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Aim: The anti-breast cancer effect and mechanism of ethyl acetate extract of persimmon leaves (PLE) were determined. Methods: Persimmon leaves were extracted by reflux at 80°C with 80% ethanol as the solvent. The total extracts of persimmon leaves were extracted with ethyl acetate, and the yield was calculated by weighing. The mouse breast cancer cell line 4T1 was cultured in vitro, and different concentrations of PLE were added. At the same time, the effects of PLE at different concentrations (25, 50, 100 µg/ml) on cell apoptosis ability were detected by Acridine Orange and Ethidium Bromide (AOEB) and flow cytometry experiments. In addition, real-time quantitative PCR (real-time PCR, RT-PCR) was used to test the expression of the Bax, Bcl-2, ERK1/2, MEK1/2 and RAF genes. In vivo tumor-bearing mouse model: A breast cancer transplant tumor model was established with BALB/c mice. The doses of PLE were 30, 60 and 120 mg/kg body weight/d, and the dose of CTX was 20 mg/kg body weight/d. The tumor inhibition rate and the effects of PLE on immune organs in tumor-bearing mice with 4T1 breast cancer were determined. The expression levels of IL-6, TNF-α, TGF-β and VEGFA in the serum of mice were detected by ELISA. The expression of the Bax, Bcl2, ERK1/2, MEK1/2 and RAF genes was determined by RT-PCR. The protein expression levels of Bax, Bcl-2, Caspase-3, p-MEK, p-JNK and p-P38 in tumor tissues were detected by immunohistochemistry. In addition, the protein expression levels of MAPK pathway components were assessed through Western blotting.Results: A total of 119.34 g ethyl acetate extract was obtained from 3 kg persimmon leaves with a yield of 3.98%. In vitro: MTT results indicated a strong antiproliferative effect of PLE on breast cancer cell lines. AOEB and flow cytometry assays showed that PLE promoted the apoptosis of breast cancer cells. PCR results showed that PLE could inhibit Bcl-2, promote Bax expression, and downregulate ERK1/2, MEK1/2, and RAF gene expression. In vivo: PLE had a significant inhibitory effect on breast cancer, and the tumor inhibition rates were 11.65%, 33.71% and 47.24% from low dose to high dose, respectively, showing a concentration dependence. The tumor inhibition rate of CTX was 57.74%. Meanwhile, PLE can increase the spleen and thymus index of 4T1 mice and decrease the liver index of 4T1 mice. Compared with the model group, PLE significantly reduced the expression levels of IL-6, TNF-α, TGF-β and VEGFA in the serum of mice. PCR results showed that PLE could inhibit Bcl-2, promote Bax expression, and downregulate ERK1/2, MEK1/2, and RAF gene expression. Immunohistochemical results showed that the PLE group and CTX group significantly promoted the expression of Bax and Caspase-3 proteins and downregulated the expression of Bcl-2, p-MEK, p-JNK and p-P38 proteins. WB results showed that PLE regulated the expression of proteins in the MAPK pathway.Conclusion: PLE enhances immunity, inhibits angiogenesis, inhibits 4T1 cell proliferation and induces apoptosis. Its apoptosis mechanism is related to the regulation of Bax/Bcl-2/Caspase-3 protein and the phosphorylation of regulatory proteins related to the MAPK signaling pathway.

Two low cytotoxic fluorescence probes Rb1 and Rb2 detecting Fe 3+ were synthesized and evaluated. Rb1 and Rb2 exhibited an excellent selectivity to Fe 3+ , which was not disturbed by Ag + , Li + , K + , Na + , NH 4 + , Fe 2+ , Pb 2+ , Ba 2+ , Cd 2+ , Ni 2+ , Co 2+ , Mn 2+ , Zn 2+ , Mg 2+ , Hg 2+ , Ca 2+ , Cu 2+ , Ce 3+ , AcO − , Br − , Cl − , HPO 4 2− , HSO 3 − , I − , NO 3 − , S 2 O 3 2− , SO 3 2− and SO 4 2− ions. The detection limits were 1.87 × 10 −7 M for Rb1 and 5.60 × 10 −7 M for Rb2 , respectively. 1:1 stoichiometry and 1:2 stoichiometry were the most likely recognition mode of Rb1 or Rb2 towards Fe 3+ , and the corresponding OFF–ON fluorescence mechanisms of Rb1 and Rb2 were proposed.

Metastasis causes approximately 90% of breast cancer-related deaths in women. Previously, we have demonstrated that 2-dodecyl-6-methoxycyclohexa-2,5-diene- 1,4-dione (DMDD) remarkably inhibited the growth of human breast cancer cells with little toxicity. In this study, we investigated the toxicity and efficacy of DMDD to treat metastatic breast tumors using an in vivo mouse model of the 4T1 mammary carcinoma. DMDD caused no observable toxicity and significantly extended the survival of 4T1 tumor-bearing mice. DMDD effectively inhibited the growth of 4T1 cells in vitro, and suppressed the growth and metastasis of mammary tumor in vivo. The levels of inflammatory cytokines in the serum (TNF-α, IL-6, IL-12, TGF-β, and VEGF) were down regulated by DMDD. Immunohistochemical analysis demonstrated that the inhibition of tumor growth and metastasis was associated with activation of Bax, cleaved caspases-3 and -9, and down-regulation of Bcl-2, MMP-2 and -9, NF-κB and IκBα. We speculate that DMDD inhibits cytokine production in the tumor cells in mice, which leads to deactivation of NF-κB pathway, and consequently inhibits the expression of many anti-apoptosis and metastasis-promoting genes, such as Bcl-2 and MMPs. Collectively, our results demonstrate the potential of DMDD as a safe and effective antitumor agent in the treatment of late-stage breast cancer.

Local measurements of concentrations of O2, CO, SO2, and NOx were carried out inside Baima’s 300 MWe circulating fluidized bed (CFB) boiler. Custom-made probes with a length of 4.8 m were used to t...

Ethnopharmacological relevance Yulangsan polysaccharide (YLSPS) is often used in popular folk medicine in the Guangxi Zhuang Autonomous Region of China as a chief ingredient of Millettia pulchra, which is used as a hepatic protection, anti-aging and memory improving agent. Aim of the study This study was designed to investigate the protective effects of polysaccharides from Millettia pulchra Kurz var.laxior (Dunn) (Yulangsan polysaecharide, YLSPS) against nimesulide-induced hepatotoxicities in mice. Materials and methods Liver injury was induced in mice by administering nimesulide. Simultaneously, YLSPS was administered 2 h prior to the administration of nimesulide. Dimethyl diphenyl bicarboxylate (DDB) was used as a reference drug. Results Compared with the nimesulide group, YLSPS significantly decreased the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and the content of bilirubin in the serum. The anti-oxidative effect of YLSPS was observed from the increase of the superoxide dismutase (SOD) and catalase and glutathione peroxidase (GSH-Px) activities in the liver, both of which were decreased by nimesulide. Moreover, the content of malondialdehyde (MDA) was reduced, and histological findings also confirmed the anti-hepatotoxic activity. In addition, YLSPS significantly inhibited proinflammatory mediators, such as tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6). Additionally, YLSPS also enhanced the mitochondrial antioxidant and inhibited dead cells by preventing the down-regulation of Bcl-2, up-regulation and release of Bax along with caspase 9 and 3 activity, confirming the involvement of mitochondria in the nimesulide-induced apoptosis. Conclusion The protective effect of YLSPS against nimesulide-induced hepatic injury may rely on its ability to reduce oxidative stress and prevent nimesulide-induced hepatotoxicity by inhibiting critical control points of apoptosis.