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N-hexanes are prominent environmental pollutants that are able to cause neurotoxicity in vivo and in vitro. Central and peripheral neuropathies induced by n-hexane exposure are a major health concern. 2,5-Hexanedione (2,5-HD) is the most significant neurotoxic metabolite of n-hexane; however, little is known regarding the underlying mechanism of its neurotoxicity. Thus, the aim of the present study was to investigate the damaging effects of 2,5-HD on pheochromocytoma PC12 cells, and to explore the underlying mechanism. Cell viability was tested using a Cell Counting Kit-8 method, and the leakage of lactate dehydrogenase (LDH) from cells was measured using an LDH assay kit. Glutathione peroxidase (GSHPx) and superoxide dismutase (SOD) activities, and the level of malondialdehyde (MDA) were determined using corresponding assay kits. Apoptotic cells were detected using an annexin V-fluorescein isothiocyanate/propidium iodide (PI) apoptosis kit, and were subsequently observed by fluorescence microscopy. The relative expression levels of cleaved-caspase-3, Bcl-associated-X protein (Bax) and Bcl-2 were identified by western blotting. The results revealed that 2,5-HD was able to decrease the viability of PC12 cells and promoted the leakage of LDH in a concentrationdependent manner. Further analysis demonstrated that 2,5-HD decreased the activity of the antioxidative enzymes, SOD and GSHPx, and led to an increase in the levels of MDA in the supernatant of cultured PC12 cells. The annexin V/PI staining results revealed that the numbers of apoptotic cells were increased following treatment with 2,5-HD. In addition, 2,5-HD (5 and 10 mmol/l) led to significant increases in the expression levels of caspase-3 and Bax, with the concomitant downregulation of Bcl-2. The antioxidant N-acetylcysteine was identified to antagonize 2,5-HD-stimulated cleaved-caspase-3 and Bax upregulation, and Bcl-2 downregulation. Collectively, the results of the present study suggested that 2,5-HD exerts proapoptotic effects on PC12 cells via oxidative injury. These findings may be applied in the development of novel therapeutic strategies to treat neurological disorders associated with nhexane exposure.

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Sepsis-induced blood vessel dysfunction is mainly caused by microvascular endothelial cell injury. However, the mechanism underlying sepsis-induced endothelial cell injury remains unclear. The present study hypothesized that sepsis-induced inflammatory injury of endothelial cells may be the first step of endothelial barrier dysfunction. Therefore, the present study aimed to uncover the mechanism underlying the inflammatory effects of sepsis. A rat model of cecal ligation and puncture-induced sepsis was established, and septic serum was collected. Subsequently, human umbilical vein endothelial cells (HUVECs) were treated with the isolated septic or normal serum. HUVEC viability was assessed using a Cell Count Kit-8 assay. Furthermore, transmission electron microscopy and reverse transcription-quantitative PCR (RT-qPCR) analysis were carried out to observe the cell morphology and determine the mRNA expression levels in septic serum-induced HUVECs. The protein expression levels were evaluated by western blot analysis, and the secretion of the inflammatory factors interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α was determined by ELISA. Additionally, reactive oxygen species (ROS) generation and nuclear factor (NF)-κB nuclear translocation were observed under a fluorescence microscope. The results of the present study demonstrated that HUVEC viability was significantly decreased following 12- or 24-h treatment with septic serum. In addition, chromatin condensation, mitochondrial vacuolization and endoplasmic reticulum degranulation were observed following treatment with septic serum. Furthermore, the secretion levels of IL-1β, IL-6 and TNF-α were increased in septic serum-stimulated HUVECs. Septic serum treatment also enhanced superoxide anion generation, promoted extra-cellular signal regulated kinase 1/2 (ERK1/2), N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38) phosphorylation, and increased NF-κB levels in the nuclei of HUVECs. Finally, pre-treatment of HUVECs with the antioxidant N-acetylcysteine, the ERK1/2 inhibitor PD98059, the p38 inhibitor SB203580, the JNK inhibitor SP610025 or the NF-κB inhibitor pyrrolidine dithiocarbamate restored the septic serum-induced IL-1β, IL-6 and TNF-α expression. In conclusion, the results of the current study suggested that the septic serum-induced endothelial cell injury may be mediated by increasing ROS generation, activation of mitogen-activated protein kinases and NF-κB translocation.

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Abstract. To study the biotherapy effect of Shenfuweikang herbs in treatment of gastric cancer, Kunming mice were grafted with a mouse gastric adenocarcinoma cell line MFC. Mice received different doses of Shefuweikang herbs after grafting. Tumor size was periodically measured and tumor weight was determined after the animals sacrificed. Apoptotic indices (AI) were examined by TUNEL assay and flow cytometric analysis. Serum cytokines IFN-γ and granzyme B were detected by ELISA. The anti-tumor effect was determined by the cytotoxic T-lymphocyte (CTL) assays. Our results demonstrated that Shefuweikang herbs could induce apoptosis and inhibit the growth of gastric cancer by activating the CTLs and eliciting the secretion of cytokines, IFN-γ and granzyme B. Our study suggests that Shefuweikang herbs inhibit the proliferation of gastric carcinoma by inducing the apoptosis of tumor cells and activating the effects of immune cells, which may lay a better basis for further study on gastric cancer biotherapy.

To verify the anti-tumor effect of the Shenfoweikang on gastric cancer, BALB/C mice grafted with a mouse gastric adenocarcinoma cell line MFC was used as the experimental model. The mice received Shenfoweikang herbs over a 60-day period starting at the first day. The tumor size was periodically measured. Apoptotic indices (AI) were examined by the TUNEL method and flow cytometric analysis. The expression of VEGF, STAT3 and DEC1 in tumor tissues was examined by immunostaining. Compared with the control group, tumor growth in the mice treated with Shenfoweikang decoction were significantly inhibited (P<0.05). AI in the mice was significantly increased after the Shenfoweikang decoction treatment. The expressions of VEGF, STAT3 and DEC1 in tumor tissues were down-regulated after treated with Shenfoweikang decoction. The anti-tumor effect of Shenfoweikang herbs is related with the induction of the cell apoptosis and down-regulation of VEGF, STAT3 and DEC1 signal transduction system.