Although celecoxib was sufficient in suppressing the cyclo-oxygenase (COX)-2 expression in the control

organ (kidney), it failed to suppress the enhanced hepatic COX-2 expression. At week 2, celecoxib did not alter the ALT level, the severity of fibrosis and hepatic collagen contents. This was associated with unchanged alpha-smooth muscle actin protein expression and tissue inhibitor of metalloproteinase-2 Akt inhibitor (TIMP-2), matrix metalloproteinase (MMP)-2 and MMP-9 mRNA expressions in the liver. Celecoxib had no effect on the BDL-dependent increase in bilirubin levels at any time point.\n\nThe present study provides morphological and molecular biological evidences for the role of celecoxib in cholestatic

liver fibrosis. Celecoxib protects against hepatic inflammation in the early stage of BDL rats, but does not have an effect on liver fibrosis.”
“Macromolecular crowding affects most chemical equilibria in living cells, as the presence of high concentrations of macromolecules sterically restricts the available Doramapimod in vitro space. Here, we characterized the influence of crowding on a prototypical RTX protein, RCL. RTX (Repeat in ToXin) motifs are calcium-binding nonapeptide sequences that are found in many virulence factors produced by Gram-negative bacteria and secreted by dedicated type 1 secretion systems. RCL is an attractive model to investigate the effect of molecular crowding on ligand-induced protein folding, as it shifts from intrinsically disordered conformations (apo-form) to a stable structure upon calcium binding (holo-form). It thus offers the rare opportunity to characterize the crowding effects on the same polypeptide chain under two drastically distinct folding states. We showed that

the crowding agent Ficoll70 did not affect the structural content of the apo-state and holo-state of RCL but increased the protein affinity for calcium. Moreover, Ficoll70 strongly stabilized both states of RCL, increasing their half-melting temperature, without affecting enthalpy changes. The power law dependence of the melting temperature increase (Delta T-m) on the volume fraction (phi) followed theoretical excluded volume predictions DMH1 nmr and allowed the estimation of the Flory exponent (nu) of the thermally unfolded polypeptide chain in both states. Altogether, our data suggest that, in the apo-state as found in the crowded bacterial cytosol, RTX proteins adopt extended unfolded conformations that may facilitate protein export by the type I secretion machinery. Subsequently, crowding also enhances the calcium-dependent folding and stability of RTX proteins once secreted in the extracellular milieu.”
“Ca2+ is a universal second messenger in eukaryotic cells transmitting information through sequences of concentration spikes.