• Tuberculosis and Respiratory Diseases
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• v.60 no.6
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• pp.625-630
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• 2006

Background: Pulmonary hypertension in COPD patients is the result of a direct effect of tobacco smoke on the intrapulmonary vessels with the abnormal production of the mediators that control vasoconstriction, vasodilatation, and vascular cell proliferation, which ultimately lead to aberrant vascular remodeling and physiology. COPD patients are prone to the developmint of an acute and chronic thromboembolism with an elevation of the plasma procoagulant and fibrinolytic markers However, the roles of the coagulation and fibrinolysis system on the right ventricular dysfunction in COPD patients are not well defined. We examined the alteration of the coagulation and fibrinolysis system in COPD patients according to the right ventricular function measured using cardiac multidetector computed tomography (MDCT). Methods: The right ventricular ejection fraction (RVEF) was measured using cardiac MDCT in 26 patients who were diagnosed with COPD according to the definition of the GOLD guideline. The plasma level of thrombin antithrombin (TAT) and plasminogen activator inhibitor (PAI)-1 were measured using an enzyme linked immunoassay. Results: The plasma TAT was markedly elevated in COPD patients ($10.5{\pm}19.8{\mu}g/L$) compared with those of the control ($3.4{\pm}2.5{\mu}g/L$) (p<0.01). However, the plasma PAI-1 in COPD patients ($29.6{\pm}20.7ng/mL$) was similar to that in the controls. The plasma TAT showed a significant inverse relationship with the RVEF measured by the cardiac MDCT in COPD patients (r=-0.645, p<0.01). However, the plasma PAI-1 did not show a relationship with the RVEF (r=0.022, p=0.92). Conclusion: These results suggest that the coagulation system in COPD patients is markedly activated, and that the plasma level of TAT might be a marker of a right ventricular dysfunction in COPD patients.

• Development and Reproduction
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• v.4 no.1
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• pp.101-108
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• 2000

Objectives: The pleiotrophin (PTN) and midkine (MK) are secreted heparin-binding neurokines that share 50％ sequence homology. PTN and MK are expressed in the range of primary human tumors. The association of PTN and MK with carcinogenesis, enhancement of plasminogen activator activity and angiogenic factor are reported. Patients with endometriosis are characterized by the ability of the endometrium to implant; angiogenic and growth factors may play a significant role in the pathogenesis of endometriosis. To test the hypothesis that higher expression of PTN and MK in endometrium from women with endometriosis might be increase angiogenesis and growth ectopic endometriosis implants, we investigated PTN and MK expression by quantitative and competitive polymerase chain reaction (QC-PCR) in endometrium from women with and without endometriosis throughout the menstrual cycle. Design: MK and PTN mRNA expression in endomeoium from women with endometriosis and control patients without endometriosis were determined by QC-PCR throughout the menstrual cycle. Methods: Endometrial tissue was obtained from 25 patients with severe endometriosis and 30 patients without endometriosis undergoing hysterectomy or endometrial biopsy. Stage of endometrial cycle and a diagnosis of endometriosis were confirmed histologically. Total RNA was extracted and reverse transcribed into c-DNA. QC-PCR was performed to evaluate PTN and MK mRNA expression. Results were analysed by Post Hoc test. Results: MK and PTN were expressed throughout the menstrual cycle in both groups. MK expression was higher in follicular phase than luteal phase in endometrium from normal women. endometrium from endometriosis patients showed increased expression of PTN and MK compared to endometrium from normal women in the luteal phase (p<0.05). Conclusion: Our results suggest that uterine endometrium from women with endometriosis expresses higher levels of MK and PTN than endometrium from normal women during luteal phase. Increased MK and PTN expression may be related to the initiation of ectopic endometrial implants and their subsequent peritoneal invasion.

