• Journal of Yeungnam Medical Science
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• v.13 no.2
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• pp.159-172
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• 1996

대기오염물질이면서 동시에 생체내 화학반응의 산물이기도 한 nitric oxide(NO)는 그 생체내 분포가 광범위하고 생리적 역할이 다양하여, 최근의 생명과학 분야에서 가장 크게 주목받는 몇가지 연구대상 중 하나이다. 세포에서의 NO 산생은 nitric oxide synthase (NOS)에 의해 촉매되는데, 이들은 brain form (bNOS, neuronal; nNOS, NOS I), inducible form (iNOS), 및 endothelial form(eNOS)로 구분되는데, 이중 bNOS(nNOS)와 eNOS는 inducible form에 대비되는 constitutive form(cNOS)에 해당하므로 각각 ncNOS 와 ecNOS로도 불리운다. NOS는 아미노산인 L-arginine을 산소와 결합시켜 L-citrulline으로 변환시키면서 NO를 유리하고, 이 NO는 세포내의 guanylate cyclase를 활성화하여 cyclic GMP를 생산하거나, superoxide(O2-) 및 수소이온과 차례로 결합하여 반응성이 매우 높은 수산화기(-OH)를 발생시켜 세포독작용을 유발하기도 한다. 정상상태에서 뇌혈관내피세포의 ecNOS로 부터 유리된 NO는 혈관을 확장시켜 신경세포에 대한 산소공급을 원활히 유지해 주지만, 순환장애를 일으켰을 때는 뇌조직내의 iNOS로부터 대량의 NO가 유출되어 신경세포의 손상을 가져온다. 호흡기에서는 NO가 기도평활근을 이완시키고 폐혈류를 개선하므로, 미숙아나 성인의 호흡장애시에 소량의 NO를 흡입시키면 oxygenation을 호전시킬 수 있다. 그러나 대기오염이나 흡연 등으로 대량의 NO를 흡입할 경우 치명적인 폐부종이나 methemoglobin혈종을 일으킬 수 있다. 순환계에서는 cNOS가 혈관을 확장시켜 조직의 혈류를 유지하는데 일익을 담당한다. 세균내 독소(lipopolysaccharide; LPS)나 각종 명역조절물질들이 혈관내피세포와 혈관평활근세포로 부터 과다한 NO를 유리시키면 혈압이 급격히 떨어져 순환허탈상태에 빠지게 된다. 심장에서는 관상혈관 내피세포의 eNOS가 심근의 혈류를 유지해 주지만 허혈이나 세균내독소 또는 면역조절물질 등에 의하여 심근세포나 침윤된 대식세포의 iNOS로 부터 과량의 NO가 유리되면 심근세포의 손상이 초래된다. 신장에서는 내피세포의 cNOS에 의하여 사구체여과가 조절되고 있는데, 세균내독소나 면역 조절물질 등에 의하여 사구체관막세포(mesangial cell)등의 iNOS로 부터 과량의 NO가 유리되면 신조직과 사구체의 손상을 초래한다. 위와 같이 대부분의 장기에서 ecNOS는 조직의 혈류를 유지하는 역할을 하며, iNOS는 애초 세균 등 침입자에 대한 세포독작용이 그 존재 목적이라고 풀이할 수 있겠으나 일종의 부작용으로 자체조직의 손상을 초래하게 되는 것으로 본다. 따라서 NO와 관련된 각종 병변의 치료를 위해서는 NOS의 비선택성 억제제인 arginine 유도체 보다는 iNOS에 대한 선택적 억제제인 S-methylisothiourea(SMT), aminoethylisothiourea(AETU), aminoguanidine (AMG), agmatine, L-canavanine, transforming growth factor b1(TGF-b1) 등의 사용을 검토해 보는 것이 타당할 것으로 사료된다.

