• Tuberculosis and Respiratory Diseases
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• v.57 no.5
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• pp.449-460
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• 2004

Background : PS-341 is a novel, highly selective and potent proteasome inhibitor, which showed cytotoxicity against some tumor cells. Its anti-tumor activity has been suggested to be associated with modulation of the expression of apoptosis-associated proteins, such as p53, $p21^{WAF/CIP1}$, $p27^{KIP1}$, NF-${\kappa}B$, Bax and Bcl-2. c-Jun N-terminal kinase (JNK) and glycogen synthase kinase-$3{\beta}$ (GSK-$3{\beta}$) are important modulators of apoptosis. However, their role in PS-341-induced apoptosis is unclear. This study was undertaken to elucidate the role of JNK and GSK-$3{\beta}$ in the PS-341-induced apoptosis in lung cancer cells. Method : NCI-H157 and A549 cells were used in the experiments. The cell viability was assayed using the MTT assay and apoptosis was evaluated by proteolysis of PARP. The JNK activity was measured by an in vitro immuno complex kinase assay and by phosphorylation of endogenous c-Jun. The protein expression was evaluated by Western blot analysis. Dominant negative JNK1 (DN-JNK1) and GSK-$3{\beta}$ were overexpressed using plasmid and adenovirus vectors, respectively. Result : PS-341 reduced the cell viability via apoptosis, activated JNK and increased the c-Jun expression. Blocking of the JNK activation by overexpression of DN-JNK1, or pretreatment with SP600125, suppressed the apoptosis induced by PS-341. The activation of caspase 3 was mediated by JNK activation. Blocking of the caspase 3 activation suppressed PS-341-induced apoptosis. PS-341 activated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, but its blockade enhanced the PS-341-induced cell death via apoptosis. GSK-$3{\beta}$ was inactivated by PS-341 via the PI3K/Akt pathway. Overexpression of constitutively active GSK-$3{\beta}$ enhanced PS-341-induced apoptosis; in contrast, this was suppressed by dominant negative GSK-$3{\beta}$ (DN-GSK-$3{\beta}$). Inactivation of GSK-$3{\beta}$ by pretreatment with lithium chloride or the overexpression of DN-GSK-$3{\beta}$ suppressed both the JNK activation and c-Jun up-regulation induced by PS-341. Conclusion : The JNK/caspase pathway is involved in PS-341-induced apoptosis, which is negatively regulated by the PI3K/Akt-mediated inactivation of GSK-$3{\beta}$ in lung cancer cells.

• KDI Journal of Economic Policy
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• v.14 no.2
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• pp.109-153
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• 1992

This paper estimates a translog cost function for the Korea's banking industry and derives various implications on the prospect for the Korean banking structure in the future based on the estimated efficiency indicators for the banking sector. The Korean banking industry is permitted to operate trust business to the full extent and the security business to a limited extent, while it is formally subjected to the strict, specialized banking system. Security underwriting and investment businesses are allowed in a very limited extent only for stocks and bonds of maturity longer than three year and only up to 100 percent of the bank paid-in capital. Until the end of 1991, the ceiling was only up to 25 percent of the total balance of the demand deposits. However, they are prohibited from the security brokerage business. While the in-house integration of security businesses with the traditional business of deposit and commercial lending is restrictively regulated as such, Korean banks can enter the security business by establishing subsidiaries in the industry. This paper, therefore, estimates the efficiency indicators as well as the cost functions, identifying the in-house integrated trust business and security investment business as important banking activities, for various cases where both the production and the intermediation function approaches in modelling the financial intermediaries are separately applied, and the banking businesses of deposit, lending and security investment as one group and the trust businesses as another group are separately and integrally analyzed. The estimation results of the efficiency indicators for various cases are summarized in Table 1 and Table 2. First, security businesses exhibit economies of scale but also economies of scope with traditional banking activities, which implies that in-house integration of the banking and security businesses may not be a nonoptimal banking structure. Therefore, this result further implies that the transformation of Korea's banking system from the current, specialized system to the universal banking system will not impede the improvement of the banking industry's efficiency. Second, the lending businesses turn out to be subjected to diseconomies of scale, while exhibiting unclear evidence for economies of scope. In sum, it implies potential efficiency gain of the continued in-house integration of the lending activity. Third, the continued integration of the trust businesses seems to contribute to improving the efficiency of the banking businesses, since the trust businesses exhibit economies of scope. Fourth, deposit services and fee-based activities, such as foreign exchange and credit card businesses, exhibit economies of scale but constant returns to scope, which implies, the possibility of separating those businesses from other banking and trust activities. The recent trend of the credit card business being operated separately from other banking activities by an independent identity in Korea as well as in the global banking market seems to be consistent with this finding. Then, how can the possibility of separating deposit services from the remaining activities be interpreted? If one insists a strict definition of commercial banking that is confined to deposit and commercial lending activities, separating the deposit service will suggest a resolution or a disappearance of banking, itself. Recently, however, there has been a suggestion that separating banks' deposit and lending activities by allowing a depository institution which specialize in deposit taking and investing deposit fund only in the safest securities such as government securities to administer the deposit activity will alleviate the risk of a bank run. This method, in turn, will help improve the safety of the payment system (Robert E. Litan, What should Banks Do? Washington, D.C., The Brookings Institution, 1987). In this context, the possibility of separating the deposit activity will imply that a new type of depository institution will arise naturally without contradicting the efficiency of the banking businesses, as the size of the banking market grows in the future. Moreover, it is also interesting to see additional evidences confirming this statement that deposit taking and security business are cost complementarity but deposit taking and lending businesses are cost substitute (see Table 2 for cost complementarity relationship in Korea's banking industry). Finally, it has been observed that the Korea's banking industry is lacking in the characteristics of natural monopoly. Therefore, it may not be optimal to encourage the merger and acquisition in the banking industry only for the purpose of improving the efficiency.

