• Journal of Life Science
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• v.26 no.3
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• pp.376-386
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• 2016

Apoptosis induction has been proposed as an efficient mechanism by which malignant tumor cells can be removed following chemotherapy. The intrinsic mitochondria-dependent apoptotic pathway is frequently implicated in chemotherapy-induced tumor cell apoptosis. Since DNA-damaging agent (DDA)-induced apoptosis is mainly regulated by the tumor suppressor protein p53, and since more than half of clinical cancers possess inactive p53 mutants, microtubule-damaging agents (MDAs), of which apoptotic effect is mainly exerted via p53-independent routes, can be promising choice for cancer chemotherapy. Recently, we found that the apoptotic signaling pathway induced by MDAs (nocodazole, 17α-estradiol, or 2-methoxyestradiol) commonly proceeded through mitotic spindle defect-mediated prometaphase arrest, prolonged Cdk1 activation, and subsequent phosphorylation of Bcl-2, Mcl-1, and Bim in human acute leukemia Jurkat T cells. These microtubule damage-mediated alterations could render the cellular context susceptible to the onset of mitochondria-dependent apoptosis by triggering Bak activation, Δψm loss, and resultant caspase cascade activation. In contrast, when the MDA-induced Bak activation was inhibited by overexpression of anti-apoptotic Bcl-2 family proteins (Bcl-2 or Bcl-xL), the cells in prometaphase arrest failed to induce apoptosis, and instead underwent mitotic slippage and endoreduplication cycle, leading to formation of populations with 8N and 16N DNA content. These data indicate that cellular apoptogenic mechanism is critical for preventing polyploid formation following MDA treatment. Since the formation of polyploid cells, which are genetically unstable, may cause acquisition of therapy resistance and disease relapse, there is a growing interest in developing new combination chemotherapies to prevent polyploidization in tumors after MDA treatment.

• Journal of Life Science
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• v.26 no.5
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• pp.509-518
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• 2016

Asparagus cochinchinensis is a medical plant that has long been used to treat fever, cough, kidney disease, breast cancer, inflammatory disease and brain disease in northeast Asian countries. Although several studies have been conducted on the anti-neuroinflammatory effects of A. cochinchinensis, the correlation between these effects and nerve growth factor (NGF) has not yet been examined. In this study, we investigated the effects of an aqueous extract of A. cochinchinensis (AEAC) on the secretion and action mechanism of NGF in neuronal cells. The concentration of the NGF protein in the supernatant collected from cultured cells increased significantly in B35 cells treated with AEAC in comparison with the vehicle-treated group without any specific cytotoxicity. Furthermore, the mRNA expression of NGF showed a very similar pattern to its protein concentration. To examine the bioactivity of NGF secreted from B35 cells, undifferentiated PC12 cells were cultured in an AEAC-conditioned medium and neuritic outgrowth was observed. The dendrite length of PC12 cells in the AEAC-treated group was significantly higher than that in the vehicle-treated group. Moreover, the level of the downstream effectors p-TrkA and p-ERK of the high-affinity NGF receptor was significantly higher in the AEAC-treated group, while the expression of the downstream effectors of the low-affinity NGF receptor was significantly lower in the same group. These results suggest that AEAC may contribute to the regulation of NGF expression and secretion in neuronal cells; it is therefore an excellent candidate for further investigation as a therapeutic drug for neurodegenerative diseases.

• Journal of Life Science
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• v.24 no.10
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• pp.1151-1156
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• 2014

Traditional medicinal plants are widely used to treat many diseases, such as inflammation, infections, and even cancer. Ulmus macrocarpa Hance, a Chinese elm species, is distributed in Korea, China, and Japan. The stem bark is widely employed in Korean traditional medicine to treat dermatitis, mastitis, and edema. The aim of this study was to investigate whether water extract of U. macrocarpa Hance bark (Ulmus cortex) has a immune-modulating function in a mouse model. Three different concentrations (30 mg/kg, 100 mg/kg, and 300 mg/kg) of Ulmus cortex water extract (UCWE) were orally administered to mice for 14 days, and their immune responses were analyzed. Cytokines, such as interleukin (IL)-2, IL-12, and IFN-${\gamma}$, increased in the blood of UCWE-fed groups when compared with a control group. In contrast, the IL-4 level did not change in any of the UCWE-fed groups Cell-mediated cytotoxicity was also assayed using lymphokine-activated killer cells (LAK). LAK showed greater cytotoxicity in the UCWE-fed groups than LAK in the control group. Internal organ indices, such as liver, kidney, spleen, and thymus, were similar in all the groups, including the control group, indicating that UCWE may have been nontoxic in the experimental animals. These data suggest that UCWE has an immune-modulating function in a mouse model.

