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( Kyo Eun Kook ),( Changhee Kim ),( Wonku Kang ),( Jae-kwan Hwang ) 한국미생물생명공학회(구 한국산업미생물학회) 2018 Journal of microbiology and biotechnology Vol.28 No.10
Periodontitis, which is a severe inflammatory disease caused by endotoxins secreted from oral pathogens, destructs gingival tissue and alveolar bone. Curcuma xanthorrhiza, commonly called Java turmeric, has been shown to possess anti-bacterial and anti-inflammatory activities. The present study evaluated the inhibitory effect of C. xanthorrhiza supercritical extract (CXS) standardized with xanthorrhizol on lipopolysaccharide (LPS)-induced periodontitis in an animal model. LPS was topically injected into the periodontium of Sprague-Dawley rats to induce periodontitis and CXS (30 and 100 mg·kg<sup>-1</sup>·day<sup>-1</sup>) was orally administered after day 12. Histologically, CXS inhibited the collapse of gingival tissue by preventing cell infiltration. CXS significantly downregulated the expression of matrix metalloproteases (MMPs) and inflammation-related biomarkers, such as nuclear factor-kappa B (NF-κB) and interleukin-1 beta (IL-1β) in gingival tissue. CXS also improved bone remodeling by downregulating osteoclastic transcription factors, such as nuclear factor of activated T-cells c1 (NFATc1), tartrate-resistant acid phosphatase (TRAP), and cathepsin K. In addition, CXS upregulated osteoblast differentiation-related markers, alkaline phosphate (ALP) and collagen type I alpha (COLA1). Thus, CXS can ameliorate periodontitis by inhibiting inflammation and improving bone remodeling.
Analysis of porcine macrophage immune response to antigenic molecules and short chain fatty acids
Na-Eun Han,Eun-Joo Lee,Kwan-Sik Park,In-Sook Jeon,Hak-Kyo Lee,Ki-Duk Song,Joong-Kook Choi 충북대학교 동물의학연구소 2015 Journal of Biomedical and Translational Research Vol.16 No.2
Macrophages play an important role in both the innate and adaptive immune responses. These include phagocytosis, killing of microorganisms, antigen presentation, and induction of immune cytokines and antimicrobial genes. Macrophage activity is reported to be controlled by diverse exogenous antigenic or endogenous metabolic molecules, and the underlying mechanisms are well documented in human and mouse macrophage cells. Bacterial lipopolysaccharide (LPS) is known to be one of the most potent stimuli activating macrophages through the toll like receptor 4 (TLR4) signaling pathway. There are other antigenic molecules, such as muramyl dipeptide (MDP) and outer membrane protein A (OmpA), that are also known to activate immune cells. On the other hand, short chain fatty acids (SCFAs) such as acetate and butyrate are produced by gut microbiota and control host energy metabolism and signal transduction through GPR receptors. However, there are few studies demonstrating the effects of these molecules in macrophages from domestic animals, including domestic pigs. In this study, we attempted to characterize gene expression regulation in porcine macrophages (PoM2, Pig Monocytes clone 2) following treatment with LPS, MDP, OmpA, and two short chain fatty acids using porcine genome microarray and RT-PCR techniques. A number of novel porcine genes, including anti-microbial peptides and others, appeared to be regulated at the transcriptional level. Our study reports novel biomarkers such as SLC37A2, TMEN184C, and LEAP2 that are involved in the porcine immune response to bacterial antigen LPS and two short chain fatty acids.
Synthesis and Antiviral Activity of Novel Exomethylene Cyclopropyl Pyrimidine Nucleosides
Kook, Min Chul,Kim, Gu,Kwak, Eun Yee,Hong, Joon Hee,Lee, Chong Kyo,Choi, Bo Gil 전남대학교 약품개발연구소 2002 약품개발연구지 Vol.11 No.-
A series of novel exomethylene cyclopyl nucleosides have been synthesized starting from Feist's acid. Classical nucleophilic substitution condition (K_2CO_3, 18-crown-6) of the tosylate 2 as well as Mitsunobu reaction (DEAD, PPh_3) of alcohol 1 with pyrimidine bases afforded a series of novel cyclopropyl nucleosides. Compound 4b displayed moderate anti-HBV activity without any cytotoxicity up to 100㎛.
