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Pancreatic cancer is highly resistant to the currently available chemotherapeutic agents. Less than 5% of patients diagnosed with this disease could survive beyond 5 years. Thus, there is an urgent need for the development of novel, efficacious drugs that can treat pancreatic cancer. Herein we report the identification of artesunate (ART), a derivative of artemisinin, as a potent and selective antitumor agent against human pancreatic cancer cells in vitro and in vivo. ART exhibits selective cytotoxic activity against Panc-1, BxPC-3 and CFPAC-1 pancreatic cancer cells with IC₅₀ values that are 2.3- to 24-fold less than that of the normal human hepatic cells (HL-7702). The pan caspase inhibitor zVAD-fmk did not inhibit the cytotoxic activity of ART. Electron microscopy of ART-treated cells revealed severe cytoplasmic swelling and vacuolization, swollen and internally disorganized mitochondria, dilation (but not fragmentation) of the nuclei without chromatin condensation, and cell lysis, yielding a morphotype that is typical of oncosis. The ART-treated cells exhibited a loss of mitochondrial membrane potential (ΔΨm) and ART-induced cell death was inhibited in the presence of the reactive oxygen species (ROS) scavenger N-acetyl-cysteine (NAC). Importantly, ART produced a dose-dependent tumor regression in an in vivo pancreatic cancer xenografts model. The in vivo antitumor activity of ART was similar to that of gemcitabine. Taken together, our study suggests that ART exhibits antitumor activity against human pancreatic cancer via a novel form of oncosis-like cell death, and that ART should be considered a potential therapeutic candidate for treating pancreatic cancer.

Background: Allergen-specific sublingual immunotherapy is a potential treatment for allergic diseases. Its effective dose and underlying mechanism are still to be explored. Here, we investigated the efficacy and mechanism of sublingually administered Dermatophagoides farinae (Der f) vaccine in a murine asthma model. Methods: BALB/c mice were sensitized intraperitoneally with Der f extract absorbed to alum, followed by sublingual treatment with Der f vaccine for 6 weeks. The mice were subsequently challenged intranasally with Der f extract for 1 week. We analyzed their clinical symptoms, antibody levels, cytokine levels, T-cell proliferation and the regulatory T-cell numbers. Results: Mice treated with high-dose Der f sublingual vaccine prior to challenge displayed alleviated symptoms such as airway hyperreactivity, lung inflammation and mucus production, as well as less eosinophilic cells in bronchoalveolar lavage fluid. Interestingly, reduced responses of Der-f-specific IgE and increased responses of Der-f-specific IgA and IgG1 were aroused in the high-dose Der f sublingual vaccine group. We also observed that interleukin-4 was reduced and interferon-γ and interleukin-10 were increased among splenocytes and in bronchoalveolar lavage fluid, which inhibited Der-f-specific T-cell proliferation of the spleen and increased CD4+CD25+Foxp3+regulatory T cells in the spleen. However, mice treated with low-dose Der f sublingual vaccine developed allergic asthma. Conclusion: Our results illustrate that high-doseDer f sublingual vaccine may play a role in immunologic protection in murine allergic asthma, possibly by inducing regulatory T cells and Th1 reaction.

The viral lytic gene BZLF1 triggers replication of the Epstein-Barr virus (EBV), which is commonly found in nasopharyngeal carcinoma (NPC). Here, RT-PCR revealed five new BZLF1 variants in 8 of 12 NPC and 4 of 12 non-NPC nasopharyngeal biopsies from an NPC-endemic area in southern China. The deduced peptide sequence of the dominant BZLF1 variant differed by 11 amino acids from that of the prototypical strain B95.8 (V01555). Anti-ZEBRA antibody levels were higher in NPC than that in non-NPC patients (P < 0.001). These findings demonstrated a dominant BZLF1 variant in southern Chinese EBV-associated NPC and non-NPC patients.

Home dust mite derived materials are known to be a major source of problematic inhalant allergens. The aim of this study was to determine the localization of the group 3 allergen, Der f 3, within Dermatophagoides farinae, in order to assess the relative importance of excreted materials and nonexcreted body components as allergen sources. Recombinant Der f 3 (rDer f 3) was expressed in bacteria and purified as an immunogen for production of monoclonal antibodies (mAb) against it. Dermatophagoides farinae mites and their faecal pellets were embedded in paraffin, and serial sections were immunoprobed with mAb clone 3D3 against Der f 3. D. farinae midgut mucosa, gut contents and faecal pellets were strongly immunopositive for Der f 3. Der f 3 immunoreactive products were not detected in any other internal organs of the mite. These results suggest that Der f 3 allergen may be synthesized in and secreted from the digestive tract and excreted from the mite's body in the faecal pellets.

