• Korean Circulation Journal
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• v.53 no.8
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• pp.499-518
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• 2023

Cardiovascular diseases (CVDs), including coronary artery disease, stroke, heart failure, and hypertension, are the global leading causes of death, accounting for more than 30% of deaths worldwide. Although the risk factors of CVDs have been well understood and various treatment and preventive measures have been established, the mortality rate and the financial burden of CVDs are expected to grow exponentially over time due to the changes in lifestyles and increasing life expectancies of the present generation. Recent advancements in metagenomics and metabolomics analysis have identified gut microbiome and its associated metabolites as potential risk factors for CVDs, suggesting the possibility of developing more effective novel therapeutic strategies against CVD. In addition, increasing evidence has demonstrated the alterations in the ratio of Firmicutes to Bacteroidetes and the imbalance of microbial-dependent metabolites, including short-chain fatty acids and trimethylamine N-oxide, play a crucial role in the pathogenesis of CVD. However, the exact mechanism of action remains undefined to this day. In this review, we focus on the compositional changes in the gut microbiome and its related metabolites in various CVDs. Moreover, the potential treatment and preventive strategies targeting the gut microbiome and its metabolites are discussed.

• Journal of Microbiology and Biotechnology
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• v.27 no.4
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• pp.709-717
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• 2017

Mucosal tissues are the initial site through which most pathogens invade. As such, vaccines and adjuvants that modulate mucosal immune functions have emerged as important agents for disease prevention. Herein, we investigated the immunomodulatory mechanisms of the B subunit of Escherichia coli heat-labile enterotoxin type IIa ($LT-IIa-B_5$), a potent non-toxic mucosal adjuvant. Alternations in gene expression in response to $LT-IIa-B_5$ were identified using a genome-wide transcriptional microarray that focused on dendritic cells (DC), a type of cell that broadly orchestrates adaptive and innate immune responses. We found that $LT-IIa-B_5$ enhanced the homing capacity of DC into the lymph nodes and selectively regulated transcription of pro-inflammatory cytokines, chemokines, and cytokine receptors. These data are consistent with a model in which directional activation and differentiation of immune cells by $LT-IIa-B_5$ serve as a critical mechanism whereby this potent adjuvant amplifies mucosal immunity to co-administered antigens.

• Biomedical Science Letters
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• v.20 no.1
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• pp.25-31
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• 2014

Atopic dermatitis (AD) is an inflammatory, relapsing, chronic skin disease and lesions in AD are frequently colonized with Staphylococcus aureus (S. aureus). Activation of T cells and IgE production by staphylococcal enterotoxins B (SEB) plays a crucial role in the pathogenesis of AD. Enterococcus faecalis (E. faecalis) is a nonpathogenic bacterium and produces the probiotic products that have been shown to have inhibitory effects on inflammatory responses. In present study, we carried out to assess the anti-inflammatory role of lyzed E. faecalis against the damaging effects of SEB on AD related immune responses. Furthermore, we attempted to determine whether the co-cultured lyzed E. faecalis can influence the colonization of S. aureus. As a result, we identified the effect of E. faecalis lysate as a potent therapeutic agent for atopic dermatitis (AD). E. faecalis lysate reduces the productions of total IgE and cytokines of AD-related immune cells in response to SEB stimulation. The proliferation of S. aureus was also inhibited by E. faecalis lysate. In conclusions, E. faecalis lysate may improve the skin-defense system disturbed by atopic condition, and may prevent subsequent secondary infection of S. aureus and development of AD.

• Proceedings of the Microbiological Society of Korea Conference
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• 2002.10a
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• pp.40-50
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• 2002

Fruit fly, Drosophila melanogaster has developed efficient immune mechanisms to prevent microbial infection, which are consisted of cellular and humoral responses. During the systemic or local infection, two distinct pathways (Toll and Imd) play major roles in antimicrobial peptide synthesis. The Toll pathway is required to defend Gram-positive bacterial and fungal infections, whereas the Imd pathway is important in Gram-negative bacterial infection. We have shown that the infection of the opportunistic Gram-negative bacterium, Pseudomonas aeruginosa strain PA14 (PA14) into fly dorsal thorax can kill the flies within 48 h ($100\%$ mortality) in our optimized infection condition, suggesting that the PA14 strain can cause disease progress in fly model system. We found that flies carrying a constitutively activated mutant form of the Toll receptor $(Tl^{10b})$ showed increased resistance to P. aeruginosa infection and that flies carrying mutations in the Toll signaling pathway as well as in the Imd signaling pathway was more susceptible to PA14 infection. All these results imply that the Toll pathway might be important in the resistance to this pathogenic Gram-negative bacterial infection.

