RelA Is an Essential Target for Enhancing Cellular Responses to the DNA Repair/Ref-1 Redox Signaling Protein and Restoring Perturbated Cellular Redox Homeostasis in Mouse PDAC Cells.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers with a poor response to current treatment regimens. The multifunctional DNA repair-redox signaling protein Ref-1 has a redox signaling function that activates several transcriptional factors (TFs) including NF-κB (RelA), STAT3, AP-1. These have been implicated in signaling in PDAC and associated with cancer progression and therapy resistance.

Mechanical Reversibility of Strain-Promoted Azide-Alkyne Cycloaddition Reactions.

Mechanophores, that is, molecules that show a defined response to force, are crucial building blocks of mechanoresponsive materials. The possibility of mechanically induced cycloreversion for a series of triazoles formed via strain-promoted azide-alkyne cycloaddition reactions was investigated by density functional theory calculations, and these triazoles were compared to the 1,4- and 1,5-regioisomers formed in the reaction of an azide with a terminal alkyne. We show that cycloreversion is in principal possible and that the pulling geometry is the most important parameter that determines the probability of cycloreversion.

Combined inhibition of BET family proteins and histone deacetylases as a potential epigenetics-based therapy for pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers and shows resistance to any therapeutic strategy used. Here we tested small-molecule inhibitors targeting chromatin regulators as possible therapeutic agents in PDAC. We show that JQ1, an inhibitor of the bromodomain and extraterminal (BET) family of proteins, suppresses PDAC development in mice by inhibiting both MYC activity and inflammatory signals.

Modeling the electrostatic signature of single enzyme activity.

Charge sensors based on nanoscale field-effect transistors are a promising new tool to probe the dynamics of individual enzymes. However, it is currently unknown whether the electrostatic signals associated with biological activity exceed detection limits. We report calculations of electrostatic signatures of two representative enzymes, deoxyribonuclease I and T4 lysozyme.