A novel multi-epitope vaccine of HPV16 E5E6E7 oncoprotein delivered by HBc VLPs induced efficient prophylactic and therapeutic antitumor immunity in tumor mice model.

Human papilloma virus type 16 (HPV16) is the most prevalent etiologic agent associated with cervical cancer, and its early proteins E5, E6 and E7 play important roles in cervical epithelium transformation to cervical intraepithelial neoplasia and even cervical cancer. Hence, these oncoproteins are ideal target antigens for developing immunotherapeutic vaccines against HPV-associated infection and cervical cancer. Currently, multi-epitope vaccines have been a promising strategy for immunotherapy for viral infection or cancers. In this study, the E5aa28-46, E6aa37-57 and E7aa26-57 peptides were selected and linked to form a novel multi-epitopes vaccine (E765m), which was inserted into the major immune dominant region (MIR) of hepatitis B virus core antigen (HBc) to construct a HBc-E765m chimeric virus-like particles (cVLPs). The immunogenicity and immunotherapeutic effect of the cVLPs vaccine was evaluated in immunized mice and a tumor-bearing mouse model. The results showed that HBc-E765m cVLPs elicited high E5-, E6- and E7- specific CTL and serum IgG antibody responses, and also relatively high levels of the cytokines IFN-γ, IL-4 and IL-5. More importantly, the cVLPs vaccine significant suppressed tumor growth in mice bearing E5-TC-1 tumors. Our findings provide strong evidence that this novel HBc-E765m cVLPs vaccine could be a candidate vaccine for specific immunotherapy in HPV16-associated cervical intraepithelial neoplasia or cervical cancer.

Clinical effect of the extract of TCM Fructus akebiae combined with ursodeoxycholic acid on nonalcoholic fatty liver disease.

.Fructus akebiae extract (FAE) is a commonly used drug in the clinical treatment of liver cancer. FAE has many pharmacological activities, such as liver protection, anti-tumor, spasmolysis, pain relief and antifungal activity. Its clinical application is extensive, so far no toxic reports have been reported, and new drugs can be developed. This study was designed to investigate the therapeutic effect of predictor extract on non-alcoholic fatty liver disease (NAFLD). 180 patients with NAFLD were randomly divided into 2 groups. The control group was treated with ursodeoxycholic acid (UDCA), and the experimental group was treated with Fructus akebiae extract combined with ursodeoxycholic acid. The results showed that the comprehensive clinical efficacy of the treatment group was 95.56%, which was higher than that of the control group (93.33%), and P < 0.01. In the experimental group, 63 cases (70%) were improved after one course of treatment, main symptom score as (5.09 ±3.98), body mass index as (24.65±3.86), and liver CT value increased. It can be seen that the addition of FAE can significantly improve the clinical symptoms and serum biochemical indicators such as ALT, AST, TG and TC in patients with non-alcoholic fatty liver disease, which is supported by some histological evidence. These findings suggest that FAE combined with Ursodeoxycholic Acid is safe and effective in the treatment of fatty liver.

A heading date QTL, qHD7.2, from wild rice (Oryza rufipogon) delays flowering and shortens panicle length under long-day conditions.

Heading date (HD) and panicle length (PL) are important traits that affect rice breeding and are controlled by pleiotropic genes. Some alleles associated with HD and PL from wild relatives might differ from those in cultivated rice. In this study, a main effect HD quantitative trait locus from wild rice, qHD7.2, was identified using a chromosomal segment substitution line (CSSL) population. First, qHD7.2 was determined to be located near RM172 on chromosome 7 based on association analysis of phenotype data from six environments and 181 polymorphic molecular markers. CSSL39, which has the latest flowering of all CSSLs and carries qHD7.2, was selected for further study, and qHD7.2 was narrowed to a 101.1-kb interval using a CSSL39/9311 F2 population. An OsPRR37-homologous gene was found within this region. The wild type allele delayed flowering and shortened PL under long-day conditions. The HD7.2, which was identified as a candidate gene for qHD7.2, transcript level was substantially higher than that in 9311. Our data showed that HD7.2 is likely a novel OsPRR37 allele. Sequence analysis revealed that OsPRR37 in cultivated rice had multiple origins, and natural variation in the coding domain sequence and promoter region contribute to flowering time diversity in cultivated rice.

Inferring the evolutionary mechanism of the chloroplast genome size by comparing whole-chloroplast genome sequences in seed plants.

The chloroplast genome originated from photosynthetic organisms and has retained the core genes that mainly encode components of photosynthesis. However, the causes of variations in chloroplast genome size in seed plants have only been thoroughly analyzed within small subsets of spermatophytes. In this study, we conducted the first comparative analysis on a large scale to examine the relationship between sequence characteristics and genome size in 272 seed plants based on cross-species and phylogenetic signal analysis. Our results showed that inverted repeat regions, large or small single copies, intergenic regions, and gene number can be attributed to the variations in chloroplast genome size among closely related species. However, chloroplast gene length underwent evolution affecting chloroplast genome size in seed plants irrespective of whether phylogenetic information was incorporated. Among chloroplast genes, atpA, accD and ycf1 account for 13% of the variation in genome size, and the average Ka/Ks values of homologous pairs of the three genes are larger than 1. The relationship between chloroplast genome size and gene length might be affected by selection during the evolution of spermatophytes. The variation in chloroplast genome size may influence energy generation and ecological strategy in seed plants.

Mutational spectrum of N-hydroxy-N-acetyl-4-aminobiphenyl at exon 3 of the HPRT gene.

4-Aminobiphenyl is a human bladder carcinogen present in many environmental sources, including cigarette smoke. It can be metabolized in two steps to the mutagen N-hydroxy-N-acetyl-4-aminobiphenyl (N-OH-AABP). In this study the mutational spectrum of N-OH-AABP-exposed human lymphoblastoid cells (TK6) was determined using HPRT.