• Tuberculosis and Respiratory Diseases
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• v.53 no.5
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• pp.510-518
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• 2002

Background : Bronchial anthracofibrosis (BAF) is a dark black or brown pigmentation of multiple large bronchi associated with a fibrotic stenosis or obliteration that is incidentally found during a diagnostic bronchoscopy some reporters have suggested endobronchial tuberculosis or tuberculous lymphadenitis as a possible cause of BAF. However, some BAF patients do not have any medical history of tuberculosis. The aim of this study was to elucidate the clinical features of simple BAF patients, which were not associated with tuberculosis. Methods : We reviewed the patients' charts retrospectiely and interviewed all BAF patients who were followed up for 1 year or more. Among the 114 BAF patients, 43 patents (38 %) had no associated tuberculosis, cancer and pneumoconiosis. The clinical characteristics, radiological findings and associated pulmonary diseases of these patients were evaluated. Results : Most patients were non-smokers, old aged, housewifes who resided in a farming village. The common respiratory symptoms were dyspnea, cough and hemoptysis. The predominant X-ray findings were a multiple bronchial wall thickening(89%), bronchial narrowing or atelectasis (76%) and a mediastinal lymph node enlargement with/without calcification (78%). Pulmonary function test usually showed mild obstructive ventilatory abnormalities but no patient showed a restrictive ventilatory pattern and the patients were frequently affected with chronic bronchitis(51%), post-obstructive pneumonia(40%) and chronic asthma(4%). Conclusion : Because BAF is frequently associated with chronic bronchitis and obstructive pneumonia as well as tuberculosis, a careful clinical evaluation and accurate differential diagnosis is more essential than empirical anti-tuberculous medication.

• Journal of Chest Surgery
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• v.39 no.12 s.269
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• pp.920-926
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• 2006

Background: Mortality and morbidity of anastomotic complications after esophagectomy have gradually decreased in recent years. However, swallowing difficulties and reflux symptoms after esophagogastrostomy continue to be a burden jeopardizing the quality of life. In the present study, we evaluated the quality of esophagogastrostomy by analyzing anastomotic stenosis and reflux esophagitis. Material and Method: A retrospective analysis was made in 74 patients who underwent esophagogastrostomy after esophagectomy by one surgeon between January 1995 and December 2004. 53 patients of them received endoscopic examination during follow-up($29{\pm}23.6$ months, range $5{\sim}111$ months). Reflux esophagitis and stenosis at anastomostic site were analyzed according to the techniques and locations of esophagogastrostomy. Result: The median age at the time of repair was $60.3{\pm}8.87$ years(range $39{\sim}81$ years). 23 patients received a hand-sewn esophagogastric anastomosis and 30 patients a circular stapled one. There was no significant statistical difference in terms of anastomotic stenosis(p=0.64) and reflux esophagitis(p=0.41) between the two groups. Cervical anastomosis was peformed in 26 patients and intrathoracic anastomosis in 27 patients. No significant statistical difference in anastomotic stenosis between the two groups was found(p=0.44), but reflux esophagitis was noted in 3 patients in the cervical anastomosis group and 14 patients in the intrathoracic anastomosis group(p=0.003). Conclusion: Cervical anastomosis was supposed to have a better quality of esophagogastrostomy by lowering the risk of reflux esophagitis. In the future, the comprehensive study including a patient's subjective symptom and Barrett's metaplasia should be performed in larger cases.

• Korean Journal of Veterinary Service
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• v.29 no.3
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• pp.347-364
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• 2006

