8-Fluorociprofloxacin과 Ciprofloxacin의 시험관내 및 생체내 항균 효과와 약물동태의 비교

최경업(Kyung Eob Choi),정용환(Yong Hwan Jung),김제학(Je Hak Kim) 대한약학회 1993 약학회지 Vol.37 No.3

8-Fluorociprofloxacin(8-FCP) is an investigational quinolone derivative that is substituted with fluorine at the C-8 position of ciprofloxacin(CP). It was found that the in vitro activity of 8-FCP against Gram(+) bacteria was more potent that of CP, but the opposite against Gram(-) bacteria was true. However, 8-FCP showed better in vivo efficacy than CP against representative Gram(-) organisms, E. coli and K pneumoniae. In an attempt to seek for factors causing this discrepancy in the antibacterial activities, a comparative pharmacokinetic study of 8-FCP and CP was conducted in mice and rats treated either intravenously or orally at a single dose of 30mg/kg. The pharmacokinetic parameters in mice were as follows; the mean peak serum concentrations(Cmax) following i.v. and oral doses were 12.4 and 5.3mcg/ml for 8-FCP, and 9.5 and 2.5mcg/ml for CP, respectively. The terminal half-life(tl/2beta) was 72.9 min for 8-FCP, and 98.2 min for CP, and the oral bioavailability(F) was 89.9% for 8-FCP, and 50.5% for CP. In rats, the mean (+/-SD) Cmax after i.v. administration were 11.6 +/- 1.6 mcg/ml for 8-FCP, and 10.2 +/- 1.3 mcg/ml for CP, whereas oral administration produced Cmax of 5.9 +/- 1.8 mcg/ml for 8-FCP and 1.1 +/- 0.9 mcg/ml for CP, respectively. The tl/2beta was 67.9 +/- 8.4 min for 8-FCP, and 76.4 +/- 7.2 min for CP. The F was 88.6 +/- 6.3% for 8-FCP, and 40.7 +/- 6.5% for CP. Marked differences were observed between the two quinolones in the Cmaxand the area under the concentration-time curve obtained after oral administration in mice and rats. The extent of 8-FCP absorption in both mice and rats was approximately 2-fold higher than that of CP, suggesting that the fluorine atom attached to C-8 plays an important role in facilitating oral absorption from the gastrointestinal tract.

SU-8 패시베이션을 이용한 솔루션 IZO-TFT의안정성 향상에 대한 연구

김상조(Sang-Jo Kim),이문석(Moonsuk Yi) 대한전자공학회 2015 전자공학회논문지 Vol.52 No.7

8-Methoxypsoralen Induces Apoptosis by Upregulating p53 and Inhibits Metastasis by Downregulating MMP-2 and MMP-9 in Human Gastric Cancer Cells

( Eun Kyoung Choi ),( Hae Dong Kim ),( Eun Jung Park ),( Seuk Young Song ),( Tien Thuy Phan ),( Miyoung Nam ),( Minjung Kim ),( Dong-uk Kim ),( Kwang-lae Hoe ) 한국응용약물학회 2023 Biomolecules & Therapeutics(구 응용약물학회지) Vol.31 No.2

Furanocoumarin 8-methoxypsoralen (8-MOP) is the parent compound that naturally occurs in traditional medicinal plants used historically. 8-MOP has been employed as a photochemotherapeutic component of Psoralen + Ultraviolet A (PUVA) therapy for the treatment of vitiligo and psoriasis. Although the role of 8-MOP in PUVA therapy has been studied, little is known about the effects of 8-MOP alone on human gastric cancer cells. In this study, we observed anti-proliferative effect of 8-MOP in several human cancer cell lines. Among these, the human gastric cancer cell line SNU1 is the most sensitive to 8-MOP. 8-MOP treated SNU1 cells showed G1-arrest by upregulating p53 and apoptosis by activating caspase-3 in a dose-dependent manner, which was confirmed by loss-of-function analysis through the knockdown of p53-siRNA and inhibition of apoptosis by Z-VAD-FMK. Moreover, 8-MOPinduced apoptosis is not associated with autophagy or necrosis. The signaling pathway responsible for the effect of 8-MOP on SNU1 cells was confirmed to be related to phosphorylated PI3K, ERK2, and STAT3. In contrast, 8-MOP treatment decreased the expression of the typical metastasis-related proteins MMP-2, MMP-9, and Snail in a p53-independent manner. In accordance with the serendipitous findings, treatment with 8-MOP decreased the wound healing, migration, and invasion ability of cells in a dose-dependent manner. In addition, combination treatment with 8-MOP and gemcitabine was effective at the lowest concentrations. Overall, our findings indicate that oral 8-MOP has the potential to treat early human gastric cancer, with fewer side effects.

