Proceedings of the Korea Society of Environmental Toocicology Conference
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2003.05a
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pp.183-184
/
2003
Sophoricoside was isolated as the inhibitor of IL-5 bioactivity from Sophora japonica (Leguminosae). It has been reported to have an anti-inflammatory effect on rat paw edema model. To develop as an anti-allergic drug, genotoxicity of sophoricoside was investigated in bacterial and mammalian cell system such as Ames bacterial test, chromosomal aberration assay, Comet assay and MOLY assay. In Ames test, sophoricoside of 5000 ∼ 313 $\mu\textrm{g}$/plate concentrations was not shown significant mutagenic effect in Salmonella typhimurium TA98, TA100, TA1535 and TA1537 strains. The cytotoxicity (IC$\_$50/ and IC$\_$20/) of sophoricoside was determined above the concentration of 5000 $\mu\textrm{g}$/ml in Chinese hamster lung (CHL) fibroblast cell and L5178Y mouse lymphoma cell line. At concentrations of 5000, 2500 and 1250 $\mu\textrm{g}$/ml, this compound was not induced chromosomal aberration in CHL fibroblast cell in the absence and presence of S-9 metabolic activation system. Also in comet assay, DNA damage was not observed in L5178Y cell line. Also in MOLY assay, sophoricoside of 5000 ∼ 313 $\mu\textrm{g}$/ml concentrations was not shown significant mutagenic effect in absence of S-9 metabolic activation system. However, the higher concentration of 5000 and 2500 $\mu\textrm{g}$/ml of sophoricoside induced the increased mutation frequency (MF) in the presence of S-9 metabolic activation system. From these results, no genotoxic effects of sophoricoside observed in bacterial systems whereas, genotoxic effects observed in mammalian cell systems in the presence of metabolic activation system. These results suggested that the metabolite(s) of sophoricoside can cause some genotoxic effects in mammalian cells.
Liposomes are spherical vesicles composed of lipid bilayer membranes. However, the conventional liposomes have been found to be plagued by rapid opsonization and taken up by the reticuloendothelial system (RES), resulting in shortened circulation time and limited intracellular uptake to target cell. In this study, polyethyleneglycol-cationic liposomes (PCL) containing cationic lipid and DSPE-mPEG were prepared by thin film cast-hydration method. The PEG liposomes had approximately $97.0{\pm}1.3\;nm$ of mean particle diameter and $-21.7{\pm}1.2\;mV$ of zeta potential value. PCL had $96.4{\pm}1.8\;nm$ of mean particle diameter and $-8.7{\pm}1.1\;mV$ of zeta potential value with a decrease of about 10 mV compared to the PEG liposomes. Loading of model drug, doxorubicin (DOX), in liposomes were carried out by using remote loading method and the loading efficiency of DOX in liposomes was about $95.0{\pm}1.9%$. Intracellular uptake and cytotoxicity of PCL were higher than that of PEG liposomes to murine B16F10 melanoma cells. In addition, anti-tumor activity of PCL was similar to that of PEG liposomes on growth of A549 human lung carcinoma in BALB/c mice. Consequently, PCL modified with cationic lipid may be applicable as anticancer drug carriers that can increase intracellular uptake and therapeutic efficacy.
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vascular remodeling of pulmonary arteries (PAs) and increased vascular resistance in the lung. Monocrotaline (MCT), a toxic alkaloid, is widely used for developing rat models of PAH caused by injury to pulmonary endothelial cells; however, characteristics of vascular functions in MCT-induced PAH vary and are not fully understood. Here, we investigated hypoxic pulmonary vasoconstriction (HPV) responses and effects of various vasoconstrictors with isolated/perfused lungs of MCT-induced PAH (PAH-MCT) rats. Using hematoxylin and eosin staining, we confirmed vascular remodeling (i.e., medial thickening of PA) and right ventricle hypertrophy in PAH-MCT rats. The basal pulmonary arterial pressure (PAP) and PAP increase by a raised flow rate (40 mL/min) were higher in the PAH-MCT than in the control rats. In addition, both high $K^+$ (40 mM KCl)- and angiotensin II-induced PAP increases were higher in the PAH-MCT than in the control rats. Surprisingly, application of a nitric oxide synthase inhibitor, L-$N^G$-Nitroarginine methyl ester (L-NAME), induced a marked PAP increase in the PAH-MCT rats, suggesting that endothelial functions were recovered in the three-week PAH-MCT rats. In addition, the medial thickening of the PA was similar to that in chronic hypoxia-induced PAH (PAH-CH) rats. However, the HPV response (i.e., PAP increased by acute hypoxia) was not affected in the MCT rats, whereas HPV disappeared in the PAH-CH rats. These results showed that vascular contractility and HPV remain robust in the MCT-induced PAH rat model with vascular remodeling.
