Immunogenicity noninferiority study of 2 doses and 3 doses of an Escherichia coli-produced HPV bivalent vaccine in girls vs. 3 doses in young women.

A new HPV-16/18 bivalent vaccine expressed by the Escherichia coli has been proven to be efficacious in adult women. A randomized, immunogenicity noninferiority study of this candidate vaccine was conducted in December 2015 in China. Girls aged 9-14 years were randomized to receive 2 doses at months 0 and 6 (n=301) or 3 doses at months 0, 1 and 6 (n=304). Girls aged 15-17 years (n=149) and women aged 18-26 years (n=225) received 3 doses. The objectives included noninferiority analysis of the IgG geometric mean concentration (GMC) ratio (95% CI, lower bound>0.5) to HPV-16 and HPV-18 at month 7 in girls compared with women. In the per-protocol set, the GMC ratio of IgG was noninferior for girls aged 9-17 years receiving 3 doses compared with women (1.76 (95% CI, 1.56, 1.99) for HPV-16 and 1.93 (95% CI, 1.69, 2.21) for HPV-18) and noninferior for girls aged 9-14 years receiving 2 doses compared with women (1.45 (95% CI, 1.25, 1.62) for HPV-16 and 1.17 (95% CI, 1.02, 1.33) for HPV-18). Noninferiority was also demonstrated for neutralizing antibodies. The immunogenicity of the HPV vaccine in girls receiving 3 or 2 doses was noninferior compared with that in young adult women.

MiR-324-5p reduces viability and induces apoptosis in gastric cancer cells through modulating TSPAN8.

OBJECTIVES: The purpose of this study was to further clarify the role and underlying mechanism of miR-324-5p in gastric cancer. METHODS: The expressions of miR-324-5p and TSPAN8 as determined by qRT-PCR or Western blot were compared between the gastric cancer tissues and normal tissues. Human gastric cancer cell line SGC-7901 was cultured and transfected with miR-324-5p mimic/inhibitor or pcDNA-TSPAN8. The cell survival was assessed by the cell viability and apoptosis. Luciferase reporter gene assays were performed to explore the interaction between miR-324-5p and TSPAN8 in SGC-7901 cells. KEY FINDINGS: MiR-324-5p was decreased in human gastric carcinoma tissues (n = 33), but TSPAN8 protein expression was increased in the gastric carcinoma tissues (n = 33). Moreover, miR-324-5p inhibited the viability and induced the apoptosis of gastric cancer cells in vitro. TSPAN8 is a functional target of miR-324-5p in gastric cancer. MiR-324-5p was further confirmed to reduce gastric cancer cell viability and induce apoptosis via downregulating TSPAN8 in SGC-7901 cells in vitro. Additionally, miR-324-5p overexpression markedly inhibited the tumorigenesis of gastric cancer cells in vivo, as shown by the smaller tumour volume compared with the control. CONCLUSIONS: This study suggested a novel, probable mechanism of miR-324-5p in gastric cancer context and revealed that miR-324-5p inhibited gastric cancer cell survival by targeting TSPAN8.

S-adenosylmethionine inhibits the activated phenotype of human hepatic stellate cells via Rac1 and matrix metalloproteinases.

OBJECTIVE: To investigate the effects of S-adenosylmethionine (SAM) on the proliferation, adhesion, migration, invasion and apoptosis of activated human hepatic stellate cells (HSCs) and to explore the relevant potential mechanisms. METHODS: Human HSCs LX-2 were cultured with SAM. The proliferation and adhesion were detected by CCK-8. Cell apoptosis rate were analyzed by flow cytometry, and cell migration and invasion were tested by the transwell assay. The expression of Rac1 and MMP-2 was identified by real-time PCR or Western blotting, and activated Rac1 was detected by GST pull-down assay. The activity of MMP-2 and MMP-9 was analyzed by substrate zymography. RESULTS: The proliferation of LX-2 cells was inhibited by SAM, exhibiting a dose-dependent manner. Cell apoptosis rate induced by SAM was remarkably increased. SAM decreased the adhesion, migration and invasion of LX-2 cells. The expression and activation of Rac1 in LX-2 cells were significantly suppressed by SAM. In contrast, the activity of MMP-2 and MMP-9 was enhanced by SAM. SAM attenuated the up-regulated expression of Smad3/4 and Rac1 induced by TGF-ß1. CONCLUSION: SAM inhibits the proliferation, adhesion, migration and invasion of LX-2 cells in vitro probably via attenuating the expression and activation of Rac1 and up-regulating MMP-2 and MMP-9 expression, which possibly provide a molecular basis for potential application of SAM in the therapy of liver fibrosis.