Grp78 promotes the invasion of hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>Glucose regulated protein 78 (Grp78) is involved in the invasion and metastasis in many human cancers including gastric cancer, breast cancer, prostate cancer. But the role of Grp78 in the invasion of human hepatocellular carcinoma has not been reported. In this article, we examined if Grp78 was associated with the invasion of hepatocellular carcinoma and explored the possible underlying mechanism.</p> <p>Methods</p> <p>The Grp78 and FAK expression levels in 44 patients with hepatocellular carcinoma were examined using immunohistochemistry. Grp78 overexpressing SMMC7721 cells were established by pcDNA3.1 (+)-Grp78 transfection and screened by G418. Grp78 and FAK levels in Grp78 overexpressing cells were down-regulated by siRNA transfection. The invasion status of tumor cells was evaluated by transwell assay in vitro, and chick embryo metastasis model in vivo. Cell spreading was determined by cell spreading assay, and quantitatively measured by Orisis software HUG. Grp78, pY397 FAK, pY576/577 FAK and FAK levels were detected by western blot. RhoA activity was detected by GST pulldown assay. The distribution of actin cytoskeleton was observed by fluorescent staining.</p> <p>Results</p> <p>Grp78 expression levels in 44 patients with hepatocellular carcinoma were negatively correlated with tumor grading, and positively correlated with portal invasion and intra-hepatic invasion. Overexpression of Grp78 in SMMC7721 cells promoted the invasion of cancer cells in vitro and in vivo, and this increase in tumor cell invasion was blocked by Grp78 siRNA knockdown. Our results also revealed that overexpression of Grp78 in SMMC7721 cells accelerated the process of cell spreading and promoted lamellipodia formation. Further analysis showed that overexpression of Grp78 in SMMC7721 cells increased pY397 and pY576/577 levels of FAK. Grp78 siRNA knockdown decreased FAK activation and activity. Our results also revealed that Grp78 overexpression in SMMC7721 cells decreased RhoA-GTP level, and Grp78 siRNA knockdown rescued RhoA-GTP level in Grp78 overexpressing cells, indicating Grp78 inhibited RhoA activity in hepatocellular carcinoma cells. Furthermore, overexpression of Grp78 in SMMC7721 cells increased phospho-p190RhoGAP level. FAK siRNA knockdown in Grp78 overexpressing cells reversed phospho-p190RhoGAP level. These data suggested that Grp78 inhibited RhoA activity by up-regulated phospho-p190RhoGAP level and Grp78 mediated p190RhoGAP phosphorylation is FAK dependent.</p> <p>Conclusion</p> <p>Grp78 promoted the invasion of hepatocellular carcinoma both in vitro and in vivo. Overexpression of Grp78 in hepatocellular carcinoma cells enhanced the activation and activity of FAK which negatively regulated Rock kinase activity by promoting the phosphorylation of p190RhoGAP.</p

Tuberculosis among Full-Time Teachers in Southeast China, 2005–2016

Objective: To explore the incidence rate and characteristics of tuberculosis (TB) among full-time teachers from 2005 to 2016 in southeast China and to provide a basis for TB prevention and control measures in schools. Methods: Information about full-time teachers with TB was obtained from the National Tuberculosis Information Management System (NTIMS). Population data were collected from the Zhejiang Statistical Yearbook and the Zhejiang Education Yearbook. The TB incidence rates and epidemiological characteristics of full-time teachers were analyzed and the Chi-square test was used to analyze influencing factors of epidemiological characteristics and clinical characteristics, case-finding delay, and treatment outcomes. Results: A total of 1795 teachers with TB were reported from 2005 to 2016, and the annual incidence rate was 28.87 per 100,000. The average annual PTB (pulmonary TB) incidence rate among full-time teachers was 25.43/100,000 from 2005 to 2016 and the average annual PTB incidence rate among students was 15.40/100,000 from 2005 to 2016. The highest average incidence rates were observed in the QZ (Quzhou) and HZ (Hangzhou) districts. The male-to-female ratio of the patients was 0.95:1. Approximately half of the patients were 15&ndash;40 years old. The mean case-finding interval was 45.3 days. Multivariable logistic regression analysis of TB case-finding delay among full-time teachers revealed that the older (OR = 1.44, 95% CI = 1.18&ndash;1.76, p &lt; 0.01), not local (OR = 1.81, 95% CI = 1.20&ndash;2.73, p &lt; 0.01), retreatment (OR = 2.06, 95% CI = 1.39&ndash;3.08, p &lt; 0.01) and extra-pulmonary tuberculosis (OR = 1.71, 95% CI = 1.13&ndash;2.61, p = 0.01) cases were at high risk of case-finding delay. Compared to physical examination, patients detected by referrals and tracking (OR = 2.26, 95% CI = 1.16&ndash;4.38, p = 0.02) and patients who directly visited the designated TB hospital (OR = 2.00, 95% CI = 1.03&ndash;3.88, p = 0.04) were more prone to case-finding delay. The cure rate of full-time teachers with TB was 77.10%. The cure rates differed significantly between groups classified based on age, case-finding patterns, diagnostic results, treatment classifications, and strategies of patient management. Conclusion: The TB incidence rate among full-time teachers decreased from 2005 to 2016, but teachers suffered a higher risk of TB than students. Western Zhejiang was a hotspot for TB incidence among full-time teachers. Female teacher and young and middle-aged teacher cases account for the majority of the reported patients. There was a case-finding delay among full-time teachers with TB. We should conduct regular physical examinations and strengthen full-course supervision to reduce the risk of TB patients with case-finding delay and increase the TB cure rate

