• Biomolecules & Therapeutics
• /
• 제8권1호
• /
• pp.78-83
• /
• 2000

The objective of this study was to prevalidate the Organization for Economic Cooperation and Development's (OECD) rodent uterotrophic assay as a test method for screening of potential endocrine disrupting chemicals (EDCs). This study was conducted exactly as described in the OECD protocol documents. A positive control substance, 17$\alpha$-ethinyl estradiol (EE), was administered daily for three days to ovariectomized (OVX) Sprague-Dawley rats at various doses for determine the dose-response curve. Additionally, a pure antiestrogenic chemical, ZM189, 154 was administered to OVX rats at the same time EE to determine the effectiveness of the material against blocking the estrogenic effects of EE. At higher concentration of EE (10 $\mu\textrm{g}$/kg), a statistically significant difference in body weight gain and food consumption was observed compared to vehicle controls. In uterine responses, EE produced a dose-related increase in uterus weights compared to vehicle control. These increases were statistically significant at the >1.0 $\mu\textrm{g}$/kg doses. However, a similar dose-response relationship was not observed in vagina weight. A comparison of the two groups receiving ZM189,154 (0.1 and 1.0 mg/kg) with 0.3 $\mu\textrm{g}$/kg of EE and the group receiving only 0.3 $\mu\textrm{g}$/kg of EE showed dose-related decreases in uterus weights. However, statistical significance was shown in 1.0 mg/kg of ZM189,154. In conclusion, administration of EE produced a dose-related increase in uterine (wet and blotted) weights. Additionally, the 1.0mg/kg dose of ZM189,154 was effective in blocking the estrogenic activity of EE. These data suggest 3-day uterotrophic assay using OVX rats may serve as a good tool for EDCs screening.

• 약학회지
• /
• 제41권6호
• /
• pp.797-801
• /
• 1997

Recently we reported that water extracts of Coptidis Rhizomas showed calcium antagonistic action and alpha-adrenoceptor inhibitory action in the vascular smooth muscle. Since ca lcium antagonistic properties are important in the treatment of various diseases including asthma. In the present study, the bronchodilatory effects of crude extract of three kinds of Coptidis Rhizoma (Coptidis chinensis, Coptis japonica and root hair of Coptis japonica) was investigated using rat isolated trachea. The result showed that all extracts relaxed carbachol-contracted tracheal smooth muscle. Concentration-dependently, in which the root hair of Coptis japonica was the least potent. The inhibitory potency expressed in terms of $IC_{50}$ against carbachol contraction was 1.8${\mu}$g/ml and 2.7${\mu}$g/ml for Coptidis chinensis and Coptis japonica, respectively. These extracts also inhibited KCI-contracted tracheal smooth muscle. But the relative potency ($IC_{50}$) was 3.5 and 4.1 folds weaker than carbachol-induced contraction for Coptidics chinenesis and Coptis japonica, respectively. Pretreatment of crude extracts also inhibited carbachol- or KCI-induced contraction, non-competitively. These findings indicate that the extracts have muscarinic blocking as well as $Ca^{2+}$ channel blocking action. When provoked intracellular stored $Ca^{2+}$ release by carbachol in $Ca^{2+}$-free conditions, initial phasic contraction due to $Ca^{2+}$ release was significantly inhibited by the extracts. As taken together, we conclude that water extracts of Coptidis Rhizoma may be beneficial in bronchospasm or other broncheal tube narrowing conditions such as asthma.

• Journal of Microbiology and Biotechnology
• /
• 제33권7호
• /
• pp.864-874
• /
• 2023

Natural killer (NK) cell dysfunctions against hepatocellular carcinoma (HCC) in a hypoxic environment. Many solid tumors are present in a hypoxic condition, which changes the effector function of various immune cells. The transcription of hypoxic-inducible factors (HIFs) in cancer cells make it possible to adapt to their hypoxic environment and to escape the immune surveillance of NK cells. Recently, the correlation between the transcription of HIF-1α and pro-inflammatory cytokines has been reported. Interleukin (IL)-6 is higher in cancers with a highly invasive ability, and is closely related to the metastasis of cancers. This study showed that the expression of HIF-1α in HCC cells was associated with the presence of IL-6 in the environment of HCC-NK cells. Blocking of IL-6 by antibody in the HCC-NK interaction changed the production of several cytokines including TGF-β, IL-1, IL-18 and IL-21. Interestingly, in a co-culture of HIF-1α-expressed HCC cells and NK cells, blocking of IL-6 increased the production of IL-21 in their supernatants. In addition, the absence of IL-6 significantly enhanced the cytotoxic ability and the expression of the activating receptors (NKG2D, NKp44, and NKG2C) in NK cells to HIF-1α-expressed HCC cells. These effects might be made by the decreased expression of HIF-1α in HCC cells through the inhibited phosphorylation of STAT3. In conclusion, the absence of IL-6 in the interaction of HIF-1α-expressed HCC cells and NK cells could enhance the antitumor activity of NK cells to HCC cells.

