Nrf2-regulated antioxidant response ameliorating ionizing radiation-induced damages explored through in vitro and molecular dynamics simulations.

This study aims to investigate the mechanism of natural antioxidant ferulic acid (FA) in reducing oxidative stress followed by its inhibitory effect on the Keap1-Nrf2 complex. FA was treated ex vivo with human blood for 30 min at 37 °C ± 1 °C and exposed to 1.5 Gy of γ- rays of 60Co (0.789 Gy/min) and allowed for repair for an hour at 37 °C ± 1 °C. FA's free radical scavenging capacity was measured using 2,7-dichlorofluorescein diacetate assay and cytogenetic assays. Further, a possible mechanism of protein-ligand interaction between FA and Keap1-Nrf2 pathway protein as a cellular drug target was studied using docking and molecular dynamics simulation. The 1.5 Gy of γ- rays exposed to pre-treated blood with FA showed a significant (p < 0.05) reduction in reactive oxygen species and DNA damage compared to the normal control blood group sample. The ligand-protein transient binding interaction in molecular dynamic simulation over a period of 100 ns was consistent and stable emphasizing complementary charge between the protein and ligand, speculating higher hydrophobic amino acid residues in the Keap1 active pocket. This might sway the Keap1 from interaction with Nrf2, and could lead to nuclear translocation of Nrf2 during radiation-induced oxidative stress. The present study emphasizes the radioprotective effect of FA against 1.5 Gy of γ- rays exposed to human blood and the application of in silico approaches helpful for the possible protective effect of FA.Communicated by Ramaswamy H. Sarma.

Network topology analysis of essential genes interactome of Helicobacter pylori to explore novel therapeutic targets.

The Helicobacter pylori chronic colonization produces a wide range of gastric diseases in the gastric mucosa by abetting inflammation. Amidst coevolution and reorganization of its metabolism with humans, it has become difficult still imperative to understand and prevent its growth. This study focus to explore functional insights into identification of hub proteins/genes by aggregating the behavior of genes connected in a protein-protein interaction (PPI) network. We have constructed a PPI network of 123 essential genes along with 1213 interactions in H. pylori 26695. The degree and other centrality measures analysis assist in identifying the important hub nodes, which are top-ranked proteins. A total of nine proteins (recA, guaA, dnaK, rpsB, rplQ, rpmA, rpmC, rpmF, and rpsE) were obtained with high degree (k), betweenness centrality (BC) value. Gene ontology analysis reveals 8, 5 and 3 GO terms correspond to biological processes, cellular components and molecular function respectively. Gene complexes of hypothetical proteins (HPs) were related to aminoacyl-tRNA biosynthesis, biosynthesis of secondary metabolites, bacterial secretion system and protein export. The MCODE analysis revealed that protein from module M1, M3 and M6 include the proteins which have highest degree and BC values. It is noteworthy to mention that the bifunctional GMP synthase/glutamine amidotransferase protein (guaA), molecular chaperon (dnaK), recombinase A (recA) constitute as hub proteins. As a result, these genes are considered as network hub nodes that might be used as therapeutic targets. Our analysis affords a detailed understanding of the molecular process and pathways regulated by the essential genes in H. pylori 26695.

Is butyrate a natural alternative to dexamethasone in the management of CoVID-19?

Coronavirus disease 2019 (CoVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 has affected more than 100 million lives. Severe CoVID-19 infection may lead to acute respiratory distress syndrome and death of the patient, and is associated with hyperinflammation and cytokine storm. The broad spectrum immunosuppressant corticosteroid, dexamethasone, is being used to manage the cytokine storm and hyperinflammation in CoVID-19 patients. However, the extensive use of corticosteroids leads to serious adverse events and disruption of the gut-lung axis. Various micronutrients and probiotic supplementations are known to aid in the reduction of hyperinflammation and restoration of gut microbiota. The attenuation of the deleterious immune response and hyperinflammation could be mediated by short chain fatty acids produced by the gut microbiota. Butyric acid, the most extensively studied short chain fatty acid, is known for its anti-inflammatory properties. Additionally, butyric acid has been shown to ameliorate hyperinflammation and reduce oxidative stress in various pathologies, including respiratory viral infections. In this review, the potential anti-inflammatory effects of butyric acid that aid in cytokine storm depletion, and its usefulness in effective management of critical illness related to CoVID-19 have been discussed.