• Biomolecules & Therapeutics
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• 제28권4호
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• pp.320-327
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• 2020

In current study, we aimed to investigate whether the gentiopicroside (GPS) derived from Gentiana manshurica Kitagawa could block the progression of alcoholic hepatic steatosis to fibrosis induced by chronic ethanol intake. C57BL/6 mice were fed an ethanol-containing Lieber-DeCarli diet for 4 weeks. LX-2 human hepatic stellate cells were treated with GPS 1 h prior to transforming growth factor-β (TGF-β) stimulation, and murine hepatocyte AML12 cells were pretreated by GPS 1 h prior to ethanol treatment. GPS inhibited the expression of type I collagen (collagen I), α-smooth muscle actin (α-SMA) and tissue inhibitor of metal protease 1 in ethanol-fed mouse livers with mild fibrosis. In addition, the imbalanced lipid metabolism induced by chronic ethanol-feeding was ameliorated by GPS pretreatment, characterized by the modulation of lipid accumulation. Consistently, GPS inhibited the expression of collagen I and α-SMA in LX-2 cells stimulated by TGF-β. Inhibition of lipid synthesis and promotion of oxidation by GPS were also confirmed in ethanol-treated AML12 cells. GPS could prevent hepatic steatosis advancing to the inception of a mild fibrosis caused by chronic alcohol exposure, suggesting GPS might be a promising therapy for targeting the early stage of alcoholic liver disease.

• Archives of Pharmacal Research
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• 제29권10호
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• pp.911-920
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• 2006

Phenolic antioxidant butylated hydroxyanisole (BHA) is a commonly used food preservative with broad biological activities, including protection against chemical-induced carcinogenesis, acute toxicity of chemicals, modulation of macromolecule synthesis and immune response, induction of phase II detoxifying enzymes, as well as its undesirable potential tumor-promoting activities. Understanding the molecular basis underlying these diverse biological actions of BHA is thus of great importance. Here we studied the pharmacokinetics, activation of signaling kinases and induction of phase II/III drug metabolizing enzymes/transporter gene expression by BHA in the mice. The peak plasma concentration of BHA achieved in our current study after oral administration of 200 mg/kg BHA was around $10\;{\mu}M$. This in vivo concentration might offer some insights for the many in vitro cell culture studies on signal transduction and induction of phase II genes using similar concentrations. The oral bioavailability (F) of BHA was about 43% in the mice. In the mouse liver, BHA induced the expression of phase II genes including NQO-1, HO-1, ${\gamma}-GCS$, GST-pi and UGT 1A6, as well as some of the phase III transporter genes, such as MRP1 and Slco1b2. In addition, BHA activated distinct mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), as well as p38, suggesting that the MAPK pathways may play an important role in early signaling events leading to the regulation of gene expression including phase II drug metabolizing and some phase III drug transporter genes. This is the first study to demonstrate the in vivo pharmacokinetics of BHA, the in vivo activation of MAPK signaling proteins, as well as the in vivo induction of Phase II/III drug metabolizing enzymes/transporters in the mouse livers.

• Archives of Pharmacal Research
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• 제29권8호
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• pp.633-644
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• 2006

In last couple of decades the use of natural compounds like flavonoids as chemopreventive agents has gained much attention. Our current study focuses on identifying chemopreventive flavonoids and their mechanism of action on human prostate cancer cells. Human prostate cancer cells (PC3), stably transfected with activator protein 1 (AP-1) luciferase reporter gene were treated with four main classes of flavonoids namely flavonols, flavones, flavonones, and isoflavones. The maximum AP-1 luciferase induction of about 3 fold over control was observed with $20\;{\mu}M$ concentrations of quercetin, chrysin and genistein and $50\;{\mu}M$ concentration of kaempferol. At higher concentrations, most of the flavonoids demonstrated inhibition of AP-1 activity. The MTS assay for cell viability at 24 h showed that even at a very high concentration $(500\;{\mu}M)$, cell death was minimal for most of the flavonoids. To determine the role of MAPK pathway in the induction of AP-1 by flavonoids, Western blot of phospho MAPK proteins was performed. Four out of the eight flavonoids namely kaempferol, apigenin, genistein and naringenin were used for the Western Blot analysis. Induction of phospho-JNK and phospho-ERK activity was observed after two hour incubation of PC3-AP1 cells with flavonoids. However no induction of phospho-p38 activity was observed. Furthermore, pretreating the cells with specific inhibitors of JNK reduced the AP-1 luciferase activity that was induced by genistein while pretreatment with MEK inhibitor reduced the AP-1 luciferase activity induced by kaempferol. The pharmacological inhibitors did not affect the AP-1 luciferase activity induced by apigenin and naringenin. These results suggest the possible involvement of JNK pathway in genistein induced AP-1 activity while the ERK pathway seems to play an important role in kaempferol induced AP-1 activity.

