• BMB Reports
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• 제51권6호
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• pp.308-313
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• 2018

Small-molecule inhibitors are widely used to treat a variety of inflammatory diseases. In this study, we found a novel anti-inflammatory compound, 1-[(2R,4S)-2-methyl-4-(phenylamino)-1,2,3,4-tetrahydroquinolin-1-yl]prop-2-en-1-one (MPQP). It showed strong anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. These effects were exerted through the inhibition of the production of NO and pro-inflammatory cytokines, such as interleukin (IL)-6, $IL-1{\beta}$, and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$). Furthermore, MPQP decreased the expression levels of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2). Additionally, it mediated the inhibition of the phosphorylation of p38, c-Jun N-terminal kinase (JNK), the inhibitor of ${\kappa}B{\alpha}$ ($I{\kappa}B{\alpha}$), and their upstream kinases, $I{\kappa}B$ kinase (IKK) ${\alpha}/{\beta}$, mitogen-activated protein kinase kinase (MKK) 3/6, and MKK4. Furthermore, the expression of IL-1 receptor-associated kinase 1 (IRAK1) that regulates $NF-{\kappa}B$, p38, and the JNK signaling pathways, was also increased by MPQP. These results indicate that MPQP regulates the IRAK1-mediated inflammatory signaling pathways by targeting IRAK1 or its upstream factors.

• Parasites, Hosts and Diseases
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• 제51권1호
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• pp.133-137
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• 2013

This study aimed to measure the levels of interferon-gamma (IFN-${\gamma}$), tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin 1 (IL-1), interleukin 6 (IL-6), and nitrite/nitrate ($NO_x$) in serum of dogs experimentally infected with Rangelia vitalii. Twelve female mongrel dogs were divided into 2 groups; group A (uninfected controls) composed by healthy dogs (n=5) and group B consisting of dogs inoculated with R. vitalii (n=7). Animals were monitored by blood smear examinations, which showed intraerythrocytic forms of the parasite on day 5 post-infection (PI). Blood samples were collected through the jugular vein on days 0, 10, and 20 PI to determine the serum levels of IFN-${\gamma}$, TNF-${\alpha}$, IL-1, IL-6, and $NO_x$. Cytokines were assessed by ELISA quantitative sandwich technique, and $NO_x$ was measured by the modified Griess method. Cytokine levels (IFN-${\gamma}$, TNF-${\alpha}$, IL-1, and IL-6) were increased (P<0.01) in serum of infected animals. Serum levels of $NO_x$ were also increased on days 10 PI (P<0.01) and 20 PI (P<0.05) in infected animals. Therefore, the infection with R. vitalii causes an increase in proinflammatory cytokines and nitric oxide content. These alterations may be associated with host immune protection against the parasite.

• Journal of Microbiology and Biotechnology
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• 제14권4호
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• pp.693-697
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• 2004

YH-1715R, (2R,3R)-2-(2,4-difluorophenyl)-3-(3-methoxy-1,2,4-isothiazol-3-yl-thio)-1-( 1H-1,2,4-triazol-l-yl)-2-butanol, a new triazole derivative obtained by the structural modification of fluconazole, was found to exhibit potent anti-Candida activity against a wide variety of Candida albicans (C. albicans) (MIC: 0.4-12.5 mg/l). To investigate the mode of action of YH-1715R, its effect on ergosterol biosynthesis in cell-free extracts and whole cells of C. albicans was examined. The inhibitory activity of YH-1715R was approximately ten-fold higher than that of fluconazole. To determine the primary action mechanism of YH-1715R, its inhibitory activity against lanosterol $14\alpha$-demethylase (14$\alpha$-DM), a major target for azole, was measured using gas-liquid chromatography. YH-1715R and fluconazole were found to inhibit 14a-DM with an $IC_{50}$ of 0.015 $\mu$M and 0.01$8\mu$M, respectively, plus the mode of inhibition of YH-1715R and fluconozole was noncompetitive with a $K_i$ of 0.0533$\mu$M and 0.0975$\mu$M.

