Search

Purpose. A bimodal nanoprobe for thyroid cancer targeting human epidermal growth factor receptor 2 (HER2) was synthesized by coupling the magnetic resonance contrast agent Gd3+ with the fluorescent dyes Cy5.5 and pertuzumab as a preliminary study of Gd-Cy5.5-pertuzumab in magnetic resonance and fluorescence imaging. Methods. The bifunctional chelate p-SCN-Bn-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic-acid (DOTA) was dissolved in deionized water, added to pertuzumab solution, and stirred overnight at room temperature to obtain the product DOTA pertuzumab. 1,2-dichloroethane and N-hydroxysuccinimide were added to activate the carboxyl group on DOTA. After 0.5 hr of activation, the amino fluorescent dye Cy5.5 was further added to react with it to synthesize the intermediate product Cy5.5-DOTA-pertuzumab. Finally, we added GdCl3-6H2O and placed it in a magnetic stirrer for 6 hr before the unreacted substance was removed by dialysis to obtain Gd-Cy5.5-pertuzumab. Following that, the hydrated particle size and zeta potential of the nanoprobe were measured by particle size analyzer, the fluorescence spectrum by a fluorescence detector, the infrared spectrum by the infrared analyzer, the cytotoxicity by CCK-8 method, the relaxation rate by Niumai small nuclear magnetic field, and the binding ability of HER2 to thyroid cancer 8505C by laser confocal microscope. Nanoprobes were injected into a subcutaneous thyroid cancer nude mouse model through the tail vein, and in vivo MRI and near-infrared (NIR) fluorescence imaging were performed. Finally, the nude mice were dissected and hematoxylin and eosin (HE) staining of pathological tissues was performed to evaluate the imaging performance of the prepared bimodal probes. Results. The synthesized bimodal probe Gd-Cy5.5-pertuzumab had a hydrodynamic size of 131.34 ± 9.43 nm and zeta potential of −31.73 ± 6.24 mV with a significant absorption peak at 685 nm. The relaxation rate of the probe was 46.53 mM−1 s−1, which was determined by Niumai small nuclear magnetism, and the T1 signal intensity increased gradually with the concentration of the probe. Laser confocal microscopy showed that HER2 was mainly expressed in cell membranes. In vitro and in vivo experiments indicated that the probe had low cytotoxicity. MRI and small animal fluorescence imaging of tumor-bearing nude mice showed that the probe could clearly image tumor tissue. Conclusion. The bimodal probe Gd-Cy5.5-pertuzumab was successfully synthesized with good stability, which can specifically bind to target cells in vivo and has good magnetic resonance/fluorescence imaging performance.

Immunotherapy is effective in the treatment of melanoma due to its immunogenicity. In recent years, researchers have identified LTP is rich in active substances that can induce apoptosis in tumor cells and trigger an immune response. However, it is unclear how LTP works to antitumor by enhancing immune cell function. Therefore, the purpose of this study is to investigate the effects of direct and indirect LTP treatments on the quantity and function of Treg cells and CD8+ T cells in B16-F10 melanoma-bearing mice and their associated mechanisms. The results revealed that both direct and indirect LTP treatments were effective at inhibiting tumor growth and extending the survival of B16-F10 melanoma-bearing mice. In addition, both direct and indirect LTP treatments reduced the number of Treg cells and improved the immune function of CD8+ T cells in the spleen and tumor. Nevertheless, the indirect LTP treatment proved to be more effective than the LTP direct treatment. Mechanistic studies demonstrated that direct LTP treatment might affect the quantity and function of Treg cells and CD8+ T cells by modulating cytokine level changes. However, indirect LTP treatment might have a greater tumor immunotherapeutic potential by inhibiting the activation of key protein molecules in the IL-6/STAT3 signaling pathway and regulating cytokine level changes. In conclusion, this study reveals that LTP exerts an anti-melanoma effect by regulating the level and function of Treg cells and CD8+ T cells. This study is expected to provide new ideas for LTP anti-tumor immunotherapy.

Blast lung injury (BLI) is the major cause of death in explosion-derived shock waves; however, the mechanisms of BLI are not well understood. To identify the time-dependent manner of BLI, a model of lung injury of rats induced by shock waves was established by a fuel air explosive. The model was evaluated by hematoxylin and eosin staining and pathological score. The inflammation and oxidative stress of lung injury were also investigated. The pathological scores of rats' lung injury at 2 h, 24 h, 3 days, and 7 days post-blast were 9.75±2.96, 13.00±1.85, 8.50±1.51, and 4.00±1.41, respectively, which were significantly increased compared with those in the control group (1.13±0.64; P

