• 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.

• Clinical and Experimental Reproductive Medicine
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• v.29 no.3
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• pp.209-214
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• 2002

Objective : To analyze the clinical characteristics of obese infertile women. Material and Method: Height, weight, body mass index, menstrual pattern, glucose, insulin, glucose/insulin ratio, dehydroepiandrosterone sulfate (DHEA-S), testosterone, free testosterone and plasminogen activator inhibitor (PAI-1) of 15 obese infertile women were tested. Results: Of 15 obese infertile women, the number of diabetes mellitus, hyperinsulinemia, and insulin resistance was 2 (13%), 2 (13%), 2 (13%), respectively. The incidence of increased DHEA-S, testosterone, and free testosterone was 7 (47%), 1 (7%), 6 (40%), respectively. Notably, all patients showed increased PAI-1. Conclusions: Obesity is associated with infertility as well as many kinds of health problems. Obesity is closely related to insulin resistance and it also causes hyperandrogenism. Increased PAI-1 is one of the important causes of thrombophilia. Consequently, in the workup of obese infertile patient, many aspects of health problems should be considered.

• 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.49 no.2
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• pp.149-161
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• 2000

Background : Residual pleural thickening (RPT) develops in about 50% of tuberculous pleurisy ($PL_{TB}$). Some reports have suggested that elevated TNF-$\alpha$ and impaired fibrinolysis could be the cause of RPT, but until now, the mechanism and predictors of RPT have not been well known. TGF-$\beta$ has been known to promote fibrogenesis and is increased in tuberculous pleural fluid (PF). $PL_{TB}$ and malignant pleurisy ($PL_{MAL}$) manifest lymphocyte-dominant exudative pleural effusion, and it has clinical implications in the differentiation of the two diseases based on the findings of pleural effusion. We performed this study to compare pleural fluid TNF-$\alpha$ TGF-$\beta$, and fibrinolytic parameters between $PL_{TB}$ and $PL_{MAL}$, and to find the predictors of RPT in $PL_{TB}$. Methods : Thirty-five $PL_{TB}$ and 14 $PL_{MAL}$ patients who were admitted to the Asan Medical Center from February 1997 to August 1999 were enrolled. All $PL_{TB}$ patients were prescribed a primary, short-course, anti-tuberculosis regimen. INF-$\alpha$ tissue plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1), plasminogen, $\alpha$2-antiplasmin, and D-dimer were measured in both PF and PB. TGF-$\beta$was measured only in PF. Clinical characteristics, TNF-$\alpha$ TGF-$\beta$ and fibrinolytic parameters were compared between patients with RPT less than 2 mm and patients with more than 2 mm of the thirty patients who completed the anti-tuberculosis treatment. Results : The levels of TNF-$\alpha$ tPA, PAI-1, plasminogen, $\alpha$2-antiplasmin, and D-dimer in PF were higher than those in peripheral blood (PB) in $PL_{TB}$, whereas only plasminogen, $\alpha$2-antiplasmin, and D-dimer were higher in PF than in PB in $PL_{MAL}$. Pleural fluid TNF-$\alpha$ TGF-$\beta$, PAI-1, plasminogen, $\alpha$2-antiplasmin were increased in $PL_{TB}$ compared with $PL_{MAL}$, but these factors did not show any further advantages over ADA in differentiation between $PL_{TB}$ and $PL_{MAL}$. TNF-$\alpha$ TGF-$\beta$ and fibrinolytic parameters did not show any differences between patients with RPT less than 2 mm and patients with RPT more than 2 mm. Conclusion : Our data suggest that TNF-$\alpha$, TGF-$\beta$ and fibrinolytic parameters may play some role for the development of RPT in $PL_{TB}$, but they failed to predict the occurrence of RPT in $PL_{TB}$. Also these parameters did not seem to have any advantages over ADA in differentiating between two diseases.

