• Title/Summary/Keyword: MEK1

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Mechanisms involved in adenosine pharmacological preconditioning-induced cardioprotection

  • Singh, Lovedeep;Kulshrestha, Ritu;Singh, Nirmal;Jaggi, Amteshwar Singh
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.3
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    • pp.225-234
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    • 2018
  • Adenosine is a naturally occurring breakdown product of adenosine triphosphate and plays an important role in different physiological and pathological conditions. Adenosine also serves as an important trigger in ischemic and remote preconditioning and its release may impart cardioprotection. Exogenous administration of adenosine in the form of adenosine preconditioning may also protect heart from ischemia-reperfusion injury. Endogenous release of adenosine during ischemic/remote preconditioning or exogenous adenosine during pharmacological preconditioning activates adenosine receptors to activate plethora of mechanisms, which either independently or in association with one another may confer cardioprotection during ischemia-reperfusion injury. These mechanisms include activation of $K_{ATP}$ channels, an increase in the levels of antioxidant enzymes, functional interaction with opioid receptors; increase in nitric oxide production; decrease in inflammation; activation of transient receptor potential vanilloid (TRPV) channels; activation of kinases such as protein kinase B (Akt), protein kinase C, tyrosine kinase, mitogen activated protein (MAP) kinases such as ERK 1/2, p38 MAP kinases and MAP kinase kinase (MEK 1) MMP. The present review discusses the role and mechanisms involved in adenosine preconditioning-induced cardioprotection.

The inhibitory effect of egg white lysosome extract (LOE) on melanogenesis through ERK and MITF regulation

  • Park, Jung Eun;Hwang, Hyung Seo
    • Journal of Applied Biological Chemistry
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    • v.65 no.2
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    • pp.93-99
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    • 2022
  • Lysosome organelle extract (LOE) was derived from egg whites. The lysosome is an intracellular organelle that contains several hydrolysis enzymes. Previous studies have reported that LOE performs important functions, such as melanin de-colorization and anti-melanin production in B16F10 melanoma cells. However, its principal molecular and cellular mechanisms have not been elucidated till date. In non-cytotoxic conditions, LOE significantly inhibited α-MSH induced melanin synthesis of murine B16F10 cells. The anti-melanogenic activity of LOE was mediated by suppressing the mRNA expression of tyrosinase enzyme, tyrosinase related protein-1/2 (TRP-1/2), and microphthalmia-associated transcription factor (MITF) genes. By performing western blot analysis, we found that LOE significantly attenuated melanogenesis. In this case, LOE helped in increasing extracellular receptor kinase (ERK) phosphorylation in α-MSH induced B16F10 cells. Furthermore, MITF is found to be a key regulatory transcription factor in melanin synthesis; it was down-regulated by LOE through ERK phosphorylation. In this experiment, PD98059 (MEK inhibitor) was used to check whether LOE directly regulated the activity of ERK. Although LOE exerted inhibitory effect on melanin synthesis, we could not observe this effect in PD98059-treated α-MSH induced B16F10. These results strongly indicate that LOE is related to ERK activation and MITF degradation in anti-skin pigmentation. Hence, LOE should be utilized as a whitening agent of skin in the near future.

What's New in Molecular Targeted Therapies for Thyroid Cancer? (갑상선암 표적치료의 최신지견)

  • Min, Seonyoung;Kang, Hyunseok
    • Korean Journal of Head & Neck Oncology
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    • v.37 no.2
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    • pp.1-9
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    • 2021
  • Thyroid cancer refers to various cancers arising from thyroid gland. Differentiated thyroid cancers (DTCs) include papillary, follicular, and Hurthle cell carcinomas and represent cancers retain normal thyroid functions such as iodine uptake. Radioactive iodine (RAI) is generally used for upfront treatment of metastatic DTCs, but RAI refractory DTCs remain to be clinical challenges. Sorafenib and lenvatinib were approved for the treatment of RAI refractory DTCs and more recently, genomics-based targeted therapies have been developed for NTRK and RET gene fusion-positive DTCs. Poorly differentiated and anaplastic thyroid cancers (ATCs) are extremely challenging diseases with aggressive courses. BRAF/MEK inhibition has been proven to be highly effective in BRAF V600E mutation-positive ATCs and immune checkpoint inhibitors have shown promising activities. Medullary thyroid cancers, which arise from parafollicular cells of thyroid, represent a unique subset of thyroid cancer and mainly driven by RET mutation. In addition to vandetanib and cabozantinib, highly specific RET inhibitors such as selpercatinib and pralsetinib have demonstrated impressive activity and are in clinical use.