Influence of loneliness on human survival has been established epidemiologically, but genomic research remains undeveloped. We identified 34 loneliness-associated genes which were statistically significant for high-lonely and low-lonely individuals. With the univariate Cox proportional hazards regression model, we obtained corresponding regression coefficients for loneliness-associated genes fo individual cancer patients. Furthermore, risk scores could be generated with the combination of gene expression level multiplied by corresponding regression coefficients of loneliness-associated genes. We verified that high-risk score cancer patients had shorter mean survival time than their low-risk score counterparts. Then we validated the loneliness-associated gene signature in three independent brain cancer cohorts with Kaplan-Meier survival curves (n=77, 85 and 191), significantly separable by log-rank test with hazard ratios (HR) >1 and p-values <0.0001 (HR=2.94, 3.82, and 1.78). Moreover, we validated the loneliness-associated gene signature in bone cancer (HR=5.10, p-value=4.69e-3), lung cancer (HR=2.86, p-value=4.71e-5), ovarian cancer (HR=1.97, p-value=3.11e-5), and leukemia (HR=2.06, p-value=1.79e-4) cohorts. The last lymphoma cohort proved to have an HR=3.50, p-value=1.15e-7. Loneliness-associated genes had good survival prediction for cancer patients, especially bone cancer patients. Our study provided the first indication that expression of loneliness-associated genes are related to survival time of cancer patients.
Purpose : This study was performed to evaluate anti-thrombotic and anti-inflammatory effects of BokbangHongdeungPaejangSan water extract (BHPS). Methods : BHPS was investigated using cultured cells and a murine models. As for the parameters of inflammation, levels of several inflammatory cytokines and chemical mediators which are known to be related to inflammation were determined in mouse lung fibroblast cells (mLFC) and RAW 264.7 cells. Results : In experiment of anti-thrombotic effect, BHPS inhibited the platelet aggregation induced by ADP and epinephrine, and inhibited pulmonary embolism induced by collagen and epinephrine. BHPS increased Platelet number and fibrinogen amount, and shortened PT and APTT in thrombus model induced by dextran. In experiment of anti-inflammatory effect, BHPS inhibited IL-1${\beta}$, IL-6, TNF-${\alpha}$, COX-2 and NOS-II mRNA expression in a concentration-dependent manner in RAW 264.7 cell line, and inhibited significantly NO production at 50, 100 ${\mu}g/ml$, and also inhibited ROS production in a concentration-dependent manner. BHPS inhibited IL-1${\beta}$, IL-6 and TNF-${\alpha}$ production significantly in serum of acute inflammation-induced Balb/c mice, and decreased IL-1${\beta}$, IL-6 and TNF-${\alpha}$ production in spleen tissue, but increased IL-1${\beta}$, IL-6 and TNF-${\alpha}$ production in liver tissue. BHPS increased survival rate at the 3th day in ICR mice with lethal endotoxemia induced by LPS. Conclusion : These results suggest that BHPS can be used for treating diverse female diseases caused by thrombosis and inflammation such as endometriosis, pelvic pain, cervicitis, pelvic inflammatory disease and pelvic tuberculosis and so forth.
Ahn, Yeh-Chan;Chae, Yu-Gyeong;Hwang, Sang Seok;Chun, Bong-Kwon;Jung, Maan Hong;Nam, Sung Jin;Lee, Hae-Young;Chung, Jae Min;Oak, Chulho;Park, Eun-Kee
Journal of the Optical Society of Korea
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v.19
no.1
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pp.69-73
/
2015
The mesothelium is an essential lining for maintaining the normal homeostasis of the closed body cavity and a central component of pathophysiologic processes. The mesothelium has been known as the end target for asbestos which induces asbestos-related lung diseases. Malignant mesothelioma (MM) is a rare and fatal neoplasm predominantly due to asbestos exposure. Adaptation of an advanced and reliable technology is necessary for early detection of MM because it is difficult to diagnose this disease in its early stages. Optical coherence tomography (OCT) provides cross-sectional images of micro-tissue structures with a resolution of $2-10{\mu}m$ that can image the mesothelium with a thickness of ${\sim}100{\mu}m$ and, therefore, enable investigation of early development of MM. The mesothelium is typically located at the pleura and tunica vaginalis of the scrotum. In this study, we developed animal window models in the above two anatomical sites to visualize mesothelial layers within the mesothelium. OCT images at the two locations were also acquired.
Colorectal cancer is second only to lung cancer as a cause of death due to cancer in the united States. Studies have shown that fecal occult blood(FOB) tests are effective in detecting colorectal cancer in its early stages. To motivate worksite FOB testing, a randomized controlled trial was conducted. Employees 40 years or older from three federal agencies in Washington State were randomized to a control group(n=139) which received a letter stating the availability of the FOB test at the worksite clinic or to an intervention group(n=139) which received the letter about facts on colorectal cancer and a Colorectal Cancer Risk Appraisal. The Colorectal Cancer Risk Appraisal included a feedback on an individual's risk of developing colorectal cancer compared to his / her peers in terms of ‘normal’, ‘moderate’, or ‘high’ risk status. After 3 months, a follow-up questionnaire was sent to all participants to measure the effectiveness of the intervention. In the analysis of the three major outcomes, two possible confounding factors(dietary fat and family history of colorectal cancer) were controlled by logistic regression. Based on a review of the worksite clinic records, the Intervention group had 4.3% higher compliance rate with the FOB test during the follow-up period compared to the control group(p=.10). The largest effect of the intervention was on the employees' intention to get a FOB test within the next year(62.6% in the intervention group vs. 36.2% in the control group, OR=3.18, p<.001). In the final Multivariate logistic model, the employees who were more likely to intend to get a FOB test within the next year were in the intervention group ; were at ‘moderate’ or ‘high’ risk of colorectal cancer ; knew more about the availability of the FOB test at the worksite clinic ; and had a FOB test during the last three years.