8-Oxo-7,8-dihydroguanosine triphosphate(8-oxoGTP) down-regulates respiratory burst of neutrophils by antagonizing GTP toward Rac, a small GTP binding protein

Kim, Hee Joon,Yoon, Sun-Hee,Ryu, Hyun-Ok,Yoon, Byung-Hak,Choi, Seongwon,Ye, Sang-Kyu,Chung, Myung-Hee Harwood Academic 2007 Free radical research Vol.41 No.6

<P> 8-Oxo-7,8-dihydroguanosine triphosphate (8-oxoGTP) has been regarded simply as a oxidative mutagenic byproduct. The results obtained in this study imply that it may act as a down-regulator of respiratory burst of neutrophils. Human neutrophils treated with PMA produced superoxides and at the same time, the cytosol of these cells was intensely immunostained by 8-oxo-7,8-dihydroguanosine(8-oxoG) antibody, indicating that 8-oxoG-containing chemical species including 8-oxoGTP are produced. Human neutrophil lysates treated with PMA also produced superoxides, which was stimulated by GTP&ggr;S but inhibited by 8-oxoGTP&ggr;S. Moreover, 8-oxoGTP&ggr;S suppressed the stimulatory action of GTP&ggr;S. Likewise, GTP&ggr;S stimulated Rac activity in neutrophil lysates but 8-oxoGTP&ggr;S and GDP inhibited it. The inhibitory effect of GDP was one tenth that of 8-oxoGTP&ggr;S. Here again, 8-oxoGTP&ggr;S also suppressed the stimulatory action of GTP&ggr;S on Rac activity. These results imply the possibility that 8-oxoGTP is formed during respiratory burst of neutrophils and limits neutrophil production of superoxides by antagonizing GTP toward Rac.</P>

8-Methyl-8,14-cycloberbine 유도체 합성

황순호(Soon Ho Hwang),김재현(Jae Hyun Kim),임형엽(Hyung Yub Yim),김신규(Sin Kyu Kim) 대한약학회 1994 약학회지 Vol.38 No.4

In accordance with reported references, 8-methyl-8,14-cycloberbine was derived from berberinephenolbetaine. On acidic treatment the 8-methyl-8,14-cycloberbines were converted easily to the compounds 1-7 in good yields. We developed a novel method for a Synthesis of the C8-N bond adduct compounds 8 and 9 from 8-methyl-8,14-cycloberbine by treatment with oxalyl chloride, and 1,3-dichloroaceton.

The effect of neuropeptides on secretion of Interleukin-8(IL-8)

Kim, Kyung-Jun,Park, Sang-Hyuk,Choi, Kyoung-Kyu,Park, Sang-Jin 大韓齒科保存學會 2006 Restorative Dentistry & Endodontics Vol.31 No.3