• Korean Journal of Food Science and Technology
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• v.43 no.2
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• pp.213-219
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• 2011

The metastatic effect of Eupatorium japonicum extract (EJE) on MDA-MB-231 human breast cancer cells was investigated. MDA-MB-231 cells were treated with various concentrations of EJE (0, 5, 10 and $20{\mu}g/mL$). EJE inhibited cell migration, invasion and adhesion of MDA-MB-231 cells in dose-dependent manners. Gelatin zymography exhibited that EJE significantly down regulated secretion of matrix metalloproteinase (MMP)-9 and MMP-2. EJE decreased the protein levels of tissue inhibitor of metalloproteinase (TIMP)-1 but increased TIMP-2 levels. Additionally, EJE reduced the protein and mRNA levels of urokinase-type plasminogen activator (uPA), vascular endothelial growth factor (VEGF) and intercellular adhesion molecule (ICAM). In several solvent fractions of EJE, the hexane fraction markedly decreased MDAMB-231 cell migration. Thus, these finding suggest that EJE may be a potential antimetastatic agent, which can considerably inhibit the metastatic and invasive capacity of breast cancer cells.

• Reproductive and Developmental Biology
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• v.29 no.3
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• pp.187-191
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• 2005

This study was designed to investigate the changes of quantity and quality of proteins in medium and cytoplasm during in vitro maturation of bovine oocytes. The total quantity of proteins in medium decreased from 0 to 4.5 hr, but increased from 13.5 to 18 hr after the onset of in vitro maturation. The total quantity of protein in cytoplasm increased from 0 to 4.5 hr, decreased from 4.5 to 9 hr, and increased after 18 hr after the onset of in vitro maturation. A total of 298 protein spots was detected on a gel of 2D SDS-PAGE form maturation medium. Among 28 protein spots expressed significant differences in their quantity, 8 proteins were identified by peptide mass fingerprinting (aldose reductase, alpha enolase, apolipoprotein A-1 precursor, 43kDa collectin precursor, heat shock 27kDa protein, plasminogen activator inhibitor-1 precursor, thrombospondin 1, transitional endoplasmic reticulum ATPase). Among total of 35 protein spots detected on gel of 2D SDS-PACE from oorytes cytoplasm, $\beta$-tubulin was identified by peptide mass fingerprinting.

• Journal of Microbiology and Biotechnology
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• v.12 no.3
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• pp.457-462
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• 2002

Low Electromagnetic Field (EMF) intensity in the range of $1{\mu}T\;to\;10{\mu}T$(Tesla) was found to enhance the growth of CHO cells and the production of tPA in batch and perfusion cultivations. At $1{\mu}T\;intensity,\;1.3{\times}10^7$ viable cells/ml of maximum cell density and 80 mg/l of maximum tPA production were obtained in batch cultivation, compared to $2.8{\times}10^6$ viable cells/ml and 59 mg tPA/1 in unexposed case (control). A similar trend was observed in the perfusion process, where it was possible to obtain $1.2{\times}10^7$ viable cells/ml of maximum cell density and 81 mg tPA/l of maximum tPA production by more than 80 days of cultivation. However, there was not much difference between $1{\mu}T\;and\;10{\mu}T$ in perfusion cultivation, possibly due to better environmental growth conditions being maintained by continuous feeding of fresh medium into the reactor. On the contrary, both cell growth and tPA production were severely inhibited at higher than 1 mT intensity, showing no growth at 10 mT exposure. Specific growth rate was linearly correlated to specific tPA production rate at $1{\mu}T$EMF intensity, which represents a partially growth-related relationship. It was also found that a large amount of $Ca^2+$ was released at low EMF intensity, even though the cell growth was not much affected. Low EMF intensity significantly improved both cell growth and tPA production, and tPA production seemed to be more affected than the cell growth, possibly due to the changes of cell membrane characteristics. It can be concluded that the elaboration of EMF intensity less than $10{\mu}T$ could improve cell growth and tPA production, but mainly tPA secretion through batch or perfusion process in a bioreactor.

