• The Korean Journal of Physiology and Pharmacology
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• 제10권4호
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• pp.217-222
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• 2006

Atherosclerosis is considered as a chronic inflammatory process. However, the nature of the oxidant signaling that regulates monocyte adhesion and its underlying mechanism is poorly understood. We investigated the role of reactive oxygen species on the vascular cell adhesion molecule-1 (VCAM-1) and monocyte adhesion in the cultured endothelial cells. $TNF-{\alpha}$ at a range of $1{\sim}30\;ng/ml$ induced VCAM-1 expression dose-dependently. BCECF-AM-labeled U937 cells firmly adhered on the surface of endothelial cells when the endothelial cells were incubated with $TNF-{\alpha}$ (15 ng/ml). Ten $\;{\mu}mol/L$ of SB203580, an inhibitor of p38 MAPK, significantly reduced $TNF-{\alpha}-induced$ VCAM-1 expression, compared to the JNK inhibitor ($40\;{\mu}mol/L$ of SP60015) or ERK inhibitor ($40\;{\mu}mol/L$ of U0126). Also, SB203580 significantly inhibited $TNF-{\alpha}-induced$ monocyte adhesion in HUVEC. Superoxide production was minimal in the basal condition, however, treatment of $TNF-{\alpha}$ induced superoxide production in the dihydroethidineloaded endothelial cells. Diphenyleneiodonium (DPI, $10\;{\mu}mol/L$), an inhibitor of NADPH oxidase, and rotenone $(1\;{\mu}mol/L)$, an inhibitor of mitochondrial complex I inhibited $TNF-{\alpha}-induced$ superoxide production, VCAM-1 expression and monocyte adhesion in the endothelial cells. Taken together, our data suggest that NADPH oxidase and mitochondrial ROS were involved in $TNF-{\alpha}-induced$ VCAM-1 and monocyte adhesion in the endothelial cells.

• BMB Reports
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• 제51권9호
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• pp.444-449
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• 2018

Acute myeloid leukemia (AML) is one of the most common hematological malignancies all around the world. MicroRNAs have been determined to contribute various cancers initiation and progression, including AML. Although microRNA-204 (miR-204) exerts anti-tumor effects in several kinds of cancers, its function in AML remains unknown. In the present study, we assessed miR-204 expression in AML blood samples and cell lines. We also investigated the effects of miR-204 on cellular function of AML cells and the underlying mechanisms of the action of miR-204. Our results showed that miR-204 expression was significantly downregulated in AML tissues and cell lines. In addition, overexpression of miR-204 induced growth inhibition and apoptosis in AML cells, including AML5, HL-60, Kasumi-1 and U937 cells. Cell cycle analysis further confirmed an augmentation in theapoptotic subG1 population by miR-204 overexpression. Mechanistically, baculoviral inhibition of apoptosis protein repeat containing 6 (BIRC6) was identified as a direct target of miR-204. Enforcing miR-204 expression increased the luciferase activity and expression of BIRC6, as well as p53 and Bax expression. Moreover, restoration of BIRC6 reversed the pro-apoptotic effects of miR-204 overexpression in AML cells. Taken together, this study demonstrates that miR-204 causes AML cell apoptosis by targeting BIRC6, suggesting miR-204 may play an anti-carcinogenic role in AML and function as a novel biomarker and therapeutic target for the treatment of this disease.

• Journal of Microbiology and Biotechnology
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• 제14권5호
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• pp.985-990
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• 2004

Levans produced from Microbacterium laevaniformans were isolated, characterized, and fractionated by molecular weight. TLC, HPLC, and GC-MS analyses of the exopolysaccharide showed that it was a fructan-type polymer and was composed of (2,6)- and (2,1)-glycosidic linkages. $^{13}C$-NMR analysis proved that the polysaccharide was mainly a $\beta$-(2,6)-linked levan-type polysaccharide. To investigate the cytotoxicity of the acetone-precipitated levan fractions such as M1, M2, and M3, HepG2, P388D1, U937, SNU-1, and SNUC2A cell lines were screened. Among the cell lines tested, the cytotoxicity of M1- M3 fractions were detected from only SNU-1 and HepG2 cells at the dosage level of $100-800\mu\textrm{g}ml$. The M2 fraction M_r$, 80,000) at 400 $mu{g/ml}$ had the greatest cell growth inhibition (84.6%) on SNU-1, while the M1 $(M_r$, 50,000) at $800\mu\textrm{g}ml$ showed the greatest (46.32%) on HepG2. To obtain more uniform M_r$ fractions of levan, the levan was further fractionated from S1 $(M_r$ 1,000,000) to S5 $(M_r$ 10,000) using gel permeation chromatography. Again, the S1-S5 fractions had strong cytotoxicity on SNU-1 and HepG2 cell lines. The greatest inhibition effects of S4 $(M_r$ 80,000) on SNU-1 and S5 $(M_r$ 10,000) on HepG2 were shown to be 49.5% and 73.0%, respectively. The cytotoxicity of the levan fractions was more effective on SNU-1 than on HepG2. Although the relationship between the Mw and the cytotoxicity was not clear, smaller $M_r$, fractions of levan showed greater growth inhibition effect on the cancer cell lines in general. Therefore, it was indicated that a specific Mw class of levan is responsible for the effective cytotoxicity.