Synthesis and Antiviral Activity of Novel Exomethylene Cyclopropyl Pyrimidine Nucleosides
Kook, Min-Chul,Kim, Gu,Kwak, Eun-Yee,Hong, Joon-Hee,Lee, Chong-Kyo,Choi, Bo-Gil The Pharmaceutical Society of Korea 2002 Archives of Pharmacal Research Vol.25 No.6
A series of novel exomethylene cyclopropyl nucleosides have been synthesized starting from Feist's acid. Classical nucleophilic substitution conditions ($K_2CO_3$, 18-crown-6) of the tosylate 2 as well as Mitsunobu reaction (DEAD, $PPh_3$) of alcohol 1 with pyrimidine bases afforded a series of novel cyclopropyl nucleosides. Compound 4b displayed moderate anti-HBV activity without any cytotoxicity up to $100{\;}{\mu}M$.
Effect of severe neonatal morbidities on long term outcome in extremely low birthweight infants
Koo, Kyo-Yeon,Kim, Jeong-Eun,Lee, Soon-Min,NamGung, Ran,Park, Min-Soo,Park, Kook-In,Lee, Chul The Korean Pediatric Society 2010 Clinical and Experimental Pediatrics (CEP) Vol.53 No.6
Purpose: To assess the validity of individual and combined prognostic effects of severe bronchopulmonary dysplasia (BPD), brain injury, retinopathy of prematurity (ROP), and parenteral nutrition associated cholestasis(PNAC). Methods: We retrospectively analyzed the medical records of 80 extremely low birthweight (ELBW) infants admitted to the neonatal intensive care unit (NICU) of the Severance Children's Hospital, and who survived to a postmenstrual age of 36 weeks. We analyzed the relationship between 4 neonatal morbidities (severe BPD, severe brain injury, severe ROP, and severe PNAC) and poor outcome. Poor outcome indicated death after a postmenstrual age of 36 weeks or survival with neurosensory impairment (cerebral palsy, delayed development, hearing loss, or blindness) between 18 and 24 months of corrected age. Results: Each neonatal morbidity correlated with poor outcome on univariate analysis. Multiple logistic regression analysis revealed that the odds ratios (OR) were 4.9 (95% confidence interval [CI], 1.0-22.6; $P$=0.044) for severe BPD, 13.2 (3.0-57.3; $P$<.001) for severe brain injury, 5.3 (1.6-18.1; $P$=0.007) for severe ROP, and 3.4 (0.5-22.7; $P$=0.215) for severe PNAC. Severe BPD, brain injury, and ROP were significantly correlated with poor outcome, but not severe PNAC. By increasing the morbidity count, the rate of poor outcome was significantly increased (OR 5.2; 95% CI, 2.2-11.9; $P$<.001). In infants free of the above-mentioned morbidities, the rate of poor outcome was 9%, while the corresponding rates in infants with 1, 2, and more than 3 neonatal morbidities were 46%, 69%, and 100%, respectively. Conclusion: In ELBW infants 3 common neonatal mornidifies, severe BPD, brain injury and ROP, strongly predicts the risk of poor outcome.
Joong-Kook Choi,Eun-Ju Lee,Kwan-Sik Park,전인숙,Jae-Woon Choi,Sang Jeon Lee,Hyun E. Choy,Ki-Duk Song,Hak-Kyo Lee 한국분자세포생물학회 2016 Molecules and cells Vol.39 No.7
Lysosomes are cellular organelles containing diverse classes of catabolic enzymes that are implicated in diverse cellular processes including phagocytosis, autophagy, lipid transport, and aging. Lysosome-associated membrane proteins (LAMP-1 and LAMP-2) are major glycoproteins important for maintaining lysosomal integrity, pH, and catabolism. LAMP-1 and LAMP-2 are constitutively expressed in Salmonella-infected cells and are recruited to Salmonella-containing vacuoles (SCVs) as well as Salmonella-induced filaments (Sifs) that promote the survival and proliferation of the Salmonella. LAMP-3, also known as DC-LAMP/CD208, is a member of the LAMP family of proteins, but its role during Salmonella infection remains unclear. DNA microarray analysis identified LAMP-3 as one of the genes responding to LPS stimulation in THP-1 macrophage cells. Subsequent analyses reveal that LPS and Salmonella induced the expression of LAMP-3 at both the transcriptional and translational levels. Confocal Super resolution N-SIM imaging revealed that LAMP-3, like LAMP-2, shifts its localization from the cell surface to alongside Salmonella. Knock-down of LAMP-3 by specific siRNAs decreased the number of Salmonella recovered from the infected cells. Therefore, we conclude that LAMP-3 is induced by Salmonella infection and recruited to the Salmonella pathogen for intracellular proliferation.