• 대한약리학회지
• /
• 제22권1호
• /
• pp.24-33
• /
• 1986

본 연구에서는 개구리(Rana nigromaculata)의 피부에 있어서 전위차(PD), 단락전류(SCC) 및 total skin conductance(TSC)에 미치는 제종 adrenergic agonist 및 그 차단제의 영향을 관찰하여 개구리 피부에 adrenoceptors의 존재를 확인하고 Na 수송에 있어 그들의 역할을 구명코자 하였다. 1.Norepinephrine(NE, $6{\times}10^{-8}-6{\times}10^{-5}M$), phenylephrine($PE,5{\times}10^{-6}-5{\times}10^{-4}M$)의 PD 및 epinephrine(Epi, $5.5{\times}10^{-7}-5.5{\times}10^{-5}M$)의 PD 및 SCC 증가효과는 약물의 투여농도에 비례하였으며, Epi의 최대효과는 NE나 PE의 것보다 약하였다. 2. 이러한 PD 및 SCC의 증가효과는 alpha 1 adrenoceptor 차단체인 prazosin $2{\times}10^{-6}M$에 의해서 억제되었으며, 특히 Epi의 증가효과는 불가역성 alpha receptor 차단제인 phenoxybenzamine $3.3{\times}10^{-5}M$에 의하여 완전히 차단되며 대량의 Epi에 의해서는 PD 및 SCC의 감소를 초래하였다. 3. Beta adrenoceptor agonist인 isoproterenol$(5{\times}10^{-7}-5{\times}10^{-6}M)$에 의해 농도증가에 비례한 PD 및 SCC의 감소가 일어났으며, 이는 선택적 bete receptor 차단제인 propranolol $4{\times}10^{-6}M$에 의해 차단되었다. 또한 Epi의 PD 및 SCC 증가효과는 propranolol $4{\times}10M$에 의하여 강화됨을 볼 수 있었다. 4. Alpha 2 adrenoceptor agonist인 clonidine 및 guanabenz도 PD 및 SCC의 증가를 가져왔으며 이러한 효과는 alpha 2 receptor 차단제인 yohimbine에서 보다 Alpha 1 receptor 차단제인 prazosin에 의해 더 잘 억제되었다. 이상 실험의 결과 개구리 복부피부에도 포유동물에서와 같이 adrenergic alpha 및 beta receptor가 존재하며 alpha receptor는 PD 및 SCC의 증가를, beta receptor는 PD 및 SCC의 감소를 매개하여, 개구리 피부의 Na 수송에 있어 adrenergic system이 중요한 조절작용을 하고 있음을 알 수 있었다. 그러나 여기에 관여하는 alpha receptor는 다른 포유류에서와 같이 alpha 1 및 alpha 2 adrenoceptor로 구분할 수는 없었다.

• The Korean Journal of Pain
• /
• 제12권2호
• /
• pp.177-182
• /
• 1999

Background: Clonidine, an ${\alpha}_2$ adrenergic agonist blocks nerve conduction. However, in our previous experiment we found that adrenaline neither blocks nerve conduction by itself nor augment nerve conduction blockade by lidocaine near clinical concentrations. Possible explanations are: 1) there may be antagonism between some of adrenergic receptors, 2) clonidine may block nerve conduction via non-adrenergic mechanism. The purpose of this study is to obtain dose-response curves of several different forms of adrenergic receptor agonist to see the relative potencies of each adrenergic receptors to block nerve conduction. Methods: Recordings of compound action potentials of A-fiber components (A-CAPs) were obtained from isolated sciatic nerves of adult male Sprague-Dawley rats. Nerve sheath of the sciatic nerve was removed and desheathed nerve bundle was mounted on a recording chamber. Single pulse stimuli (0.5 msec, supramaximal stimuli) were repeatedly applied (2Hz) to one end of the nerve and recordings of A-CAPs were made on the other end of the nerve. Dose-response curves of epinephrine, phenylephrine, isoproterenol, clonidine were obtained. Results: $ED_{50}$ of each adrenergic agonist was: $4.51\times10^{-2}$ M for epinephrine; phenylephrine, $7.74\times10^{-2}$ M; isoproterenol, $9.61\times10^{-2}$ M; clonidine, $1.57\times10^{-3}$ M. Conclusion: This study showed that only clonidine, ${\alpha}_2$ adrenergic agonist, showed some nerve blocking action while other adrenergic agonists showed similar poor degree of nerve blockade. This data suggest that non-effectiveness of epinephrine in blocking nerve conduction is not from the antagonism between adrenergic receptors.

