A critical challenge for chemotherapy is the development of chemoresistance in breast cancer. However, the underlying mechanisms and validated predictors remain unclear. Extracellular vesicles (EVs) have gained attention as potential means for cancer cells to share intracellular contents. In adriamycin-resistant human breast cancer cells (MCF-7/ADM), we analyzed the role of transient receptor potential channel 5 (TrpC5) in EV formation and transfer as well as the diagnostic implications. Up-regulated TrpC5, accumulated in EVs, is responsible for EV formation and trapping of adriamycin (ADM) in EVs. EV-mediated intercellular transfer of TrpC5 allowed recipient cells to acquire TrpC5, consequently stimulating multidrug efflux transporter P-glycoprotein production through a Ca 2+ -and activated T-cells isoform c3-mediated mechanism and thus, conferring chemoresistance on nonresistant cells. TrpC5-containing circulating EVs were detected in nude mice bearing MCF-7/ ADM tumor xenografts, and the level was lower after TrpC5-siRNA treatment. In breast cancer patients who underwent chemotherapy, TrpC5 expression in the tumor was significantly higher in patients with progressive or stable disease than in patients with a partial or complete response. TrpC5-containing circulating EVs were found in peripheral blood from patients who underwent chemotherapy but not patients without chemotherapy. Taken together, we found that TrpC5-containing circulating EVs may transfer chemoresistance property to nonchemoresistant recipient cells. It may be worthwhile to further explore the potential of using TrpC5-containing EVs as a diagnostic biomarker for chemoresistant breast cancer.T he development of chemotherapeutic resistance in breast cancer is a serious problem (1, 2). To date, the mechanisms underlying chemoresistance are still largely unknown, and no validated predictive factor of chemoresistance is available in the clinic. Therefore, it is important to identify the signaling pathways and search for circulating markers in breast cancer resistant to chemotherapy.The extracellular environment contains a large number of mobile membrane-limited vesicles named extracellular vesicles (EVs). Major EV populations include exosomes, microvesicles, and apoptotic bodies (1, 3-5). These dynamic EVs may have essential function in intercellular communication and immune regulation (5). Tumor cells also generate EVs (3, 4). Large quantities of tumor-derived circulating EVs have been found in the blood of patients with glioblastoma multiforme (4), pancreatic cancer (6), gastric cancer (7), and acute myeloid leukemia (8). They contain cell surface proteins, RNA, and DNA (3, 4, 9, 10). They mediate intercellular cross-talk by transferring their intravesicular contents from donor to recipient cells and participating in tumor invasion and metastasis (11-13). However, how these structures are generated and their importance in chemotherapeutic resistance in breast cancer are poorly understood.On the basis of our previous finding that transient receptor...

Purpose: The incidence of hepatocellular carcinoma (HCC) is extremely high, and China accounts for approximately 50% of global liver cancer cases. Previous studies reported that CDC20 is involved in the occurrence and progression of a variety of malignant tumors. So, whether CDC20 will affect the development of HCC, we have conducted in-depth research on this. Methods: We selected Hep3B and HepG2 for cell culture, and performed siRNA transfection, lentiviral infection, western blot, MTS determination, cell cycle determination, apoptosis test, immunodeficiency test, clone survival test and subcutaneous parthenogenesis in nude mice. Results: Knockdown of CDC20 greatly enhanced the radiation efficacy on the growth retardation in HepG2, and protein level of CDC20 was decreased for the activation of P53 by radiation. Downregulation of CDC20 combined with radiation can inhibit proliferation, aggravate DNA damage, increase G2/M arrest, and promote apoptosis of HCC cells to a greater extent, and the relative survival fraction of HCC cells was gradually reduced with radiation dose increased in P53 mutated Hep3B cells. After knocking down CDC20 in HCC, Bcl-2 was down-regulated and Bax expression increased. Down-regulation of CDC20 can inhibit further invasion by promoting the radiosensitivity of HCC. Conclusion: In this study, we found that that CDC20 was highly expressed in HCC and participated in radio resistance of HCC cells with P53 mutation Bcl-2/Bax via signaling pathway. This study is the first to present evidence that CDC20 may play a role in improving the efficacy of radiotherapy in HCC.