• The Journal of Internal Korean Medicine
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• v.25 no.4
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• pp.18-24
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• 2004

연구배경 : 플라스미노겐 활성 억제인자-1 (plasminogen activator inhibitor-1; PAI-1)은 허혈성 뇌경색의 발생의 원인이 되는 섬유소 용해작용의 저하를 매개하는 인자로서, PAI-1의 작용이 촉진되면 섬유소 용해기능이 저하되어 관상동맥 및 뇌혈관질환의 발생을 증가시키게 된다. PAI-1 유전자의 촉진자(promoter) 영역에는 -675 4G/5G (4G/5G)와A -844G (A/G)의 두 개의 유전자 다형성이 존재하며, 이는 PAI-1의 유전자 전사과정에 영향을 미쳐 혈청 PAI-1의 농도를 증가시키고 결과적으로 허혈성 뇌경색의 발생확률을 높이는 작용을 하게 된다. 연구방법 : 허혈성 뇌경색으로 진단 받은 167명의 환자와 173명의 건강인의 말초혈액에서 DNA를 분리한 후 PAI-1의 4G/5G와 A/G 유전자 다형성에 대한 연쇄중합반응 및 제한효소 절편길이 다형성 (polymerase chain reaction-restriction fragment length polymorphism; PCR-RFLP) 방법을 이용하여 허혈성 뇌경색 발생과 유전자 다형성과의 관계를 비교 분석하였다. 결과 : 허혈성 뇌경색 환자에서의 4G/4G의 유전자형의 빈도는 15.0%으로 정상 대조군의 33.5%에 비해 현저하게 낮게 나타났다 (P < 0.0001). 각각의 유전자형과 허혈성 뇌경색의 발생 위험도 (odd ratio ; OR)와의 관계를 분석했을 때 4G/4G 유전자형을 가질 경우 위험도는 0.35배로 현저하게 낮아졌으며, (P < 0.0001), 5G/5G 유전자형을 가질 경우 위험도는 4.49배 로 현저하게 높아졌다 (P < 0.0001). 그러나, A/G 유전자 다형성과 허혈성 뇌경색의 발생과는 유의한 연관성을 발견하지 못하였다. 결론 : 이상의 결과로 볼 때 PAI-1 유전자의 4G/4G 유전자형은 허혈성 뇌경색의 발생 비율을 감소시키는 작용을 하는 것으로 여겨진다.

• Journal of Life Science
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• v.17 no.7 s.87
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• pp.1019-1022
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• 2007

Thrombolytic therapy with tissue plasminogen activator (tPA) can improve the clinical outcome of ischemic stroke patients. However, its clinical application is limited by narrow therapeutic time windows and elevated risks of cerebral hemorrhage and brain injury. In part, these effects of tPA has been related to matrix metalloproteinase-9 (MMP-9) dysregulation. Here, we investigate that the effects of alteplase (tPA with short half-life) and pamiteplase (a modified tPA with long half-life) on the MMP-9 regulation in neurovascualr unit. The total levels of MMP-2 and MMP-9 in neuronal cells are lower than astrocytes. Alteplase (1-10 ${\mu}g/ml$) induced upregulation of MMP-2 and MMP-9 in rat cortical neurons and astrocytes, respectively. Whereas pamiteplase in a wide range of dose did not affect the MMP-2 and MMP-9 responses in both of cells. These results suggest that pamiteplase with long half-life can be provided as a agent that overcome the side effects of alteplase.

• Molecules and Cells
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• v.38 no.11
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• pp.991-997
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• 2015

Tristetraprolin (TTP) is an AU-rich elements (AREs)-binding protein, which regulates the decay of ARE-scontaining mRNAs such as proto-oncogenes, anti-apoptotic genes and immune regulatory genes. Despite the low expression of TTP in various human cancers, the mechanism involving suppressed expression of TTP is not fully understood. Here, we demonstrate that Resveratrol (3,5,4'-trihydroxystilbene, Res), a naturally occurring compound, induces glioma cell apoptosis through activation of tristetraprolin (TTP). Res increased TTP expression in U87MG human glioma cells. Res-induced TTP destabilized the urokinase plasminogen activator and urokinase plasminogen activator receptor mRNAs by binding to the ARE regions containing the 3' untranslated regions of their mRNAs. Furthermore, TTP induced by Res suppressed cell growth and induced apoptosis in the human glioma cells. Because of its regulation of TTP expression, these findings suggest that the bioactive dietary compound Res can be used as a novel anti-cancer agent for the treatment of human malignant gliomas.