• 대한화장품학회지
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• 제34권2호
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• pp.101-107
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• 2008

신선초 추출물 및 그의 분획물의 미백 효과를 알아보기 위하여, B16 멜라노마와 정상 사람 표피 세포를 이용하여 멜라닌 생성에 관련된 다양한 실험을 실시하였다. 70% ethanol 용매로 추출한 신선초 추출물을 연속적으로 분획하여 hexane, ethyl acetate, n-butanol, 물 분획물을 얻었다. 버섯 티로시나제 활성 실험에서 신선초 추출물 및 그의 분획물은 저해 효과를 보이지 않았으나, B16 멜라노마를 이용한 멜라닌 생성 실험에서는 hexane 분획물과 ethyl acetate 분획물에서 억제 효과를 보였다. 세포내 멜라닌 생성의 초기 단계에 작용하는 티로시나제 단백질의 활성을 조사한 결과, hexane 분획($IC_{50}$ < $25{\mu}g/mL$)과 ethyl acetate분획($IC_{50}$ < $5{\mu}g/mL$)은 알부틴($IC_{50}{\leq}250{\mu}g/mL$)과 비교 시 더 낮은 농도에서 현저하게 티로시나제 활성을 저해시켰다. 따라서 신선초 추출물의 미백 작용 기전을 규명하기 위하여, 멜라노 사이트의 mitogen으로 작용하는 endothelin-1(ET-1)과 UVB에 의해 생성되어 염증을 매개하는 interleukin-$1{\alpha}$(IL-$1{\alpha})$의 생성량을 측정하였다. Hexane 및 ethyl acetate 분획물은 IL-$1{\alpha}$의 생성에 영향을 끼치지 못했으나, 표피세포에서 UVB에 의해 생성된 ET-1을 농도에 따라 감소시킴으로써 멜라노사이트의 melanogenesis를 저해하는 것으로 확인되었다. 따라서 신선초 추출물은 미백 효능을 갖는 화장품 소재로써 사용 가능하리라 판단된다.

• Journal of Acupuncture Research
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• 제20권5호
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• pp.50-62
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• 2003

Objective: Bee Venom(BV) has been used for various kinds of inflammatory or painful conditions in Oriental Medicine clinics, and there publishes reports on its therapeutic effects and the probable mechanism of those therapeutic effects, where CDs and cytokines plays important role. This study investigated the influences of bee venom on the expressions of CDs and cytokines of HMC cell line Methods: In this study we analysed the expression profile of HMC cell line treated with BV of 10-2ug/ml in relation to that of HMC cell line treated with vehicle by way of CD/cytokine microarray hybridization with 342 genes on it. Results: There were no upregulated genes by more than 3 fold, while there showed some downregulated genes by less than 1/3 fold as follows: colony stimulating factor 2, CD122, IL-7, CD112, TNF-alpha, CD138, CD166, TGFbetaR2, CD42b, CD62L, CD111, interleukin 10 receptor alpha, colony stimulating factor 1(macrophage), CD38 antigen(p45), CD121a, CD33 antigen(gp67), colony stimulating factor 1 receptor, B cell linker protein (SLP65) mRNA, CD94, alanyl(membrane) aminopeptidase, immunoglobulin(CD79A) binding protein 1, CD205, CD241, CD207, CDw121b, integrin alpha L(CD11a), integrin beta 1(CD29), CD91, CD42b. Conclusions: Bee venom treatment induced downregulation of some CDs or cytokines including $TNF-{\alpha}$. IL-1R with its possible implication in an antiinflammatory action of BV. Further research on expression profile changes induced by BV treatment is expected.

