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PURPOSE: Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor, the prognosis of which remains poor. Recently, microRNAs have been reported to play crucial functions in multiple tumors, including HCC. However, the molecular mechanisms of miR-370 in HCC still remain largely unknown. The present study focused on the effects of miR-370 on HCC migration, invasion, and epithelial-mesenchymal transition (EMT). MATERIALS AND METHODS: We investigated the key roles and possible regulatory mechanism of miR-370 in regulating HCC metastasis with functional assays, such as transwell assay. Quantitative real-time PCR (qRT-PCR) was used to detect miR-370 and guanylylcyclase domain containing 1 (GUCD1) expression in HCC tissues and cells. Subsequently, we performed transwell assays to determine the functions of miR-370 in HCC cell invasion and migration. Western blot was used to determine protein expressions of relevant genes. Luciferase reporter assays were conducted to confirm the target gene of miR-370. RESULTS: qRT-PCR analysis demonstrated that miR-370 was dramatically downregulated in HCC. Moreover, downregulated miR-370 was found to be associated with poor survival and adverse clinicopathologic characteristics of HCC patients. Transwell assays revealed that miR-370 overexpression dramatically suppressed HCC invasion and migration. Meanwhile, miR-370 restoration prominently inhibited EMT progression in HCC cells. Luciferase reporter assays confirmed GUCD1 as a downstream target gene of miR-370. GUCD1 expression in HCC tissues was prominently increased and inversely correlated with miR-370 expression. Furthermore, GUCD1 was verified as mediating the suppressive influence of miR-370 on cell metastasis and EMT in HCC. CONCLUSION: Taken together, our study confirmed that miR-370 suppressed HCC cell metastasis and EMT via regulating GUCD1. Accordingly, the miR-370/GUCD1 axis may potentially acts as attractive therapeutic targets and novel biomarkers for HCC treatment.
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Humans , Biomarkers , Blotting, Western , Carcinoma, Hepatocellular , Epithelial-Mesenchymal Transition , Luciferases , MicroRNAs , Negotiating , Neoplasm Metastasis , Prognosis , Real-Time Polymerase Chain ReactionABSTRACT
OBJECTIVE@#To determine the immune-protective effect of Japan Schistosoma (Chinese mainland strain) 23 kD membrane protein-heat shock protein (SjC23-Hsp70) DNA vaccine plus adjuvantinduced interleukin-12 (IL-12) plasmid DNA on Schistosoma japonicum infection in water buffalos.@*METHODS@#Forty-five health water buffalos (8-10 months old) in non-endemic area of schistosomiasis were randomly assigned into group A (SjC23-Hsp70+IL-12, 300 μg), group B (SjC23+IL-12, 300 μg) and group C (pVAX+IL-12, 300 μg), 15 in each group. Each buffalo was immuned by shoulder intramuscular injection for 3 times, at an interval of 28 days. Twenty-eight days after the last immunization, each buffalo was infected with 1000 Japan cercariae of Schistosoma. Fecal examinations were conducted 2 days and 1 day before the perfusion, and on the day of perfusion. The number of hatching miracidia and eggs per gram feces was recorded. Fifty-six days after the infection, the buffalos were sacrificed and perfused via the descending aorta. The recovered adult worms and eggs in the liver tissue were counted.@*RESULTS@#We compared group A and B with group C: the estrogen reduction rate was 45.7% and 26.61%; bug reduction rate was 44.51% and 25.84%; the fecal egg reduction rate was 41.1% and 31.63%; the miracidium reduction rate was 48.11% and 38.07%; and the liver egg reduction rate was 43.39% and 31.95%. The above rates in group A were higher than those in group B (P<0.05).@*CONCLUSION@#SjC23-Hsp70 DNA vaccine combined with IL-12 may have a significant immunoprotective effect on buffalos.
Subject(s)
Animals , Cattle , Antigens, Helminth , Allergy and Immunology , Buffaloes , HSP70 Heat-Shock Proteins , Genetics , Allergy and Immunology , Helminth Proteins , Allergy and Immunology , Immunization , Methods , Interleukin-12 , Genetics , Allergy and Immunology , Membrane Proteins , Allergy and Immunology , Schistosomiasis japonica , Allergy and Immunology , Vaccines, DNA , Allergy and Immunology , Vaccines, Synthetic , Allergy and ImmunologyABSTRACT
Although identification of water contact patterns is one of the most important factors for the prevention of <I>Schistosoma japonicum</I> infection, it is still insufficient for clarifying specific high-risk behaviors and their implications. Parasitological studies and behavioral observations were carried out in a rural village, the Dongting Lake region, China. A time-allocation study conducted by a time-saving spot-check method was implemented to quantify the behavioral risks. Of the 122 participants, 18 (14.8%; 95% confidence interval: 8.5, 21.0) were positive for S. japonicum. Among those diagnosed, the median (25−75% quartile) eggs per gram was 8 (8−16). A significant positive correlation with worm intensity was found among people who repair ships on the marshland (p&It;0.001), and this potential risk was consistent with previous suggestions. Although the parasitological techniques and study design require further improvements, our observational methods may be of use to explicitly identify behaviors at the local level that could be relevant to prevention.
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In this paper,the authors elaborated the difficulties of schistosomiasis control and analyzed shortages and problems of the skills currently used.In order to consolidate the progress in schistosomiasis control and reach the transmission-blocking target,research priorities on the disease control technologies are proposed.
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ObjectiveTo observe the dynamics of antibodies and protection against Schistosoma japonicum infections in buffaloes after immunized with recombinant 26 kDa glutathione S transferase (reSjc26GST). Methods Buffaloes in 2 villages endemic for schistosomiasis japonica were selected as test and control groups, respectively.In test group initially 96 buffaloes were vaccinated with reSjc26GST, and 90 buffaloes in the control group did not experience vaccination. The indicators included levels of antibodies to reSjc26GST in buffaloes before and after infection with S japonicum and changes in infection rate. Results Specific antibodies, which showed a trend of trapezoid increase, were induced in buffaloes after immunized with reSjc26GST. Twenty months after immunization, the infection rate of the test group was decreased by 62 2% when compared with that before vaccination,and by 67 7% when compared with that of the control in the corresponding period.Conclusion Specific antibodies and a certain extent of protection were induced in buffaloes after immunized with reSjc26GST, which played an significant role in ameliorating morbidity.
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0.05), and the all had significant differences in 2 to 4 months post-infection compared with the normal controls (P
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Objective To understand and identify the molecules related to the natural resistance to Schistosoma japonicum infection in Mirotus fortis. Methods Sera from Mirotus fortis without schistosome infection were collected. The S.japonicum adult worm cDNA library was immunologically screened with the sera. The positive recombinants were identified, cloned, sequenced and analysed with software and internet. Results Seven genes encoding antigens relevant to sera antibodies in Mirotus fortis were cloned and sequenced. These antigens included glyceraldehyde 3-phosphate dehydrogenase (GAPDH), serine protease inhibitors(SERPIN), 70 kDa heat shock protein(HSP70), 22^6 kDa membrane-associated antigen, paramyosin (Sj97), cytochrome C and cathepsin B. Conclusion Many protein molecules might have been involved in natural resistance to \{S.japonicum\} infection in Mirotus fortis. The above 7 kinds of molecules may be identified as new candidates of vaccine against \{S.japonicum\} infection.