SB203580 : a potent p38 MAPK inhibitor reduces the profibrotic bronchial fibroblasts transition associated with asthma

Subepithelial fibrosis is a component of the remodeling observed in the bronchial wall of patients diagnosed with asthma. In this process, human bronchial fibroblasts (HBFs) drive the fibroblast-to-myofibroblast transition (FMT) in response to transforming growth factor-β(1) (TGF-β(1)), which activates the canonical Smad-dependent signaling. However, the pleiotropic properties of TGF-β(1) also promote the activation of non-canonical signaling pathways which can affect the FMT. In this study we investigated the effect of p38 mitogen-activated protein kinase (MAPK) inhibition by SB203580 on the FMT potential of HBFs derived from asthmatic patients using immunocytofluorescence, real-time PCR and Western blotting methods. Our results demonstrate for the first time the strong effect of p38 MAPK inhibition on the TGF-β(1)-induced FMT potential throughout the strong attenuation of myofibroblast-related markers: α-smooth muscle actin (α-SMA), collagen I, fibronectin and connexin 43 in HBFs. We suggest the pleiotropic mechanism of SB203580 on FMT impairment in HBF populations by the diminishing of TGF-β/Smad signaling activation and disturbances in the actin cytoskeleton architecture along with the maturation of focal adhesion sites. These observations justify future research on the role of p38 kinase in FMT efficiency and bronchial wall remodeling in asthma

Working electrode geometry effect : a new concept for fabrication of patterned polymer brushes via SI-seATRP at ambient conditions

First reports concerning the use of atom transfer radical polymerization (ATRP) to prepare patterned hybrid materials appeared more than 20 years ago. However, the development of new methods of preparation of patterned materials is still at the forefront of scientific interest. In this paper, we describe surface-initiated simplified electrochemically mediated ATRP (SI-seATRP) under constant current conditions, used for the fabrication of patterned polymer brushes under ambient conditions at the microliter scale. It is shown that appropriate selection of surface and shape of the working electrode (WE) allows handling the polymerization of (meth)acrylates, acrylates and acrylamides directly on the laboratory bench. The complete procedure includes a minimum amount of reagents and an optimal amount of a catalytic complex equal to 300 ppm. The use of a platinum wire mesh electrode guarantees obtaining polymers forming unique patterns. The observed patterning phenomenon could be explained by the mechanism of electrochemically mediated ATRP (eATRP) and is directly related to the working electrode geometry, and diffusion of the catalyst CuIBr/TPMA (where TPMA: tris(2-pyridylmethyl)amine)

Design and Synthesis of Menthol and Thymol Derived Ciprofloxacin: Influence of Structural Modifications on the Antibacterial Activity and Anticancer Properties

Sixteen new Ciprofloxacin derivatives were designed and successfully synthesized. In an in silico experiment, lipophilicity was established for obtained compounds. All compounds were screened for antimicrobial activity using standard and clinical strains. As for Gram-positive hospital microorganisms, all tested derivatives were active. Measured MICs were in the range 1–16 µg/mL, confirming high antimicrobial potency. Derivative 12 demonstrated activity against all standard Gram-positive Staphylococci, within the range of 0.8–1.6 µg/mL and was confirmed as the leading structure with MICs 1 µg/mL for S. pasteuri KR 4358 and S. aureus T 5591 (clinical strains). All compounds were screened for their in vitro cytotoxic properties via the MTT method. Three of the examined compounds (3, 11 and 16) showed good activity against cancer cells, and in parallel were found not to be cytotoxic toward normal cells. Doxorubicin SI ranged 0.14–1.11 while the mentioned three ranged 1.9–3.4. Selected Ciprofloxacin derivatives were docked into the crystal structure of topoisomerase II (DNA gyrase) in complex with DNA (PDB ID: 5BTC). In summary, leading structures were established (3, 11, 12 and 16). We have observed poor results in preformed studies for disubstituted derivatives, suggesting that 3-oxo-4-carboxylic acid core is the active DNA-gyrase binding site, and when structural changes were made in this fragment, there was an observed decrease in antibacterial potency