• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.355-362
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• 2014

Objective: Altered regulation of many transcription factors has been shown to play important roles in the development of leukemia. hMSH2 can modulate the activity of some important transcription factors and is known to be a regulator of hematopoietic differentiation. Herein, we investigated epigenetic regulation of hMSH2 and its influence on cell growth and overall survival of acute lymphoblastic leukemia (ALL) patients. Methods: hMSH2 promoter methylation status was assessed by COBRA and pyrosequencing in 60 ALL patients and 30 healthy volunteers. mRNA and protein expression levels of hMSH2, PCNA, CyclinD1, Bcl-2 and Bax were determined by real time PCR and Western blotting, respectively. The influence of hMSH2 on cell proliferation and survival was assessed in transient and stable expression systems. Results: mRNA and protein expression of hMSH2 and Bcl-2 was decreased, and that of PCNA, CyclinD1 and Bax was increased in ALL patients as compared to healthy volunteers (P<0.05). hMSH2 was inactivated in ALL patients through promoter hypermethylation. Furthermore, hMSH2 hypermethylation was found in relapsed ALL patients (85.7% of all cases). The median survival of patients with hMSH2 methylation was shorter than that of patients without hMSH2 methylation (log-rank test, P=0.0035). Over-expression of hMSH2 in cell lines resulted in a significant reduction in growth and induction of apoptosis. Conclusions: This study suggests that aberrant DNA methylation and epigenetic inactivation of hMSH2 play an important role in the development of ALL through altering cell growth and survival.

• KSBB Journal
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• v.19 no.6 s.89
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• pp.462-466
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• 2004

Mycothiol (MSH), a low molecular antioxidant thiol compound, was purified and analyzed from Streptomyns coelicolor A[3]2 by the monobromobimane fluorescence detection method modified by this lab. Through HPLC chromatpgram, MSH fraction was obtained following the elution time of standard MSH (donated by Dr. Robert C. Fahey). That MSH showed the highest concentration among the thiol compounds contained in the cell indicated that MSH was the key thiol compound having antioxidant activity. To understand the role of gene of inositol monophosphatase (I-1-Pase) involved in the MSH biosynthesis, it was isolated from S. coelicolor A(3)2 and cloned and overexpressed in the Escherichia coli. The expressed I-1-Pase was purified through Ni-NTA column. The soluble protein consisted of 281 amino acids, and the molecular weight was 32 kDa. I-1-Pase of S. coelicolor A(3)2 had the sequence homology with those of human and E. coli by 24 and $25\%$, respectively, and had two conserved domains (mofif A and motif B) which were typical of I-1-Pase.

• Journal of Microbiology and Biotechnology
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• v.18 no.12
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• pp.1975-1983
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• 2008

The neuropeptide ${\alpha}$-melanocyte-stimulating hormone (${\alpha}$-MSH) has anti-inflammatory property by down regulating the expressions of proinflammatory cytokines. Because ${\alpha}$-MSH elicits the anti-inflammatory effect in various inflammatory disease models, we examined the therapeutic effect of oral administration of recombinant Lactobacillus casei, which secretes ${\alpha}$-MSH (L. casei-${\alpha}$-MSH), on dextran sulfate sodium (DSS)-induced colitis in Balb/c mice. Thus, we constructed the ${\alpha}$-MSH-secreting Lactobacillus casei by the basic plasmid, pLUAT-ss, which was composed of a PldhUTLS promoter and ${\alpha}$-amylase signal sequence from Streptococcus bovis strain. Acute colitis was induced by oral administration of 5% DSS in drinking water for 7 days. To investigate the effect of L. casei-${\alpha}$-MSH on the colitis, L. casei or L. casei-${\alpha}$-MSH was orally administered for 7 days and their effects on body weight, mortality rate, cytokine production, and tissue myeloperoxidase (MPO) activity were observed. Administration of L. casei-${\alpha}$-MSH reduced the symptom of acute colitis as assessed by body weight loss (DSS alone: $14.45{\pm}0.2\;g$; L. casei-${\alpha}$-MSH: $18.2{\pm}0.12\;g$), colitis score (DSS alone: $3.6{\pm}0.4$; L. casei-${\alpha}$-MSH: $1.4{\pm}0.6$), MPO activity (DSS alone: $42.7{\pm}4.5\;U/g$; L. casei-${\alpha}$-MSH: $10.25{\pm}0.5\;U/g$), survival rate, and histological damage compared with the DSS alone mice. L. casei-${\alpha}$-MSH-administered entire colon showed reduced in vitro production of proinflammatory cytokines and $NF-{\kappa}B$ activation. The ${\alpha}$-MSH-secreting recombinant L. casei showed significant anti-inflammatory effects in the murine model of acute colitis and suggests a potential therapeutic role for this agent in clinical inflammatory bowel diseases.