• Journal of Sericultural and Entomological Science
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• v.40 no.2
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• pp.117-125
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• 1998

Entomopathogenic nematodes, Heterorhabditidae and Steinernematidae, were isolated from the soil of mulberry field, and the high infectivity and invesiveness were confirmed in the silkworm, Bombyx mori. The cause of non-microbial and acute flacherie was found as an disease by infection with soil-born nematodes through the mulberry leaves contaminated with soil and rainwater. The causal nematodes were isolated by silkworm trap from all of the 5 soil samples collected on the 5 mulberry fields, and identified as 3 strains of Heterorhabditis sp. and 2 of Steinernema sp. Rainwater itself, however, wasn't engaged in the silkworm disease, mulberry leaves with rainwater was rather profitable for cocoon production when the leaf quality was too hard to feed silkworm. Feeding of wet mulberry leaves with rain might not so harm to silkworm when the condition of rearing room to be kept at suitable temperature and ventilated well. Nematode infection of silkworm could be occurred by harvesting and feeding of contaminated mulberry leaves on the weather condition of rainy and wind. For the prevention of nematode infection, silkworms should be fed the leaves harvested from the higher portion of the mulberry tree in rainy days. For an oppositional application of this susceptibility of silkworms to nematode, might be useful on the collection and amplification of nematode agents for biotic control of pest insects.

• Journal of Microbiology and Biotechnology
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• v.23 no.7
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• pp.885-896
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• 2013

2,3-Butanediol (2,3-BDO) has immense industrial applications. Recently, microbial fermentation has emerged as an alternative way to produce this industrially important chemical. Although 2,3-BDO is produced by several microorganisms, the Klebsiella genera has an excellent production compared with other 2,3-BDO-producing microorganisms. In order to produce 2,3-BDO on a large scale, the challenges of removing pathogenic factors from Klebsiella pneumoniae need to be addressed. K. pneumoniae produces a number of virulence factors that contribute to its pathogenesis, including lipopolysaccharides, capsules, fimbrial adhesins, etc. Removal of these pathogenic factors from 2,3-BDO-producing Klebsiella strains will result in avirulent strains for the safe, economic, and efficient production of 2,3-BDO. In this review, we summarize the current trends in 2,3-BDO production using K. pneumoniae and insights into the removal of its virulence factors for industrial applications.

• Journal of the Korean Chemical Society
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• v.50 no.2
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• pp.123-128
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• 2006

Behcet's disease (BD) is a systemic vasculitis characterized by recurrent oral and genital ulcers, and ocular inflammation, and which may involve the joints, skin, central nervous system and gastrointestinal tract. Although the exact pathogenesis for BD is not completely understood, it has been suggested that the disease is triggered in genetically susceptible individuals by environmental factors, such as microbial agents. It is noted that multiple genes, including MHC (major histocompatibility complex) and non-MHC genes, are implicated in the pathogenesis of BD. This study tries to determine whether IL-6 gene polymorphisms are associated with susceptibility to Behcet's disease in Koreans. Gene polymorphisms were typed by VNTR (variable number of tandem repeat), RFLP (restriction fragment length polymorphism), DHPLC (denaturing high performance liquid chromatography).There were no evidences for genetic association conferred by the IL-6prom polymorphism. However, significant differences in the IL-6vntr genotype and allele frequencies were found between patients with BD and controls. The IL-6vntr*C allele appeared to be an additional susceptibility gene to Korean BD. Further studies in other populations and gene are required to confirm these results.