• Journal of Korean Medical classics
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• v.5
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• pp.200-251
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• 1992

As concerned the life and the medical idea of Choo, Tan-Kye(朱丹溪), which it can be summarized as follows by studying. 1. Tan-Kye(丹溪) lived in the end of the won dynasty(元代末期), When the people starved and suffered from a flood-disaster and drought. etc, also the social conditions were in disorder on account of the corrupt ion of politics. And Cheol Kang seong(浙江省), located in the south region of China, has sterile soil and the climate condition humid and heatful. So the south district peoples have very weak constitution. So We can found that his medical idea reflected the phases of the periods and the regional enviornmental situations. 2. For that reason, Tan-Kye(丹溪) rejected the prescription of the "WHa Che Gook Bang(和劑局方)" which was prevalent at that time, in which the the pungent-dried herbs were widly used ; So he persisted in the "Sang Wha Lon(相火論)" and the "Positivity is usually excedeed while the negativity deficient(陽有餘陰不足論)". Then he treated with the drugs to nourish the negativity for the prime object to be applied in the clinic. 3. Tan-Kye(丹溪) refined the follows from the natural law; Heaven is to the positivity(陽) and the Earth is defined the negativity(陰), so the heaven is to the Macro(大) and the earth, micro(小):So the Sun is to the Positivity(陽), the Moon, the Negativity(陰): as to the Sun is always full while the moon always defected too. Therefore the "positivity is always excedeed for that the negativity is deficientalways(陽有餘陰不足)". In Human body, "the negativity energy (陰精) "is hard formed-easily defected(難成易虧)". And the heat(相火) in the body can be moved easily and let the negative energy to leak out. Therefore the more the positivity excedeed, the more the negativity deficient"(陽當有餘陰常不足). 4. He made it expanded the contents of the "Heat(相火)" in the Chapter Woon Chi of the Nae Kyeong(內徑) and discribed, the Life-string of the human body is originated from the movement of the "Heat with unique energy(相火一氣)". And more in human body, it is specifically regulated by the two visceras, Liver and Kidney, and is distributed in the 'Pericardium(心包絡)' 'Tripie Warmer(三焦)' 'Gallbladder(膽)' etc. In the point of his assertion of heat(相火), it is concluded both the physiological and the pathological heat of all. 5. Tan-Kye(丹溪) grew up in the family or the Confucianism. He was instructed the Confucianism(性理學) from Heo-Kyeom(許謙), the fourth diciple of Chu-Ja(朱子), and was received the Yoo Chang Ri(劉 張 李)'s triple doctrine from the La Tae Moo(羅太無), the second disciple of Yoo Wan So(劉完素). So there are much of content of Confucianism(性理學) in his medical thedry, and his theory has succeeded the achievements of the triple study. 6. About the theory of the "positivity is usually excedeed while the negativity deficient"(陽常有餘陰常不足論) of Tan-Kye, it was asserted that the positivity is never sufficient for the vital mainspring, by Chang, Kye-Pin(張介賓) and Lee, Kyoo-Zoon(李奎晙) etc. And for the Heat theory(相火論), eventhough the scholars of postorior generations criicized all of that, there are defect of the content and unification between them. 7. The father of the "Cha Eum Pa(滋陰派), Tan-Kye(丹溪) contributed considerably to the development of the oriental medicine and to the general therapy for the various diseases(一般雜病施治). 8. there are handed down and remained twenty or more of volumes of list of his writings. Among them, except "Kyeok Chi Yeo Ron"(格致餘論), "Kuk Pang Pal Hyeu"(局方發揮), they are reorganized by posteriority. There are Cho, Do-Chin(趙道震). Cho, Ee-Teok(趙以德), Tae, Sa-Gong(戴思恭), Wang Ri(王履) and Yoo, Suk-Yeon(劉淑淵) etc as disciples of his. And Wang Ryoon(王論) and Woo Pak(虞搏) as the admirer of him.

