Antitumor activity of RUNX3: Upregulation of E-cadherin and downregulation of the epithelial-mesenchymal transition in clear-cell renal cell carcinoma.

RUNX3 is a transcription factor and tumor suppressor that is silenced or inactivated in diverse tumors. The effect of RUNX3 on the epithelial-mesenchymal transition in clear-cell renal cell carcinoma (CCRCC) remains unclear. We determined the expression of RUNX3 and E-cadherin in tumor tissues and adjacent normal tissues of 30 CCRCC patients; established cultured CCRCC cells with the overexpression of RUNX3; and examined the in vivo tumorigenic function of RUNX3 in a nude mouse xenograft model of CCRCC. RUNX3 and E-cadherin were downregulated in human CCRCC samples. Cell lines with RUNX3 overexpression had reduced cell proliferation, invasion, and migration, a prolonged cell cycle, increased apoptosis, and increased expression of E-cadherin. In the nude mouse xenograft model of CCRCC, tumors with the overexpression of RUNX3 had smaller volumes and weights and had increased expression of E-cadherin. In conclusion, RUNX3 overexpression increased the level of E-cadherin and inhibited the proliferation, invasion, and migration of CCRCC in vitro and in vivo. RUNX3 has potential use as a biomarker for prognostic monitoring of CCRCC and as a therapeutic target for the treatment of this cancer.

Mechanistic insights into NO‒H2 reaction over Pt/boron-doped graphene catalyst.

This work presents a systematical experimental and density functional theory (DFT) studies to reveal the mechanism of NO reduction by H2 reaction over platinum nanoparticles (NPs) deposited on boron-doped graphene (denoted as Pt/BG) catalyst. Both characterizations and DFT calculations identified boron (in Pt/BG) as an additional NO adsorption site other than the widely recognized Pt NPs. Moreover, BG led to a decrease of Pt NPs size in Pt/BG, which facilitated hydrogen spillover. The mathematical and physical criteria of the Langmuir-Hinshelwood dual-site kinetic model over the Pt/BG were satisfied, indicating that adsorbed NO on boron (in Pt/BG) was further activated by H-spillover. On the other hand, Pt/graphene (Pt/Gr) demonstrated a typical Langmuir-Hinshelwood single-site mechanism where Pt NPs solely served as active sites for NO adsorption. This work helps understand NO-H2 reaction over Pt/BG and Pt/Gr catalysts in a closely mechanistic view and provides new insights into roles of active sites for improving the design of catalysts for NO abatement.

The size-dependent genotoxicity and oxidative stress of silica nanoparticles on endothelial cells.

Concerns over the health risk of the widely distributed, commonly used silica nanoparticles (SiNPs) are increasing worldwide. Yet, up to now, there are still many major knowledge gaps over the potential adverse effects of SiNP exposure on human cardiovascular health and the underlying mechanisms. In this study, comet assay and micronucleus test were employed to determine the genotoxic potentials of four sizes (10, 25, 50, 100 nm) of SiNPs to human umbilical vein endothelial cells (HUVECs) in culture. The intracellular redox statuses were explored through the determination of the levels of reactive oxygen species (ROS) and reduced glutathione (GSH) with kits, respectively. The protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) were also detected by Western blot. The results showed that at the administrative levels (1, 5, 25 µg/mL), all the four sizes of SiNPs could induce an increase of both DNA damages and MN frequencies in HUVECs in culture, with a positive dose- and negative size-dependent effect relationship (S100 < S50 < S25 < S10). Also, significantly enhanced levels of intracellular ROS, but decreased levels of GSH, were observed in the SiNP-treated groups. Interestingly, a very similar manner of dose- and size-dependent effect relationship was observed between the ROS test and both comet assay and MN test, but contrary to that of GSH assay. Correspondingly, the levels of Nrf2 protein were also enhanced in the SiNP-treated HUVECs, with a negative size-dependent effect relationship. These results implicated that induction of oxidative stress and subsequent genotoxicity may be an important biological mechanism by which SiNP exposure may affect human cardiovascular health.