• IMMUNE NETWORK
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• v.2 no.4
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• pp.208-216
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• 2002

Background: Reactive oxygen and nitrogen are produced by rheumatoid arthritis (RA) synovial tissue and can induce mutations in key genes. Normally, this process is prevented by a DNA mismatch repair (MMR) system that maintains sequence fidelity. Key members of the MMR system include MutS${\alpha}$ (comprised of hMSH2 and hMSH6), which can sense and repair single base mismatches and 8-oxoguanine, and MutS${\beta}$ (comprised of hMSH2 and hMSH3), which repairs longer insertion/deletion loops. Methods: To provide further evidence of DNA damage, we analyzed synovial tissues for microsatellite instability (MSI). MSI was examined by PCR on genomic DNA of paired synovial tissue and peripheral blood cells (PBC) of RA patients using specific primer sequences for 5 key microsatellites. Results: Surprisingly, abundant MSI was observed in RA synovium compared with osteoarthritis (OA) tissue. Western blot analysis of the same tissues for the expression of MMR proteins demonstrated decreased hMSH6 and increased hMSH3 in RA synovium. To evaluate potential mechanisms of MMR regulation in arthritis, fibroblast-like synoviocytes (FLS) were isolated from synovial tissues and incubated with the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP). Western blot analysis demonstrated constitutive expression of hMSH2, 3 and 6 in RA and OA FLS. When FLS were cultured with SNAP, the RA synovial pattern of MMR expression was reproduced (high hMSH3, low hMSH6). Conclusion: Therefore, oxidative stress can relax the DNA MMR system in RA by suppressing hMSH6. Decreased hMSH6 can subsequently interfere with repair of single base mutations, which is the type observed in RA. We propose that oxidative stress not only creates DNA adducts that are potentially mutagenic, but also suppresses the mechanisms that limit the DNA damage.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.3
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• pp.574-580
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• 2009

Melanogenesis is induced mainly by ultraviolet radiation of sunlight and ${\alpha}$-Melanocyte stimulation hormone (${\alpha}$-MSH) which binds to a specific G protein coupled receptor. ${\alpha}$-MSH and cAMP-elevating agents are known to melanin syntheisis and dendrite outgrowth. The purpose of this study was to investigate the mechanism of melanogenesis inhibition in B16/F10 cells by ethanol extract of Artemisiae Capillaris Herba. In the present study, ${\alpha}$-MSH led to a stimulation of melanin synthesis that appeared to result from an increased tyrosinase activity and melanin content. However, the ethanol extract of Artemisiae Capillaris Herba inhibited the ${\alpha}$-MSH-induced tyrosinase activity and melanin content. In control conditions, B16/F10 cells displayed a fibroblastic appearance while ${\alpha}$-MSH treatment promoted the emergence of small and numerous dendrites from the plasma membrane. The ethanol extract of Artemisiae Capillaris Herba abolished the ${\alpha}$-MSH-induced dendricity. Regarding protein levels of the melanogenic enzymes, the amounts of tyrosinase were increased after incubation with ${\alpha}$-MSH. The treatment of Artemisiae Capillaris Herba ethanol extract decreased the ${\alpha}$-MSH expression levels of tyrosinase. Based on these findings, it is likely that the ethanol extract of Artemisiae Capillaris Herba exerts its depigmenting effects in B16/F10 cells through the suppression of tyrosinase expression, which are key enzymes for melanogenesis.

• Journal of the korean Society of Automotive Engineers
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• v.14 no.3
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• pp.80-89
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• 1992

An experimental study of in-cylinder of flow and combustion characteristics in two gasoline engines of different intake ports which are denoted as original port and masked shroud head (MSH) ports is presented. The flows generated by the MSH and the original port are invest- igated by laser Doppler velocimeter(LDV) under steady flow and motoring (non-firing) condit -ions. Combustion characteristics with different swirl levels produced by two intake ports are analyzed by combustion pressure measurement and statistical calculation. The swirl inside the cylinder of the MSH port engine is found to be much higher than the original port, and the MSH has a large eddy motion of cylinder diameter size. Using ensemble average method to valuate engine turbulence under motoring condition, the MSH port engine is shown to have h -igher turbulence intensity than the original port, so that the effect of the MSH port on fast burn is shown. Also the cyclic variations of peak pressure and the reaching time in the MSH port are apparently reduced.