• Journal of Acupuncture Research
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• 제17권2호
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• pp.231-246
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• 2000

Acupuncture has been used for treatment of numerous diseases, especially for pain control in the oriental culture. However, the mechanism of pain control by acupuncture was not clear so far. The present study was examined that the effects of electro-acupuncture (EA) applied to the acu-point of extra-segmental area on modulation of formalin induced pain in Sprague - Dawley rats. In order to apply EA to acu-points in the plantar area of right fore paws, a pair of teflon - coated stainless steel wires were implanted in HT 7 (shin-mun) and PC 7 (dae-neong) 5 days before behavioral test. A behavioral test was performed by means of video camera after injection of 5% formalin ($50{\mu}l$) into the lateral plantar region of left hind paw. EA was delivered by a constant current stimulator at 4~5 mA, 2 ms, and 10 Hz for 30 min. The electromyographic activities were recorded in the biceps femoris muscle under chloral hydrate anesthesia. Test stimuli with 1~9mA were applied to the sural nerve territory including the medial portion of the 4th toe and the lateral portion of the 5th toe. Behavioral responses including favoring, flinching and bitting were occured in the biphasic pattern, such as the lst phase (0~5 min) and the 2nd phase (20~45 min) after formalin injection. However, EA (4~5 mA, 2 ms, 10 Hz) significantly inhibited Che behavioral responses. EMG activities of flexor reflex had a latency of 100~300 ms and thresholds of test stimuli for EMG were 4~5 mA in normal rats. Injection of formalin decreased threshold of test stimuli and increased EMG activities for 2hrs after injection. However, EA significantly inhibited EMG activities of flexor reflex increased by formalin and recovered EMG evoked thresholds. These results suggest that contralateral extra-segmental EA inhibits the first and second phases of formalin induced pain but their mechanism be needed to examine additionally.

• Journal of Ginseng Research
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• 제45권6호
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• pp.617-630
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• 2021

Chemotherapy-induced side effects affect the quality of life and efficacy of treatment of cancer patients. Current approaches for treating the side effects of chemotherapy are poorly effective and may cause numerous harmful side effects. Therefore, developing new and effective drugs derived from natural nontoxic compounds for the treatment of chemotherapy-induced side effects is necessary. Experiments in vivo and in vitro indicate that Panax ginseng (PG) and its ginsenosides are undoubtedly non-toxic and effective options for the treatment of chemotherapy-induced side effects, such as nephrotoxicity, hepatotoxicity, cardiotoxicity, immunotoxicity, and hematopoietic inhibition. The mechanism focus on anti-oxidation, anti-inflammation, and anti-apoptosis, as well as the modulation of signaling pathways, such as nuclear factor erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), P62/keap1/Nrf2, c-jun Nterminal kinase (JNK)/P53/caspase 3, mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinases (ERK), AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase kinase 4 (MKK4)/JNK, and phosphatidylinositol 3-kinase (PI3K)/AKT. Since a systemic review of the effect and mechanism of PG and its ginsenosides on chemotherapy-induced side effects has not yet been published, we provide a comprehensive summarization with this aim and shed light on the future research of PG.