This study is concerned with assessment of diethylnitrosamine (DEN 0.01 %) induced liver cell carcinogenesis by measurement of changes preceding the development of neoplasms. Therefore, it was undertaken to investigate changes of liver-specific enzyme activities in Sprague-Dawley (SD) rats by ad libitum feeding of DEN. And also. the changes of hepatic morphology in SD rats were detected by haematoxylineosin stain and immunohistochemistry (PCNA). 5- Fluorouracil (5- FU) is one of the most widely used anticancer agents for digestive cancers including hepatocellular carcinoma, and is known to affect the cell cycle and induce apoptosis of cancer cells. In the present study, SD rats were given drinking water containing 0.01% diethylnitrosamine (DEN) for 8 weeks. Minor behavioral change, brittleness of hair and decreased amount of water and diet intake were observed in rats 4 weeks after DEN administration. The body and liver weights were significantly (p < 0.05) decreased in rats 11 weeks after DEN administration. The liver weight ratio to body weight was rather stable and not significantly decreased in the all treatment groups. The liver specific enzyme activities (AST, ALT, ${\gamma}$-GTP) were significantly increased in all treatment groups compared to control group (p < 0.05). Variable size of liver tumor and hepatomegaly were observed in rats treated with DEN after 10 weeks. Numerous vacuoles were seen on the midzonal and or peripheral areas of hepatic lobules. The large and polymorphological hepatocytes with eosinophilic cytoplasm or densely basophilic mitotic nucleoli were seen. Several proliferative small round cells were seen on vacuolated and necrotic areas in peripheral hepatic lobules or portal areas. PCNA-positive cells were seen on the vacuolated portal areas and peripheral areas of hepatic lobules in the areas of small round cells. We examined functional and morphological changes of livers by 5 - FU treatments on DEN -treated rat. The DEN -treated rats compared to 5 - FU -treated rats after DEN treatment for 8 weeks. The serum total protein and triglyceride were significantly (p < 0.05) decreased, and the liver enzyme activities of AST and ALT were significantly(p < 0.05) increased. After 8 weeks, in the non-5-FU -treated group, the size of liver tumor were varied and hepatomegaly were observed, hepatocellular vacuolization, necrosis and steatosis were observed on the midzonal and peripheral areas of hepatic lobules. The large and polymorphological hepatocytes were seen, the interlobular connective tissues were proliferated. PCNA positive cells were seen in the portal areas and peripheral areas of hepatic lobules in the non-5-FU-treated group. In hepatocytes, condensation of nuclear chromatin and vacuolization were observed, shape of the nuclei were irregular, the degraded nuclei and organelles were observed. The livers of rats in the 5 - FU treatment group were seen grossly brilliant, red-brown color, and the vacuolated and degenerated regions, hyperplastic nodules were not nearly observed. In the electron microscope, the cytoplasm of the hepatocytes contained a large number of mitochondria, rough endoplasmic reticulum, developed organelles surrounding nuclei. The above findings suggest that 5 - FU will be effective as anti -liver tumor drug.

• Tuberculosis and Respiratory Diseases
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• v.59 no.1
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• pp.30-38
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• 2005

Background : Arsenic trioxide ($As_2O_3$) has been used to treat acute promyelocytic leukemia, and it induces apoptosis in a variety of solid tumor cell lines including non-small cell lung cancer cells. However, nonsteroidal antiinflammatory drugs (NSAID) can enhance tumor response to chemotherapeutic drugs or radiation. It was previously demonstrated that a combination treatment with $As_2O_3$ and sulindac induces the apoptosis of NCI-H157 human lung carcinoma cells by activating the caspase cascade. This study aimed to determine if a combination treatment augmented its apoptotic potential through other pathways except for the activation of the caspase cascade. Material and Methods : The NCI-H157 cells were treated with $As_2O_3$, sulindac and antioxidants such as glutathione (GSH) and N-acetylcysteine (NAC). The cell viability was measured by a MTT assay, and the level of intracellular hydrogen peroxide ($H_2O_2$) generation was monitored fluorimetrically using a scopoletin-horse radish peroxidase (HRP) assay. Western blotting and mitochondrial membrane potential transition analysis were performed in order to define the mechanical basis of apoptosis. Results : The viability of the cells was decreased by a combination treatment of $As_2O_3$ and sulindac, and the cells were protected using antioxidants in a dose-dependent manner. The increased $H_2O_2$ generation by the combination treatment was inhibited by antioxidants. The combination treatment induced changes in the mitochondrial transmembrane potential as well as the expression of the Bcl-2 family proteins, and increased cytochrome c release into the cytosol. However, the antioxidants inhibited the effects of the combination treatment. Conclusion : Combination treatment with $As_2O_3$ and sulindac induces apoptosis in NCI-H157 human lung carcinoma cells via ROS generation with a mitochondrial dysfunction.