본 연구는 치수조직, 치은, 치주인대로부터 배양된 조직을 SP (Substance P)로 4시간, SP, CGRP (Calcitonin Gene-related Peptide), Tumor necrosis factor-α (TNF-α)로 8시간 자극 후 RNase Protection Assay를 시행하고, IL-8의 분비량을 측정해 다음 결과를 얻었다. 1. IL-8 mRNA는 모든세포에서 발현됐다. 2. IL-8 mRNA 발현은 SP (10^(-5)M)와 SP (10^(-8)M)로 4시간 자극 시 증가되지 않았다. 3. IL-8 mRNA 발현은 SP (10^(-4)M)와 CGRP (10^(-6)M)로 8시간 자극 시 증가되지 않았다. 4. TNF-α (2 ng/㎖) 자극 시, IL-8 mRNA 발현이 증가됐다. 5. 치은 세포를 CGRP (10^(-6)M)로 8시간 자극 시, IL-8 분비량이 증가했다 (p < 0.05). 6. 치주인대 세포를 SP (10^(-4)M)로 8시간 자극 시 IL-8 분비량이 증가했다 (p < 0.05). We investigated the secretion of Interleukin-8 (IL-8) from ginviva and periodontal ligament stimulated with Substance P (SP) and Calcitonin Gene-related Peptide (CGRP). Gingiva (GF), periodontal ligament (PDLF) and pulp (PF) tissues were collected from extracted instact 3rd molars. Cultured cells were stimulated with different concentrations of SP for 4 hrs, and stimulated with SP, CGRP and Tumor Necrosis Factor-α (TNF-α) for 8 hrs. Then RNase Protection Assay was carried out. ELISA was performed using supernatants of stimulated cells for quantitative analysis of IL-8. Results were assessed using supernatants of stimulated cells for quantitative analysis of IL-8. Results were assessed using student t-test with significance of P < 0.05. According to this study, the results were as follows: 1. IL-8 mRNA was detected in all type of cells studied (PF, GF and PDLF). 2. IL-8 mRNA expression was not increased after stimulating 4 hrs with SP (10^(-5)M) and SP (10^(-8)M) compared with Mock stimulation in all type of cells studied. 3. IL-8 mRNA expression was not increased after stimulating 8 hrs with SP (10^(-4)M) and CGRP (10^(-6)M) compared with Mock stimulation in all type of cells studied. 4. TNF-α (2 ng/㎖) increased the expression of IL-8 mRNA in all kind of cells studied. 5. The secretion of IL-8 from GF was increased 8 hrs after the stimulation with CGRP (10^(-6)M) (p < 0.05). 6. The secretion of IL-8 from PDLF was increased 8 hrs after the stimulation with SP (10^(-4)M) (p < 0.05). Calcitonin Gene-related Peptide (CGRP) increased Interleukin-8 (IL-8) which plays an important role in chemotaxis of neutrophil in Calcitonin Gene-related Peptide (CGRP) gingival tissue, whereas Substance P increased the secretion of IL-8 from periodontal ligament.

적산(赤山) 법화원(法華院)의 8월 15일 명절 연구

김인희 동아시아고대학회 2014 동아시아고대학 Vol.0 No.34

8월 15일 명절은 동아시아에서 유일하게 신라에만 있었는데 그 이유는 이 명절이 신라의 오묘제(五廟 祭)에서 기원하였기 때문이다. 8월 15일 명절이 형성되고 정착되는 과정에는 오묘제, 천신의례, 달숭배 , 고구려정복과 같은 다양한 요소들이 작용하였는데 적산 법화원의 노승들이 고구려정복만을 말한 것 은 타국에서 생활하는 재당신라인들이 영광된 역사를 통하여 타국에서의 고단한 삶을 극복하고자 하 는 심리적 의도가 담겨 있다. 적산 법화원의 8월 15일 명절 음식 중 가장 중요한 음식은 박돈(餺飩)이다. 한국 학자들은 일반적으로 박돈을 수제비로 번역하고 있으나 박돈은 제조방식이나 이후의 문헌자료로 보아 국수로 번역하는 것 이 옳다. 당시 국수는 보편화된 음식이 아니어서 사신접대, 제사음식, 잔치음식으로 사용되는 매우 귀 한 음식이었다. 귀한 박돈을 8월 15일 명절에 먹었다는 것은 8월 15일 명절이 매우 중요한 명절이었음 을 말한다. 박돈뿐만 아니라 매우 많은 음식을 설(設)하였다고 하는데 이는 잔치의 규격과 형식에 맞게 음식을 체계적으로 안배한 것으로 8월 15일 명절이 이미 체계를 갖춘 명절이었음을 말한다. 그리고 8월 15일 명절은 전문적인 공연단에 의해 3일 동안 밤낮으로 공연이 이루어지는 열정적인 축제였다. 적산 법화원의 8월 15일 명절이 체계를 갖춘 명절로 성대하게 거행되었으며, 적산 법화원이 나당간의 국제교류와 무역의 중심지이며, 중국 중추절이 전승기념일적 요소가 있는 것은 중국 중추절의 기원이 신라의 8월 15일 명절일 가능성을 보여준다. 그러나 이를 증명하기 위해서는 송나라 시기 중추절과 신 라 8월 15일 명절의 내용상에 있어 나타나는 현저한 차이, 엔닌(圓仁)의 기록 후 364년이 지난 후에 중 추절이 정식 명절로 지정된다는 시간적 차이를 극복해야 한다. The reason that the holiday on August 15 was existed in Silla only in East Asia was this holiday was oriented from Omyoje (五廟祭) of Silla. As for the process that the holiday on August 15 was formed and settled, various factors were worked such as Omyoje, offering the first harvest of the season to the gods, the moon worship and Goguryeo conquest etc, but the reason that old Buddhist priests of Jeoksan Beophwawon mentioned Goguryeo conquest only had a psychological intention that the people of Silla who resided in Tang would overcome their exhaustion in a foreign land through the glorious history. Jeoksan Beophwawon’s most important food among foods of holiday on August 15 is Bakdon (餺 飩). Korean scholars translated Bakdon into sujebi (clear soup with dumplings) but it is proper to translate into noodles by considering its making method or literature materials afterwards. At that time, noodles were not generalized food, so it was very important and precious food which were used to treat ambassadors and as the ritual foods and feast foods. The thing to eat precious Bakdon on the holiday on August 15 means that the holiday on August 15 was very important holiday. Not only Bakdon but “It was prepared plenty of foods”, and this arranged food systematically according to the standard and convention of the feast, so the holiday on August 15 was the one to have its own system already. And it was an enthusiastic festival to deliver performances three days and nights due to professional performance group. That the holiday on August 15 of Jeoksan Beophwawon was held magnificently with its system and Jeoksan Beophwawon was a center of international exchange and trade between Silla and Tang, and the Mid-Autumn Day in China has an element as an anniversary of a victory shows that it would have the possibility the origin of the Mid-Autumn Day was a holiday on August 15 of Silla. However, to verify this, it should have overcome the noticeable difference appeared in the contents between the holiday on August 15 of Silla and the Mid-Autumn Day of Sung, and the temporal difference that the Mid-Autumn Day was designated as an official holiday after 364 years after the record of yennin (圓仁).