• 생약학회지
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• 제35권4호통권139호
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• pp.288-292
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• 2004

To evaluate the quality of the crude drugs using three kinds of Cinnamomum Cortex (CC), Vietnamese CC (VCC, the stem bark of Cinnamomum obtusifolium), periderm-peeled Chinese CC (PPCC, periderm-peeled stem bark of C. cassia), Chinese CC (CCC, stem bark of C. cassia) and a Cinnamomi Ramulus (CR, the twig of C. cassia), the four essential oils were prepared by steam distillation method. Cinnamaldehdye (CAN) and an unknown substance tentatively named hydroxy-cinnamaldehdye(HCNA) were detected in the four essential oils by gas chromatography-mass spectrometry, the contents of which are significantly different one another. Vietnamese CC had the highest content of HCNA whereas CR had the highest CAN content and the lowest HCNA. Vietnamese CC exhibited the greatest cytotoxic activity against the cancer cell lines, A549, HepG-2, HL-60, P-388, U-937, and KB and CR the lowest cytotoxicity. Contents of CAN and HCNA in CCC and PPCC are positioned between VCC and CR. These results suggest that measurement of HCNA and cytotoxicity may determine the quality of CC and CR.

• Journal of Microbiology and Biotechnology
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• 제22권2호
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• pp.264-269
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• 2012

Recently, we reported that the synthetic Coprisin analog peptide 9-mer dimer CopA3 (consisted of all-L amino acid sequence) was designed based on a defensin-like peptide, Coprisin isolated from Copris tripartitus. The 9-mer dimer CopA3 (L-CopA3) had antibacterial activity and induced apoptosis in human leukemia cells via a caspase-independent pathway. In this study, all of amino acid sequences of L-CopA3 were modified to all D-form amino acids (DCopA3) to develop a more effective antimicrobial peptide. We investigated whether D-CopA3 had antimicrobial activities against pathogenic microorganisms and pro-apoptotic effects in human leukemia cells (U937, Jurkat, and AML-2). The synthetic peptide D-CopA3 had antimicrobial activities against various pathogenic bacteria and yeast fungus with MIC values in the 4~64 ${\mu}M$ range. Moreover, D-CopA3 caused cell growth inhibition, and increased the chromosomal DNA fragmentation and the expression of inflammatory cytokines, TNF-${\alpha}$ and IL1-${\beta}$, transcripts in human leukemia cells. The all-D amino acid peptide DCopA3 proved as effective as the L-CopA3 reported previously. These results provide the basis for developing D-CopA3 as a new antibiotic peptide.

• 동의생리병리학회지
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• 제20권5호
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• pp.1321-1326
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• 2006

Total ginsenosides were purified and their antioxidant, antibacterial and anticancer activities were measured. The crude extracts of ginseng, which were extracted with 75% ethanol by ultrasonification method, were firstly purified on AB-8 macroporous adsorption column to remove water soluble impurities, and decolored on Amberlite IRA 900 Cl anion-exchange column. Then, they were purified on Amberlite XAD16 adsorption column to delete the non-polar impurities. Total ginsenosides contents of the purified extracts were 79.4%, 71.7% and 72.5% in cultured wild ginseng, red ginseng and white ginseng, which were significantly increased than those of crude extracts. All of the three extracts showed concentration-dependant scavenging activities against DPPH radicals, among which white ginseng showed the most powerful activity. Cultured wild ginseng roots showed strongest effect against both B. subtilis PM 125(Gram-positive) and E. coli D31 (Gram-negative) bacteria, while red ginseng and white ginseng only showed the activity against B. subtilis. According to the result of the MTT assay, ail of the three extracts inhibited the growth of U-937 human hohistiocytic lympma cell, which were significantly different (p < 0.05) when compared to the control.