• Journal of Life Science
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• v.20 no.11
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• pp.1617-1624
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• 2010

Recently, it has been found that Asiasari radix showed a hypopigmenting effect on melanogenesis through activation of mitogen-activated protein kinase (MEK)/extracellular signal-activated kinase (ERK) in B16F10 melanoma cells. However, the hypopigmenting effect of A. radix on the $\alpha$-melanocyte stimulating hormone ($\alpha$-MSH)-stimulated melanogenesis has remained unknown. The purpose of this study was to investigate the inhibitory mechanism of the partially purified A. radix (PPAR)-induced hypopigmentating effects on $\alpha$-MSH-stimulated melanogenesis in B16F10 mouse melanoma cells. PPAR strongly inhibited tyrosinase activity and leads to decreased melanin synthesis in $\alpha$-MSH-stimulated B16F10 melanoma cells. PPAR also decreased the $\alpha$-MSH-induced over-expression of the melanogenic enzymes, tyrosinase, tyrosinase-related protein (TRP)-1, dopachrome tautomerase (Dct) and microphthalmia-associated transcription factor (MITF). We further showed that PPAR inhibits $\alpha$-MSH-induced melanogenesis via phosphorylation of MEK/ERK and PI3K/Akt, and that their activation was blocked by MEK inhibitors, PD98059 and PI3K inhibitors, LY294002 in $\alpha$-MSH-stimulated B16F10 melanoma cells. These results suggest that PPAR inhibits $\alpha$-MSH-induced melanogenesis by activation of MEK/ERK and PI3K/Akt through MITF degradation, which may lead to down-regulation of tyrosinase.

• Journal of KIISE:Computing Practices and Letters
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• v.9 no.2
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• pp.205-212
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• 2003

Recently, as electronic commerce service via the Internet has expanded over the world, the standardization for the e-commerce has been strongly required. Therefore UN/CEFACT and OASIS adopted ebXML standard for the purpose of creating single global electronic marketplace. New e-Business systems should require ebXMl- based messaging system for reliable messaging delivery. In this paper, we have implemented Message Service Handler(MSH) packaging, transporting and managing e-Business messages for supporting ebXML messaging service. The MSH supports various system environments and allows high-level applications running either local or remote hosts with Remote Method Invocation(RMI) interface. In addition, MSH guarantees reliable message delivery on internet since it retransmits message in case of delivery failure and handles duplicated message and applies acknowledgement message for secure message delivery. Nowadays MSH has applied to ebXML registry/repository.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6055-6057
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• 2012

The mismatch repair system (MMR) is a post-replicative DNA repair mechanism whose defects can lead to cancer. The MSH3 protein is an essential component of the system. We postulated that MSH3 gene polymorphisms might therefore be associated with prostate cancer (PC). We studied MSH3 codon 222 and MSH3 codon 1036 polymorphisms in a group of Iranian sporadic PC patients. A total of 60 controls and 18 patients were assessed using the polymerase chain reaction and single strand conformational polymorphism. For comparing the genotype frequencies of patients and controls the chi-square test was applied. The obtained result indicated that there was significantly association between G/A genotype of MSH3 codon 222 and G/G genotype of MSH3 codon 1036 with an increased PC risk (P=0.012 and P=0.02 respectively). Our results demonstrated that MSH3 codon 222 and MSH3 codon 1036 polymorphisms may be risk factors for sporadic prostate cancer in the Iranian population.

• Journal of Microbiology
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• v.44 no.1
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• pp.121-125
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• 2006

Mycothiol is a low molecular weight thiol compound produced by a number of actinomycetes, and has been suggested to serve both anti-oxidative and detoxifying roles. To investigate the metabolism and the role of mycothiol in Streptomyces coelicolor, the biosynthetic genes (mshA, B, C, and D) were predicted based on sequence homology with the mycobacterial genes and confirmed experimentally. Disruption of the mshA, C, and D genes by PCR targeting mutagenesis resulted in no synthesis of mycothiol, whereas the mshB mutation reduced its level to about $10\%$ of the wild type. The results indicate that the mshA, C, and D genes encode non-redundant biosynthetic enzymes, whereas the enzymatic activity of MshB (acetylase) is shared by at least one other gene product, most likely the mca gene product (amidase).