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Fibroblast growth factor (FGF) signaling has been implicated in the pathogenesis of pulmonary fibrosis. Mice lacking FGF2 have increased mortality and impaired epithelial recovery after bleomycin exposure, supporting a protective or reparative function following lung injury. To determine whether FGF2 overexpression reduces bleomycin-induced injury, we developed an inducible genetic system to express FGF2 in type II pneumocytes. Double-transgenic (DTG) mice with doxycycline-inducible overexpression of human FGF2 (SPC-rtTA;TRE-hFGF2) or single-transgenic controls were administered intratracheal bleomycin and fed doxycycline chow, starting at either day 0 or day 7. In addition, wild-type mice received intratracheal or intravenous recombinant FGF2, starting at the time of bleomycin treatment. Compared to controls, doxycycline-induced DTG mice had decreased pulmonary fibrosis 21 days after bleomycin, as assessed by gene expression and histology. This beneficial effect was seen when FGF2 overexpression was induced at day 0 or day 7 after bleomycin. FGF2 overexpression did not alter epithelial gene expression, bronchoalveolar lavage cellularity or total protein. In vitro studies using primary mouse and human lung fibroblasts showed that FGF2 strongly inhibited baseline and TGFβ1-induced expression of alpha smooth muscle actin (αSMA), collagen, and connective tissue growth factor. While FGF2 did not suppress phosphorylation of Smad2 or Smad-dependent gene expression, FGF2 inhibited TGFβ1-induced stress fiber formation and serum response factor-dependent gene expression. FGF2 inhibition of stress fiber formation and αSMA requires FGF receptor 1 (FGFR1) and downstream MEK/ERK, but not AKT signaling. In summary, overexpression of FGF2 protects against bleomycin-induced pulmonary fibrosis in vivo and reverses TGFβ1-induced collagen and αSMA expression and stress fiber formation in lung fibroblasts in vitro, without affecting either inflammation or epithelial gene expression. Our results suggest that in the lung, FGF2 is antifibrotic in part through decreased collagen expression and fibroblast to myofibroblast differentiation. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Infection with hepatitis C virus (HCV) is a public health burden in several countries. Although transmission through blood is the most likely potential route of HCV infection, other sources warrant exploration. This study was designed to examine the possibility that the mosquito Culex pipiens (Diptera: Culicidae) might serve as a vector of HCV. A series of laboratory experiments were conducted in female Cx. pipiens that were fed on blood taken from HCV patients and tested for the presence of HCV RNAs using a reverse transcription polymerase chain reaction technique. In addition, the ability of the female mosquito to transmit HCV to human blood through membrane feeding or to its offspring (larvae) was tested. Although positive strand RNA was detected on days 1,7 and 14, negative strand HCV RNA was detected in mosquito body homogenate on days 7 and 14. Positive strands were also detected in the head, alimentary canal and salivary glands of mosquito adults at 1 week post-feeding, as well as in their offspring (larvae). An ex vivo assay demonstrated that HCV-infected mosquitoes were able to transmit the virus RNA into naive human blood samples via a membrane feeder. The present data indicate that the mosquito Cx. pipiens may be a potential vector of HCV.

Combination of natural biodegradable polymer with a synthetic polymer offers excellent properties for the support in drug delivery system. For this purpose, biodegradable conductive nanoparticle polypyrrole based on chitosan (PPC) has been prepared via oxidative polymerization of pyrrole in presence of chitosan using FeCl3 as oxidant in acidic medium and used as a carrier for 1,2,4-triazoles. The resultant nanoparticles were characterized by X-ray diffraction, Fourier transform infrared analysis, transmission electron microscopy, scanning electron microscopy, and thermal gravimetric analysis. The results indicate that spherical nanoparticle of average diameter 52 ± 8 nm was successfully prepared. The spherical particles were composed of dark sphere surrounded by grey shell. A circumferential dark ring is observed in the shell after loading 1,2,4-triazoles into PPC nanoparticles. The loaded triazoles were released almost linearly against time in a sustained fashion into different pH media. The mechanism of triazoles release was determined using different kinetics equations. The antibacterial activities against the gram-negative and gram-positive bacteria were examined. Furthermore, the antitumor activity of PPC nanoparticles loaded 1,2,4-triazoles was also examined against Ehrlich ascites carcinoma cells and breast cancer cell line (MCF7). Polypyrrole chitosan loaded nanoparticles exhibited higher antitumor activity than 1,2,4-triazoles.