Aim Low-temperature plasma (LTP) has potential applications in cancer therapy. Herein, we explored the molecular mechanisms of proliferation inhibition induced by LTP. Methods LTP was generated by a helium atmospheric-pressure plasma jet and used to treat A549 and H1299 cells. CCK-8 and cell apoptosis assays were performed to evaluate the effects of LTP treatment on A549 and H1299 cells. The qRT-PCR was performed to measure the expression of miR-203a after treating with LTP. CCK-8, colony formation, cell apoptosis assays, and Western blotting were performed to analyse the function of miR-203a in the development of lung cancer. Dual-luciferase assay and Western blotting were used to probe the relationship between miR-203a and BIRC5, and gene silencing using si-BIRC5 was carried out to explore the effect of knocking down BIRC5 on lung cancer cells. Results We found that LTP significantly suppressed proliferation and promoted apoptosis in A549 and H1299 cells. The miR-203a expression was increased after cells were treated with LTP. The miR-203a expression was downregulated among lung cancer tissue samples, and overexpression of miR-203a suppressed cell growth and induced apoptosis in lung cancer cells. We showed that miR-203a targeted BIRC5. Moreover, silencing of BIRC5 caused proliferation inhibition and induced apoptosis in lung cancer cells. Conclusion Our study revealed that LTP inhibited proliferation and induced apoptosis in A549 and H1299 cells through the miR-203a/BIRC5 axis. These findings showed that LTP could potentially be used to treat lung cancer.

Polycyclic aromatic hydrocarbons (PAHs) are the most common contaminants in the air pollutants. Inhalation exposure to PAHs could increase the risk of respiratory disease, cardiovascular disease and even cancer. However, the biotoxicity of multi-component PAHs from atmospheric pollutants has been poorly studies. The main topic of this study was to investigate the PAHs mixture, which derived from atmospheric pollutants, induced toxic effects and inflammatory effects on human bronchial epithelial cells in vitro. The results showed that PAHs mixture could decrease the cell viability, increase the apoptosis rate, and induce cell cycle arrest at S-phase. Furthermore, the expression of inflammatory factors IL-1β and IL-6 were increased and NF-κB signaling pathway was activated in PAHs mixture-treated cells. The findings of this study indicate that PAHs mixture-induced cytotoxicity and inflammation may be related to intracellular ROS generation and to the activated NF-κB signaling pathway.

Purpose Blast lung injury (BLI) is the most common damage resulted from explosion-derived shock wave in military, terrorism and industrial accidents. However, the molecular mechanisms underlying BLI induced by shock wave are still unclear. Methods In this study, a goat BLI model was established by a fuel air explosive power. The key genes involved in were identified. The goats of the experimental group were fixed on the edge of the explosion cloud, while the goats of the control group were 3 km far away from the explosive environment. After successful modeling for 24 h, all the goats were sacrificed and the lung tissue was harvested for histopathological observation and RNA sequencing. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis were performed to identify the main enriched biological functions of differentially expressed genes (DEGs). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the consistency of gene expression. Results Of the sampled goat lungs, 895 genes were identified to be significantly differentially expressed, and they were involved in 52 significantly enriched GO categories. KEGG analysis revealed that DEGs were highly enriched in 26 pathways, such as cytokine-cytokine receptor interaction, antifolate resistance, arachidonic acid metabolism, amoebiasis and bile secretion, JAK-STAT, and IL-17 signaling pathway. Furthermore, 15 key DEGs involved in the biological processes of BLI were confirmed by qRT-PCR, and the results were consistent with RNA sequencing. Conclusion Gene expression profiling provide a better understanding of the molecular mechanisms of BLI, which will help to set strategy for treating lung injury and preventing secondary lung injury induced by shock wave.

Aim Low-temperature plasma (LTP) has potential applications in cancer therapy. Herein, we explored the molecular mechanisms of proliferation inhibition induced by LTP. Methods LTP was generated by a helium atmospheric-pressure plasma jet and used to treat A549 and H1299 cells. CCK-8 and cell apoptosis assays were performed to evaluate the effects of LTP treatment on A549 and H1299 cells. The qRT-PCR was performed to measure the expression of miR-203a after treating with LTP. CCK-8, colony formation, cell apoptosis assays, and Western blotting were performed to analyse the function of miR-203a in the development of lung cancer. Dual-luciferase assay and Western blotting were used to probe the relationship between miR-203a and BIRC5, and gene silencing using si-BIRC5 was carried out to explore the effect of knocking down BIRC5 on lung cancer cells. Results We found that LTP significantly suppressed proliferation and promoted apoptosis in A549 and H1299 cells. The miR-203a expression was increased after cells were treated with LTP. The miR-203a expression was downregulated among lung cancer tissue samples, and overexpression of miR-203a suppressed cell growth and induced apoptosis in lung cancer cells. We showed that miR-203a targeted BIRC5. Moreover, silencing of BIRC5 caused proliferation inhibition and induced apoptosis in lung cancer cells. Conclusion Our study revealed that LTP inhibited proliferation and induced apoptosis in A549 and H1299 cells through the miR-203a/BIRC5 axis. These findings showed that LTP could potentially be used to treat lung cancer.