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Transcript
Microbial and Biofunctional Biotechnology for the Benefit of
Human Health
I have always interested in application of bacteria to human health since I
started to study in field of life science. First, I have started research with bacteria and
its bacteriphages and then extended my research to natural functional materials.
The aim of this study is to establish the integrase database of temperate
phage from various samples and to determine the site-specific recombination
mechanism. A vector system based on the site-specific recombination apparatus of
temperate bacteriophage EFC1 was constructed. The vector we constructed which
included attP site and the integrase, could integrate into the , can be recombined two
short DNA sequences that are called attP and attB site on chromosomal DNA of
human cell. Among the isolated bacteriophages, the EFC1 integrase-mediated sitespecific recombination system can very useful tool for gene therapy and gene
delivery system in human cells. Also, Phages entering eukaryotic hosts are
considered as a highly immunogenic foreign antigen which could interact with the
innate immune system.
we also examined whether ES-II and ESP-2949 phages can influence
surface molecule expression, cytokine production, and their underlying signaling
pathways in murine bone marrow-derived DCs. The bacteriophage ESP2949-1 is a
lytic phage of Cronobacter sakazakii which has been isolated from sewage samples.
To evaluate its therapeutic effect, the production of the proinflammatory cytokines
TNF-α, IL-6, IL-1α, and IL-1β, the expression of the dendritic cell maturation markers
CD86 and CD40, and the underlying of NF-κB signaling pathways in murine bone
marrow-derived dendritic cells (BM-DCs) in response to ESP2949-1 phage infection
were studied. The bacteriophage ESP2949-1 affected the expression of the cell
surface molecules and proinflammatory cytokines that are related with the DC
maturation processes. Treatment with ESP2949-1 phage also induced the NF-κBIL12p40 signaling pathways. Our chromatin immunoprecipitation assay(ChIP)
showed that p65 could bind the IL12-p40 promoter via translocation to the nucleus
which indicates the activation of NF-κB signaling. Furthermore, the ESP2949-1
phage induced the promoter activity of IL-12p40. Our ChIP assay also revealed that
p65 was enriched at the IL12-p40 promoter as a direct target of chromatin. The
present study demonstrates that the ESP2949-1 phage potently induces DC
maturation via immune-enhancement processes.
I also have interested in function of glycosylation, polysaccharides and fuctional
materials. O-linked N-acetylglucosamine (O-GlcNAc), a monosaccharide Nacetylglucosamine on the serine and threonine residues of nucleocytoplasmic
proteins, regulates cooperative binding of Sp1 and its collaborating transcription
fators,Oct1 and Elf-1 onto DNA templates in vivo.
As well as thermoprotection of Sp1
Natural pigments have bio-functional properties, which are antioxidant, antiinflammatory and anticancer activities. The β-glucan, anthocyanin, astaxanthin,
genipin and shikonin were isolated from yeasts and natural materials. The pigments
protect the rat gastric mucosa by its ability to increase the activities of free radical
scavenging enzymes such as SOD, CAT, and GPx in the mucosa.
The Natural pigments also have many applications in inflammatory, and
oxidative related damage as well as in cancer chemotherapy. Recently, precise
cellular roles of natural pigments, such as modulator of key cellular signaling
pathway on variety diseases, are elucidated. On based on antioxidant, anthocyanins
reduced naproxen-induced gastric ulcer. Anthocyanins reduced the level of lipid
peroxidation and increased the level of the antioxidant enzymes. Anthocyanins
increased the expression of Nuclear factor E2-related factor 2 (Nrf2) which is
transactivator for cellular defense genes. Interestingly, anthocyanins induced
gastrointestinal-glutathione peroxidase expression via Nrf2 that bind to regions of
antioxidant response element (ARE) in GI-GPX promoter. Otherwise, Shikonin, and
genipin stimulates production reactive oxygen species (ROS) in gastric cancer cells.
They induced apoptotic cell death in gastric cancer cells in a caspase dependent
manner. They also induced cell cycle arrest at G2/M phase via regulation of p21 by
early growth response1 (Egr1). The p21 contains promoter region of Egr1 binding
motif. Transient expression of Egr1 in AGS cells enhanced shikonin and genipin-
induced p21 promoter activity, whereas suppression of Egr1 expression by small
interfering RNA attenuated the ability of shikonin and genipin induced p21 promoter
activity. Anthocyanins improve gastric ulceration through Nrf2 associated with
antioxidant enzymes, such as GI-Gpx pathways. And, shikonin and genipin induced
cell damage in AGS cells through the Egr1/p21 pathways.