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Background: Cystic echinococcosis is a global parasitic disease caused by infection with Echinococcus granulosus larvae with potentially life-threatening complications in humans. To date, the status of the immune cells believed to be associated with the pathogenicity of E. granulosus infection has not been demonstrated clearly. Methodology/Principal Findings: In this study, we developed a multiplex flow cytometry assay to investigate the systemic immune status of innate and adaptive immunity at 30, 180, 360 days post-infection (dpi) in mice infected with E. granulousus. At 30 dpi, an increase in the number of CD11b+ and CD11c+ antigen-presenting cells (APCs) was observed. This was accompanied by the slight down-regulated expression of the co-stimulatory molecule MHC-II, indicating the impairment of APCs in early infection through the release of secretory-excretory products. In all infected groups, we observed a significant increase in innate immune cells, including APCs and GR-1+ cells, and a dramatic increase in the myeloid-derived suppressor cells (MDSC) expressing CD11b+/GR-1+. Moreover, the upregulation of the activated markers CD69, CD44, CD40L, and the downregulation of CD62L were observed in the CD4+ and CD8+ T cells following infection. Regulatory T cells expressing CD4+/CD25+/FoxP3+ increased significantly over the course of infection. Conclusions: Our findings demonstrate that the microenvironment in the peripheral immune system after E. granulosus infection changes in subtle but detectably ways, especially during the persistent period of infection. We found that T cells were activated following infection, but observed that the significant increase of immunosuppressive cells such as MDSC and Treg cells could inhibit T cell response to E. granulosus antigens. We suggest these cells may play a neglected but key role in the downregulation of the immune response in long-term parasitic infection. Understanding the basic functions and temporal interactions of these immunosuppressive cells will pave the way for new strategies of parasite vaccine design. [ABSTRACT FROM AUTHOR]

SET7 is the first lysine methyltransferase and plays vital roles in tumorigenesis. This study aims to seek clinical value of SET7 in colorectal cancer (CRC) patients, along with its biological impact on cell proliferation and migration. In patients with CRC, the expression of SET7 in cancer tissue was significantly lower than that in adjacent tissue, and down-regulated SET7 was closely correlated with poor prognosis. Loss-of-function and gain-of-function studies indicated that SET7 inhibited cell proliferation and migration by acting on HDAC6 substrate in colon cancer cells. Besides, the co-immunoprecipitation assay showed that SET7 and HDAC6 can interact reciprocally. The interaction effect between SET7 and HDAC6 could significantly reduce cell viability, scratch healing rate, and migrated cells in colon cancer cells. Instead of acting on each endogenous expression, the results demonstrated that the level of acetylated α-tubulin was greatly decreased in HDAC6 overexpression group, while significantly increased in SET7 overexpressed group. However, changes were partly restored in both SET7 and HDAC6-transfected group. On the contrary, the expression of acetylated α-tubulin protein was significantly increased in HDAC6 knockdown group, but higher in both HDAC6 and SET7 silencing group. These results indicated that SET7 played a role in tumor suppression via increasing levels of acetylated-α-tubulin mediated by HDAC6. In addition, the interaction effect significantly decreased the ratios of p-ERK/ERK, which indicated that it may partly suppress ERK signaling pathway. In conclusion, SET7 is a promising therapeutic target for preventing metastasis and improving prognosis in colon cancer., Competing Interests: None., (AJTR Copyright © 2020.)