• Journal of Life Science
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• v.23 no.9
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• pp.1109-1117
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• 2013

Induction of G1 Arrest by Methanol Extract of Lycopus lucidus in Human Lung Adenocarcinoma A549 Cells Lycopus lucidus, a herbaceous perennial, is used as a traditional remedy in East Asia, including China and Korea. It has been reported that L. lucidus has anti-allergic effects, inhibitory effects on cholesterol acyltransferase in high glucose-induced vascular inflammation, and anti-proliferative effects in human breast cancer cells. However, the molecular mechanisms of the anti-cancer effects of L. lucidus have not yet been fully determined. In this study, we evaluated the anti-cancer effect and the mechanism of action of L. lucidus in human lung adenocarcinoma A549 cells using methanol extracts of L. lucidus (MELL). MELL treatment showed cytotoxic activity in a dose-dependent manner and induced G1 arrest in A549 cells. The induction of G1 arrest by MELL was associated with the up-regulation of phospho-CHK2 and the down-regulation of Cdc25A phosphatase. In addition, MELL treatment induced decreased expression of G1/S transition-related proteins, including CDK2, CDK4, CDK6, cyclin D1 and cyclin E. MELL also regulated the mRNA expression of CDK2 and cyclin E. On the other hand, the expression of p53 and the cyclin-dependent kinase inhibitor p21 was not induced by MELL. Collectively, these results suggest that MELL may exert an anti-cancer effect by cell cycle arrest at G1 phase through the ATM/CHK2/Cdc25A/CDK2 pathway in A549 cells.

• The Korean Journal of Pesticide Science
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• v.17 no.4
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• pp.314-334
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• 2013

This study explored an efficient modified Quick, Easy, Cheap, Effective, Rugged and safe (QuEChERS) method combined with liquid chromatography-electrospray ionization with tandem mass spectrometric detection for the analysis of residues of 76 pesticides in brown rice, barley and corn including acidic sulfonylurea herbicides. Formic acid (1%) acid in acetonitrile and dispersive solid phase extractions used for extraction of pesticides and clean-up of the extract respectively. Two fortified spikes at 50 and 200 ng $g^{-1}$ levels were performed for recovery test. Mean recoveries of majority of pesticides at two spike levels ranged from 73.2 to 132.2, 80.9 to 136.8, 66.6 to 143.5 for brown rice, barley and corn respectively with standard error (CV) less than 10%. Good linearity of calibration curves were achieved with $R^2$ > 0.9907 within the observed concentration ranged. The modified method also provided satisfactory results for sulfonylurea herbicides. The method was applied to the determination of residues of target pesticides in real samples. A total of 26 pesticides in 36 out of 98 tasted samples were observed. The highest concentration was observed for tricyclazole at 1.17 mg $kg^{-1}$ in brown rice. This pesticide in two brown rice samples exceeded their MRLs regulated for rice in republic of Korea. Except tricyclazole none of the observed pesticides' concentration was higher than their MRLs. The results reveal that the method is effectively applicable to routine analysis of residues of target pesticides in brown rice, barley and corn.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.3
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• pp.298-305
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• 2017

Atopic dermatitis is a chronic, relapsing inflammatory skin disease. This study aimed to investigate the therapeutic benefits of Aronia melanocarpa (AM) and Moringa oleifera seed extract (MO) on experimental atopic dermatitis. We examined the effects of AM or MO and their combination on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis in BALB/c mice as well as tumor necrosis factor $(TNF)-{\alpha}$ and interferon $(IFN)-{\gamma}-stimulated$ HaCaT keratinocytes. Mice were orally treated with extract during repeated application of DNCB to shaved dorsal skin. Our results show that treatment with AM and MO in combination reduced histological manifestations such as epidermal hyperplasia and inflammatory cell infiltration. Furthermore, it significantly decreased skin thickness and serum immunoglobulin E (IgE) level compared to the AM or MO alone treated group. Combined extract of AM and MO suppressed expression of $TNF-{\alpha}/IFN-{\gamma}-induced$ T helper 2 (Th2) chemokines such as thymus and activation-regulated chemokine and macrophage-derived chemokine. To sum up, combination of AM and MO suppressed the inflammatory response and serum IgE as an indicator of several allergic diseases in DNCB-induced experimental atopic dermatitis and Th2 chemokine expression in HaCaT cells. This result suggests that combination of AM and MO could be a valuable strategy to improve atopic dermatitis.