• Journal of Life Science
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• v.19 no.6
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• pp.818-824
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• 2009

The mechanisms responsible for ischemia/reperfusion (I/R) injury have direct or indirect relevance to clinical lung injury after severe shock, cardiopulmonary bypass, and transplantation. This study investigated the effects of aspirin on intestinal I/R-induced acute lung injury (ALI) in rats. Lipopolysaccharide (LPS) induced cyclooxygenase-2 (COX-2) expression in A549 and RAW264.7 cells. RAW264.7 macrophages had shown greater expression of COX-2 than A549 cells. In addition, the NADPH oxidase inhibitor apocynin and p38 MAPK inhibitor SB203580 attenuated LPS-stimulated COX-2 expression. To induce ALI, intestinal ischemia was performed for 60 min prior to the 4 hr reperfusion by clamping the superior mesenteric artery in Sprague-Dawley rats. In order to test and compare the effect of non-specific COX inhibitor aspirin with the effect of mepacrine, a well known phospholipase$A_{2}$ inhibitor, rats were divided into 4 groups: Sham, I/R, Mepa+I/R (mepacrine, 60 mg/kg, i.p.), ASA+I/R (aspirin, 10 mg/kg, i.p.). In the present investigation, myeloperoxidase activities in the lung and intestinal tissues were increased by I/R. These changes were reduced by single pretreatment of mepacrine (60 mg/kg, i.p.) or aspirin (10 mg/kg, i.p.) 30 min before I/R. Structural studies demonstrated that the tissue injuries in the lung and intestine after I/R were also attenuated by the pretreatment of mepacrine or aspirin. These results suggest that I/R-induced ALI is mediated, in part, by the activation of COX. In addition, pretreatment of aspirin might be helpful for the prevention of ALI in ARDS-prone patients. In addition, the p38 MAPK inhibitor and apocynin also might be helpful to ALI through the inhibition of COX-2 expression.

• Journal of Life Science
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• v.25 no.5
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• pp.607-614
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• 2015

Cancers are the largest cause of mortality and morbidity all over the world. Cordycepin, an adenosine analog, is a major functional component of the Cordyceps species, which has been widely used in traditional Oriental medicine. Over the last decade, this compound has been reported to possess many pharmacological properties, such as an ability to enhance immune function, as well as anti-inflammatory, antioxidant and anti-cancer effects. Recently, numerous studies have reported interesting properties of cordycepin as a chemopreventive agent as well. There is an accumulating body of experimental evidences suggesting that cordycepin impedes cancer progression by promoting apoptosis, inducing cell cycle arrest, modulating intracellular signaling pathways, and inhibiting invasion and metastasis of cancer cells. In many cancer cell lines, cordycepin inhibits growth and cell cycle progression by inducing arrest of the G2/M phase, resulting from the inhibition of retinoblastoma protein phosphorylation and induction of cyclin-dependent kinase inhibitors. To induce apoptosis, cordycepin activates the extrinsic and intrinsic pathways, which promotes reactive oxygen species generation and the downstream activation of kinase cascades. Cordycepin also can activate alternative pathways to cell death such autophagy. In addition, cordycepin can inhibit the pro-metastatic processes of cancer cell detachment, migration, and invasion through a variety of mechanisms, including the nuclear factor-kappa B and activated protein-1 signaling pathways. In this review, we summarized the variety of action mechanisms by which cordycepin may mediate chemopreventive effects on cancer and discussed the potential of this natural product as a promising therapeutic inhibitor of cancer development.