One primary school and one middle school were selected from Gudong Town, Tengyue Town and Puchuan Township of Tengchong County, respectively, by using the lamination stochastic group sampling method. The intestinal parasite infections were investigated with the iodine-stained direct smear method and modified Kato-Katz thick smears method. A total of 1 134 students were investigated and the total infection rate of intestinal nematodes was 12.4% (141/1 134). The infection rate of Ascaris lumbricoides, Trichuris trichura, and hookworm was 9.4% (106/1 134), 2.8% (32/1 134), and 0.3% (3/1 134), respectively. The prevalence of intestinal nematodes among the students of urban (2.2%, 8/363) was lower than those of rural (17.3%, 133/771) (P < 0.01). The infection rate in students from Gudong Town was higher than those of Tengyue (2.2%, 8/363) and Puchuan County (2.3%, 8/35) (P < 0.01), whereas the economy level of Gudong Town (29.9%, 123/412) was the best in the three towns. After all, the infection rate of the middle school students (13.7%, 59/432) was higher than that of pupils (11.7%, 82/702) (P < 0.01). Compared with 2003, the prevalence of nematode infection among the school students in Tengchong County decreased significantly in 2013.

Objective: To determine the accumulation of CD11b+ Gr-1+ myeloid-derived suppressor cells (MDSC) in Schistosorna japonicum-infected mice., Methods: Twenty-four C57BL/6 mice were infected cutaneously with S. japonicum cercariae. Peripheral blood samples were collected at 1, 2, 6 and 8 weeks post-infection (6 mice for each group). At 6 and 8 weeks post-infection, spleens were removed and a single-cell suspension was prepared. At the same time, 6 healthy mice each served as control. During the different stages of infection, the levels of MDSC, Gr-1+ cells, CD11b+ cells in murine peripheral blood and spleen were detected by flow cytometry. The possible function of MDSC on T cells was evaluated by using a CCK-8 method and CFSE proliferation assay., Results: At 6 and 8 weeks post-infection, the levels of MDSC (38.2%-57.8% and 47.1-77.6%, respectively), Gr-1+ cells (28.9%-44.6%, 40.4%-72.9%), and CD11b+ cells (36.0%-48.1%, 40.3%-68.3%) in infection group were significantly higher than that of the controls (15.1%-20.4%, 8.4%-17.3%, 9.8%-22.6%), and that of infection group at 1 week (16.2%-19.8%, 13.0%-16.8%, 17.6%-19.4%) and 2 weeks (19.8%-29.5%, 17.2%-22.2%, 20.9%-33.3%) post-infection (P < 0.01). No significant difference was found in the levels of MDSC, Gr-1+ cells, CD11b+ cells among infection group at 1 and 2 weeks post-infection and control group. Moreover, the fluctuation trends of these cells in the spleens of infected mice were similar to those cells in peripheral blood (P > 0.05). Strikingly, the proliferation index of normal CD4 T cells was significantly lower after co-culture with Gr-1+ cells isolated from infected mice., Conclusion: Schistosoma japonicum infection induces higher level of MDSC in mice, and Gr-1+ cells isolated from the infected mice can significantly inhibit the proliferation of the normal CD4+ T cells.

