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Summary Bacillus Calmette-Guerin (BCG) vaccines are attenuated live strains of Mycobacterium bovis and are among the most widely used vaccines in the world. BCG is proven effective in preventing severe infant meningitis and miliary tuberculosis. Intravesical instillation of BCG is also a standard treatment for non-muscle invasive bladder cancer. In the past few decades, recombinant BCG (rBCG) technology had been extensively applied to develop vaccine candidates against a variety of infectious diseases, including bacterial, viral, and parasite infections, and to improve the efficacy of BCG in bladder cancer therapy. This review is intended to show the vast applications of BCG and rBCG in prevention of infectious diseases and in cancer immunotherapy, with a special emphasis on recent approaches and trends on both pre-clinical and clinical levels.

During mammalian embryonic development, DNA methylation and histone modifications are important in gene expression regulation and epigenetic reprogramming. In cloned embryos, high levels of DNA methylation and abnormal demethylation were widely observed during the preimplantation period. Little is known whether there is a difference in histone modifications between in vitro fertilization (IVF) and cloned embryos during preimplantation development. In the present study, the distributions and intensity patterns of acetylations in H3 lysine 9, 18 and H4 lysine 8, 5 and tri-methyl lysine 4 and dimethyl-lysine 9 in histone H3 were compared in cloned and IVF bovine preimplantation embryos by using indirect immunofluorescence and scanning confocal microscopy. The results showed that the acetylation and methylation levels of H3K9ac, H3K18ac, H4K5ac, H4K8ac, H3K4me3 and H3K9me2 were abnormally high in the cloned embryos from the pronuclear to the 8-cell stage. H4K8ac and H4K5ac in the cloned embryos were particularly abnormal when compared with the IVF controls. At the blastocyst stage differences dissipated between cloned and IVF embryos and the distribution and intensity patterns of all histone modifications showed no obvious difference. These results suggest that somatic cells in recipient oocytes produced aberrant histone modifications at multiple sites before the donor cell genome is activated. After zygotic genome activation, distributions and intensity patterns of histone modifications were comparable with both cloned and IVF embryos.

BackgroundInterspecies somatic cell nuclear transfer (iSCNT) has been regarded as a potential alternative for rescuing highly endangered species and can be used as a model for studying nuclear–cytoplasmic interactions. However, iSCNT embryos often fail to produce viable offspring. The alterations in normal molecular mechanisms contributing to extremely poor development are for the most part unknown.ResultsPrzewalski’s gazelle–bovine iSCNT embryos (PBNT) were produced by transferring Przewalski’s gazelle fibroblast nuclei into enucleated bovine oocytes. The percentages of PBNT embryos that developed to morula/blastocyst stages were extremely low even with the use of various treatments that included different SCNT protocols and treatment of embryos with small molecules. Transcriptional microarray analyses of the cloned embryos showed that the upregulation of reprogramming-associated genes in bovine–bovine SCNT (BBNT) embryos was significantly higher than those observed in PBNT embryos (1527:643). In all, 139 transcripts related to various transcription regulation factors (TFs) were unsuccessfully activated in the iSCNT embryos. Maternal degradation profiles showed that 1515 genes were uniquely downregulated in the BBNT embryos, while 343 genes were downregulated in the PBNT embryos. Incompatibilities between mitochondrial DNA (mtDNA) and nuclear DNA revealed that the TOMM (translocase of outer mitochondrial membrane)/TIMM (translocase of inner mitochondrial membrane) complex-associated genes in BBNT embryos had the highest expression levels, while the PBNT embryos exhibited much lower expression rates.ConclusionsImproper degradation of maternal transcripts, incomplete activation of TFs and abnormal expression of genes associated with mitochondrial function in PBNT embryos likely contributed to incomplete reprogramming of the donor cell nuclei and therefore led to the developmental failure of these cloned embryos.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-1113) contains supplementary material, which is available to authorized users.