Visualizing Drug Release from a Stimuli-Responsive Soft Material Based on Amine-Thiol Displacement.

In this research, we developed a photoluminescent platform using amine-coupled fluorophores, generated from a single conjugate acceptor containing bis-vinylogous thioesters. Based on the experimental and computational results, the fluorescence turn-on mechanism was proposed to be charge separated induced energy radiative transition for the amine-coupled fluorophore, while the sulfur-containing precursor was not fluorescent since the energy internal conversion occurred through vibrational 2RS- (R represents alkyl groups) as energy acceptor(s). Further utilizing the conjugate acceptor, we establish a new fluorogenic approach via a highly cross-linked soft material to selectively detect cysteine under neutral aqueous conditions. Turn-on fluorescence emission and macroscopic degradation occurred in the presence of cysteine as the stimuli, which can be visually tracked due to the generation of an optical indicator and the cleavage of linkers within the matrix. Furthermore, a novel drug delivery system was constructed, achieving controlled release of sulfhydryl drug (6-mercaptopurine) which was tracked by photoluminescence and high-performance liquid chromatography. The photoluminescent molecules developed herein are suitable for visualizing polymeric degradation, making them suitable for additional "smart" material applications.

mRNA expression and DNA methylation analysis of the inhibitory mechanism of H2O2 on the proliferation of A549 cells.

Reactive oxygen species, particularly hydrogen peroxide (H2O2), can induce proliferation inhibition and death of A549 cells via oxidative stress. Oxidative stress has effect on DNA methylation. Oxidative stress and DNA methylation feature a common denominator: The one carbon cycle. To explore the inhibitory mechanism of H2O2 on the proliferation of lung cancer cells, the present study analysed the mRNA expression and methylation profiles in A549 cells treated with H2O2 for 24 h, as adenocarcinoma is the most common pathological type of lung cancer. The DNA methylation profile was constructed using reduced representation bisulphite sequencing, which identified 29,755 differentially methylated sites (15,365 upregulated and 14,390 downregulated), and 1,575 differentially methylated regions located in the gene promoters were identified using the methylKit. Analysis of the assocaition between gene expression and methylation levels revealed that several genes were downregulated and hypermethylated, including cyclin-dependent kinase inhibitor 3, denticleless E3 ubiquitin protein ligase homolog, centromere protein (CENP)F, kinesin family member (KIF)20A, CENPA, KIF11, PCNA clamp-associated factor and GINS complex subunit 2, which may be involved in the inhibitory process of H2O2 on the proliferation of A549 cells.