As titanium dioxide (TiO(2)) nanoparticles are widely used commercially, the potential effects of TiO(2) nanoparticles on humans are a concern. To evaluate the effects of TiO(2) nanoparticles on hepatic and renal functions and correlate changes to oxidative stress, Sprague-Dawley rats were treated with TiO(2) particles of two different specific surface areas (TiO(2-S50): 50 m(2)/g, and TiO(2-S210): 210 m(2)/g) at 0.5, 5, or 50 mg/kg body weight by intratracheal instillation. After 7 d, TiO(2) nanoparticles produced no obvious acute toxicity on hepatic and renal functions. However, superoxide dismutase (SOD) activity of plasma and glutathione peroxidase (GSH-PX) activity of kidney in the low-dose TiO(2-S210) group were significantly decreased. After TiO(2-S210) exposure, malondialdehyde (MDA) levels of liver and kidney in intermediate and high-dose groups were significantly increased. This change only appeared in liver after TiO(2-S50) exposure. Furthermore, SOD activity in liver and kidney and GSH-PX activity in kidney with low TiO(2-S210) exposure group were significantly less than with low TiO(2-S50). No apparent pathological changes in liver and kidney were observed. Intratracheal exposure to TiO(2) nanoparticles may induce oxidative stress in liver and kidney, but does not influence hepatic or renal functions. There was no apparent evidence that TiO(2-S210) was more toxic than TiO(2-S50). In general, intratracheal exposure to TiO(2) did not markedly affect extrapulmonary tissue functions.
To determine the relevance of O-6-methylguanine-DNA methyltransferase (MGMT), human mutS homolog 2 (hMSH2), and human mutL homolog 1 (hMLH1) in TP53 mutations in esophageal squamous cell carcinoma, we employed methylation-sensitive high-resolution melting technology and methylation-specific polymerase chain reaction (PCR) to analyze promoter hypermethylation of MGMT, hMSH2, and hMLH1, respectively, in 51 paired tumors and their adjacent normal tissues. The protein expression of the three proteins was also evaluated by Western blot analysis, and the PCR products of TP53, from exon 5 to exon 8, were directly sequenced to measure the mutation spectrum. Esophageal tumor tissues embraced statistically higher MGMT and hMSH2 promoter methylation level than normal tissue. The promoter methylation status of MGMT and hMSH2 corresponds positively with the protein expression level of MGMT and hMSH2. However, such relevance was not found for hMLH1. Furthermore, TP53 mutation status was well associated with MGMT and hMSH2 promoter methylation status, indicating that silencing of the two genes could lead to TP53 mutation in ESCC.
The abnormal function of O(6)-methylguanine-DNA methyltransferase (MGMT) is reported to be associated with the occurrence of various tumors and malignant tumor progression. However, little evidence is available to describe its role in esophageal carcinogenesis. To address this issue, we constructed a stable MGMT-silenced esophageal cancer cell line by RNA interference, and exposed the cells to N-methyl-N-nitro-N-nitrosoguanidine (MNNG) to investigate the role that MGMT plays in toxicity. During this time, we also observed the malignant behavior of cells in vitro and in vivo. In addition, two-dimensional electrophoresis and mass spectrometry were used to detect and confirm the proteins that were differentially expressed in the MGMT-deficient and MGMT-proficient cells, which might be responsible for the malignant alteration of cells. Results showed that the IC(50) of MGMT-deficient and MGMT-proficient cells exposed to MNNG was 30 μM and 65 μM, respectively, and MGMT-deficient cells had more aggressive motility and invasive abilities compared with MGMT-proficient cells. Nineteen differentially expressed proteins were detected between the MGMT-deficient and MGMT-proficient cells, 14 of which were identified, including the membrane-cytoskeleton linker protein, Ezrin, which was confirmed by both mass spectrometry and western blot analysis. The correlation between MGMT, Ezrin expression, and the malignant behavior of one normal epithelial esophageal cell line and seven esophageal cancer lines is discussed. In conclusion, loss of MGMT expression leads EC109 esophageal cancer cells to have increased malignant behavior, which may correlate with its high Ezrin protein expression.
Music is a form of artistic expression and an important carrier of cultural and historical development, containing rich cultural content. This paper summarizes the characteristics and differences between typical musical instruments by analyzing the origin and historical development of national music and popular music. It analyzes the distribution of music-cultural circle, at the same time, to analyze the interaction between national music and popular music more comprehensively, this paper discusses the promotion and promotion between national music and popular music from the perspective of cultural identity and historical integration. Cross the border of national music and popular music, further enrich the forms and ways of mutual reference between the two, and strengthen the integration and development of the two, which can enrich the cultural connotation of popular music and make the expression form and content of national music more diversified, laying a foundation for the spread and development of national music and popular music in modern society.
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