• Journal of Life Science
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• v.25 no.10
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• pp.1081-1090
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• 2015

Diabetes has been one of major health risks in industrialized countries. Allium hookeri is a wild herb distributed in India and Myanmar. The root of the plant has been used as food and medicine in Southeast Asia. We investigated Allium hookeri extract improves type 2 diabetes mellitus in C57BL/KSJ db/db obese mouse. C57BL/KSJ db/db obese mouse arise out of Type 2 diabetes and we treated Allium hookeri methanol extract 400 mg/kg (AH 400), 800 mg/kg (AH 800), positive control group (thiazolidinedine;TZDs) were administered orally for 8weeks. AH treated group normalized lipid enzyme system (triglyceride, total cholesterol, HDL-cholesterol and LDL-cholesterol) and serum glucose, HbA1c and plasma insulin level. AH treated group recovered β-cell damage by hyperglycemia and fatty liver disease. AH treated group significantly up regulated expression of Peroxisome proliferator-activated receptor gamma (PPAR-γ), pyruvate dehydrogenase kinase4 (PDK4), Sterol regulatory element-binding protein 1c (SREBP 1) and fork head box O1 (FOX 01) proteins in C57BL/KSJ db/db obese mouse liver. And we found that AH treated group decreased hepatic malondialdehyde formation in C57BL/KSJ db/db obese mouse liver. These results indicate that Allium hookeri methanol extract might be a potential anti-diabetic agent and could be useful in the treatment of type 2 diabetes mellitus.

• Microbiology and Biotechnology Letters
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• v.37 no.2
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• pp.160-169
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• 2009

Poly-$\gamma$-glutamic acid ($\gamma$-PGA) was mixed natural flora of Bacillus subtilis, contaminated from cooked soybeans. Also, it was performed to find out the antiallergic activity by using NC/Nga mice, in vitro. The $\gamma$-PGA (PGA-HM : PGA-high molecular weight), Molecular weight 300 kDa, was decomposed and made PGA-LM (PGA-low molecular weight) which has molecular weight below 30 kDa by sonication. Therefore, it was same result between PGA-HM and PGA-LM, and reported PGA-LM as basic result. We found that PGA-LM contains antiallergic efficacy that inhibit B cells and Th2 cells activation from isolated CD4+T cells in NC/Nga atopic dermatitis model mice, and not show a cytotoxicity in the hFCs. To investigate the effects of these PGA-LM in vitro, isolation of splenic B cell and CD4+ T cells in atopic dermatitis mice were used. To elucidate the role of PGA-LM in anti-CD40+ interleukin-4 (IL-4)-mediated B-cell activation, showed that the capacity of B cells to expression IL-$1\beta$, IL-6, and TNF-$\alpha$ mRNA down-regulated, and IL-10 mRNA up-regulation by PGA-LM treatment, but it had no effect on TGF-$\beta$ expression. In addition to CD4+IFN-$\gamma$+ and CD4+CD25+foxp3+, the functions of PGA-LM in the development of the CD4+CD25+foxp3+ and CD4+IFN-$\gamma$+cells, the phenotype and functions of PGA-LM induced CD4+CD25+foxp3+, and CD4+IFN-$\gamma$+cells in CD4+T cells. These results suggested that PGA-LM could change cytokine production and generate CD4+CD25+foxp3+ Tregs in NC/Nga mice, and may be effective for immunotherapy in patients with AD.

