ABSTRACT
Background: Although hepatitis B vaccination has a significant impact on the reduction hepatitis B virus (HBV) infection, babies born to hepatitis B surface antigen (HBsAg) positive mothers bear a high risk of being poor responsive to the vaccine with unilluminated mechanism. Toll-like receptor 3 (TLR3) plays a vital role in placental immunity, which affects the immune response of these babies. This study investigated the role of placental TLR3 in the immune responses of babies born to HBsAg-positive mothers to the HBV vaccine. Methods: One hundred pairs of HBsAg-positive mothers and their newborns were recruited. Maternal blood samples were collected before delivery, and placental tissues were collected after delivery. Newborns were administered standard passive and active immunoprophylaxis and followed up until the age of 1. Infant blood samples were collected at 1 year of age. Mothers and infants were tested for HBV serological markers and HBV DNA by electrochemiluminescence immunoassay and fluorescence quantitative polymerase chain reaction. respectively. Placental TLR3 was detected by immunohistochemistry and score in a semi-quantitative fashion, circulating cytokines in infants were detected by enzyme-linked immunosorbent assay. Infants with anti-HBs ≥100 and <100 mIU/mL were classified into the high-responsiveness group and the non- or hypo-responsiveness group. Results: The TLR3 protein was expressed in all placentas. Compared with the high-responsiveness group, the expression of TLR3 in the non- or hypo-responsiveness group was significantly decreased (χ2=10.39, P=0.001). A non-conditional logistic regression model showed that the increased expression of placental TLR3 protein decreased the odds of HBV vaccine non- or hypo-responsiveness in the babies of HBsAg-positive mothers [OR =0.25 (95% CI: 0.11-0.58)], and this association remained significant after accounting for maternal factors, such as HBeAg and HBV DNA, as well as infant cytokines, including IL-6, IL-12, TNF-α, IFN-α, and IFN-γ [OR =0.15 (95% CI: 0.05-0.44)]. Conclusions: Decreased placental TLR3 expression is associated with impaired responsiveness to HBV vaccination in babies born to HBsAg-positive mothers.
ABSTRACT
OBJECT: To identify the expression levels of ECT2 (epithelial cell transforming sequence 2) in triple-negative breast cancer (TNBC) before and after administration of paclitaxel (PTX) and explore the interaction between ECT2 and PTX in breast cancer treatment. METHODS: Lentiviral (LV) packaging ECT2 overexpression and interference plasmids were constructed for in vitro assays. The effects of ECT2 expression on the TNBC cell line (HCC1806), particularly its roles in the proliferation, invasion, migration and apoptosis and cell cycle, were evaluated using the CCK-8 and other methods before and after PTX treatment. In nude mouse xenograft settings were performed to detect cell apoptosis and Ki-67 expression levels by TUNEL and immunohistochemical staining, respectively. RESULTS: In the vitro assays, before and after the PTX treatment, comparison of the LV-ECT2 and sh-ECT2 groups and the remaining three groups (control, LV-NC, sh-NC) showed statistically significant differences in terms of cell proliferation, invasion and migration and apoptosis and changes in the cell cycle. In the vivo assays, the control, LV-ECT2 and sh-ECT2 groups markedly outweighed the corresponding PTX-treated groups. The LV-ECT2, PTX, sh-ECT2 and sh-ECT2-PTX were all significantly different from the control group in terms of body weight and tumour size changes. Cell apoptosis occurred in the PTX, sh-ECT2 and sh-ECT2-PTX groups. About the Ki-67 proliferation index, the PTX, LV-ECT2-PTX, sh-ECT2 and sh-ECT2-PTX groups were significantly different from the control group. CONCLUSION: ECT2, which is a major driving factor in the growth of breast cancer cells, plays an important role in regulating TNBC growth. PTX therapy had significantly improved efficacy after silencing ECT2. This finding indicates that the inhibition of ECT2 expression may facilitate the treatment of breast cancer as a new regimen and provide a theoretical basis for the development of new targeted drugs as a replacement for PTX in breast cancer treatment.
ABSTRACT
OBJECTIVE: Yes-associated protein (YAP) was defined as a candidate oncogene in multiple cancers. Yet, the role of YAP in cervical cancer is largely unknown. The aim of this study was to determine whether YAP could be used as a predictive biomarker in cervical precancerous lesions. METHODS: Immunohistochemical analysis of YAP expression was performed in 10 chronic cervicitis, 49 cervical intraepithelial neoplasia (CIN) 1, 55 CIN 2, 34 CIN 3, and 32 cervical squamous cell carcinoma (SCC) samples. Human papillomavirus (HPV) was detected by HPV genotype detection kit in 70 cases including 10 chronic cervicitis cases, 13 CIN 1 cases, 19 CIN 2 cases, 14 CIN 3 cases, and 14 SCC cases. Furthermore, the relationship between YAP expression and HPV integration status was analyzed using Spearman rank correlation coefficient test. RESULT: Samples of chronic cervicitis had negative or weak expression of YAP in cytoplasm. In the CIN 1 group, YAP expression was primarily confined to the lower third part of squamous epithelia or basal layer, whereas higher-grade CIN (2 and 3) and SCC groups had a strong nuclear expression of YAP. The expression levels of YAP in chronic cervicitis and CIN 1 were significantly lower compared to those in higher-grade CIN and SCC. Moreover, YAP expression was correlated with HPV integration status. Most high-risk HPV(+)/YAP(+) cases were found in the CIN 3 and SCC groups. CONCLUSION: This study suggested that YAP could function as a predictive marker in CIN and cervical cancer. YAP expression, in combination of HPV, might facilitate the identification of precancerous cervical lesions.