• 한국응용과학기술학회지
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• 제35권2호
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• pp.509-518
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• 2018

이 연구의 목적은 신체활동이 마이오카인 발현에 미치는 영향을 보고자 문헌고찰을 하였다. 신체적인 활동은 제2형 당뇨, 심혈관질환, 대장암, 치매 및 우울증과 같은 질환을 예방하는 역할을 하고 있다. 그리고 마이오카인(myokine)은 운동 훈련에 의해 분비되는 호르몬으로 뇌성장이나 알츠하이머 같은 질환 예방에 도움을 준다. 운동수행과정에서 수축하는 근육으로부터 분비되는 항염증 마이오카인의 생성과 대사 조절에 필요한 분비 활성화가 건강증진에 중요한 요인으로 보고 있다. 인체 골격근에서 분비되는 마이오카인 가운데 IL-4, IL-6, IL-7, IL-8, IL-15 등은 근육비대(hypertrophy)와 세포(myogenesis) 및 혈관생성(angiogenesis) 등의 조절에 관여한다. IL-6는 AMPK 활성화로 인한 대사중 지방 산화를 촉진시키는 작용을 하고, IL-1Ra, IL-10 과 sTNF-R 는 염증성 싸이토카인 $TNF-{\alpha}$의 분비를 억제한다. IL-15는 저항 운동시 근수축을 통한 발현량이 증가하어 근육 성장의 중요 합성요인으로 작용한다. 한편 IL-7 및 IL-8도 신호 전달 수용체 C-X-C를 통해 혈관신생을 촉진시킨다.

• Journal of Microbiology and Biotechnology
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• 제27권6호
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• pp.1189-1197
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• 2017

Lichen-forming fungi are known to have various biological activities, such as antioxidant, antimicrobial, antitumor, antiviral, anti-inflammation, and anti proliferative effects. However, the immunosuppressive effects of Bryoria sp. extract (BSE) have not previously been investigated. In this study, the inhibitory activity of BSE on the proliferation of $CD8^+$ T cells and the mixed lymphocytes reaction (MLR) was evaluated in vitro. BSE was non-toxic in spleen cells and suppressed the growth of splenocytes induced by anti-CD3. The suppressed cell population in spleen cells consisted of $CD8^+$ T cells and their proliferation was inhibited by the treatment with BSE. This extract significantly suppressed the IL-2 associated with T cell growth and $IFN-{\gamma}$ as the $CD8^+$ T cell marker. Furthermore, BSE reduced the expression of the IL-2 receptor alpha chain ($IL-2R{\alpha}$) on $CD8^+$ T cells and CD86 on dendritic cells by acting as antigen-presenting cells. Finally, the MLR produced by the co-culture of C57BL/6 and MMC-treated BALB/c was suppressed by BSE. IL-2, $IFN-{\gamma}$, and CD69 on $CD8^+$ T cells in MLR condition were inhibited by BSE. These results indicate that BSE inhibits the MLR via the suppression of $IL-2R{\alpha}$ expression in $CD8^+$ T cells. BSE has the potential to be developed as an anti-immunosuppression agent for organ transplants.

• International Journal of Industrial Entomology and Biomaterials
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• 제21권2호
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• pp.163-167
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• 2010

[ $\alpha$ ]Glucosidase (EC 3.2.1.20) is a glycosidase that hydrolyzes disaccharides, oligosaccharides, and polysaccharides resulting in the release of α-D-glucose. In this study, $\alpha$-glucosidase activity in the hemolymph and midgut of the mulberry silkworm Bombyx mori and Japanese oak silkmoth Antheraea yamamai was measured using maltose, sucrose, trehalose, and p-nitrophenyl $\alpha$-D-glucopyranoside as substrates. In general, hemolymph $\alpha$-glucosidase activity was higher in B. mori than in A. yamamai. In contrast, midgut $\alpha$-glucosidase activity was higher in A. yamamai than in B. mori for all of the substrates tested. $\alpha$-Glucosidase activity in the midgut of both B. mori and A. yamamai showed similar responses to changes in pH and temperature for all of the substrates tested. Native (7.5%) PAGE of hemolymph and midgut proteins from B. mori and A. yamamai followed by staining with 4-methylumbelliferyl $\alpha$-D-glucoside (MUG) indicated that the $\alpha$-glucosidases of these related lepidopterans are functionally similar but structurally different. In comparison to $\alpha$-glucosidase activity from A. yamamai, $\alpha$-glucosidase activity from B. mori was generally less sensitive to the $\alpha$-glucosidase inhibitors, 1-deoxynojirimycin (DNJ), acarbose, and voglibose when the activity was determined using maltose, sucrose, and trehalose.

