Wnt/β-catenin signaling pathway, having a crucial role in regulating diverse cellular processes, can be a new therapeutic target in cancer. To investigate the role of Dkk-1 (Dickkopf-1) and Dkk-3 in tumors and cirrhoses of the liver tissue in hepatocellular carcinoma (HCC), tissues from 38 patients with HCC resections including 5 patients who underwent hemangioma surgery of adjacent tumor tissues at the same time were obtained. Tissues were divided into three groups (nonfibrosis, cirrhosis, and carcinoma) through hematoxylin-eosin (HE) staining. Methylation-specific polymerase chain reaction (PCR) (MSP) measured the methylation status, and reverse transcription-PCR tested the messenger RNA (mRNA) levels, and immunohistochemical analysis provided levels of protein expression. The methylation detection rate of Dkk-1 and Dkk-3 was the highest (P < 0.05) and the mRNA levels of Dkk-1 and Dkk-3 were the lowest (P < 0.05) in the carcinoma tissues. The mRNA levels of β-catenin were significantly higher in the carcinoma tissue than the other tissues (P < 0.05). The expression of Dkk-1 and Dkk-3 was significantly higher in the carcinoma tissues than the other tissues (P < 0.05); but the β-catenin expression was the highest (P < 0.05). Compared with the control, the mRNA levels of β-catenin in the Dkk-1 and Dkk-3 silencing cells increased 5.34 (P < 0.05) and 3.5 times (P > 0.05). After the interference of 5-aza-2'-deoxycytidine, the mRNA levels of Dkk-1 and Dkk-3 significantly increased 58.9 and 59.3 times (P < 0.0001), and the mRNA levels of β-catenin decreased 6.02 times (P < 0.05). In the process of HCC, the abnormal activity of Wnt/β-catenin signaling may be associated with the methylation of Dkk-1 and Dkk-3.

Background: The well-known fact that avian pathogenic Escherichia coli (APEC) is harder to prevent due to its numerous serogroups has promoted the development of biological immunostimulatory materials as new vaccine candidates in poultry farms. Bacterial outer membrane vesicles (OMVs), known as spherical nanovesicles enriched with various immunostimulants, are naturally secreted by Gram-negative bacteria, and have gained much attention for developing effective vaccine candidates. Recent report has demonstrated that OMVs of APEC O78 can induce protective immunity in chickens. Here, a novel multi-serogroup OMVs (MOMVs) vaccine was developed to achieve cross-protection against APEC infection in broiler chickens. Results: In this study, OMVs produced by three APEC strains were isolated, purified and prepared into MOMVs by mixing these three OMVs. By using SDS-PAGE and LC-MS/MS, 159 proteins were identified in MOMVs and the subcellular location and biological functions of 20 most abundant proteins were analyzed. The immunogenicity of MOMVs was evaluated, and the results showed that MOMVs could elicit innate immune responses, including internalization by chicken macrophage and production of immunomodulatory cytokines. Vaccination with MOMVs induced specific broad-spectrum antibodies as well as Th1 and Th17 immune responses. The animal experiment has confirmed that immunization with an appropriate dose of MOMVs could not cause any adverse effect and was able to reduce bacteria loads and pro-inflammatory cytokines production, thus providing effective cross-protection against lethal infections induced by multi-serogroup APEC strains in chickens. Further experiments indicated that, although vesicular proteins were able to induce stronger protective efficiency than lipopolysaccharide, both vesicular proteins and lipopolysaccharide are crucial in MOMVs-mediated protection. Conclusions: The multi-serogroup nanovesicles produced by APEC strains will open up a new way for the development of next generation vaccines with low toxicity and broad protection in the treatment and control of APEC infection.

Folate metabolism plays an essential role in the processes of DNA synthesis and methylation. An aberrant folate metabolism caused by a genetic polymorphism may lead to genomic instability and affect the susceptibility to malignancies including acute lymphoblastic leukemia (ALL). This study was designed to explore the correlation between the polymorphisms in folate-related genes and the risk of ALL in Han Chinese. The DNA was isolated from 231 patients with pediatric ALL, 130 patients with adult ALL, and 367 healthy subjects (as controls). Polymorphisms were examined for RFC1 80G > A, DHFR 19 bp del/ins and 317A > G, SHMT1 1420C > T, MTHFR 677C > T and 1298A > C, MTR 2756A > G, MTRR 66A > G, TYMS 3R/2R, MTHFD1 1958G > A, and ABCG2 421G > T using real-time polymerase chain reaction (PCR) or PCR-restriction fragment length polymorphism (RFLP). The risk of adult ALL was increased by the RFC1 80AA variant (odds ratio [OR] = 2.09; 95% confidence interval [CI] 1.19-3.67) and MTRR 66GG variant (OR = 2.15; 95% CI 1.06-4.39) but reduced by the MTHFR 677TT variant (OR = 0.47; 95% CI 0.25-0.88), ABCG2 421GT variant (OR = 0.62; 95% CI 0.41-0.96), and ABCG2 421GT + TT variant (OR = 0.60; 95% CI 0.40-0.90). The increase in risk of adult ALL with the RFC1 80AA associated with the MTRR 66GG variant was even more significant (OR = 8.92; 95% CI 1.97-40.42). Furthermore, the MTHFR 677TT associated with the ABCG2 421GT + TT variant more significantly reduced the risk of adult ALL (OR = 0.32; 95% CI 0.12-0.85). However, all gene polymorphisms tested in this study failed to affect the pediatric ALL risk. Our study clearly demonstrates that polymorphisms in folate-related genes only modulate the susceptibility to adult ALL, but not to pediatric ALL, in Han Chinese.

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The incidence of thyroid carcinoma has obviously been rising throughout the world during the past ten years.