• Molecules and Cells
• /
• 제40권2호
• /
• pp.109-116
• /
• 2017

Soybean agglutinin (SBA) is an anti-nutritional factor of soybean, affecting cell proliferation and inducing cytotoxicity. Integrins are transmembrane receptors, mediating a variety of cell biological processes. This research aims to study the effects of SBA on cell proliferation and cell cycle progression of the intestinal epithelial cell line from piglets (IPEC-J2), to identify the integrin subunits especially expressed in IPEC-J2s, and to analyze the functions of these integrins on IPEC-J2 cell cycle progression and SBA-induced IPEC-J2 cell cycle alteration. The results showed that SBA lowered cell proliferation rate as the cell cycle progression from G0/G1 to S phase (P < 0.05) was inhibited. Moreover, SBA lowered mRNA expression of cell cycle-related gene CDK4, Cyclin E and Cyclin D1 (P < 0.05). We successfully identified integrins ${\alpha}2$, ${\alpha}3$, ${\alpha}6$, ${\beta}1$, and ${\beta}4$ in IPEC-J2s. These five subunits were crucial to maintain normal cell proliferation and cell cycle progression in IPEC-J2s. Restrain of either these five subunits by their inhibitors, lowered cell proliferation rate, and arrested the cells at G0/G1 phase of cell cycle (P < 0.05). Further analysis indicated that integrin ${\alpha}2$, ${\alpha}6$, and ${\beta}1$ were involved in the blocking of G0/G1 phase induced by SBA. In conclusion, these results suggested that SBA lowered the IPEC-J2 cell proliferation rate through the perturbation of cell cycle progression. Furthermore, integrins were important for IPEC-J2 cell cycle progression, and they were involved in the process of SBA-induced cell cycle progression alteration, which provide a basis for further revealing SBA anti-proliferation and anti-nutritional mechanism.

• Molecules and Cells
• /
• 제41권12호
• /
• pp.1008-1015
• /
• 2018

$I{\kappa}B$, a cytoplasmic inhibitor of nuclear factor-${\kappa}B$ ($NF-{\kappa}B$), is reportedly degraded via the proteasome. However, we recently found that long-term incubation with proteasome inhibitors (PIs) such as PS-341 or MG132 induces $I{\kappa}B{\alpha}$ degradation via an alternative pathway, lysosome, which results in $NF-{\kappa}B$ activation and confers resistance to PI-induced lung cancer cell death. To enhance the anti-cancer efficacy of PIs, elucidation of the regulatory mechanism of PI-induced $I{\kappa}B{\alpha}$ degradation is necessary. Here, we demonstrated that PI up-regulates nuclear factor (erythroid-derived 2)-like 2 (Nrf2) via both de novo protein synthesis and Kelch-like ECH-associated protein 1 (KEAP1) degradation, which is responsible for $I{\kappa}B{\alpha}$ degradation via macroautophagy activation. PIs increased the protein level of light chain 3B (LC3B, macroautophagy marker), but not lysosome-associated membrane protein 2a (Lamp2a, the receptor for chaperone-mediated autophagy) in NCI-H157 and A549 lung cancer cells. Pretreatment with macroautophagy inhibitor or knock-down of LC3B blocked PI-induced $I{\kappa}B{\alpha}$ degradation. PIs up-regulated Nrf2 by increasing its transcription and mediating degradation of KEAP1 (cytoplasmic inhibitor of Nrf2). Overexpression of dominant-negative Nrf2, which lacks an N-terminal transactivating domain, or knock-down of Nrf2 suppressed PI-induced LC3B protein expression and subsequent $I{\kappa}B{\alpha}$ degradation. Thus, blocking of the Nrf2 pathway enhanced PI-induced cell death. These findings suggest that Nrf2-driven induction of LC3B plays an essential role in PI-induced activation of the $I{\kappa}B$/$NF-{\kappa}B$ pathway, which attenuates the anti-tumor efficacy of PIs.