• IMMUNE NETWORK
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• v.3 no.1
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• pp.1-7
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• 2003

Type II collagen (CII), major component of hyaline cartilage, has been considered as an auto-antigen in rheumatoid arthritis (RA). However, the clinical and biological significances with regard to the CII autoimmunity need to be clarified in human RA. The presence of antibodies to CII has been identified in sera, synovial fluid, and cartilage of patients with RA. In our study, the increased titer of IgG anti-CII in sera was well correlated with C-reactive protein, suggesting that this antibody may reflect the inflammatory status of RA. The titer of anti-CII antibodies (anti-CII Abs) tended to be higher in early stages of diseases. In our extending study, among 997 patients with RA, 269 (27.0%) were positive for circulatory IgG antibody to CII, those levels were fluctuated over time. It is hard to assess the significant amount of T cell responses to CII and CII (255~274) in RA. By using a sensitive method of antigen specific mixed lymphocyte culture, we can detect the presence of CII-reactive T cells in peripheral blood mononuclear cells of RA patients. Sixty seven (46.9%) of 143 patients showed positive CII reactive T cell responses to CII or CII (255~274). The frequencies of CII reactive T cells were more prominent in inflamed synovial fluid (SF) than in peripheral blood. These T cells could be clonally expanded after consecutive stimulation of CII with feeding of autologous irradiated antigen presenting cells (APC). Moreover, the production of Th1-related cytokine, such as IFN-${\gamma}$, was strongly up-regulated by CII reactive T cells. These data suggest that T cells responding to CII, which are probably presenting the IFN-${\gamma}$ producing cells, may play an important role in the perpetuation of inflammatory process in RA. To evaluate the effector function of CII reactive T cells, we investigated the effect of CII reactive T cells and fibroblasts-like synoviocytes (FLS) interaction on the production of pro-inflammatory cytokines. When the CII reactive T cells were co-cultured with FLS, the production of IL-15 and TNF-${\alpha}$ from FLS were significantly increased (2 to 3 fold increase) and this increase was clearly presented in accord to the expansion of CII reactive T cells. In addition, the production of IFN-${\gamma}$ and IL-17, T cell derived cytokines, were also increased by the co-incubation of CII reactive T cells with FLS. We also examined the impact of CII reactive T cells on chemokines production. When FLS were co-cultured with CII stimulated T cells, the production of IL-8, MCP-1, and MIP-1${\alpha}$ were significantly enhanced. The increased production of these chemokines was strongly correlated with increase the frequency of CII reactive T cells. Conclusively, immune response to CII was frequently found in RA. Activated T cells in response to CII contributed to increase the production of proinflammatory cytokines and chemokines, which were critical for inflammatory responses in RA. The interaction of CII-reactive T cells with FLS further augmented this phenomenon. Taken together, our recent studies have suggested that autoimmunity to CII could play a crucial role not only in the initiation but amplification/perpetuation of inflammatory process in human RA.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.3
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• pp.209-217
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• 2007

Purpose: Multidrug resistance (MDR) of the cancer cells related to mdr1 gene expression can be effectively treated by selective short hairpin RNA for mdr1 gene (shMDR). Sodium/iodide symporter (NIS) gene is well known to have both reporter and therapeutic gene characteristics. We have co-transfected both shMDR and NIS gene into colon cancer cells (HCT15 cell) expressing MDR and Tc-99m sestamibi and I-125 uptake were measured. In addition, cytotoxic effects of doxorubicin and I-131 therapy were also assessed after transfection. Material and Methods: At first, shMDR was transfected with liposome reagent into human embryonic kidney cells (HEK293) and HCT cells. shMDR transfection was confirmed by RT-PCR and western blot analysis. Adenovirus expressing NIS (Ad-NIS) gene and shMDR (Ad-shMDR) were co-transfected with Ad-NIS into HCT15 cells. Forty-eight hours after infection, inhibition of P-gycoprotein (Pgp) function by shMDR was analyzed by a change of Tc-99m sestamibi uptake and doxorubicin cytotoxicity, and functional activity of induced NIS gene expression was assessed with I-125 uptake assay. Results: In HEK293 cells transfected with shMDR, mdr1 mRNA and Pgp protein expressions were down regulated. HCT15 cells infected with 20 MOI of Ad-NIS was higher NIS protein expression than control cells. After transfection of 300 MOI of Ad-shMDR either with or without 10 MOI of Ad-NIS, uptake of Tc-99m sestamibi increased up to 1.5-fold than control cells. HCT15 cells infected with 10 MOI of Ad-NIS showed approximately 25-fold higher I-125 uptake than control cells. Cotransfection of Ad-shMDR and Ad-NIS resulted in enhanced cytotoxic by doxorubicin in HCT15 cells. I-131 treatment on HCT15 cells infected with 20 MOI of Ad-NIS revealed increased cytotoxic effect. Conclusion: Suppression of mdr1 gene expression, retention of Tc-99m sestamibi, enhanced doxorubicin cytotoxicity and increases in I-125 uptake were achieved in MDR expressing cancer cell by co-transfection of shMDR and NIS gene. Dual therapy with doxorubicin and radioiodine after cotransfection shMDR and NIS gene can be used to overcome MDR.