Role of non-neuronal cholinergic system in the early stage response of epithelial-mesenchymal transformation related markers in A549 cells induced by coal particles.

Objective: This study was aimed to investigate the role of non-neuronal cholinergic system (NNCS) in the early stage response of epithelial-mesenchymal transformation (EMT) related markers in human lung adenocarcinoma A549 cells induced by coal particles. Methods: A549 cells were exposed to different concentrations of GBW11110K, GBW11126D and exogenous acetylcholinesterase (AChE) (the exposure doses were determined according to the results of CCK-8 experiment, and the doses that had no significant effects on cell viability were selected) for 24 h. After exposure, the indexes of oxidative stress (SOD and MDA), inflammatory factors (IL-6 and TNF-α), EMT marker proteins (E-cadherin and vimentin), AChE enzymatic activity and mRNA expression levels of different types of acetylcholine receptors (CHRM3, CHRM5, CHRNA5, CHRNA7, CHRNA9 and CHRNB2) were determined. Results: GBW11110K and GBW11126D exposure could lead to the following injury effects: the levels of oxidative stress and inflammatory factors changed to a certain extent (SOD decreased gradually, while MDA, IL-6 and TNF-α increased). The protein level of E-cadherin decreased while the vimentin level increased (P < 0.05), suggesting the occurrence of EMT. The AChE enzymatic activity decreased gradually. The expression of acetylcholine receptor mRNA changed as follows (GBW11110K/GBW11126D: CHRM3 (↑↑), CHRM5 (↓↓), CHRNA5 (↓↓), CHRNA7 (↓↓), CHRNA9 (- ↑), CHRNB2 (- -). The addition of exogenous AChE recombinant protein could antagonize the damage effects caused by the coal particles to a certain extent. Conclusion: The coal particle exposure could induce the change of oxidative stress response, inflammatory response and EMT related markers, down-regulate the AChE enzymatic activity, and interfere the mRNA expression levels of AChRs in A549 cells. The addition of exogenous AChE recombinant protein could reverse the above effects to a certain extent.

Cytotoxicity of mesoporous silica modified by amino and carboxyl groups on vascular endothelial cells.

Mesoporous silica is widely used because of its unique and excellent properties, especially it can be used as a drug carrier and gene carrier in the biomedical field. After the mesoporous silica is put into clinical use, it is more likely to be exposed in human body. Therefore, the effect of mesoporous silica on human body cannot be ignored. The injury of vascular endothelial cells is a prerequisite for the occurrence of many cardiovascular diseases. As a drug and gene carrier, mesoporous silica increases its contact with vascular endothelial cells, so its toxic effect on cardiovascular system cannot be ignored. In this study, amino (NH2 ) and carboxyl (COOH) were modified on mesoporous silica SBA-15 by post-grafting. The results showed that it still maintained the one-dimensional hexagonal mesoporous structure of SBA-15 and had typical mesoporous structure. Then human umbilical vein endothelial cells (HUVECs) were infected with SBA-15, NH2 -SBA-15, and COOH-SBA-15. The results showed that the functionalized mesoporous silica SBA-15 had cytotoxicity to HUVECs and damaged the cell membrane, but compared with the unmodified mesoporous silica SBA-15 the cytotoxicity of functionalized mesoporous silica SBA-15 was lower and the toxicity of carboxyl modified group was the lowest. By comparing the cell inhibition rate and the expression level of lactate dehydrogenate and reactive oxygen species induced by the three materials, oxidative damage and cell membrane damage may be two mechanisms of cytotoxicity. Mesoporous silica SBA-15 has an effect on cardiovascular system by inducing the high expression of nitric oxide, intercellular adhesive molecule-1 and vascular cell adhesive molecule-1 in HUVECs. In summary, our results show that mesoporous silica is toxic to vascular endothelial cells.

[Distribution, Sources, and Ecological Risk Assessment of Polycyclic Aromatic Hydrocarbons in the Surface Waters of the Yinchuan Wetlands].

In order to explore the composition, sources and ecological risks of polycyclic aromatic hydrocarbons (PAHs) in water from Yinchuan wetlands, water samples were collected in the dry season and plentiful season from 15 wetlands. Sixteen species of PAHs were analyzed by gas-mass spectrometry, and source identification of PAHs was investigated by PCA and EPA positive matrix factorization 5.0. Ecological risk was assessed using the risk entropy method based on the neglected concentrations (NCs) and the maximum permissible concentrations (MPCs). The results showed that:① in the dry season, eight kinds of PAHs were detected, the concentrations of which ranged from 1455.38 ng·L-1to 2538.84 ng·L-1. In the plentiful season, 12 kinds of PAHs were detected, the concentrations of which ranged from 818.69 ng·L-1 to 1582.14 ng·L-1. The concentrations of PAHs in the dry season in Yinchuan were higher than that during the plentiful season. Compared with other domestic and overseas surface waters, PAH pollution was high; ② in the dry season, PAHs were mainly composed of 3-5 rings, and 2-3 and 4-6rings accounted for 35.6%-59.2% and 40.8%-59.7%, respectively. In the plentiful season, PAHs were mainly composed of 4-5 rings, and 2-3 and 4-6rings accounted for 10.2%-45.07% and 54.92%-89.76%, respectively; ③ the source analysis showed that in both the dry season and in the plentiful season, the main source were combustion and automobile emissions; ④ the ecological risk assessment indicated that the RQMPCs of BaA, BbF, InP, DBA, and BghiP during both the dry and plentiful seasons, and RQMPCs of Phe during the dry season, were higher than 1.0, indicating that attention needs to be paid to pollution levels. The RQNCs of Nap, Ace, Fla, Pyr, and BaP during the plentiful season and the RQNCs of Nap during the dry season were higher than 1.0, indicating the pollution risk was moderate and control and prevision of pollution from PAHs are required in the region.

Synthesis, DNA Binding, and Anticancer Properties of Bis-Naphthalimide Derivatives with Lysine-Modified Polyamine Linkers.

A series of bis-naphthalimide derivatives with different diamine linkers were designed and synthesized. All of the synthesized bis-naphthalimide derivatives were characterized by NMR and HRMS spectra. The binding ability between the compounds and CT DNA was evaluated by using UV-Vis titration experiments. The bis-naphthalimide compound with an ethylenediamine linker showed the largest binding constant with CT DNA. Hence, it was used as the model compound to study the DNA binding selectivity by UV-Vis titration aiming at different DNA duplexes. As a result, this compound showed binding preference to AT-rich duplexes. The DNA binding modes of the compounds were also measured by viscosity titration. The cytotoxicity of the compounds was evaluated by MTT assay. Compounds with 1,6-diaminohexane or 1,4-phenylenedimethanamine linkers showed higher cytotoxicity compared with other bis-naphthalimide derivatives.