• Journal of Microbiology and Biotechnology
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• v.15 no.6
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• pp.1337-1345
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• 2005

Vibrio vulnificus is the causative agent of foodborne diseases such as gastroenteritis and life-threatening septicemia. Microbial pathogenicity is a complex phenomenon in which expression of numerous virulence factors is frequently controlled by a common regulatory system. In the present study, a mutant exhibiting decreased cytotoxic activity toward intestinal epithelial cells was screened from a library of V. vulnificus mutants constructed by a random transposon mutagenesis. By a transposon-tagging method, an open reading frame, fexA, a homologue of Escherichia coli areA, was identified and cloned. The nucleotide and deduced amino acid sequences of the fexA were analyzed, and the amino acid sequence of FexA from V. vulnificus was $84\%\;to\;97\%$ similar to those of AreA, an aerobic respiration control global regulator, from other Enterobacteriaceae. Functions of the FexA were assessed by the construction of an isogenic mutant, whose fexA gene was inactivated by allelic exchanges, and by evaluating its phenotype changes in vitro and in mice. The disruption of fexA resulted in a significant alteration in growth rate under aerobic as well as anaerobic conditions. When compared to the wild-type, the fexA mutant exhibited a substantial decrease in motility and cytotoxicity toward intestinal epithelial cell lines in vitro. Furthermore, the intraperitoneal $LD_{50}$ of the fexA mutant was approximately $10^{1}-10^{2}$ times higher than that of parental wild-type. Therefore, it appears that FexA is a novel global regulator controlling numerous genes and contributing to the pathogenesis as well as growth of V. vulnificus.

• Journal of Microbiology and Biotechnology
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• v.13 no.5
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• pp.809-814
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• 2003

${\beta}-amyloid$ ($A{\beta}$) peptides from the proteolytic processing of ${\beta}-amyloid$ precursor protein (${\beta}-APP$) aggregates in the brain to form senile plaques, and their aggregation plays a key role in pathogenesis of Alzheimer's disease (AD). To isolate an active compound that has an $A{\beta}$ aggregation-inhibitory activity, 2,000 microbial metabolite libraries were screened based on their ability to inhibit $A{\beta}$ aggregation by using both Congo red and thioflavin T assays. As a result, a water-soluble fraction of a soil microorganism, KK565, showed a potent $A{\beta}$ aggregation-inhibitory activity. The strain was identified as Streptomyces species, based on the cultural and morphological characteristics, the presence of diaminopimelic acid in the cell wall, and the sugar patterns for the whole-cell extract. In addition, the purification of active principle resulted in identifying a heat-unstable protein responsible for the $A{\beta}$ aggregation-inhibitory activity.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.11a
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• pp.69-80
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• 1994

Although ureases play important roles in microbial nitrogen metabolism and in the pathogenesis of several human diseases, little is known of the mechanism of metallocenter biosynthesis in this Ni-Containing enzyme. Klebsiella aerogenes urease apo-protein was purified from cells grown in the absence of Ni. The purified apo-enzyme showed the same native molecular weight, charge, and subunit stoichiometry as the holo-enzyme. Chemical modification studies were consistent with histidinyl ligation of Ni. Apo-enzyme could not be activated by simple addition of Ni ions suggesting a requirement for a cellular factor. Deletion analysis showed that four accessory genes (ureD, ureE, ureF, and ureG) are necessary for the functional incorporation of the urease metallocenter. Whereas the $\Delta$ureD, $\Delta$ureF, and $\Delta$ureG mutants are inactive and their ureases lack Ni, the $\Delta$ureE mutants retain partial activity and their ureases possess corresponding lower levels of Ni. UreE and UreG peptides were identified by SDS-polyacrylamide gel comparisons of mutant and wild type cells and by N-terminal sequencing. UreD and UreF peptides, which are synthesized at ve교 low levels, were identified by using in vitro transcription/translation methods. Cotransformation of E. coli cells with the complementing plasmids confirmed that ureD and ureF gene products act in trans. UreE was purified and characterized. immunogold electron microscopic studies were used to localize UreE to the cytoplasm. Equilibrium dialysis studies of purified UreE with $^{63}$ NiC1$_2$ showed that it binds ～6 Ni in a specific manner with a $K_{d}$ of 9.6 $\pm$1.3 $\mu$M. Results from spectroscopic studies demonstrated that Ni ions are ligated by 5 histidinyl residues and a sixth N or O atom, consistent with participation of the polyhistidine tail at the carboxyl termini of the dimeric UreE in Ni binding. With these results and other known features of the urease-related gene products, a model for urease metallocenter biosynthesis is proposed in which UreE binds Ni and acts as a Ni donor to the urease apo-protein while UreG binds ATP and couples its Hydrolysis to the Ni incorporation process.ouples its Hydrolysis to the Ni incorporation process.s.