Replicative senescence of human diploid fibroblasts (HDFs) occurs when cells lose their capacity to proliferate and enter a phase of irreversible growth arrest. Stress-induced premature senescence (SIPS) on the other hand is caused by subcytotoxic concentrations of various oxidants which trigger accelerated cellular senescence. In this study, a SIPS model was established by exposing human diploid fibroblasts (HDFs) to 20 μM H2O2 for 2 weeks. A proteomic comparison between young, senescent and SIPS cells was done using two dimensional gel electrophoresis (2DGE) to elucidate the changes in protein expression associated with cellular aging. Our analysis showed that 28 protein spots were differentially expressed in senescent cells whereas 10 protein spots were differentially expressed in SIPS as compared to young cells. Three similar protein spots were differentially expressed in both senescent and SIPS cells when compared to the young cells. These results indicate that a difference in protein expression exists between senescent cells and SIPS cells compared to young cells.
Dengue is a potentially deadly disease with no effective drug. An in silico molecular docking was performed using Autodock
4.2.6 to investigate the molecular interactions between protease inhibitors, comprising antibiotic derivatives namely
doxycycline (3), rolitetracycline (5) and a non-steroidal anti-inflammatory drug (NSAID), meclofenamic acid (4), against
the NS2B-NS3 protease from dengue virus-2 (DENV-2). The non-competitive inhibitor (3) showed lower binding energy
(-5.15 kcal/mol) than the predicted competitive inhibitors 4 and 5 (-3.64 and -3.21 kcal/mol, respectively). Structural
analyses showed compound 3 that bound to a specific allosteric site, interacted with Lys74, a significant amino acid
residue bonded to one of the catalytic triad, Asp75. Compounds 4 and 5 showed direct binding with two of the catalytic
triad, His51 and Ser135, hence, predicted to be competitive inhibitors.