Inflammation-associated ectopic mineralization

Nicotine Enantioselectively Targets Myeloid Differentiation Protein 2 and Inhibits the Toll-like Receptor 4 Signaling

“…The TLR4/MD2 complex bound with the ligand was solvated in a TIP3P water box with 150 mM NaCl to neutralize the net charges of the system through the CHARMM-GUI web server. 18 The size of the periodic boundary box was set to 130 × 130 × 130 Å 3 , containing approximately 206,600 atoms. All molecular dynamics (MD) simulations were conducted using the GROMACS-2021.2 software package, 22 applying the CHARMM36m force field.…”

“…Toll-like receptor 4 (TLR4) is a critical player in the innate immune system, acting as a key mediator in the inflammatory response to bacterial endotoxin lipopolysaccharides (LPSs). − Together with its coreceptor, myeloid differentiation protein 2 (MD2), which plays a key role in ligand recognition, TLR4 detects LPSs on the cell walls of Gram-negative bacteria, identifying these as pathogen-associated molecular patterns (PAMPs) and triggering the TLR4 signaling pathway. − This process leads to the overproduction of proinflammatory factors . Recent studies have expanded our understanding of TLR4’s function, revealing that it not only detects PAMPs but also identifies various psychoactive substances as xenobiotic-associated molecular patterns (XAMPs).…”