Objective: To study the difference among immune responses of three kinds of experimental animals with different susceptibility to the infection of Schistosoma japonicum, and preliminarily explore the mechanism of the immune response in permissive and non-permissive hosts., Methods: Twelve animals of each kind of rodents, C57BL/6 mice, Sprague Dawley (SD) rats and Microtus fortis, were randomly divided into the infected group and uninfected group each with 6 animals. In infected groups of C57BL/6 mice, SD rats, and M. fortis, each animal was infected with 20, 200 and 1000 cercariae of S. japonicum, respectively. 42 d later, all rodents were sacrificed. Adult worms in portal vein and granulomas in liver were observed and the sera were collected. The levels of cytokines IL-10 and IFN-gamma as well as serum IgG, IgG2a, and IgG1 were detected by ELISA., Results: At the 42th day post infection, worms in portal vein and liver granulomas were observed in C57BL/6 mice and SD rats, but not in M. fortis. The level of IL-10 in the sera of SD rats [(2.21 +/- 0.12) pg/ml] was significantly higher than that in the sera of M. fortis [(1.64 +/- 0.39) pg/ml] and C57BL/6 mice [(0.10 +/- 0.04) pg/ml] (P<0.01). IL-10 in the sera of M. fortis was also significantly higher than that in the sera of C57BL/6 mice (P<0.01). IFN-gamma in the sera of SD rats [(0.21 +/- 0.11) pg/ml] was significantly higher than that in the sera of M. fortis [(0.11 +/- 0.03) pg/ml] and C57BL/6 mice [(0.09 +/- 0.02) pg/ml] (P<0.05), but no difference between M. fortis and C57BL/6 mice (P>0.05). The levels of IgG (1.53 +/- 0.31), IgG1 (1.48 +/- 0.44) and IgG2a (0.41 +/- 0.11) in SD rats were significantly higher than that in the sera of M. fortis (0.48 +/- 0.14, 0.15 +/- 0.03 and 0.12 +/- 0.061) (P<0.01). The levels of IgG (1.21 +/- 0.16), IgG1 (0.88 +/- 0.31) in C57BL/6 mice were significantly higher than that in the sera of M. fortis (P<0.01). IgG1 antibody is the predominant subclass in the three kinds of rodents. The levels of IL-10, IFN-gamma and antibody subclass IgG, IgG1, IgG2a in all non-infected rodents were not detected., Conclusion: IL-10 in non-permissive hosts, which is an essential agent in the regulation of Th2 immune response, is higher than that in permissive host It may play an important role in the resistance to schistosome in the non-permissive hosts.

Objective: To observe the destructive effect of eggs of Schistosomajaponicum on the splenic structure in C57BL/6 mice., Methods: The C57BL/6 mice were injected intravenously with eggs of S. japonicum or soluble egg antigen (SEA), or the eggs were injected surgically into the spleens of the mice. Four weeks later, the mice were sacrificed, the splenic paraffin sections were stained with H & E and the splenic structures were observed. Other two groups of mice were infected with single-sex and both sexes of schistosome cercariae, respectively. Nine weeks after the infection, the mice were sacrificed, and the splenic structures were observed and compared among the groups aforementioned., Results: The splenic structure of mice injected intravenously with eggs were destroyed, and characterized with decreased number of lymphoid follicles and blurred marginal zone. Lymphoid follicles around the eggs injected into the spleen were also seriously depauperated. The splenic weight (0.15 +/- 0.01) g of the mice infected with single-sex cercariae significantly less than that (0.41 +/- 0.03) g of the mice infected with both sexes cercariae (P < 0.01). However, the splenic structure of the mice infected with single-sex cercariae kept integrated., Conclusion: Eggs of S. japonicum have a destructive effect on the splenic structure in C57BL/6 mice.

Objective: To study the immunomodulation effect of the recombination Sj16 from Schistosoma japonicum (reSj16) on inflammation response of host., Methods: reSj16 expressed in pGEX-4T-1 was purified by GST purification kit and detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectra (MS). The immunomodulation effect of reSj16 was observed by means of dimethylbenzene inducing mouse ear edema model, carrageenan inducing rat voix pedis swell model and acetic acid inducing mouse experiment peritonitis model., Results: The soluble protein of reSjl6 was obtained and identified by SDS-PAGE and MS. reSjl6 1.0, 5.0, 10.0 microg/kg evidently suppressed the mouse ear edema induced by dimethyl-benzene, significantly mitigated the rat voix pedis swelling induced by carrageenan, and remarkably suppressed the increase of the capillary permeability of abdominal cavity in experiment peritonitis mouse model., Conclusion: The results further prove that Sj16 may be a potential immunosuppressive molecule and may have a notable effect on immunomodulation.