• The Korean Journal of Physiology and Pharmacology
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• 제19권3호
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• pp.229-234
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• 2015

Nafamostat mesilate (NM) is a serine protease inhibitor with anticoagulant and anti-inflammatory effects. NM has been used in Asia for anticoagulation during extracorporeal circulation in patients undergoing continuous renal replacement therapy and extra corporeal membrane oxygenation. Oxidative stress is an independent risk factor for atherosclerotic vascular disease and is associated with vascular endothelial function. We investigated whether NM could inhibit endothelial dysfunction induced by tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$ ). Human umbilical vein endothelial cells (HUVECs) were treated with TNF-${\alpha}$ for 24 h. The effects of NM on monocyte adhesion, vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) protein expression, p38 mitogenactivated protein kinase (MAPK) activation, and intracellular superoxide production were then examined. NM ($0.01{\sim}100{\mu}g/mL$) did not affect HUVEC viability; however, it inhibited the increases in reactive oxygen species (ROS) production and p66shc expression elicited by TNF-${\alpha}$ (3 ng/mL), and it dose dependently prevented the TNF-${\alpha}$ -induced upregulation of endothelial VCAM-1 and ICAM-1. In addition, it mitigated TNF-${\alpha}$ -induced p38 MAPK phosphorylation and the adhesion of U937 monocytes. These data suggest that NM mitigates TNF-${\alpha}$ -induced monocyte adhesion and the expression of endothelial cell adhesion molecules, and that the anti-adhesive effect of NM is mediated through the inhibition of p66shc, ROS production, and p38 MAPK activation.

• 생명과학회지
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• 제17권8호통권88호
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• pp.1121-1128
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• 2007

초피나무(Z. piperitum) 열매는 다양한 생리활성을 갖고 있으며, 과피 용매추출물은 세균에 대한 강한 항균활성을 갖고 있어, 간장과 된장제조에 초피를 첨가하여 생리활성효과를 조사하였다. 초피를 간장제조에 1%, 2%, 4% 첨가하여 제조하고, 간장추출물을 식중독균(Sta. aureus, Sal. typhimurium, V. parahemolyticus, E. coli 0157:H7)에 대한 항균활성을 조사했다. 초피를 2% 첨가한 간장은 E. coli 0157:H7과 V. parahemolyticuS 의 생육을 각각 70%와 50% 억제했으며, Sal. typhimurium 과 Sta. aureus 에 대한 항균효과는 농도와 간장제조시기에 따라 40% ${\sim}$ 60% 의 생육을 억제했다. 초피된장의 용매추출물에서는 약한 항균활성을 확인할 수 있었다. 초피간장의 추출물을 백혈병세포 U-937에 처리하여 caspase-3 활성으로 항암활성을 조사했다. 그 결과 초피의 량을 1%, 2%, 4% 첨가한 간장의 추출물은 초피를 침가하지 않은 간장보다 caspase-3 활성이 각각 4배, 12배, 15배 활성이 증가하는 것이 확인되어졌다. 이는 초피간장의 추출물이 apoptosis를 유도하는 것을 의미하며, 된장의 용매추출물은 caspase-3 활성에 아무런 영향이 없었다. 초피간장 추출물을 처리한 세포의 죽음이 necrosis인지 apoptosis인지 알아보기 위하여 세포내의 DNA fragmentation을 확인한 결과, 초피간장 추출물을 처리한 세포는 DNA 단편화가 형성되어졌다. 초피틀 1% 첨가한 것에서는 fragmentation을 확인하기 힘들었고, 2%와 4%초피를 첨가한 간장추출물은 DNA fragmentation을 강하게 일으켰다. 초피를 첨가한 간장추출물이 caspase를 활성화시키고, DNA fragmentation을 일으키는 apoptosis 기작에 의해 암세포를 죽음으로 유도하는 초피간장의 항암효과를 입증했다.

• 동의생리병리학회지
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• 제25권2호
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• pp.195-201
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• 2011

Nardostachys chinensis;Anti-proliferation;Cell cycle arrest;Differentiation;U937 cells; This study was conducted to determine the analgesic effect of Sokyungwhalhyul-tang(SKWHT) using the model of peripheral neuropathic pain model. A model of neuropathic pain was made by ligating left 5th lumbar spinal nerve of rats. After 1 days, the extract of SKWHT was orally administered daily. Rats were divided into four groups; (1) Control group(n=6), (2) Experimental group I(SKWHT-OA1, 100 mg/kg, n=6), (3) Experimental group II(SKWHT-OA2, 300 mg/kg, n=6), (4) Experimental group III(SKWHT-OA3, 500 mg/kg, n=6). After that, we examined the withdrawl response of neuropathic rats legs by von Frey filament and Hot plate at pre, $1^{th}$, $4^{th}$, $7^{th}$, $14^{th}$, $21^{th}$ days after the induction of neuropathic pain. And also we examined c-fos, GOT, GPT and histological study of Liver at 21th days. von Frey filament and Hot plate were increase in experimental group I, II, III than Con. especially group III was most significantly analgesic effect than the other groups at $14^{th}$, $21^{th}$ days. In c-fos protein expression on spinal cord, group III was most significantly reduction immunoreactivity at $21^{th}$ days and in blood serum GOT & GPT levels and histologic finding of Liver in all experimental groups were no significant difference with Con at $21^{th}$ days. According to the above results, SKWHT(500 mg/kg) may have a significant analgesic effect on the neuropathic pain.