The size-dependent apoptotic effect of titanium dioxide nanoparticles on endothelial cells by the intracellular pathway.

Concerns over the health risk of the widely distributed, commonly used titanium dioxide nanoparticles (nano-TiO2 ) are increasing worldwide. Yet, up-to-now, our understanding in their potential effects on the cardiovascular system is very limited and the toxicological mechanisms are still unclear. In the present study, the CCK-8 assay was performed to determine the cytotoxicity of four sizes (10, 30, 50, and 100 nm) of anatase nano-TiO2 on human umbilical vein endothelial cells (HUVECs) in culture, and the flow cytometry was employed to investigate the potential of these nano-TiO2 to induce the apoptosis of HUVECs. The apoptotic pathway was also probed through the determination of the protein expression and activation of p53, Bax, Bcl-2, caspases-9, -7, -3, and PARP by western blot. The results showed that at the administrative levels (1, 5, 25 µg/mL), all the four sizes of nano-TiO2 could significantly inhibit the viability of HUVECs and elicit significant apoptosis in them, compared with the negative control (P < .05, P < .01). Moreover, the apoptotic rates of HUVECs were increased respectively with the elevating levels and decreasing sizes of the administrative nano-TiO2 , showing a clear dose- and size-dependent effect relationships. Interestingly, the increasing phosphorylation of p53, decreasing ratio of Bcl-2/Bax, and enhancing activation of the downstream proteins caspase-9, -7, -3, and PARP, were also observed with the decreasing sizes of the administrative nano-TiO2 in the western blot, indicating that the intracellular approach of apoptosis, the p53-caspase pathway, is the major way of the nano-TiO2 -mediated apoptosis in HUVECs in culture and that the size is an important parameter that may determine the potential of nano-TiO2 to induce cellular response. In conclusion, these results suggested that high levels of nano-TiO2 exposure may pose potential risks to human cardiovascular health by inducing cardiovascular EC apoptosis.

The size-dependent effects of silica nanoparticles on endothelial cell apoptosis through activating the p53-caspase pathway.

With the growing production and applications of silica nanoparticles (SiNPs), human exposure to these nanoparticles continues to increase. However, the possible hazards that SiNP exposure may pose to human cardiovascular system and the underlying mechanisms remain unclear. In the present study, the flow cytometry was employed to investigate the potential of four sizes (10, 25, 50, 100 nm) of SiNPs to induce the apoptosis of human umbilical vein endothelial cells (HUVECs) in culture. The apoptotic pathway was also explored through the determination of the protein expression and/or activation of p53, Bcl-2, Bax, caspases-9, -7, -3, and PARP by western blot. The results showed that all the four sizes of SiNPs could significantly elicit apoptosis in HUVECs at the tested concentrations (1, 5, 25 µg/mL), compared with the negative control (p < 0.05, p < 0.01). Moreover, the apoptotic rates were increased with the elevating levels and decreasing sizes of administrative SiNPs, showing both dose- and size-dependent effect relationships. Interestingly, the enhancing phosphorylation of p53 protein (Ser15), decreasing ratio of Bcl-2/Bax protein, and elevating activation of the downstream proteins, caspase-9, -7, -3 and PARP, were also observed with the decreasing sizes of tested SiNPs, indicating that the p53-caspase pathway is the main way of the SiNP-mediated apoptosis in HUVECs and that the size is an important parameter that determines the SiNPs' potential to induce cellular response.

PM2.5 induced apoptosis in endothelial cell through the activation of the p53-bax-caspase pathway.