• 대한환경공학회지
• /
• 제39권5호
• /
• pp.255-264
• /
• 2017

본 연구는 수상 태양광 발전시설의 설치로 인한 농업용 저수지의 수질변화를 평가하기 위해 경기도 안성시 금광저수지에 위치한 수상 회전식 태양광 발전시설에서 발전시설 설치에 따른 차광구역 6지점과 비차광구역 4지점을 선정하여 1년 동안 총 16회에 걸쳐 차광으로 인한 수질변화를 시간과 수심 별로 분석하였다. 이를 위해 수온, pH, DO, Chl-a, BGA 항목을 0.3 m, 1 m, 3 m, 5 m의 수심별로 측정하고, 표층의 시료를 채수하여 COD, TN, TP 항목을 분석하였다. 연구결과, 금광저수지 내 10곳의 측정지점 간의 관측된 전 수질항목에서 차이는 유의확률(p - value) 0.05 이상으로 유의수준(${\alpha}=0.05$)에서 서로 다르지 않다고 통계학적으로 분석되었다. 이러한 결과를 토대로 측정지점을 차광구역(site 1~6)과 비차광구역(site 7~10)으로 그룹화 후 시간 및 수심에 따른 변화를 확인하였다. 차광구역과 비차광구역 간의 수온, pH, DO, COD, TN, TP, Chl-a, BGA의 계절 및 수심에 따른 차이는 유의한 수준에서 통계학적으로 다르지 않았다(p > 0.05). Chl-a와 BGA의 경우, 7월에 비차광구역보다 차광구역에서 일부 높은 농도가 관측되었으나 이는 기록적인 가뭄과 낮은 저수량, 발전시설 구조물에 부착된 부착조류의 과다성장으로 인한 일시적 현상으로 전체 수질은 통계학적으로 유의할 만한 차이가 없는 것으로 조사되었다. 이러한 결과는 수상 회전식 태양광 발전시설의 설치로 인한 저수지 수면의 차광이 전체 수면적 대비 0.5% 미만으로 일사량 유입 감소효과는 취송 및 방류를 통한 저수지 수체의 혼합 효과 대비 미미했기 때문인 것으로 판단된다. 향후, 수상 태양광 발전시설 설치로 인한 수질변화를 면밀히 연구하기 위해서는 보다 넓은 면적의 태양광 발전시설의 설치로 인한 차광과 함께 장기적인 수질 및 수생태계 관측이 필요할 것으로 판단된다.

• 공업화학
• /
• 제21권1호
• /
• pp.46-51
• /
• 2010

양말단에 하이드록시프로필 기를 갖는 폴리올가노실옥산을 합성한 다음 이를 isophorone diisocyanate (IPDI), propylene glycol (PPG) 및 2,2-bis(hydroxymethyl) propionic acid (DMPA)와 함께 공중합하여 폴리올가노실옥산변성 폴리우레탄 중합체(PDMS- PU)를 제조하였다. 이중합체의 양말단에 있는 이소시아네이트기를 butanon oxime으로 blocking시킨 다음 트리에틸아민(TEA)으로 중화시켜 PDMS-PU 수분체를 얻었다. 열분해로 deblocking되는 온도를 측정하였으며 수분산체는 우수한 수분산 안정성을 보였다. 중합 시 NCO/OH의 당량비를 1.12~1.53으로 하고 DMPA의 함량을 변화시켜 제조한 PDMS-PU 중합체의 수분산체에 대한 분산입자크기를 측정하였으며 반응물에서 DMPA의 함량을 7.2, 13.5, 18.7 mole%로 증가시킴에 따라 입자의 크기는 136, 100, 65 dnm로 감소하는 경향을 나타내었다. DMPA의 함량을 변화시켜 얻은 PDMS- PU 필름의 접촉각 및 접착강도를 측정하였다.

• 대한본초학회지
• /
• 제25권4호
• /
• pp.103-112
• /
• 2010

Objective : The aim of this study was to determine whether methanol extract of Do-Ki-Tang (DKT) inhibit free radical generation and production of nitrite an index of NO, $PGE_2$, iNOS, COX-2 and pro-inflammatory cytokines such as TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and MCP-1 in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Methods : Cytotoxic activity of extract on RAW 264.7 cells was measured using 5-(3-caroboxymeth-oxyphenyl)-2H-tetra-zolium inner salt (MTS) assay. The expression level of inflammatory response-related proteins was confirmed by western blot. The production of proinflammatory cytokines was measured by ELISA. Results : Our results indicated that DKT scavenged DPPH radical and nitric oxide in vitro. Moreover, DKT significantly inhibited the LPS-induced NO, $PGE_2$ production and iNOS, COX-2 expression accompanied by an attenuation of TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and MCP-1 formation in macrophages. Furthermore, DKT treatment also blocked LPS-induced intracellular ROS production and the activation of NF-${\kappa}B$ and MAPKs. Conclusion : Our data suggest that the anti-inflammatory effect of DKT is mediated through down-modulation of pro-inflammatory mediators and cytokines by blocking the signaling pathways of NF-${\kappa}B$ and MAPKs. These inhibitory effects by DKT represent a potential therapeutic approach to the treatment of inflammatory diseases.