• Korean journal of applied entomology
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• v.57 no.2
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• pp.97-104
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• 2018

The larva of the white-spotted flower chafer, Protaetia brevitarsis seulensis (Coleoptera: Cetoniidae), is known to have important medicinal properties, such as anti-cancer activity. However, the consumer market for the larvae is depressed because of its high production cost which needs to be reduced. This study was carried out to evaluate two spent mushroom substrates as food source for chafer larvae to improve the productivity and reduce production cost. The larvae were fed with spent substrates of king oyster mushroom (Pleurotus eryngii) (P-SMS) and shiitake mushroom (Lentinula edodes) (L-SMS), with a control of fermented oak sawdust. Effects of the diets on the development of P. brevitarsis seulensis and contents of minor nutrient components in the larvae produced were examined. In the P-SMS diet, the larval rearing period was shorter at 16.2 days, while the rate of larval weight gain and the cocoon weight were higher at 156.3% and 4.1 g, respectively, than that in the L-SMS diet. The pupation rate was 100% and the adult emergence was higher at 93.3% in the P-SMS diet than in the L-SMS diet with no difference to the control diet. In the P-SMS diet, the total nitrogen content during rearing was higher at 10.28% and the minor nutrient component, particularly Fe (145.8 mg/kg), was higher than that in other diets. The oviposition preference of adults showed no significant difference among the diets. Economic analysis showed that P-SMS costs approximately 667,960 Won less per 100 kg of larvae produced, compared to that of the control diet.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.4
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• pp.377-382
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• 2007

This study was designed to investigate the effect of Plebeiae Herba (Salvia plebeia R. Br.) on the proliferation of AGS cell lines and the activation of splenocytes. In an anti-cancer test using AGS cells, water and ethanol extracts of Plebeiae Herba inhibited the growth of AGS cell lines and morphological changes were also observed in a dose-dependent manner. Water extract of Plebeiae Herba showed growth-inhibitory effect of 43.3% at $1,000{\mu}g/mL$ and 69.7% at $3,000{\mu}g/mL$. Ethanol extracts of Plebeiae Herba showed growth-inhibitory effect of approximately 37.3% for $1,000{\mu}g/mL$ and 75.8% for $3,000{\mu}g/mL$. The Plebeiae Herba induced the proliferation of spleen cells and increased interleukin (IL)-2, interleukin (IL)-6 and tumor necrosis factor $(TNF)-{\alpha}$. In conclusion, these results suggest that the Plebeiae Herba seems to have antiproliferationg effect against the AGS cell and acts as a potent immunomodulator.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.10
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• pp.1552-1559
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• 2013

Rubus coreanus Miquel (RCM) has been used as one of the Korean traditional medicines for prostate health. In addition, recent studies have reported that RCM reduced chronic inflammatory diseases such as cancer, and rheumatoid arthritis. Therefore, in this study, we investigated the effects of unripe and ripe RCM on inflammationrelated gene expressions in LPS-stimulated mouse peritoneal macrophages. Mice were fed with 2% unripe RCM (U2), 10% unripe RCM (U10), 2% ripe RCM (R2), and 10% ripe RCM (R10) for 8 weeks. Peritoneal macrophages were isolated and stimulated with LPS then proinflammatory mediators (TNF-${\alpha}$, IL-$1{\beta}$, and IL-6), and prostaglandin E2 ($PGE_2$) productions were assessed. Moreover, gene expression profiles were analyzed by cDNA microarray method. Unripe and ripe RCM significantly reduced TNF-${\alpha}$ production but only unripe RCM decreased IL-$1{\beta}$ and IL-6 production. RCM intake significantly reduced inflammatory-related gene expressions such as arachidonate 5-lipoxygenase, interleukin 11, and nitric oxide synthase 2. Furthermore, unripe and ripe RCM significantly decreased ceruloplasmin, tissue plasminogen activator, thrombospondin 1, and vascular endothelial growth factor A expression which modulates symptoms of chronic inflammatory diseases. RCM intake also significantly increased hypoxia inducible factor 3, alpha which is the negative regulators of hypoxia-inducible gene expression. Furthermore, only unripe RCM reduced chemokine (C-C motif) ligand 8, chemokine (C-X-C motif) ligand 14, and phospholipase A2 expression. In this study, we showed that RCM had anti-inflammatory effects by suppression of pro-inflammatory mediator expressions and may reduce chronic inflammatory disease progress through regulation of gene expressions. These findings suggest that RCM might be used as a potential functional material to reduce chronic inflammatory responses.