• Journal of Life Science
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• v.27 no.11
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• pp.1357-1368
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• 2017

The purpose of this study was to investigate the anti-obesity and anti-inflammation effect of the cheonggukjang (a soybean paste fermented for only a few days) in diet induced obesity mice. Weight gain was significantly decreased in the mice fed cheonggukjang compared High Fat Diets (HFD). The HFD plus cheonggukjang (CGJ) were also effective in improving the lipid metabolism. The levels of plasma triglyceride, cholesterol, ALT, AST, leptin, glucose, and insulin were significantly lower in CGJ than HFD group (p<0.05). The adiponectin level of CGJ group was significantly increased compared to the HFD group (p<0.05). In the CGJ group, the mRNA expression of adipogenic genes in the liver and adipose tissues, which are transcription factors crucial for adipogenesis, were significantly suppressed (p<0.05). The number of $CD11b^+F4/80^+$ T cells, $Gr-1^{int}CD11b^{high}$ cells, and $Gr-1^{int}CD11b^{high}$ cells were significantly higher in HFD group than CGJ group (p<0.05). The size of adipocyte was significantly reduced in CGJ group compared to HFD group. In addition, the contents of liver lipid droplets were significantly downregulated in the CGJ mice than HFD mice (p<0.05). Collectively, these data suggest the novel function of cheonggukjang in modulating adipogenesis through an immune function-alteration involving downregulation of adipogenic transcription factors and macrophage activation.

• Journal of the Korean Geosynthetics Society
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• v.9 no.3
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• pp.77-85
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• 2010

The change of water level in reservoirs is an important factor causing failure of bank slopes, i.e. landslide. The water level of Three Gorges reservoir in China fluctuate between 145 m and 175 m, as a matter of flood control. During its normal operational state, the rate of water level fluctuation is supposed to range from 0.67 m/d to 3.0 m/d. Majiagou slope is located on the left bank of Zhaxi River, 2.1 km up from the outlet. Zhaxi River is a tributary of the Yangtze River within the Three Gorges area, of which the water level changes with the reservoir. At the back of Majiagou slope, a 20 m long and 3~10 cm wide fissure developed just after the reservoir water level rose from 95 m to 135 m in 2003. This big fissure was a full suggestion of potential failure of this slope. In this study, unsaturated-saturated seepage analyses were carried out to simulate the change of pore-water pressures in the bank slope subjected to the reservoir water level change. The obtained pore-water pressures were then used to evaluate the change in factor of safety (FS) with reservoir water level. It was found that the phreatic line showed a delayed response with respect to the change of the reservoir water level, because the seepage through soil layer was generally slower than water flows itself. During the rising and drawdown process, the phreatic lines take the shapes of concave and convex, respectively. And the fluctuation of reservoir water level just affected the front part of the bank slope, but had little influence on the back of the slope.

• Restorative Dentistry and Endodontics
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• v.28 no.6
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• pp.475-484
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• 2003