The present study aimed to determine the protective effects and the underlying mechanisms of astragalin (AG) on ovalbumin (OVA)-induced allergic inflammation in a mouse model of allergic asthma. Our study demonstrated that AG inhibited OVA-induced increases in eosinophil count; IL-4, IL-5, IL-13, and IgE were recovered in bronchoalveolar lavage fluid, and increased IFN-γ level in bronchoalveolar lavage fluid. Histological studies demonstrated that AG substantially inhibited OVA-induced eosinophilia in lung tissue. Western blot analysis demonstrated that AG treatments markedly inhibited OVA-induced SOCS-3 expression and enhancement of SOCS-5 expression in an asthma model. Our findings support the possible use of AG as a therapeutic drug for patients with allergic asthma.

A sensitive and reliable HPLC-UV method coupled with MS identification was developed for the first time to simultaneously determine the ability of 10 compounds, including caffeic acid, hesperidin, rosmarinic acid, quercetin, luteolin, oleanolic acid 3-O-monoglucuronide, rhein, corosolic acid, oleanolic acid and ursolic acid, to inhibit cancer cell proliferation and their antioxidant activities in the spikes of Prunella vulgaris L.(PV). HPLC analysis of these compounds was performed using a reversed-phase Alltima C 18 column (150 mm  4.6 mm, 5 mm). The mobile phase consisted of acetonitrile (A) and 0.1% glacial acetic acid solution (B) with gradient elution; the column temperature was maintained at 30 C and the detection wavelength was set to 215 nm. The flow rate was 1.0 ml min À1 for 0-60 min and was then changed to 0.4 ml min À1 between 60 min and 105 min. The enhanced method has good linear regression (R 2 > 0.9994), good precision and accuracy (RSD < 3%). The recoveries of the ten compounds ranged from 95.6-103.8% (RSD < 5%). This HPLC-UV method coupled with MS identification was successfully applied to quantify these anti-tumor and antioxidant compounds in 14 batches of PV, collected from different cultivation regions. Based on the content of these compounds, these PV samples were classified using hierarchical clustering analysis (HCA). Our results demonstrated that established HPLC-UV coupled with MS identification was a useful and reliable tool for quality control of PV.

The fall armyworm (FAW), Spodoptera frugiperda, is a highly polyphagous lepidopteran pest, with its growth and adaptation affected by different host plants. However, little is known about the effects of host plants on ovarian development in this species. Thus, we evaluated the effects of feeding on corn (Zea mays L.) and goosegrass (Eleusine indica), on the ovarian development of S. frugiperda. Using various stages of S. frugiperda, we also evaluated the larval and pupal weights, number of eggs, and differentiation of ovarioles over time. Results showed that females fed on goosegrass had shorter ovarioles and laid less eggs than those fed on corn. Transcriptome analysis identified 3,213 genes involved in ovarian development in the fall armyworm. Of these, 881 genes were differentially expressed when fed on corn and goosegrass. The analysis also indicated that the hormone biosynthetic pathways may be involved in the reproductive system. In relation to the reproductive function, nine juvenile hormone (JH) biosynthetic genes, four 20-hydroxyecdysone (20E) biosynthetic genes, and four ovary-relevant functional genes were identified. The time course of the expression profiles of these hormone- and ovary development-related genes was measured by quantitative real-time PCR (qRT-PCR). In total, six of them showed a decreasing trend in the ovary of the FAW fed on goosegrass, while two genes showed an increasing trend. Our results showed that significant changes in the reproductive activity/ovary development in the FAW occurred in response to different diets. These results serve as bases for evaluating how optimal host plants and feeding preference affect ovarian development in the FAW.