• Journal of Rheumatic Diseases
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• 제24권4호
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• pp.192-202
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• 2017

Objective. Rebampide is a gastroprotective agent used to treat gastritis. It possesses anti-inflammatory and anti-arthritis effects, but the mechanisms of these effects are not well understood. The objective of this study was to explore mechanisms underlying the therapeutic effects of rebamipide in inflammatory arthritis. Methods. Collagen-induced arthritis (CIA) was induced in DBA/1J mice. DBA/1J mice were immunized with chicken type II collagen, then treated intraperitoneally with rebamipide (10 mg/kg or 30 mg/kg) or vehicle (10% carboxymethylcellulose solution) alone. Seven weeks later, plasma samples were collected. Plasma metabolic profiles were analyzed using ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry-based metabolomics study and metabolite biomarkers were identified through multivariate data analysis. Results. Low dose rebamipide treatment reduced the clinical arthritis score compared with vehicle treatment, whereas high dose rebamipide in CIA aggravated arthritis severity. Based on multivariate analysis, 17 metabolites were identified. The plasma levels of metabolites associated with fatty acids and phospholipid metabolism were significantly lower with rebamipide treatment than with vehicle. The levels of $15-deoxy-^{{\Delta}12,14}$ prostaglandin J2 and thromboxane B3 decreased only in high dose-treated groups. Certain peptide molecules, including enterostatin (VPDPR) enterostatin and bradykinin dramatically increased in rebamipide-treated groups at both doses. Additionally, corticosterone increased in the low dose-treated group and decreased in the high dose-treated group. Conclusion. Metabolomics analysis revealed the anti-inflammatory effects of rebamipide and suggested the potential of the drug repositioning in metabolism- and lipid-associated diseases.

• 대한수의학회지
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• 제26권2호
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• pp.307-319
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• 1986

성숙한 A/J, $C_{57}BL/6N$, DBA/2 및 NIH-GP계(系) 마우스에 benzo(a) pyrene과 charcoal powder를, $C_{57}/6N$ 및 NIH-GP계(系) 마우스에 Urethan을 기관내(氣管內) 주입(注入)하여 폐장(肺臟)의 종양발생(腫瘍發生)과 조직변화(組織變化)를 관찰(觀察)한 바 다음과 같은 결과(結果)를 얻었다. Benzo(a)pyrene을 주입(注入)한 군(群)에서는 편평상피암(扁平上皮癌) 및 선암(腺癌), 그리고 편평상피암(扁平上皮癌)과 선암(腺癌)의 혼합 발생예(例)를 볼 수 있었다. 이와 같은 병변(病變)은 A/J 및 $C_{57}BL/6N$계(系) 마우스에서 발생률(發生率)이 높았으며 A/J계(系) 마우스에서 편평상피암(扁平上皮癌)의 발생(發生) 및 분화(分化)가 현저하였다. 한편 DBA/2 및 NIH-GP계(系) 마우스에서는 종양(腫瘍) 발생률(發生率)이 극히 낮았다. Benzo(a)pyrene의 주입시(注入時) 동일 계통의 마우스에서도 대량을 주입(注入)할 때 선암(腺癌)보다 편평상피암(扁平上皮癌)의 발생(發生)이 많았으며 A/J계(系) 마우스에서는 편평상피암(扁平上皮癌) 단독(單獨) 발생예(發生例)가 다수 관찰(觀察)되었고 $C_{57}BL/6N$계(系) 마우스에서는 선암(腺癌) 및 선암(腺癌)과 편평상피암(扁平上皮癌)의 혼합 형태(形態)가 주(主)로 관찰(觀察)되었다. 그리고 기관지상피(氣管支上皮)의 편평상피화생(扁平上皮化生) 및 편평상피암(扁平上皮癌)의 발생시(發生時) alcian blue-PAS 양성반응세포가 관여함을 알 수 있었고 선종양조직(腺腫樣組織) 발생예(發生例)에서도 편평상피화생(扁平上皮化生) 및 편평상피암(扁平上皮癌)으로 분화(分化)되는 경우도 관찰(觀察)되었다. Urethan 주입군(注入群)은 극히 낮은 종양발생률(腫瘍發生率)을 나타내어 발암물질(發癌物質)의 종류(種類), 용량(用量) 및 마우스의 계통(系統)에 따라 종양(腫瘍)의 발생률(發生率) 및 형태(形態)의 차이가 인정되었다.