• Herbal Formula Science
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• v.26 no.3
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• pp.183-193
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• 2018

Objectives : In Traditional Korean Medicine, Epimedium koreanum Nakai has diverse pharmacological activities to treat impotence, forgetfulness, cataract and exophthalmos. Present study investigated anti-fibrogenic effects of E. koreanum water extract (EKE) in hepatic stellate cells (HSCs). Methods : To study anti-fibrogenic effects of EKE, LX-2 cells, a human immortalized HSCs, were pre-treated with $3-300{\mu}g/mL$ of EKE, and then subsequently exposed to 5 ng/mL of transforming growth $factor-{\beta}1$ ($TGF-{\beta}1$). Expression level of ${\alpha}-smooth$ muscle actin was determined by immunoblot analysis. Phosphorylation of Smad, transactivation of Smad, and expression of plasminogen activator inhibitor-1 (PAI-1) were monitored to investigate the effect of EKE on $TGF-{\beta}1-mediated$ signaling pathway. Results : Up to $100{\mu}g/mL$, EKE did not show any cytotoxicity on LX-2 cells. Pre-treatment of EKE ($100{\mu}g/mL$) significantly inhibited ${\alpha}-smooth$ muscle actin expression induced by $TGF-{\beta}1$. In addition, EKE significantly decreased Smad2 and Smad3 phosphorylations, Smad binding element-driven luciferase activity and PAI-1 expression by $TGF-{\beta}1$. Of three flavonoid compounds found in EKE, only quercertin ($30{\mu}M$) attenuated $TGF-{\beta}1-mediated$ PAI-1 expression. Conclusion : These results suggest that EKE has an ability to suppress fibrogenic process in HSCs via inhibition of $TGF-{\beta}1/Smad$ signaling pathway.

• Journal of Life Science
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• v.22 no.10
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• pp.1371-1377
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• 2012

Fibrosis in kidney by internal and external factors causes progressive loss of renal function. Renal fibrosis is the inevitable consequence of an excessive accumulation of the extracellular matrix. TGF-${\beta}$ plays an important role in the process of renal fibrosis and stimulates the synthesis of profibrotic factors, including collagens, fibronectin, and plasminogen activator inhibitor (PAI-1). We examined the effect of Moringa oleifera Lam (moringa) extracts in a rat kidney fibrosis model. We found that moringa root extract suppresses protein expression/mRNA levels of Type I collagen, fibronectin, and PAI-1 induced by TGF-${\beta}$ in renal fibroblasts. Moringa root extract selectively inhibited phosphorylation of TGF-${\beta}$-induced $T{\beta}RII$ and the downstream signaling pathway (e.g., Smad4), and phospho-ERK, but not JNK, p38, or PI3K/AKT. These results suggest that moringa root extract can act against TGF-${\beta}$-induced renal fibrosis in rat kidney fibroblast cells by a mechanism related to its antifibrotic activity, which regulates expression of fibronectin, Type I collagen, and PAI-1 through $T{\beta}RII$-Smad2/3-Smad4 and ERK. Therefore, moringa root extract is an effective substance for fibrosis therapy and provides a new therapeutic strategy for diseases associated with elevated profibrotic factor synthesis.

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.116-126
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• 2023

Mainly due to the slanted focus on the mechanism and regulation of neuronal aging, research on astrocyte aging and its modulation during brain aging is scarce. In this study, we established aged astrocyte culture model by long-term culturing. Cellular senescence was confirmed through SA-β-gal staining as well as through the examination of morphological, molecular, and functional markers. RNA sequencing and functional analysis of astrocytes were performed to further investigate the detailed characteristics of the aged astrocyte model. Along with aged phenotypes, decreased astrocytic proliferation, migration, mitochondrial energetic function and support for neuronal survival and differentiation has been observed in aged astrocytes. In addition, increased expression of cytokines and chemokine-related factors including plasminogen activator inhibitor -1 (PAI-1) was observed in aged astrocytes. Using the RNA sequencing results, we searched potential drugs that can normalize the dysregulated gene expression pattern observed in long-term cultured aged astrocytes. Among several candidates, minoxidil, a pyrimidine-derived anti-hypertensive and anti-pattern hair loss drug, normalized the increased number of SA-β-gal positive cells and nuclear size in aged astrocytes. In addition, minoxidil restored up-regulated activity of PAI-1 and increased mitochondrial superoxide production in aged astrocytes. We concluded that long term culture of astrocytes can be used as a reliable model for the study of astrocyte senescence and minoxidil can be a plausible candidate for the regulation of brain aging.