8-Oxo-7,8-dihydro-2′??deoxyguanosine is not salvaged for DNA synthesis in human leukemic U937 cells

Kim, Ja-Eun,Chung, Myung-Hee Informa UK Ltd 2006 Free radical research Vol.40 No.5

<P>8-Oxo-7,8-dihydro-2′??deoxyguanosine (8-oxo-dG), the most common oxidatively modified nucleoside, is released from oxidized DNA and oxidized nucleotide pool. However, little information is available regarding the metabolic pathway of free 8-oxo-dG. In this study, we generated radiolabeled 8-oxo-dG to track its metabolic fate. We report that 8-oxo-dG is neither phosphorylated to 8-oxo-dGMP nor degraded to the free base, 8-oxo-7,8-dihydroguanine (8-oxo-Gua), indicating that 8-oxo-dG is not a substrate for nucleotide synthesis. This result was confirmed by the finding that no radioactivity was detected in the DNA of U937 cells after incubating the cells with radiolabeled 8-oxo-dG. These observations indicate that 8-oxo-dG produced by oxidative stress is not reutilized for DNA synthesis.</P>

Oh⁸dG induces G₁ arrest in a human acute leukemia cell line by upregulating P21 and blocking the RAS to ERK signaling pathway

Hyun, Jin Won,Yoon, Sun Hee,Yu, Younsil,Han, Chang Soo,Park, Jin Sun,Kim, Hee Sun,Lee, Su Jae,Lee, Yun Sil,You, Ho Jin,Chung, Myung-Hee Wiley Subscription Services, Inc., A Wiley Company 2006 International journal of cancer: Journal internati Vol.118 No.2

<P>We reported previously that KG-1, a human acute leukemia cell line, has mutational loss of 8-oxoguanine (8-hydroxyguanine; oh<SUP>8</SUP>Gua) glycosylase 1 (OGG1) activity and undergoes apoptotic death after treatment with 7,8-dihydro-8-oxo-2′-deoxyguanosine (8-oxodeoxyguanosine, 8-hydroxydeoxyguanosine; oh<SUP>8</SUP>dG). In our present study, we further characterized the effects of oh<SUP>8</SUP>dG in KG-1 cells and found that, in addition to apoptosis, oh<SUP>8</SUP>dG induced the arrest of KG-1 at the G<SUB>1</SUB> phase. Simultaneously, oh<SUP>8</SUP>dG-treated KG-1 showed an increase in the oh<SUP>8</SUP>Gua content of DNA, upregulation of p21 (an inhibitor of cdk), and Ras inactivation. Moreover, the upregulation of p21 was followed by the inactivations of cdk4 and cdk2, the hypophosphorylation of Rb, and a marked decline in the expression of c-myc (a gene regulated by E2F that is a transcription factor whose activity is suppressed when it is bound to hypophosphorylated Rb). Ras inactivation was also followed by the inactivation of ERK kinase (MEK) and the inactivation of AP-1, a downstream target of the Ras signaling pathway. The specific MEK inhibitors, PD98059 and U0126, also induced G<SUB>1</SUB> arrest. These findings suggest that p21 upregulation and Ras inactivation contribute to G<SUB>1</SUB> arrest. An increase of oh<SUP>8</SUP>Gua content in DNA does not seem to be a principal contributor to G<SUB>1</SUB> arrest, however, because the kinetics of increases of oh<SUP>8</SUP>Gua content in DNA and of G<SUB>1</SUB> cell number did not coincide. We report that oh<SUP>8</SUP>dG induces the arrest of KG-1 growth at the G<SUB>1</SUB> phase mainly by upregulating p21 and inactivating Ras. © 2005 Wiley-Liss, Inc.</P>

