MS-275 potentiates the effect of YM-155 in lung adenocarcinoma via survivin downregulation induced by miR-138 and miR-195.

BACKGROUND: YM-155 has been proven to be an efficient antitumor suppressor in non-small cell lung cancer (NSCLC) cells. However, the suppressive effect of YM-155 on the expression of survivin is not sufficient and has a short half-life. MS-275, a histone deacetylase inhibitor, has significant antitumor capacity with a relatively long half-life. Our study explored whether MS-275 could enhance the inhibitory effect of YM-155 on LUAD proliferation. METHODS: To investigate the synergistic effect of MS-275 and YM-155, we employed methyl thiazolyl tetrazolium and colony formation assays to access the inhibition effect of MS-275, YM-155, or a combination in A549 and HCC827 cell lines. We then detected the effect of MS-275 and YM-155 on the expression of survivin and pro-apoptotic proteins by Western blot and miR-138 or miR-195 expression by quantitative PCR. We also analyzed the methylation level of microRNAs (miRNAs) using methylation-sensitive quantitative PCR. Finally, we investigated the interaction between miRNAs and survivin by luciferase reporter assay. RESULTS: MS-275 facilitated an inhibitory effect of YM-155 on lung adenocarcinoma cell proliferation. MS-275 can upregulate the level of acetylated H3, promote the degradation of DNA methyltransferases, and inhibit the methylation of miR-138 and miR-195 genes to elevate the expression of miR-138 and miR-195. Moreover, miR-138 and miR-195 showed a synergistic effect with YM-155 by directly binding to the 3 untranslated region of survivin to attenuate its expression. CONCLUSION: For the first time, we report the synergistic effective of MS-275 and YM-155 and suggest a new direction for the future application of YM-155.

MOF Thin Film-Coated Metal Oxide Nanowire Array: Significantly Improved Chemiresistor Sensor Performance.

A strategy for combining metal oxides and metal-organic frameworks is proposed to design new materials for sensing volatile organic compounds, for the first time. The prepared ZnO@ZIF-CoZn core-sheath nanowire arrays show greatly enhanced performance not only on its selectivity but also on its response, recovery behavior, and working temperature.

[Effects of tumor necrosis factor alpha on proteolysis of respiratory muscles in rats with chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the impact of tumor necrosis factor alpha (TNF-alpha) on proteolysis of respiratory muscles in rats with chronic obstructive pulmonary disease (COPD). METHODS: Ninety healthy male adult Wistar rats were randomly divided into two groups: a normal control group (n = 20) and a model group (n = 70). The COPD rat model was established by intratracheal instillation of porcine pancreatic elastase and exposure to cigarette smoke for 60 days. Malnutrition was defined as the weight of the rats in the model group lower than 90% of the mean body weight of the control group. Two weeks after the establishment of the COPD model, 10 rats were randomly chosen in the malnutrition group, and received 4 days' therapy of intravenous injection of TNF-alpha monoclonal antibody (McAb) 0.1 mg/kg. The concentrations of TNF-alpha in the homogenates of respiratory muscles were measured by ELISA, and the contents of 3-methylhistidine, tyrosine in homogenates of respiratory muscle were measured by high performance liquid chromatography. RESULTS: The levels of TNF-alpha in the homogenates of diaphragmatic muscle of the malnutrition group [(125 +/- 11) pg/g] were significantly higher than that of the control group [(64 +/- 5) pg/g]; The levels of TNF-alpha in the homogenates of internal intercostal muscle of the malnutrition group [(119 +/- 11) pg/g] were significantly higher than that of the control group [(59 +/- 5) pg/g]. The contents of 3-methylhistidine in homogenates of diaphragmatic muscle [(7.1 +/- 0.6) nmol/g] and internal intercostal muscle [(7.4 +/- 0.6) nmol/g] of the malnutrition group were significantly higher than that of the control group [(4.0 +/- 0.5) nmol/g]. The contents of tyrosine in homogenates of diaphragmatic muscle [(639 +/- 24) nmol/g] and internal intercostal muscle [(660 +/- 25) nmol/g] of the malnutrition group were significantly higher than that of the control group [(579 +/- 26) nmol/g]. TNF-alpha in the respiratory muscle showed a strong positive correlation with proteolysis of respiratory muscle (r = 0.854, P < 0.01). CONCLUSION: An increase of proteolysis of respiratory muscles was found in COPD rats, more significant in the malnutrition rats. TNF-alpha is one of the causes for the increase of proteolysis of respiratory muscles.