• Korean Journal of Community Nutrition
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• v.3 no.5
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• pp.695-706
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• 1998

This study was designed to investigate the associations of the percent body fat dietary intake, plasma lipoprotein profile, lipoprotein(a), and plasminogen activator inhibitor-1(PAI-1) concentrations of 1982 Korean subjects(men : 1000 and women : 982) between the ages of 40 and 59 years. The dietary assessment consisted of twenty-four hour dietary records and food frequency questionnaires. The subjects were identified into one of the five rating groups of % body fat : lean, underweight, normal, overweight and obese groups. The biochemical assessment included measurements of plasma total cholesterol(TC), HDL-cholesterol(HDL-C), LDL-cholesterol(LDL-C), triglyceride(TG), lipoprotein(a)(Lp(a)), and PAI-1. With respect to the ratio of percent energy intake of carbohydrate : protein : fat of the normal group of the women was 62% : 17% : 20%, respectively. Women apparently had a higher intake of carbohydrates than men(52% : 17 : 20%) did. There was a linear relationship between energy intake and % body fat in both mean and women(with the exception of the underweight group of women). The relationship of % body fat of men to the protein and fat intake was higher than that of the carbohydrate intake. Of the men in the study, intakes of energy, protein and alcohol were positively correlated to % body fat. In women, energy, carbohydrate and protein intake were positively correlated to % body fat, however, the fat, cholesterol and alcohol intake did not show any correlation to the % body fat in women. This study showed that % body fat was positively correlated with plasma TC, LDL-C, PAI-1 levels, and TG, but the % body fat was negatively correlated with plasma HDL-C level in both men and women. These results indicated that the high energy intake of obese or overweight subjects might contribute to several of the biochemical indices fo coronary heart disease(CHD) risk. In conclusion, increased energy intake is associated with overweight or obesity in middle aged Korean people. There was no relationship between % energy intake of fat and % body fat in the study, in middle-aged Korean men and women. The plasma lipid profile and PAI-1 level thought to be the risk factors of CHD were positively associated with percent body fat in middle aged Korean people.

• Korean Journal of Community Nutrition
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• v.6 no.1
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• pp.51-68
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• 2001

