GAS5 regulates viability and apoptosis in TGF-ß1-stimulated bronchial epithelial cells by regulating miR-217/HDAC4 axis.

BACKGROUND: Asthma is a serious respiratory disease that affects the physical and mental health of children. Airway epithelial apoptosis concomitantly mediated by transforming growth factor-ß1 (TGF-ß1) is a crucial component of asthma pathogenesis. LncRNA growth Arrest Specific 5 (GAS5), microRNA-217 (miR-217) and Histone deacetylase 4 (HDAC4) shown a close relationship with TGF-ß1-induced injury of airway epithelial. However, the mechanism underlying TGF-ß1-induced injury of airway epithelial in asthma still needs to be investigated. OBJECTIVE: We aimed to investigate the effect and underlying mechanism of GAS5/miR-217/HDAC4 axis in TGF-ß1-stimulated bronchial epithelial cells. METHODS: The levels of were detected by quantitative real-time polymerase chain reaction (RT-qPCR). All protein levels were determined by western blot. Cell viability and apoptosis rate were assessed by Methyl thiazolyl tetrazolium (MTT) and Flow cytometry, respectively. The targeting relationship between miR-217 and GAS5 or HDAC4 was examined with dual-luciferase reporter assay. RESULTS: TGF-ß1, GAS5, HDAC4 were up-regulated, while miR-217 was down-regulated in bronchial mucosal tissues of asthmatic children and TGF-ß1-treated BEAS-2B cells. TGF-ß1 could reduce cell viability and induce apoptosis, while these effects could be reversed by downregulation of GAS5 or HDAC4. Mechanically, GAS5 acted as a sponge for miR-217 to regulate the expression of HDAC4. Furthermore, overexpression of HDAC4 rescued the effects of GAS5 knockdown on viability and apoptosis of TGF-ß1-induced BEAS-2B cells. GAS5 knockdown induced cell viability and hampered cell apoptosis in TGF-ß1-stimulated BEAS-2B cells by regulating the miR-217/HDAC4 axis. CONCLUSIONS: The lncRNA GAS5/miR-217/HDAC4 axis played an important role in regulating TGF-ß1-induced bronchial epithelial cells injury, thus contributing to asthma.

In Vivo Pharmacokinetics Assessment of Indocyanine Green-Loaded Nanoparticles in Tumor Tissue with a Dynamic Diffuse Fluorescence Tomography System.

PURPOSE: The purpose of this study was to show a systematic strategy for assessing the pharmacokinetics of indocyanine green (ICG)-loaded nanoparticles in the tumor tissue based on a dynamic diffuse fluorescence tomography (DFT) system. PROCEDURES: Twelve-seven-week-old male Balb/c nude mice bearing HepG2/ADR hepatocellular carcinoma were randomly divided into four groups (n = 3 per group). Four hundred microliters of three types of ICG-loaded nanoparticles (content of ICG: 50 µg/ml) and free ICG (50 µg/ml) was intravenously injected into the mice in each group, respectively. Afterwards, the real-time tomographic images on the spatial level were acquired at 2-11 min, 30 min, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h post-injection, and pharmacokinetic rates were derived for semi-quantitative assessment of the pharmacokinetics of nanoparticles at the tumor site using our proposed pharmacokinetic analysis method. RESULTS: The results obtained from our proposed dynamic DFT experiment demonstrated the distribution of different ICG formulations on the spatial level and enabled the semi-quantitative analysis of the pharmacokinetics of nanoparticles in the tumor tissue. CONCLUSIONS: The obtained pharmacokinetic rates effectively reflected the metabolic processes of nanoparticles in the tumor tissue, which proves to be beneficial for the development of tumor diagnosis and therapy.

Assessing indocyanine green pharmacokinetics in mouse liver with a dynamic diffuse fluorescence tomography system.

Fluorescence pharmacokinetic rates in tissues can provide additional specific and quantitative physiological and pathological information for evaluating organ function. This modality requires a highly sensitive diffuse fluorescence tomography (DFT) working in dynamic way to finally extract the pharmacokinetic rates from the measured pharmacokinetics-associated temporally varying boundary intensity, normally with the support of a priori anatomy. This paper is devoted to study pharmacokinetics of indocyanine green (ICG) in mouse liver based on synergistic dynamic-DFT and X-ray computer tomography (XCT): A highly sensitive dynamic DFT system of CT-scanning mode working with parallel 4 photomultiplier-tube photon-counting channels generates informative and instantaneous sampling datasets; An XCT system provides priori information of the target localization for improvement of the reconstruction quality; An analysis procedure extracts the pharmacokinetic rates from the reconstructed ICG concentration-time curves, using the Gauss-Newton scheme for fitting to a 2-compartment model. The uptake and excretion rates of ICG which were obtained in livers of 10 healthy mice in the in vivo experiments can be used to quantitatively evaluate liver function. The results can validate the effectiveness of both the imaging measurements system and pharmacokinetic analysis method.

Broken ring solitons in Bessel optical lattices.

We address the existence of ring solitons broken by several nodes in a defocusing saturable nonlinear medium with an imprinted Bessel optical lattice. Such a multipolelike soliton is composed of two or more arc patterns with opposite phase between the adjacent components. The width of existence domain is determined only by the saturation degree of medium. The maximum number of soliton components depends on the radius of the lattice ring, where they reside. Those novel solitons can be trapped entirely on any ring of the Bessel lattice provided that the lattice is modulated deep enough. This study offers a smooth transition from the multipole soliton to necklace soliton.