Interleukin-24 enhancing antitumor activity of chimeric oncolytic adenovirus for treating acute promyelocytic leukemia cell.

BACKGROUND: Acute promyelocytic leukaemia (APL) is a clonal disease arising by hematopoietic stem cell (HSC), which characterized by inappropriate proliferation/differentiation or survival of immature myeloid progenitors. Oncolytic adenoviruses have been under widespread investigation as anticancer agents. Recently, our data suggested that tumor cells were cured by AdCN205-IL-24, an adenovirus serotype 5-based conditionally replicating adenovirus expressing IL-24 after infection. METHODS: In this study, we created a novel fiber chimeric oncolytic adenovirus AdCN306-IL-24 that has Ad11 tropism and approved CAR (coxsackie adenovirus receptor, CAR)-independent cell entry, which could allow development of selective cytopathic effects (CPE) in APL cells in vitro. RESULTS: Formidable cytotoxic effect was specifically implemented in APL cells after infection with AdCN306-IL-24. The expression of IL-24 was up-regulated upon treated with accepted tumors. And the vector also induced superior cytolytic effects activity in APL cells by activation of programmed cell death. CONCLUSIONS: Taken together, our data suggested that chimeric oncolytic adenovirus AdCN306-IL-24 could express IL-24 gene, representing a potential therapeutics for acute promyelocytic leukemia.

Transposable Element Bm1645 is a Source of BmAGO2-associated Small RNAs that affect its expression in Bombyx mori.

BACKGROUND: A transposable element (TE) is a DNA fragment that can change its position within a genome. Transposable elements play important roles in maintaining the stability and diversity of organisms by transposition. Recent studies have shown that approximately half of the genes in Bombyx mori are TEs. RESULTS: We systematically identified and analyzed the BmAGO2-associated TEs, which exceed 100 in the B. mori genome. Additionally, we also mapped the small RNAs associated with BmAGO2 in B.mori. The transposon Bm1645 is the most abundant TE associated with BmAGO2, and Bm1645-derived small RNAs represent a small RNA pool. We determined the expression patterns of several Bm1645-derived small RNAs by northern blotting, and the results showed there was differential expression of multiple small RNAs in normal and BmNPV-infected BmN cells and silkworms from various developmental stages. We confirmed that four TE-siRNAs could bind to BmAGO2 using EMSA and also validated the recognition sites of these four TE-siRNAs in Bm1645 by dual-luciferase reporter assays. Furthermore, qRT-PCR analysis revealed the overexpression of the four TE-siRNAs could downregulate the expression of Bm1645 in BmN cells, and the transcription of Bm1645 was upregulated by the downregulation of BmAGO2. CONCLUSIONS: Our results suggest Bm1645 functions as a source of small RNAs pool and this pool can produce many BmAGO2-associated small RNAs that regulate TE's expression.

Serum miR-23a, a potential biomarker for diagnosis of pre-diabetes and type 2 diabetes.

MicroRNAs (miRNAs) play a crucial role in the pathogenesis of type 2 diabetes (T2D); they regulate several metabolic pathways including insulin secretion, glucose homeostasis, so their potential as biomarkers of diagnosis and prognosis has became increasingly appreciated. In this study, we explore serum miRNA profiles in T2D patients. A total of ten candidate miRNAs were identified by Solexa sequencing scanning and followed by a stem-loop quantitative reverse transcription PCR (qRT-PCR) to assess these candidate serum miRNAs. The results of qRT-PCR assessment revealed low serum levels of miR-23a, let-7i, miR-486, miR-96, miR-186, miR-191, miR-192, and miR-146a in T2D. Except for significantly lower in T2D and pre-diabetes patients compared with normal glucose tolerance (NGT) controls (P = 2.87E-05 and P = 3.75E-02), the levels of miR-23a demonstrated also significant decline in T2D patients compared with pre-diabetes patients (P = 1.06E-02). This marker yielded an AUC of 0.835 (95 % CI 0.717-0.954). At a cutoff value of 1.645, the sensitivity was 79.2 % and the specificity was 75.0 % in discriminating T2D patients from NGT normal controls. These results revealed that serum miR-23a was a valuable biomarker for early detection of T2D and pre-diabetes with NGT.