• The Korean Journal of Physiology and Pharmacology
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• 제23권4호
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• pp.271-279
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• 2019

The lamina II, also called the substantia gelatinosa (SG), of the trigeminal subnucleus caudalis (Vc), is thought to play an essential role in the control of orofacial nociception. Glycine and serotonin (5-hydroxytryptamine, 5-HT) are the important neurotransmitters that have the individual parts on the modulation of nociceptive transmission. However, the electrophysiological effects of 5-HT on the glycine receptors on SG neurons of the Vc have not been well studied yet. For this reason, we applied the whole-cell patch clamp technique to explore the interaction of intracellular signal transduction between 5-HT and the glycine receptors on SG neurons of the Vc in mice. In nine of 13 neurons tested (69.2%), pretreatment with 5-HT potentiated glycine-induced current ($I_{Gly}$). Firstly, we examined with a $5-HT_1$ receptor agonist (8-OH-DPAT, $5-HT_{1/7}$ agonist, co-applied with SB-269970, $5-HT_7$ antagonist) and antagonist (WAY-100635), but $5-HT_1$ receptor agonist did not increase $I_{Gly}$ and in the presence of $5-HT_1$ antagonist, the potentiation of 5-HT on $I_{Gly}$ still happened. However, an agonist (${\alpha}$-methyl-5-HT) and antagonist (ketanserin) of the $5-HT_2$ receptor mimicked and inhibited the enhancing effect of 5-HT on $I_{Gly}$ in the SG neurons, respectively. We also verified the role of the $5-HT_7$ receptor by using a $5-HT_7$ antagonist (SB-269970) but it also did not block the enhancement of 5-HT on $I_{Gly}$. Our study demonstrated that 5-HT facilitated $I_{Gly}$ in the SG neurons of the Vc through the $5-HT_2$ receptor. The interaction between 5-HT and glycine appears to have a significant role in modulating the transmission of the nociceptive pathway.

• 전기전자학회논문지
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• 제25권2호
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• pp.399-407
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• 2021

본 논문에서는 계통망 사업자의 High Voltage Ride-Through(HVRT) 기능 요구조건을 만족하며, 정상상태에서의 손실을 최소화할 수 있는 Type 4 풍력발전기의 직류단 전압 설계 방법을 제안한다. 대용량 해상 풍력 발전에 사용되는 Type 4 풍력발전기는 전력 계통과 연계된 컨버터와 풍력 발전기와 연계된 컨버터가 직류단을 공유하는 Back-to-Back 컨버터 형태이다. Type 4 풍력발전기에서 HVRT 조건인 계통 고전압 사고가 발생한 경우 사고 전압 크기에 비해 직류단 전압이 부족하다면 과변조로 인해 계통측 컨버터의 전류 제어기가 원활하게 동작되지 못한다. 따라서 HVRT 기능을 만족하기 위해서는 고전압 사고의 전압 크기를 기준으로 직류단 전압을 설계해야 한다. 그러나 직류단 전압의 크기의 증가는 정상상태에서의 컨버터 손실 증가를 야기하므로, 직류단 전압을 크게 설계하였을 때 증가될 손실에 대한 고려가 포함되어야 한다. 본 논문에서는 사고 전압의 크기와 발생 손실이 고려된 직류단 전압을 설계하는 방법에 대해 설명하고, 제안하는 설계 방법의 타당성을 2MVA급 Type 4 풍력발전기의 PSCAD 모델 기반 HVRT 기능 시뮬레이션을 통해 확인하였다.

• 한국환경보건학회지
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• 제49권1호
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• pp.22-29
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• 2023

Background: The existing research results on the combined toxicity of these pollutants using mammals, such as rodents, are insufficient, especially in relation to changes in the immune system. Objectives: This study aims at evaluating the cellular immune response to PE-MPs solely or when combined with Pb, which possess excellent adsorption capacity with PE-MPs and is commonly co-exposed in our daily lives. Methods: The study investigated the cellular immune function of 9-week ICR mice with 28 days exposure to PE-MPs (2 mg/mouse/day) and Pb (0.1 mM in distilled water) individually and in combination. PE-MPs were administered via gastric intubation while the lead intake was conducted via the oral drinking water route. Cellular immunity was evaluated by analyzing the production for T_H1 cytokines namely, TNF-α and IFN-𝛾 and T_H2 cytokines, IL-4 and IL-6 in culture supernatants from polyclonally activated splenic mononuclear cells ex vivo. Results: Both the PE-MPs only and the PE-MPs+Pb exposure group revealed an increased T_H1 response with elevated TNF-α and IFN-𝛾 levels and downregulated T_H2 response with low IL-4, and IL-6 production levels compared to the control group. Furthermore, an increased IFN-𝛾/IL-4 ratio was found in the PE-MPs only and PE-MPs+Pb exposure groups, which indicated the skewedness to T_H1 response. Meanwhile, reduced blood hemoglobin levels and increased levels of IL-4, the dominant T_H2 cytokine in the Pb-only exposure group, were observed. Conclusions: Our current findings on the predominance of T_H1 immune response in the PE-MPs and PE-MPs+Pb groups suggest that PE-MPs could be responsible for the predominant induction of the cellular immune changes. This finding could be used as an important landmark in research related to T_H1 predominance, such as autoimmune diseases. It suggests that additional research on immune modulation using longer exposure durations or the same exposure route is required to elucidate stronger findings.