Double homeobox a pseudogene 8/miR-223-3p/PFN2 modulates radiosensitivity in lung cancer

Pang Chong,Zhang Tengyue,Yan Bo,Chen Yulong,Chen Chen,Zhang Zhenfa,Wang Changli 대한독성 유전단백체 학회 2024 Molecular & cellular toxicology Vol.20 No.3

Background Long noncoding RNA double homeobox A pseudogene 8 (DUXAP8) was revealed to facilitate lung cancer progression in vitro, but the impacts of DUXAP8 on modulating radiosensitivity have not been examined. Objective This study aimed to explore the effect and underlying mechanisms of DUXAP8 in regulating radiosensitivity in lung cancer. Methods Bioinformatic tools were used to evaluate expression level of DUXAP8 and its associations with overall survival of patients with lung cancer. RT-qPCR was applied to examine the level of DUXAP8, miR-223-3p and profilin 2 (PFN2) RNA expression. Viabilities and apoptosis rates were measured. The interactions of miR-223-3p and DUXAP8 or PFN2 were confirmed using dual-luciferase reporter test and RNA immunoprecipitation (RIP). Immunohistochemistry (IHC) was used to examine Ki67 in animal models. Results DUXAP8 was elevated in lung cancer tissue samples and decreased overall survival of patients. Moreover, DUXAP8 was elevated in lung cancer cells, while irradiation treatment suppressed DUXAP8 in A549 cells. The knockdown of DUXAP8 inhibited cell viabilities but facilitated cell apoptosis. MiR-223-3p was sponged by DUXAP8, while PFN2 was targeted by miR-223-3p but positively modulated by DUXAP8. PFN2 upregulation reversed the effect of miR-223-3p mimics. In animal models, knockdown of DUXAP8 inhibited tumor growth and enhanced radiosensitivity. Conclusion DUXAP8/miR-223-3p/PFN2 axis modulated radiosensitivity in lung cancer. Background Long noncoding RNA double homeobox A pseudogene 8 (DUXAP8) was revealed to facilitate lung cancer progression in vitro, but the impacts of DUXAP8 on modulating radiosensitivity have not been examined. Objective This study aimed to explore the effect and underlying mechanisms of DUXAP8 in regulating radiosensitivity in lung cancer. Methods Bioinformatic tools were used to evaluate expression level of DUXAP8 and its associations with overall survival of patients with lung cancer. RT-qPCR was applied to examine the level of DUXAP8, miR-223-3p and profilin 2 (PFN2) RNA expression. Viabilities and apoptosis rates were measured. The interactions of miR-223-3p and DUXAP8 or PFN2 were confirmed using dual-luciferase reporter test and RNA immunoprecipitation (RIP). Immunohistochemistry (IHC) was used to examine Ki67 in animal models. Results DUXAP8 was elevated in lung cancer tissue samples and decreased overall survival of patients. Moreover, DUXAP8 was elevated in lung cancer cells, while irradiation treatment suppressed DUXAP8 in A549 cells. The knockdown of DUXAP8 inhibited cell viabilities but facilitated cell apoptosis. MiR-223-3p was sponged by DUXAP8, while PFN2 was targeted by miR-223-3p but positively modulated by DUXAP8. PFN2 upregulation reversed the effect of miR-223-3p mimics. In animal models, knockdown of DUXAP8 inhibited tumor growth and enhanced radiosensitivity. Conclusion DUXAP8/miR-223-3p/PFN2 axis modulated radiosensitivity in lung cancer.