The effects of booster vaccination of hepatitis B vaccine on children 5–15 years after primary immunization: A 5-year follow-up study

The aim of this study was to evaluate changes in hepatitis B surface antibody titers (anti-HBs) after booster vaccinations in children aged 5–15 y and to provide suitable immunization strategies. A total of 2208 children were initially enrolled in screening, and 559 children were finally included. The participants were divided into 2 groups according to their pre-booster anti-HBs levels: Group I, <10 mIU/ml and Group II, ≥10 mIU/ml. Group I was administered 3 doses of booster hepatitis B vaccine (0-1-6 months, 10 μg), and Group II was administered 1 dose of booster hepatitis B vaccine (10 μg). The antibody titer changes were examined at 4 time points: 1 month after dose 1 and dose 3, and 1 year and 5 years after dose 3. The protective seroconversion rates at those points were 95.65%, 99.67%, 97.59% and 91.05% (p < 0.001), respectively, in Group I, and 100.00%, 99.87%, 99.66% and 98.21% (χ2 = 6.04, p = 0.11), respectively, in Group II. The GMT in subjects aged 5–9 y were higher than that in subjects aged 10–15 y in both Group I and Group II at 1 month after dose 1, but no difference was observed at the other three time points. This study demonstrates that booster vaccination has a good medium-term effect. A booster dose for subjects with protective antibodies is not necessary but effective, and 3 doses of hepatitis B vaccination are recommended for those who have lost immunological memory. Receiving booster immunization at the age of 10-15 years may be more appropriate for individuals living in HBV high epidemic area

Suitable hepatitis B vaccine for adult immunization in China: a systematic review and meta-analysis

Hepatitis B virus (HBV) infection remains an important public health problem in China, and adults need to be vaccinated. This systematic review and meta-analysis assessed the appropriate immunization of adults in China. Only randomized controlled trials (RCTs) were eligible, and seroprotection was defined as anti-HBs≥ 10 mIU/ml; 18,308 participants in 27 studies were included. Relative risk (RR) and random effects models were used. Twenty micrograms of HBV vaccine resulted in a better response than 10 μg (RR: 1.05, 95% confidence interval (CI): 1.02 to 1.08), and the 0-, 1-, and 6-month schedule was more effective than the 0-, 1-, and 2 – or 3-month schedule (RR: 0.98, 95% CI: 0.96 to 1.00). No significant differences were observed between 10 μg and 5 μg (RR: 1.05, 95% CI: 0.88 to 1.01); (yeast-derived hepatitis B vaccines) YDV and recombinant Chinese hamster ovary cell (CHO) hepatitis B vaccine (RR: 1.01, 95% CI: 0.98 to 1.04); domestic and imported (RR: 1.02, 95% CI: 0.99 to 1.05); or 0-, 1-, and 6-month and 0-, 1-, and 12-month schedules (RR: 1.02, 95% CI: 0.89 to 1.08). In conclusion, 20 μg of vaccine is recommended for adults in China, and the 0-, 1-, and 12-month immunization program schedule is also worth choosing when it is not possible to complete the 0-, 1-, and 6-month schedule