• Korean Journal of Acupuncture
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• 제24권3호
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• pp.117-137
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• 2007

Objectives & Methods : The purpose of this study is to observe the effects of Gentianae macrophyllase Radix herbal-acupuncture solution(GR-HAS) at Joksamni(ST36) on Collagen-induced arthritis(CIA) in DBA/1J mice. The author performed several experimental items to analyze arthritis evaluation, change of weight, spleen size and adhesion rate, change of cytokine level, IgG, IgM and anti-collagen II , change of immunocyte count, histological change of CIA mouse joint related with RA. Results : 1. In the GR-HA group, the arthritis index, the incidence of arthritis and joint edema were significantly decreased. 2. In GR-HA group, there were no weight loss and similarly maintained as normal group. Spleen size, adhesion rate and the edema and transformation of knee joint were low and similarly maintained as normal group. 3. In the GR-HA, cytokine level, IgG, IgM and anti-collagen II were significantly decreased. 4. In the GR-HA, the change of immunocyte count were similarly maintained as normal group. 5. In the histological changes of the CIA mouse joint, the cartilage destruction and synovial cell proliferation were decreased in the GR-HA(Hematoxylin and eosin stain). The collagen fiber expressions in the GR-HA were similar with that of the normal group(Masson's Trichrome stain) Conclusions : These results suggest that GR-HA at ST36 has an effect to control immune reaction and suppress inflammation, synovial cell proliferation and cartilage destruction in rheumatoid arthritis.

• 한국발생생물학회지:발생과생식
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• 제19권4호
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• pp.243-252
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• 2015

The pregnancy and abortion process involves a complex mechanism with various immune cells present in the implantation sites and several hormones associated with pregnancy, such as leptin, ghrelin and nesfatin-1. However, the mechanism underlying spontaneous abortion by maternal T helper 17 (Th17) present in the implantation sites and nesfatin-1, which is of anorexigenic hormones, is not fully understood so far. Therefore, the purpose of this study was to examine the possible roles of Th17 cells present in the implantation sites and nesfatin-1 expressed in the uterus on spontaneous abortion using the $CBA/j{\times}DBA/2$ mouse model. Th17 transcription factor, ROR-${\gamma}t$ mRNA expression was significantly increased in the abortion sites compared with the implantation sites of abortion model mice on day 14.5 and 19.5 of pregnancy. In addition, the expression levels of IL-17A mRNA were significantly higher in abortion sites than in implantation sites on day 14.5 and 19.5. Moreover, the nesfatin-1/NUCB2 protein and mRNA levels were increased in abortion sites compared with levels in implantation sites of both normal pregnant and abortion model mice on day 14.5 of pregnancy. Interestingly, nesfatin-1/NUCB2 serum levels were not changed throughout the whole pregnancy in abortion model mice, but its serum level was dramatically increased on day 14.5, and then rapidly decreased on day 19.5 in normal pregnant mice. In this study, we showed for the first time the expression of nesfatin-1/NUCB2 mRNA and protein in implantation sites during pregnancy. The present results suggest that Th17 cells in the uterus may play an important role in the period of implantation and for maintenance of pregnancy. Furthermore, the present results suggest that Th17 cells in implantation sites may be a key regulator for maintenance of pregnancy and provides evidence that activation of these cells may be regulated by nesfatin-1/NUCB2. Further study is needed to elucidate the role of nesfatin-1 expressed in the uterus during pregnancy.

• International Journal of Computer Science & Network Security
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• 제23권7호
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• pp.16-22
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• 2023

Enhanced radio access technologies (RAT) are deployed in Next Generation Convergence Networks by the service providers so as to satisfy the basic requirements of end-users for e.g. QoS. Whenever the available resources are being shared simultaneously and dynamically by multiple users or distribution of allocated channels randomly, the deficiency of spectral resources and dynamic behavior of Network traffic in real time Networking, we may have problem. In order to evaluate the performance of our proposed algorithm, computer simulation has been performed on NS-2 simulator and a comparison with the existing algorithms has been made.