Kim, Ji Hye;Lee, Jin Hwa;Ryu, Yon Ju;Chang, Jung Hyun
Tuberculosis and Respiratory Diseases
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v.73
no.3
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pp.162-168
/
2012
Background: Idiopathic pulmonary fibrosis (IPF) is a progressive disease. Effective treatment is not currently available and the prognosis is poor. The aim of our study was to identify clinical predictors of survival in patients with IPF. Methods: By using medical record database of a university hospital, we reviewed the records of patients who had been diagnosed as having IPF from January 1996 through December 2007. Results: Among 89 patients considered as having interstitial lung disease (ILD) on computed tomography (CT) of the chest, 22 were excluded because of the diagnosis of other ILDs or connective tissue disease, and finally, 67 met the criteria of IPF. The mean age at the diagnosis of IPF was 70 years (range, 41~87 years) and 43 (64%) were male. The mean survival time following the diagnosis of IPF was 40 months (range, 0~179 months). Among them, 28 cases were diagnosed as the progressive state of IPF on the follow-up CT examination, and the mean duration between diagnosis of IPF and progression was 31 months. Multivariate analysis using Cox regression model revealed that body mass index (BMI) less than 18.5 $kg/m^2$ (p=0.030; hazard ratio [HR], 12.085; 95% confidence interval [CI], 1.277~114.331) and CT progression before 36 months from the diagnosis of IPF (p=0.042; HR, 13.564; 95% CI, 1.101~167.166) were independently associated with mortality. Conclusion: Since low BMI at the diagnosis of IPF and progression on follow-up CT were associated with poor prognosis, IPF patients with low BMI and/or progression before 36 months following the diagnosis should be closely monitored.
Kim Sang-Gi;Jung Hyuk;Kim Bo-Ae;Choi Yoong-Suk;Kim Sang-Kook;Choi Gui-Hyang;Park Jong-Seok;Suh Tae-Soo;Kim You-Young
Biomedical Science Letters
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v.12
no.3
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pp.281-287
/
2006
Cigarette smoke causes atypical structure of pulmonary and oxidative damage. Therefore, we carried out to determine if exposure to cigarette smoke alters pulmonary structure and anti-oxidant related enzyme in a animal model, when natural product extracts using by Nebulizer. The rat were divided into four groups: $H_2O-treated$ (Control), natural product (Camellia sinensis) extracts-treated (CS), natural product extracts-treated with cigarette smoke-exposed (CS+SM) and cigarette smoke-expose (SM). All groups are similar to Control group in weight, but SM group is lower than the other groups. Microscopic image of the pulmonary structure in SM group showed deleterious alterations in the morphology, but the other groups are maintained in normal structure. In anti-oxidant related enzymes, SOD (superoxide dismutase) and catalase, SM group represents the lowest enzyme activity among all groups. But G6PD (glucose-6-phosphate dehydrogenase) and LPO (lipid peroxidation) is SM group represents the highest enzyme activity among all groups. These result indicate that the natural product extracts is an efficient tissue protective substance against smoke-induced lung injury.
Kim, Ji-Man;Kim, Hee-Moon;Jung, Bo-Young;Park, Eun-Cheol;Cho, Woo-Hyun;Lee, Sang-Gyu
Asian Pacific Journal of Cancer Prevention
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v.13
no.4
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pp.1371-1376
/
2012
Background: Economic status is known to be directly or indirectly related to cancer incidence since it affects accessibility to health-related social resources, preventive medical checkups, and lifestyle. This study investigates the relationship between cancer incidence and family income in Korea. Methods:Using the Korean National Health Insurance cancer registration data in 2009, the relationship between their family income class and cancer risk was analyzed. The age-standardized incidence rates of the major cancers were calculated for men and women separately. After adjusting for age, residential area, and number of family members, cancer risks for major cancers according to family income class were estimated using a logistic regression model. Results: In men, the risk of stomach cancer for Income Class 5 (lowest) was 1.12 times (95% CI 1.02-1.23) higher than that of Income Class 1 (highest), for lung cancer 1.61 times (95% CI 1.43-1.81) higher, for liver cancer 1.22 times (95% CI 1.08-1.37) higher, and for rectal cancer 1.37 times higher (95% CI 1.18-1.59). In women, the risk of stomach cancer for Income Class 5 was 1.22 times higher (95% CI 1.08-1.37) than that for Income Class 1, while for cervical cancer it was 2.47 times higher (95% CI 2.08-2.94). In contrast, in men, Income Class 1 showed a higher risk of thyroid cancer and prostate cancer than that of Income Class 5, while, in women the same was the case for thyroid cancer. Conclusions: The results show the relationship between family income and cancer risk differs according to type of cancer.
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