동통조절을 위해 국소마취제는 치과임상에서 광범위하게 사용되어진다. 가장 널리 쓰이는 국소마취제는 리도카인이고 이는 마취효과의 지속 및 지혈효과 등의 목적으로 혈관수축제를 포함하고 있다. 대표적 혈관수축제인 에피네프린은 임상에서 1:300,000에서부터 1:50,000의 농도로 다양하게 사용되어진다. 수복치료를 위해서는 통상적으로 1:100.000농도의 에피네프린이 사용되고 있고 외과적 근관치료시 지혈효과를 위해서는 1:50,000농도의 에피네프린이 추천되고 있다. 이들 농도의 에피네프린을 포함한 리도카인으로 국소마취시 에피네프린의 농도가 치수의 혈류 및 치은의 혈류에 미치는 영향을 이해할 필요가 있고 그 영향이 전기치수검사에 대한 치수의 반응성에 미치는 영향도 이해할 필요가 있다. 따라서 혈관수축제를 포함한 국소마취제에 의한 치수혈류의 변화와 치수신경의 반응성을 이해하는 것은 중요하다 하겠다. 본 연구의 목적은 두 가지 농도의 에피네프린을 포함한 국소마취제로 마취시 나타나는 치수 및 치은의 혈류 변화를 치수신경의 반응성과 비교, 관찰함으로써 국소마취제가 치수 및 치은에 미치는 영향을 파악하고자 함에 있다. 24세에서 27세까지의 10명의 피검자의 건전한 상악중절치를 시험에 이용하였다. Laser Doppler flowmeter의 probe을 고정하기 위한 splint를 간접법으로 인상용 putty를 이용하여 제작하고 치수 및 치은의 혈류량, 그리고 전기치수검사에 대한 반응성을 측정하기 위한 3개의 구멍을 만들었다. 피검자를 10분간 안정시킨 후 마취 전 10분간 정상 혈류량과 전기검사치를 측정하고 1:50,000 epinephrine과 1:100,00 epinephrine이 각각 함유된 2% 리도카인 용액 0.9 ml를 상악 좌측 중절치 치근단부위 협점막에 침윤마취하였다. 마취 후 70분간 치수 및 치은 혈류량을 laser Doppler flowmeter를 이용해 연속적으로 측정하여 그 수치를 컴퓨터에 저장하였고, 매 5분 간격으로 전기치수검사를 시행하여 그 측정치를 기록하였다. 매 시간 간격의 평균 혈류량을 정상 혈류량에 대한 백분율로 나타내고, 각각의 농도에서 최소 치수 및 치은 혈류량을 Paired t-test, Wilcoxon's signed rank test. Duncan's multiple range test. Fisher's exact test등을 이용. 통계분석 하여 다음과 같은 결과를 얻었다. 에피네프린이 함유되어 있지 않은 리도카인을 협점막에 주사시 혈류변화가 거의 나타나지 않았으나 1:50,000 및 1:100.000 에피네프린이 함유된 2% 리도카인을 협점막에 침윤마취시 치수 및 치은 혈류 공히 현저히 감소하였다(p<0.01). 1:50,000 에피네프린군은 1:100,000 에피네프린군에 비해 치수 혈류량이 현저히 억제되어 나타났으나(p<0.01), 치은 혈류량에서는 유의성 있는 차이를 나타내지 않았다(p>0.05). 두 농도의 에피네프린 군 공히 치은혈류는 치수혈류에 비해 유의하게 많은 감소를 나타내었다(p<0.05). 1:100,000 에피네프린 군에서 마취액 주입 후 치수혈류 최대감소가 가장 먼저 나타났고 이어서 전기검사에 대한 치수의 반응성 소실 및 치은혈류 최대 감소의 순으로 나타났다(p<0.05). 1:50,000 에피네프린군의 경우가 1:100,000 에피네프린군의 경우에 비해 마취지속시간이 길게 나타났으나 유의성은 없었다(p>0.05).

• Korean Journal of Environmental Biology
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• v.27 no.1
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• pp.58-65
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• 2009

The chemopreventive effects of naringenin derived from citrus on tumor migration and the possible mechanisms involved in this protection were investigated in HT-1080 tumor cells. In this study, we found that naringenin reduced phorbol 12-myristate 13-acetate (PMA)-enhanced matrix metalloproteinases (MMP)-9 activation in a dose-dependant manner and further inhibited HT-1080 cell migration. In addition, naringenin suppressed PMA-enhanced expression of MMP-9 protein, mRNA and transcription activity levels through suppression of nuclear factor $\kappa$B (NF-$\kappa$B) activation and activator protein-1 (AP-1) translocation without changing tissue inhibitor of metalloproteinase (TIMP)-1 level. Therefore, our results suggested that the inhibitory effects of naringenin on MMP-9 activation, relation of tumor migration in vitro possibly involve mechanisms related to its ability to suppress PMA-enhanced MMP-9 gene and protein expression through NF-$\kappa$B activation and AP-1 translocation. Overall, naringenin may be a valuable anti-invasive drug candidate for cancer therapy.