• Korean Journal of Acupuncture
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• 제24권2호
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• pp.163-184
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• 2007

Objectives & Methods : The purpose of this study is to observe the effects of Phellodendri Cortex Herbal-acupuncture solution (PC-HAS) at Joksamni (ST36) on collagen II induced arthritis in DBA-1J mice. The author performed several experimental items to analyze arthritis evaluation, change of weight, spleen size and adhesion rate, change of cytokine level, IgG, IgM and anti-collagen II, chang of immunocyte count, histological change of CIA mouse joint. Results : 1. In the PC-HA group, arthritis index, the incidence of arthritis and joint edema were significantly decreased. 2. In the PC-HA group, the change of spleen size, spleen adhesion rate and the knee joint were significantly decreased. 3. The levels of $IL-1{\beta}$, IL-6 and INF- in serum of the CIA mouse were significantly decreased by PC-HA. 4. The levels of IgG, IgM and anti-collagen II in serum of the CIA mouse were significantly decreased by PC-HA. 5. In the CIA mouse spleen cell culture, the levels of IFN- , IFN- / IL-4, IL-10 were significantly decreased by PC-HA, but the level of IL-4 was significantly increased by PC-HA. 6. In the PC-HA group, the ratios of $CD3e^+$ to $CD45R^+$ cell, $CD4^+$ to $CD8^+$ cell and $CD4^+/CD25^+$ cell were similarly maintained as normal group in the CIA mouse spleen cell. 7. In the PC-HA group, $CD4^+CD25^+$ and $CD45R^+/CD69^+$ cell were significantly decreased in the lymph nodes. 8. In the PC-HA group, $CD3^+/CD69^+$ and $CD11b^+/Gr-1^+$ cell were significantly decreased in knee joint. 9. In histology, the cartilage destruction and synovial cell proliferation in the PC-HA group were similar with that of the normal group and the collagen fiber expressions in the PC-HA group were similar with that of the normal group. Conclusions : Form the result above, the results suggest that the PC-HA at ST36 has significant effect on collagen-induced arthritis, and can be put to practical use in the future rheumatoid arthritis clinic.

• Korean Journal of Acupuncture
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• 제22권2호
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• pp.89-105
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• 2005

Objective & Methods : This study is performed to observe the effect of Herbal-acupuncture with Notopterygii Radix Herbal-Acupuncture Solution(NR-HAS) at Joksamni(ST36) on Collagen II-induced arthritis (CIA) in DBA/1J mice. Result : 1. The highest survival rate of mice lung fibroblasts were measured in the 1% NR-HAS, and the expression of $TNF-{\alpha}$ in synovial cells were significantly decreased in the 1% and 10% NR-HAS. 2. The incidence of arthritis and the spleen weight were significantly decreased by Notopterygii Radix Herbal-acupuncture(NR-HA) at ST36. 3. The levels of IL-6, $INF-{\gamma},\;TNF-{\alpha}$, IgG, IgM, anti-collagen II in serum of CIA mice were significantly decreased by NR-HA at ST36. 4. In histology, the cartilage destruction and synovial cell proliferation were decreased by NR-HA at ST36, and the collagen fiber expressions in the NR-HA I II groups were similar with that of the normal group. 5. In lymph node, the expression ratios of $CD3e^+\;to\;CD19^+$ cell and $CD4^+\;to\;CD8^+$ cell in the NR-HA I II groups were similarly maintained as those in the normal group. 6. In lymph node, $CD69^+/CD3e^+$ cells and $CD11a^+/CD19^+$ cells were decreased by NR-HA at ST36. 7. In the articular joint, $CD11b^+/Gr-1^+$ cells were decreased by NR-HA at ST36. 8. NR-HA at ST36 did not make a considerable difference in DBA/1J mice without CIA 9. Throughout the overall experimental result, NR-HA I group showed more predominant effect than the NR-HA II group. Conclusion : These results suggest that NR-HA at ST36 has an effect to control synovial cell proliferation and cartilage destruction in rheumatoid arthritis, as well as prophylaxis is important to treat rheumatoid arthritis in clinic.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.199-199
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• 1994