• BMB Reports
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• 제31권6호
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• pp.595-599
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• 1998

To investigate conformational information of a low oxygen affinity recombinant hemoglobin (rHb) containing $96Val{\rightarrow}Trp$ mutation at the ${\alpha}96$ position, we ave produced rHb (${\alpha}96Val{\rightarrow}Phe$) and rHb (${\alpha}96Val{\rightarrow}Tyr$), using the Escherichia coli expression system and site-directed mutagenesis. The oxygen affinity of rHb (${\alpha}96Val{\rightarrow}Phe$) is similar to that of human normal adult hemoglobin (Hb A). However, the oxygen affinity of rHb (${\alpha}96Val{\rightarrow}Tyr$) showed much lower oxygen affinity than Hb A which is similar to that of rHb (${\alpha}96Val{\rightarrow}Tyr$), providing an opportunity as a potential candidate for a hemoglobin-based blood substitute. Both rHb (${\alpha}96Val{\rightarrow}Phe$) and rHb (${\alpha}96Val{\rightarrow}Tyr)$ showed high cooperativity in oxygen binding. IH-NMR spectroscopy shows that both rHb (${\alpha}96Val{\rightarrow}Phe$) and rHb (${\alpha}96Val{\rightarrow}Tyr$) have very similar tertiary structure around the heme pockets and uaternary structure in the ${\alpha}_1/{\beta}_2$ subunit interface ompared to Hb A. The low oxygen affinity of rHb (${\alpha}96Val{\rightarrow}Tyr$) has been suggested to be due to a hydrogen bond caused by an extra hydroxyl group not present in rHb (${\alpha}96Val{\rightarrow}Phe$). However, investigation of the carbonmonoxy form of rHb (${\alpha}96Val{\rightarrow}Phe$) and (${\alpha}96Val{\rightarrow}Try$) in the presence of inositol hexaphosphate at low temperature suggests that low oxygen affinity of (${\alpha}96Val{\rightarrow}Try$) may arise from a mechanism different to that of rHb (${\alpha}96Val{\rightarrow}Trp$).

• Journal of Chest Surgery
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• 제32권11호
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• pp.971-977
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• 1999

Background: Immunologic and inflammatory responses of cardiopulmonary bypass(CPB) influence postoperative mortality and morbidity with multiple organ injury. It has been reported that ischemia/reperfusion induced-myocardial injury during CPB is causative of release of inflammatory cytokines such as interleukin-6(IL-6) and tumor necrosis factor-$\alpha$ (TNF-$\alpha$). The purpose of this study was to detect the time course of the activated cytokine and troponin-T(TnT), and to examine the correlation between such parameters during CPB. Material and Method: The serial samples were collected from arterial blood via radial arterial catheter in 23 patients who are underwent open heart surgery (OHS) with CPB, the IL-6, TNF-$\alpha$ and TnT were checked. Result: \circled1 IL-6, TNF$\alpha$- and TnT concentration increased significantly during CPB with a peaking level of CPB-off (p 0.05). \circled2 IL-6 had highly positive correlation with aortic cross clamping time and total bypass time(r=0.80, 0.78; p 0.05, respectively). \circled3 There was no correlation among IL-6, TNF-$\alpha$ and TnT. Conclusion: In conclusion, these data showed that elevated production of serum IL-6 during CPB was attributable to ischemia/reperfusion induced-myocardial damage. IL-6 will become a new and sensitive biological marker in assessment of myocardial damage during OHS with CPB. However, further studies will be needed to apply IL-6 in more patient population.