Comparison of the antioxidant and anti-inflammatory activities of leaf extracts from grain amaranths (Amaranthus spp.)

  • Ji, Hyo Seong;Kim, Gayeon;Ahn, Min-A;Chung, Jong-Wook;Hyun, Tae Kyung
    • Journal of Plant Biotechnology
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    • v.49 no.1
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    • pp.99-105
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    • 2022
  • This study assessed the antioxidant and anti-inflammatory activities of leaf extracts from grain amaranths (Amaranthus spp.). Among all the extracts, the ethanol extract of Amaranthus cruentus leaves (Ar) exhibited the highest antioxidant activity, including the DPPH free radical scavenging activity and ORAC. In addition, Ar strongly inhibited nitric oxide production by suppressing the MEK/ERK signaling pathway in lipopolysaccharide-stimulated RAW264 murine macrophages. HPLC analysis revealed 13 polyphenolic compounds in the leaf extracts of grain amaranth and indicated that Ar contained more rutin than the other extracts. Taken together, these results show the impact of species diversity on the phytochemical contents and bioactivities of plant extracts and suggest that the nonedible parts, such as leaves, of A. cruentus should be considered for use as crude drugs and dietary health supplements.

Effect of Repetitive Transcranial Magnetic Stimulation in Drug Resistant Depressed Patients (치료 저항성 우울증 환자에서 반복적 경두개 자기자극후 국소뇌혈류 변화)

  • Chung, Yong-An;Yoo, Ie-Ryung;Kang, Bong-Joo;Chae, Jeong-Ho;Lee, Hye-Won;Moon, Hyun-Jin;Kim, Sung-Hoon;Sohn, Hyung-Sun;Chung, Soo-Kyo
    • Nuclear Medicine and Molecular Imaging
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    • v.41 no.1
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    • pp.9-15
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    • 2007
  • Purpose: Repetitive transcranial magnetic stimulation (rTMS) has recently been clinically applied in the treatment of drug resistant depressed patients. There are mixed findings about the efficacy of rTMS on depression. Furthermore, the influence of rTMS on the physiology of the brain is not clear. We prospectively evaluated changes of regional cerebral blood flow (rCBF) between pre- and post-rTMS treatment in patients with drug resistant depression. Materials and Methods: Twelve patients with drug-resistant depression (7 male, 5 female; age range: $19{\sim}52$ years; mean age: $29.3{\pm}9.3$ years) were given rTMS on right prefrontal lobe with low frequency (1 Hz) and on left prefrontal lobe with high frequency (20 Hz), with 20-minute-duration each day for 3 weeks. Tc-99m ECD brain perfusion SPECT was obtained before and after rTMS treatment. The changes of cerebral perfusion were analyzed using statistical parametric mapping (SPM; t=3.14, uncorrected p<0.01, voxel=100). Results: Following areas showed significant increase in rCBF after 3 weeks rTMS treatment: the cingulate gyrus, fusiform gyrus of right temporal lobe, precuneus, and left lateral globus pallidus. Significant decrement was noted in: the precental and middle frontal gyrus of right frontal lobe, and fusiform gyrus of left occipital lobe. Conclusion: Low-frequency rTMS on the right prefrontal cortex and high-frequency rTMS on the left prefrontal cortex for 3 weeks as an add-on regimen have increased and decreased rCBF in the specific brain regions in drug-resistant depressed patients. Further analyses correlating clinical characteristics and treatment paradigm with functional imaging data may be helpful in clarifying the pathophysiology of drug-resistant depressed patients.