Exposure to airborne fine particulate matter (PM2.5) is associated with cardiovascular diseases (CVDs). Nevertheless, a comprehensive understanding of the underlying biological mechanisms by which PM2.5 exposure induces or aggravates CVDs remain insufficiently clear. In the present study, the flow cytometry was employed to investigate the apoptosis of human umbilical vein endothelial cells (HUVECs) induced by PM2.5 in culture. The underlying apoptotic pathway was also studied through the determination of the protein expression and activation of p53, Bax, Bcl-2, caspases-9, -7, -3, and PARP by western blot. The results showed that PM2.5 could significantly induce the apoptosis of HUVECs at the tested concentrations (0.2, 1, 5, 25 µg mL-1), compared with the negative control (p < 0.05, p < 0.01). The apoptotic rate of HUVECs increased with the elevating levels of PM2.5 exposure, showing a clear dose-effect relationship. Moreover, the increasing phosphorylation of p53, decreasing ratio of Bcl-2/Bax, and enhancing activation of the downstream proteins caspase-9, -7, -3 and PARP, were also observed with the increasing concentrations of PM2.5 administration in the western blot, indicating that the intracellular approach of apoptosis, the p53-Bax-caspases pathway, is the major way of PM2.5-induced apoptosis in HUVECs. In conclusion, these results suggested that induction of EC apoptosis is an important mechanism by which ambient PM2.5 exposure poses adverse effects on the cardiovascular system.

Eco-toxicological effects of two kinds of lead compounds on forest tree seed in alkaline soil.

In order to compare the different eco-toxicological effects of lead nitrate and lead acetate on forest tree seed, a biological incubation experiment was conducted to testify the inhibition effects of two lead compounds on rates of seed germination, root and stem elongation, and seedling fresh weight for six plants (Amaorpha fruticosa L., Robinia psedoacacia L., Pinus tabuliformis Carr., Platycladus orientalis L., Koelreuteria paniculata Laxm., Hippophae rhamnoides L.) in soil. The results indicate that the inhibition effects of the two lead compounds on the rates of root elongation of plants were greater than other indices; root elongation can possibly be used as indices to investigate the relationship between lead toxicity and plant response. The response of trees to lead toxicity varied significantly, and the order of tolerance to lead pollution was as follows: Amaorpha fruticosa L. > Platycladus orientalis L. > Koelreuteria paniculata Laxm. > Robinia psedoacacia L. > Pinus tabuliformis Carr. > Hippophae rhamnoides L. Therefore, we suggest that Amaorpha fruticosa L. and Platycladus orientalis L. be used as tolerant plants for soil phytoremediation and Hippophae rhamnoides L. as an indicative plant to diagnose the toxicity of lead pollution on soil quality. Lead nitrate and lead acetate differentially restrain seeds, with seeds being more sensitive to lead nitrate than lead acetate in the soil. Thus, the characteristics of lead compounds should be taken into full consideration to appraise its impact on the environment.

The health effects of ambient PM2.5 and potential mechanisms.

The impacts of ambient PM2.5 on public health have become great concerns worldwide, especially in the developing countries. Epidemiological and toxicological studies have shown that PM2.5 does not only induce cardiopulmonary disorders and/or impairments, but also contributes to a variety of other adverse health effects, such as driving the initiation and progression of diabetes mellitus and eliciting adverse birth outcomes. Of note, recent findings have demonstrated that PM2.5 may still pose a hazard to public health even at very low levels (far below national standards) of exposure. The proposed underlying mechanisms whereby PM2.5 causes adverse effects to public health include inducing intracellular oxidative stress, mutagenicity/genotoxicity and inflammatory responses. The present review aims to provide an brief overview of new insights into the molecular mechanisms linking ambient PM2.5 exposure and health effects, which were explored with new technologies in recent years.

N-Methyl-4-nitro-anilinium chloride.

The asymmetric unit of the title salt, C(7)H(9)N(2)O(2) (+)·Cl(-), contains two independent cations and anions. In the crystal, each N-methyl-4-nitro-anilinium cation is linked to two Cl(-) anions via N-H⋯Cl hydrogen bonds. π-π stacking is observed between the benzene rings of adjacent cations [centroid-to-centroid distances = 3.7684 (14) and 3.7917 (7) Å].