Nanotechnology using biodegradable polymer carriers with good biocompatibility and bioabsorbability has been studied and applied extensively in drug delivery systems and biomedical engineering. In this work, the triblocked oligomer poly(L-lactide)-bpoly(ethylene glycol)-b-poly(L-lactide) (PLEL) with the molecular weight of 2.08 KDa was first synthesized. Its chemistry was characterized by hydrogen nuclear magnetic resonance (1 H-NMR) spectrum and Fourier transform infrared (FTIR) spectroscopy. Subsequently, the nanoparticles (NPs) of PLEL and pranoprofen (PF)-loaded PLEL were prepared with the average particle size of (151.7 ± 5.87) nm using the method of emulsion solvent evaporation. The formula and drug releasing profile were characterized by a transmission electron microscope (TEM), dynamic light scattering (DLS), and ultraviolet spectrophotometer (US). In vitro cytotoxicity assays and in vivo ophthalmic tests were performed to measure the safety and efficacy of the formulations. The results showed that PF NPs relieved the cytotoxicity of pure PF and eliminated ophthalmic irritation. The drug encapsulated in the nanoparticles displayed long-lasting release and good anti-inflammation efficiency in animal eyes. Therefore, we concluded that the present formula (PF NPs) could provide sustained drug release with good treatment effect on eye inflammation, and is promising for its use in ophthalmology in the future.
Epigenetics modulates expression levels of various important genes in both prokaryotes and eukaryotes. These epigenetic traits are heritable without any change in genetic DNA sequences. DNA methylation is a universal mechanism of epigenetic regulation in all kingdoms of life. In bacteria, DNA methylation is the main form of epigenetic regulation and plays important roles in affecting clinically relevant phenotypes, such as virulence, host colonization, sporulation, biofilm formation et al. In this review, we survey bacterial epigenomic studies and focus on the recent developments in the structure, function, and mechanism of several highly conserved bacterial DNA methylases. These methyltransferases are relatively common in bacteria and participate in the regulation of gene expression and chromosomal DNA replication and repair control. Recent advances in sequencing techniques capable of detecting methylation signals have enabled the characterization of genome-wide epigenetic regulation. With their involvement in critical cellular processes, these highly conserved DNA methyltransferases may emerge as promising targets for developing novel epigenetic inhibitors for biomedical applications.
A computational model was developed to examine the phototriggered folding of a caged protein, a protein modified with an organic photolabile cross-linker. Molecular dynamics simulations of the modified 36-residue fragment of subdomain B of chicken villin head piece with a photolabile linker were performed, starting from both the caged and the uncaged structures. Construction of a free-energy landscape, based on principal components as well as on radius of gyration versus root-mean-square deviation, and circular dichroism calculations were employed to characterize folding behavior and structures. The folded structures observed in the molecular dynamics trajectories were found to be similar to that of the wild-type protein, in agreement with the published experimental results. The free-energy landscapes of the modified and wild-type proteins have similar topology, suggesting common thermodynamic/kinetic behavior. The existence of small differences in the free-energy surface of the modified protein from that of the native protein, however, indicates subtle differences in the folding behavior.Keywords: protein structure/folding; computational analysis of protein structure; phototriggering; uncaged protein; circular dichroism Deciphering the mechanism by which proteins acquire folded three-dimensional structures remains one of the most important challenges in structural biology. The difficulties in understanding the protein folding problem are partially due to the lack of knowledge concerning the following three major aspects of the folding process. Firstly, detailed structural information about the early stages of folding is not readily available, which is crucial in the understanding of how folding is directed along the productive channels toward the native structure (Myers and Oas 2001). Secondly, it is hard to distinguish the off-pathway intermediates from the on-pathway intermediates during folding, since, with few exceptions, current bulk experiments do not discriminate between the two types of intermediates (Shastry et al. 1998). Finally, most results from folding experiments are based on ensemble-average measurements of a property of a given protein, which can include contributions from a variety of dissimilar conformers.Refinements in the experimental methods for measuring sub-millisecond folding rates have recently been made and applied to several fast-folding systems (Gruebele 1999;Brockwell et al. 2000;Eaton et al. 2000;Ferguson et al. 2001;Qiu et al. 2002;Snow et al. 2002;Zhu et al. 2003). However, it is difficult to determine with certainty whether Article published online ahead of print. Article and publication date are at http://www.proteinscience.org/cgi
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