• Journal of Animal Reproduction and Biotechnology
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• v.35 no.4
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• pp.297-306
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• 2020

The aims of the present study were to confirm that regulation of the PA and environment via TGF-β regulation of sperm by Percoll-separated in porcine uterine epithelial cells. And, it was performed to identify the cytokines (TGF-β1, 2 and 3, TGF-β receptor1 and 2; interleukin, IL-6, IL-8) and PA-related genes (urokinase-PA, uPA; tissue-PA, tPA; PA inhibitor, PAI; uPA-receptor, uPAR) by spermatozoa. The experiment used porcine uterus epithelial cells (pUECs) and uterine tissue epithelial cells, Boar sperm were separated by discontinuous Percoll density gradient (45/90%), and tissues were co-incubated with spermatozoa, followed by real-time PCR. PA activity was measured of sperm by discontinuous Percoll density gradient (45/90%) for 24 hours. To measure viability and acrosome damage of sperm double stained propidium iodide (PI) and SYBR-14 or FITC-PNA were used. In results, binding ratio of Percoll-separated sperm was found no differences, but sperms isolated from 90% Percoll layer reduced PA activity (p < 0.05). when co-cultured sperm selected Percoll in porcine uterus tissues epithelial cells, 90% layer sperm increased TGF-β R1, contrastively tPA and PAI-1 in comparison with control (p < 0.05). 45% sperm was decreased the expression of uPA (p < 0.05). TGF-β decreased PA activity in the supernatant collected from pUECs (p < 0.05). Especially, The group including uPA, PAI-1 were induce sperm intact, while it was reduced in sperm damage when compared to control (p < 0.05). Also, there was no significant difference group of tPA and tPA+I in the dead sperm and acrosome damage compared to control. The expression of tPA and PAI showed a common response. Percoll-separated spermatozoa in 90% layer reduced tPA and IL-related gene mRNA expression. Thus, Percoll-sparated sperm in 90% layer show that it can suppress inflammation through increased expression of TGF-β and downregulation of PA and IL in epithelial cells compared to 45% layer Percoll.

• Tuberculosis and Respiratory Diseases
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• v.87 no.3
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• pp.378-385
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• 2024

Background: Intrapleural fibrinolytic therapy (IPFT) has been used as an effective agent since 1949 for managing complicated pleural effusion and empyema. Several agents, such as streptokinase, urokinase (UK), and recombinant tissue plasminogen activator (rt-PA), have been found to be effective with variable effectiveness. However, a head-tohead controlled trial comparing the efficacy of the most frequently used agents, i.e., UK and rt-PA (alteplase) for managing complicated pleural effusion has rarely been reported. Methods: A total of 50 patients were randomized in two intervention groups, i.e., UK and rt-PA. The dose of rt-PA was 10 mg, and that of UK was 1.0 lac units. UK was given thrice daily for 2 days, followed by clamping to allow the retainment of drugs in the pleural space for 2 hours. rt-PA was instilled into the pleural space twice daily for 2 days, and intercostal drainage was clamped for 1 hour. Results: A total of 50 patients were enrolled into the study, of which 84% (n=42) were males and 16% (n=8) were females. Among them, 30 (60%) patients received UK, and 20 (40%) patients received alteplase as IPFT agents. The percentage of mean±standard deviation changes in pleural opacity was -33.0%±9.9% in the UK group and -41.0%±14.9% in the alteplase group, respectively (p=0.014). Pain was the most common adverse side effect, occurring in 60% (n=18) of the patients in the UK group and in 40% (n=8) of the patients in the alteplase group (p=0.24), while fever was the second most common side effect. Patients who reported early (within 6 weeks of onset of symptoms) showed a greater response than those who reported late for the intervention. Conclusion: IPFT is a safe and effective option for managing complicated pleural effusion or empyema, and newer agents, such as alteplase, have greater efficacy and a similar adverse effect profile when compared with conventional agents, such as UK.