• 한국결정성장학회지
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• 제33권6호
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• pp.255-260
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• 2023

분자 단위의 폭발물질을 탐지하기 위하여, 고감도 응답성 센서의 개발이 요구되고 있다. 2차원 반도체는 얇은 적층형 구조를 가져 전하 캐리어가 축적될 수 있어, 전하 캐리어의 급격한 신호 변조 특성을 기대할 수 있다. WSe₂ 반도체 소재의 TNT(Trinitrotoluene) 폭발물질에 대한 탐지 효용성을 연구하기 위해, CVD(Chemical Vapor Deposition) 공정을 이용해 WSe₂ 박막을 합성하여 FET(Field Effect Transistors)을 제작하였다. 라만 분석과 FT-IR(Fourier-transform infrared) 분광 결과는 TNT 분자의 흡착과 WSe₂ 결정질의 구조적 전이 분석 정보를 나타내었다. 또한, WSe₂ 표면의 TNT 분자 흡착 전후의 전기적 특성을 비교하였다. TNT 도포 전, WSe₂ FET에 백 게이트 바이어스로 -50 V를 인가함에 따라 0.02 μA의 최대 전류 값이 관측되었고, 0.6%(w/v) TNT 용액을 도포하였을 때 Drain 전류는 p-type 거동을 보이면서 0.41 μA의 최대 전류 값을 기록하였다. 이후 On/Of f Ratio 및 캐리어 이동도, 히스테리시스를 추가적으로 평가하였다. 본 연구에서는 WSe₂의 TNT 분자에 대한 고감도와 신속한 응답성을 통해 폭발물질 탐지 센서 소재로서의 가능성을 제시하였다.

• 핵의학기술
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• 제18권1호
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• pp.82-88
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• 2014

SPECT/CT로 소아 복부를 검사 하는데 있어 저선량 CT 조건에 따른 흡수선량을 측정하고 SPECT와 CT 영상의 질을 평가하고, 우수한 영상의 질을 유지하면서 최저의 흡수 선량을 받을 수 있는 tube voltage (kVp)와 tube current (mA)의 설정 방향을 알아보는데 목적을 두었다. 장비는 Discovery NM/CT 670을 사용하였다. PMMA phatom을 이용하여 80, 100 kVp 10, 15, 20, 25 mA의 조건을 설정하여 중심방향과 주변방향(3, 6, 9, 12시 방향의 평균) 의 흡수선량을 측정하였고, 그에 따른 image를 SNRD로 평가 하였다. CT QA performance phantom으로 CT image의 resolution을 MTF로 나타내었고, jaszczak phantom을 hot sphere와 배후방사의 비를 $^{99}mTc$을 1:8로 주입하여 4개의 sphere에 대한 SPECT image를 CNR로 평가하였다. 선량측정에서는 주변방향의 선량이 중심방향 선량보다 평균 7% 높게 측정되었으며, SNRD는 조건에 따라 유의한 차이가 없었으며 Resolution 평가에서는 0.385 lp/mm 기준으로 100 kVp가 80 kVp보다 평균 12% 재현성이 우수하였으며, jaszczak phantom을 이용해서 CT를 기반으로 한 attenuation correction 된 SPECT image를 CNR로 평가한 결과 CT조건의 변화와 무관하게 4개의 sphere 모두 유의한 차이를 보이지 않았다. 본 연구는 SPECT/CT 검사에서 최저의 흡수선량을 유지하고 우수한 영상의 질을 획득하는데 추가적인 연구가 필요할 것으로 사료된다.