Background & Objective: Alpha-fetoprotein (AFP) promoter-driven target gene could be specifically expressed in AFP-positive hepatoma. Escherichia coli purine nucleoside phosphorylase/6-methylpurine-2-deoxyriboside (PNP/MeP-dR) suicide gene system has powerful killing effects on tumor cells. This study was to investigate the specific killing effect of PNP/MeP-dR suicide gene system driven by an AFP promoter, AF0.3, on AFP-positive hepatoma cells., Methods: Inserting PNP gene into pAF0.3, a eukaryotic expression vector containing PNP gene, pAF0.3/PNP, was constructed. Then it was transfected into AFP-positive HepG2 and AFP-negative SMMC7721 hepatoma cell lines, respectively. Two cell lines HepG2/AF0.3-PNP and SMMC7721/AF0.3-PNP, stably transfected with PNP gene, were obtained with G418 selection. The expression of PNP gene was detected by reverse transcription-polymerase chain reaction (RT-PCR). The proliferation of HepG2/AF0.3-PNP and SMMC7721/AF0.3-PNP cells was determined with trypan blue exclusion. The sensitivity of the cells to MeP-dR and the bystander effects were assessed with MTT assay and flow cytometry (FCM). The enzymatic activities of PNP gene products were determined with high performance liquid chromatography (HPLC)., Results: Whether hypoxia or normoxia, HepG2/AF0.3-PNP cells were sensitive to MeP-dR, whereas SMMC7721/AF0.3-PNP cells were not. Under both conditions, obvious cytotoxic effects on HepG2 cells were observed when the proportion of HepG2/AF0.3-PNP cells in the mixture reached 25%. But there were no similar effects on SMMC7721 cells under the same conditions. HPLC assay showed that the product of PNP gene driven by AF0.3 promoter could convert a spot of MeP-dR into 6-MP in HepG2 cells, but not in SMMC7721 cells., Conclusion: PNP/MeP-dR system, driven by AF0.3 promoter, has powerful killing effect on AFP-positive hepatoma HepG2 cells.

Aim: To investigate the prediction value of radiosensitivity of hepatocarcinoma cells for apoptosis and micronucleus assay., Methods: Clonogenic assay, flow cytometry, and CB micronuclei assay were used to survey the cell survival rate, radiation-induced apoptosis and micronucleus frequency of hepatocarcinoma cell lines SMMC-7721, HL-7702, and HepG2 after being irradiated by X-ray at the dosage ranging 0-8 Gy., Results: After irradiation, there was a dose-effect relationship between micronucleus frequency and radiation dosage among the three cell lines (P<0.05). A positive relationship was observed between apoptosis and radiation dosage among the three cell lines. The HepG2 cells had a significant correlation (P<0.05) but apoptosis incidence had a negative relationship with micronucleus frequency. There was a positive relationship between apoptosis and radiation dosage and the correlation between SMMC-7721 and HL-7702 cell lines had a significant difference (P<0.01). After irradiation, a negative relationship between cell survival rate and radiation dosages was found among the three cell lines (P<0.01). There was a positive relationship between cell survival rate and micronucleus frequency (P<0.01). No correlation was observed between apoptosis and cell survival rate., Conclusion: The radiosensitivity of hepatocarcinoma cells can be reflected by apoptosis and micronuclei. Detection of apoptosis and micronuclei could enhance the accuracy for predicting radiosensitivity.

Objective: To construct and express secretive endostatin eukaryotic plasmid for treatment of hepatoma., Methods: Mouse Igk signal peptide sequence was synthesized and cloned into pcDNA3.1 with endostatin gene. The supernant of BHK-21 transfected with recombinant was used to culture ECV304. The proliferation of latter was evaluated by MTT assay. H22 was inoculated intramusclely, then naked DNA of endostatin plasmid was injected into the inoculation site. Tumors were dissected and weighted after treatments. All data was analyzed by SPSS10.0., Results: The supernant of BHK-21 transfected with recombinant can inhibit the proliferation of ECV304 by 29.2%. Tumor weight lighter after injected with naked pSecES (1.34 g+/-0.96g) compared with naked pcDNA3.1 (2.70g+/-0.82g) and saline (3.73g+/-1.41g)., Conclusion: The endostatin eukaryotic plasmid was constructed and it can be used for gene therapy on hepatoma.