• Journal of Nutrition and Health
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• v.54 no.3
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• pp.321-333
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• 2021

Purpose: Reflux esophagitis is a disease caused by the reflux of stomach contents and stomach acid etc. into the esophagus due to defect in the lower esophageal sphincter and is currently increasing worldwide. This study was conducted to evaluate the effect of a mixture of Citrus Reticulata and Scutellariae Radix (CS) extract on acute reflux esophagitis in rats. Methods: Rats were divided into five groups for examination: normal group (Normal, n = 8), water-treated acute reflux esophagitis rats (Control, n = 8), tocopherol 30 mg/kg body weight-treated acute reflux esophagitis rats (Toco, n = 8), CS 100 mg/kg body weight-treated acute reflux esophagitis rats (CS100, n = 8), CS 200 mg/kg body weight-treated acute reflux esophagitis rats (CS200, n = 8). The experimental groups were administrated of each treatment compounds and after 90 min, acute reflux esophagitis was induced through surgery. Rats were sacrificed 5 h after surgery. We measured the level of reactive oxygen species (ROS) in serum and analyzed the expression of nicotinamide adenine dinucleotide phosphate, inflammatory, and tight junction-related proteins by western blot in the esophageal tissues. Results: CS administration significantly protected the esophageal mucosal damage due to reflux esophagitis, and the level of ROS in the serum was significantly reduced with CS administration as compared to Control. In addition, CS administration significantly suppressed mitogen-activated protein kinase (MAPK or MAP kinase) and nuclear factor-kappa B (NF-κB) pathways and increased protein expressions of tight junction protein. Conclusion: These results suggest that the CS not only regulates the expression of inflammatory proteins by inhibiting oxidative stress, but also reduces damage to the esophageal mucosa by inhibiting the expression of tight junction proteins.

• Journal of Life Science
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• v.33 no.9
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• pp.703-712
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• 2023

Angiogenesis, the formation of blood vessels from pre-existing vessels, is a multistep process regulated by modulators of angiogenesis. It is essential for various physiological processes, such as embryonic development, chronic inflammation, and wound repair. Dysregulation of angiogenesis causes many diseases, such as cancer, autoimmune diseases, rheumatoid arthritis, cardiovascular disease, and delayed wound healing. However, the number of effective anti-angiogenic drugs is limited. Recent research has focused on identifying potential drug candidates from natural sources. For example, marine natural products have been shown to have anti-cancer, anti-oxidant, anti-inflammatory, antiviral, and wound-healing effects. Thus, this study aimed to describe the angiogenesis inhibitory effect of Hizikia fusiforms (brown algae) extract. The hexane extract of H. fusiformis has shown inhibitory effects on in vitro angiogenesis assays, such as cell migration, invasion, and tube formation in human umbilical vein endothelial cells (HUVECs). The hexane extract of H. fusiformis (HFH) inhibited in vivo angiogenesis in a mouse Matrigel gel plug assay. In addition, the protein expression of vascular endothelial growth factor (VEGF), mitogen-activated protein kinase (MAPK)/extracellular signal kinase, and AKT serine/threonine kinase 1 decreased following treatment with H. fusiformis extracts. Our results demonstrated that the hexane extract of H. fusiformis (HFH) inhibits angiogenesis in vitro and in vivo.

• Journal of Chest Surgery
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• v.39 no.5 s.262
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• pp.403-406
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• 2006

Infarction of the lung usually results from pulmonary arterial obstruction. Pulmonary infarcts often become infected from bronchial contamination and may become lung abscesses, empyema, or bronchopleural fistula causing sepsis. Diagnosis is important for intensive therapy, since infection is prone to spread. Resection of the infarcted lung should be considered early in an attempt to control infection. A sixty-seven-year-old man was hospitalized with dyspnea. A computed tomographic scan of the chest showed left lower lobe infiltration and mild pleural effusion with pleural thickening. There was a thrombus in the left pulmonary artery leading from the lower lobe to the upper lobe artery. At operation, the left lower lobe was found to have complete hemorrhagic infarction. The left lower lobectomy was performed. The remaining thrombus was removed after the left main pulmonary arteriotomy. He has been followed up for 15 months and has done well with no recurrence of thrombus and infarction of the lung.