate transporter, glucose transporter 1, in CD8+ T cells, intermediate and nonclassical monocytes, and amino acid transporter, xCT, in classical, intermediate, and nonclassical monocytes. In in vitro lung epithelial cell (Calu-3) infection model, we found that glycolysis and glutaminolysis are essential for virus replication, and blocking these metabolic pathways caused significant reduction in virus production. Taken together, we therefore hypothesized that severe acute respiratory syndrome coronavirus-2 utilizes and rewires pathways governing central carbon metabolism leading to the efflux of toxic metabolites and associated with disease severity. Thus, the host metabolic perturbation could be an attractive strategy to limit the viral replication and disease severity