Lee, Eun-Ju,Park, Kwan-Sik,Jeon, In-Sook,Cho, Jae-Woon,Lee, Sang-Jeon,Choy, Hyun E.,Song, Ki-Duk,Lee, Hak-Kyo,Choi, Joong-Kook Korean Society for Molecular and Cellular Biology 2016 Molecules and cells Vol.39 No.7
Lysosomes are cellular organelles containing diverse classes of catabolic enzymes that are implicated in diverse cellular processes including phagocytosis, autophagy, lipid transport, and aging. Lysosome-associated membrane proteins (LAMP-1 and LAMP-2) are major glycoproteins important for maintaining lysosomal integrity, pH, and catabolism. LAMP-1 and LAMP-2 are constitutively expressed in Salmonella-infected cells and are recruited to Salmonella-containing vacuoles (SCVs) as well as Salmonella- induced filaments (Sifs) that promote the survival and proliferation of the Salmonella. LAMP-3, also known as DC-LAMP/CD208, is a member of the LAMP family of proteins, but its role during Salmonella infection remains unclear. DNA microarray analysis identified LAMP-3 as one of the genes responding to LPS stimulation in THP-1 macrophage cells. Subsequent analyses reveal that LPS and Salmonella induced the expression of LAMP-3 at both the transcriptional and translational levels. Confocal Super resolution N-SIM imaging revealed that LAMP-3, like LAMP-2, shifts its localization from the cell surface to alongside Salmonella. Knockdown of LAMP-3 by specific siRNAs decreased the number of Salmonella recovered from the infected cells. Therefore, we conclude that LAMP-3 is induced by Salmonella infection and recruited to the Salmonella pathogen for intracellular proliferation.
( Siyeon Kim ),( Kyo Eun Kook ),( Changhee Kim ),( Jae-kwan Hwang ) 한국미생물생명공학회(구 한국산업미생물학회) 2018 Journal of microbiology and biotechnology Vol.28 No.8
Periodontal disease is triggered by the host immune response to pathogens in the microbial biofilm. Worsening of periodontal disease destroys the tooth-supporting tissues and alveolar bone. As oral inflammation can induce systemic diseases in humans, it is important to prevent periodontal disease. In this study, we demonstrated that Curcuma xanthorrhiza supercritical extract (CXS) and its active compound, xanthorrhizol (XAN), exhibit anti-inflammatory effects on lipopolysaccharide (LPS)-treated human gingival fibroblast-1 cells and anti-osteoclastic effects on receptor activator of nuclear factor kappa B ligand (RANKL)-treated RAW264.7 cells. LPS-upregulated inflammatory factors, such as nuclear factor kappa B p65 and interleukin-1β, were prominently reduced by CXS and XAN. In addition, RANKL-induced osteoclastic factors, such as nuclear factor of activated T-cells c1, tartrate-resistant acid phosphatase, and cathepsin K, were decreased in the presence of CXS and XAN. CXS and XAN inhibited the mitogen-activated protein kinase (MAPK)/activator protein-1 (AP-1) signaling pathway. Collectively, these results provide evidence that CXS and XAN suppress LPS-induced inflammation and RANKL-induced osteoclastogenesis by suppressing the MAPK/AP-1 pathway.
Identification of Osteogenic Purmorphamine Derivatives.
Lee, Sung-Jin,Lee, Hak-Kyo,Cho, Sung Yun,Choi, Joong-Kwon,Shin, Hea Kyeong,Kwak, Eun-Jung,Cho, Mi-Ran,Kim, Hye-Ryun,Kim, Seung-Ryol,Kim, Yong-Min,Park, Kyoung-Jin,Choi, Joong-Kook Korean Society for Molecular Biology 2008 Molecules and cells Vol.26 No.4
<P>During embryonic and cancer development, the Hedgehog family of proteins, including Sonic Hedgehog, play an important role by relieving the inhibition of Smo by Ptc, thus activating the Smo signaling cascade. Recently, a purine compound, purmorphamine, has been reported to target the Hedgehog signaling pathway by interacting with Smo. Interestingly, both Sonic Hedgehog and purmorphamine were found to promote the osteogenic differentiation of mouse chondroprogenitor cells. However, there is insufficient information as to how the activation of this seemingly unrelated signaling pathway, either by Sonic Hedgehog or purmorphamine, contributes to osteogenesis. Using alkaline phosphatase assays, we screened 125 purmorphamine derivatives from the Korea Chemical Bank for effects on the differentiation of preosteoblast C2C12 cells. Here, we report that two purine derivatives modulate ALP activity as well as the expression of genes whose expression is known or suggested to be involved in osteogenesis.</P>