Thioglycerol과 glycerol로부터 rac-1-S-octa-decyl-2-O-palmitoyl-1-S-thioglycerol-3-phosphate (DL -PTBA-P)와 rac-1-O-octadecyl-2-O-palmitoyl-g1ycerol-3-phosphate (DL-PBA-P)등을 합성하였고, 이들에 ara-C 유도체인 ara-CMP morpholidate를 반응시켜 최종 산물인 ara-CDP-DL-PCA, ara-CDP-DL-PBA, ara-CDP-DL-PTCA 및 ara-CDP-DL-PTBA등을 합성하였다. 이들 최종산믈의 항암효과는 L1210 lymphoid leukemia, colon 26 carcioma, M5076 sarcoma, C-1300 neuroblastoma, 3-Lewis lung carcinoma, WEHI-3B leukemia, human colon cancer, hum an pancreatic cancer 등의 암세포주를 사용하여 실험하였다. L1210를 DB/2J의 뇌막 또는 복강, DBA/1J의 복강내에 이식하여 ara-C, Ehss thioether lipid의 ara-C 유도체 (ara-CDP-L-DP, ara-CDP-DL-PCA, ara-CDP-DL-PBA, ara -CDP-DL-PTCA, ara-CDP-D-PTBA, ara-CDP-L-PTBA, ara-CDP-DL-PTBA)를 단일 투여 또는 중복 투여하였고, 3-Lewis는 C57BL/6 의 발바닥 피하, colon26은 BALB/C의 견갑상부 히아조직, M5076은 C57BL/6의 피하, WEHI-3B는 BALB/C의 복강, C-1300는 A/strong Ros에 각각 이식한 후 ara-C 또는 ara-CDP-DL-PTBA를 단일 또는 중복 투여하였다.

• Archives of Pharmacal Research
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• 제20권3호
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• pp.253-258
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• 1997

Ten, heretofore unreported, $ 5^I-methyl-5^I-[2-(5-substituted uracil-1-yl)ethyl)]-2^I-oxo-3^I$-methylenetetrahydrofurans (H, F, Cl, Br, I, $ CH_3$,$CF_3$,$CH_2CH_3$,$ CH=CH2$, SePh) (7a-j) were synthesized and evaluated against four cell lines (K-562, FM-3A, P-388 and U-937). For the preparation of ${\alpha}$-methylene-${\gamma}$-butyrolactone-linked to 5-substituted uracils (7a-j), the convenient Reformasky type reaction was employed which involves the treatment of ethyl ${\alpha}$-(bromomethyl)acrylate and zinc with the respective 1-(5-substituted uracil-1-yl)-3-butanone (6a-j). The 5-substituted uracil ketones (6a-j) were directly obtained by the respective Michael type reaction of vinyl methyl ketone with the $K_2CO_3$(or NaH)-treated 5-substituted uracils (5a-j) in the presence of acetic acid in the DMF solvent. The .alpha.-methylene-.gamma.-butyrolactone compounds showing the most significant antitumor activity are 7e, 7f, 7h and 7j (inhibitory concentration $(IC_50)$ ranging from 0.69 to $2.9 {\mu}g/ml$), while 7b, 7g and 7i have shown moderate to significant activity. The compounds 7a, 7c and 7d were found to be inactive. The synthetic intermediate compounds 6a-j were also screened and found marginal to moderate activity where compounds 6b and 6g showed significant activity $(IC_50:0.4~2.8 {\mu}g/ml)$.

• Journal of Microbiology and Biotechnology
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• 제27권10호
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• pp.1892-1895
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• 2017

IK can downregulate interferon-gamma-induced major histocompatibility complex (MHC) class II expression through the MHC class II transactivator, which suggests that IK can inhibit the interactions between immune cells. We delivered adeno-associated virus serotype 2 (AAV2) encoding the genes for truncated IK (tIK) or green fluorescent protein (GFP) to DBA1/J mice via intravenous injection. Seven weeks after injection, collagen-induced arthritis was induced in the AAV2-treated mice. AAV2-tIK injection reduced the severity of arthritis and the percentage of pathogenic Th17 cells compared with AAV2-GFP injection. These results suggest a novel gene therapy strategy for treatment of inflammatory arthritis.