This investigation studied the relationship between Body Mass Index(BMI) and dietary intake, levels of serum lipid, lipoprotein(a) and plasminogen activator inhibitor-1(PAI-1) of 28.449 Korean adults(16.937 men, 11.542 women) from 1995 to 1999. The dietary assessment was conducted using 24-hour dietary records and food frequency questionnaires. During this five year study, the BMI normal-weight group, as a percentage of the annual test population, decreased from 68.0% to 60.2%, while the BMI overweight and obese groups collectively increased from 25.0% to 29.7%. The levels of serum total cholesterol (TC), LDL-cholesterol(LDL-C), Triacylglycerol(TG) and PAI-1 increased as the values of BMI increased, while the levels of HDL-cholesterol(HDL-C) and lipoprotein(a)(men only) appeared to decrease as values of BMI increased. The levels of daily energy intake also increased as values of BMI increased in both men and women. The obese group had significantly higher levels of carbohydrate, protein, fat(men only), and cholesterol intake than those of the normal-weight, underweight, and overweight groups. In men, BMI positively correlated with the levels of macronutrients and cholesterol intake(p＜0.001), % energy of protein, fat, and alcohol intake(p＜0.001), and the levels of serum TC, LDL-C, TG and PAI-1(p＜0.001), while BMI negatively correlated with % energy of carbohydrate intake, and the levels of Lp(a) and HDL-C(p＜0.001). In women, BMI negatively correlated with level of cholesterol(p＜0.01), fat(p＜0.001), alcohol intake(p＜0.05),% energy of fat (p＜0.001), % energy of alcohol intake and level of and HDL-C(p＜0.001). Subjects who had serum TC, LDL-C, HDL-C, and TG levels greater than the standard reference values(TC＞240mg/㎗, LDL-C＞130mg/㎗, HDL-C＞35, TG＞200mg/㎗) exhibited a higher intake of the three macronutrients, iron, calcium, meat, milk and fatty foods than those subjects who had serum lipid concentrations less-than-or-equal-to the standard reference values. Overall, there was positive correlation between the high risk factors of vascular disease variables, dietary intake, and BMI. Prevalence of hypertension and high blood sugar were increased as BMI increased, but the prevalence of hypertension is decreased as the year goes by. These findings showed that dietary intake, level of serum lipids and other vascular disease risk factors increased as BIM increased. Therefore, middle or upper class Korean adults who have high BMI should improve their eating habits. This involve reducing alcohol, animal fat, high carbohydrate foods, and overall food intake, and balancing intake in order to lower vascular disease risk factors, including obesity.

• Nutrition Research and Practice
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• v.16 no.6
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• pp.716-728
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• 2022

BACKGROUND/OBJECTIVES: An imbalanced adipokine profile in obesity increases the susceptibility to obesity-related cardiometabolic alterations, including type 2 diabetes, hypertension, dyslipidemia, and non-alcoholic fatty liver disease. The mulberry plant has been reported to have health benefits, such as hypolipidemic and hepatoprotective effects. This study examined the effects of a mulberry (Morus alba L.) fruit ethanol extract (MBEE) on dyslipidemia, liver steatosis, and adipokine imbalance in response to a high-fat diet. MATERIALS/METHODS: Male Sprague-Dawley rats were assigned to one of 4 groups containing 6 rats each and fed either a control diet (CON), a high-fat diet (HFD), or a high-fat diet with MBEE of 150 mg/kg/day (LMB) or 300 mg/kg/day (HMB). The triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities were measured spectrophotometrically. The leptin, adiponectin, and plasminogen activator inhibitor-1 (PAI-1) levels were determined by an enzyme-linked immunosorbent assay. RESULTS: The plasma TG levels were similar in the 4 groups. Plasma cholesterol and low-density lipoprotein cholesterol (LDL-C) levels and TC/HDL-C ratio increased in the HFD group compared with the CON group, whereas those values decreased in the LMB group (P < 0.05), indicating that MBEE had a plasma lipid-lowering effect. HDL-C decreased in the HFD group, but MBEE did not affect the HDL-C level. The HFD rats significantly increased hepatic TG and cholesterol levels and plasma ALT and AST activities compared to the CON group. The hepatic TG level and ALT and AST activities were reduced markedly by the MBEE treatment. The HFD group showed a higher PAI-1 level, whereas MBEE treatment, especially in the HMB group, significantly reduced leptin level, and leptin/adiponectin and PAI-1/ adiponectin ratios. These findings suggest that MBEE altered the imbalance between the pro-and anti-inflammatory adipokines to a more anti-inflammatory state. CONCLUSIONS: MBEE could protect against abnormal lipid metabolism and hepatic steatosis induced by a high-fat diet, lowering plasma cholesterol, LDL-C and TC/HDL-C, and hepatic TG. These findings are associated with the regulating effect of MBEE on the leptin/adiponectin and PAI-1/adiponectin ratios.