Background：Overexpression of G-protein coupled receptor 34 （GPR34） affects the progression and prognosis of human gastric adenocarcinoma,however,the role of GPR34 in gastric cancer development and progression has not been well-determined.The current study aimed to investigate the effect of GPR34 knockdown on the proliferation,migration,and apoptosis of HGC-27 gastric cancer cells and the underlying mechanisms.Methods：The expression of GPR34 in gastric cancer cell line HGC-27 was detected by quantitative real-time reverse transcription-polymerase chain reaction （RT-PCR） and Western blotting.HGC-27 cells were employed to construct the stable GPR34 knockdown cell model in this study.Real-time RT-PCR and Western blotting were applied to validate the effect of short hairpin RNA （ShRNA） on the expression of GPR34 in HGC-27 gastric cells.The proliferation,migration of these cells were examined by Cell Counting Kit-8 and transwell.We also measured expression profile of PI3K/PDK1/AKT and ERK using Western blotting.Results：The ShRNA directed against GPR34 effectively inhibited both endogenous mRNA and protein expression levels of GPR34,and significantly down-regulated the expression of PIK3CB （P ＜ 0.01）,PIK3CD （P ＜ 0.01）,PDK1 （P ＜ 0.01）,phosphorylation of PDK1 （P ＜ 0.01）,Akt （P ＜ 0.01）,and ERK （P ＜ 0.01）.Furthermore,GPR34 knockdown resulted in an obvious reduction in HGC-27 cancer cell proliferation and migration activity （P ＜ 0.01）.Conclusions：GPR34 knockdown impairs the proliferation and migration of HGC-27 gastric cancer cells in vitro and provides a potential implication for therapy of gastric cancer.

This study describes a simple method for the large‐scale isolation of pure Toxoplasma gondii tachyzoites and bradyzoites. T. gondii tachyzoites were obtained from infected human foreskin fibroblasts (HFFs) and peritoneal exudates of mice, while tissue cysts containing bradyzoites were collected from chronically infected mice. Harvested cells and brain tissues were incubated in Hanks balanced salt solution (HBSS), containing 0.25% trypsin and 0.5% taurodeoxycholic acid (TDC) for 5 min. Subsequent washes in phosphate buffered saline (PBS) were conducted, and the cell viability of the preparations was good, as determined by flow cytometry and ability to reinfect HFF cells and propagate in mice. The purification procedure allowed for a rapid preparation of pure T. gondii tachyzoites and bradyzoites in sufficient quantity that can be used for downstream procedures. The advantage of the new method is that it is convenient and inexpensive. We developed a rapid and simple method for purifying tachyzoites and bradyzoites with optimal yield and purity. The new proposed method has the following advantages: (1) zoites can be obtained quickly and easily; (2) the technique can be performed in low resource settings and capable of handling larger numbers of cells and tissues; (3) zoites obtained in this way are free of cellular debris; and (4) the viability and infectivity of tachyzoites, and bradyzoites are maintained. A more detailed study is required to explore the effect of trypsin on surface antigens of parasites.

Dear Editor, We present herein two rare cases of intractable chronic scrotal pain after vasectomy. The patients were effectively treated with microsur-gical vasovasostomy （MVV）. We also discuss the possible aetiologies of the pain and other surgical options.

Septic encephalopathy （SE） is a critical factor determining sepsis mortality. Vascular inflammation is known to be involved in SE, but the molecular events that lead to the development of encephalopathy remain unclear. Using time-lapse in vivo two-photon laser scanning microscopy, we provide the first direct evidence that cecal ligation and puncture in septic mice induces microglial trafficking to sites adjacent to leukocyte adhesion on inflamed cerebral microvessels. Our data further demonstrate that septic injury increased the chemokine CXCL1 level in brain endo- thelial cells by activating endothelial P2RX7 and eventually enhanced the binding of Mac-1 （CDllb/CD18）-expressing leukocytes to endothelial ICAM-1. In turn, leukocyte adhesion upregulated endothelial CX3CL1, thereby triggering microglia trafficking to the injured site. The sepsis-induced increase in endothelial CX3CL1 was abolished in CD18 hypomorphic mutant mice. Inhibition of the P2RX7 pathway not only decreased endothelial ICAM-1 expression and leukocyte adhesion but also prevented microglia overactivation, reduced brain injury, and consequently doubled the early survival of septic mice. These results demonstrate the role of the P2RX7 pathway in linking neurovascular inflammation to brain damage in vivo and provide a rationale for targeting endothelial P2RX7 for neurovascular pro- tection during SE.