Oxidation characterization of VOCs over noble metal catalyst using water treatment (Water 수처리를 이용한 귀금속 촉매의 VOCs 산화특성)

  • Kim, Moon-Chan
    • Analytical Science and Technology
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    • v.18 no.2
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    • pp.120-129
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    • 2005
  • Volatile organic compounds (VOCs) have been recognized as major contributor to air pollution. The catalytic oxidationis is one of the most important processes for VOCs destruction due to the possibility getting high efficiency at low temperature. In this study, monometallic Pt, Ir and bimetallic Pt-Ir were supported to $TiO_2$. In order to distribute metals uniformly, $H_2O-H_2$ treatment method was used. Xylene, toluene and MEK were used as reactants. The monometallic or bimetallic catalysts were prepared by the excess wetness impregnation method and characterized by XRD, XPS, and TEM analysis. Pt catalyst showed higher conversion than Ir catalyst and Pt-Ir bimetallic catalyst showed the highest conversion. The catalysts prepared by $H_2O-H_2$ treatment had better VOC's conversion than that of nothing treatment. In the VOCs oxidation, Pt-Ir bimetallic catalysts had multipoint active sites, so it improved the range of Pt metal state. Therefore, bimetallic catalysts showed higher conversion of VOCs than monometallic ones. $H_2O-H_2$ treatment effected an uniform distribution of Pt particles. In VOCs oxidation was found to follow first order reaetion kinetics. The activation energy of $H_2O-H_2$ treatment catalysts was lower than that of untreated ones. In this study, the a small amount of Ir was used with Pt to promote the oxidation conversion of VOCs.

A Study on the Environmental Effects of Improvement of Activated Carbon Adsorption Tower for the Application of Activated Carbon Co-Regenerated System in Sihwa/Banwal Industrial Complex (시화반월산업단지 활성탄 공동재생시스템 적용을 위한 활성탄 흡착탑 개선에 따른 환경적 효과분석)

  • Choi, Ye Jin;Rhee, Young Woo;Chung, Gu Hoi;Kim, Duk Hyun;Park, Seung Joon
    • Clean Technology
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    • v.27 no.2
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    • pp.160-167
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    • 2021
  • This study investigated the environmental effects of improving the general-type activated carbon adsorption tower used at the Sihwa/Banwol Industrial Complex with use of a cartridge-type activated carbon adsorption tower for the application of an activated carbon co-regenerated system. Four general-type activated carbon adsorption towers and two cartridge-type activated carbon adsorption towers were selected to analyze the properties of activated carbon and to compare the efficiency of reducing environmental pollutants. The results showed that the activated carbon used in the cartridge-type activated carbon adsorption towers was high quality activated carbon with an iodine adsorption force of more than 800 mg/g and that a good adsorption performance was maintained within the replacement cycle. From an analysis of the environmental pollutant reduction efficiency, it was confirmed that the cartridge-type activated carbon adsorption tower functioned properly as a prevention facility for handling emissions pollutants with a treatment efficiency of total hydrocarbons (THC), toluene, and methylethylketone (MEK) components of 71%, 77%, and 80%, respectively. The general activated carbon adsorption tower, which was confirmed to use low-performance activated carbon, had a very low treatment efficiency and did not function properly as a prevention facility for dealing with emission pollutants. It is believed that it is possible to reduce pollutants during operations by changing from the general-type activated carbon adsorption tower to a cartridge-type activated carbon adsorption tower.

Ginsenoside Rg2 Inhibits Lipopolysaccharide-Induced Adhesion Molecule Expression in Human Umbilical Vein Endothelial Cell

  • Cho, Young-Suk;Kim, Chan Hyung;Ha, Tae-Sun;Lee, Sang Jin;Ahn, Hee Yul
    • The Korean Journal of Physiology and Pharmacology
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    • v.17 no.2
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    • pp.133-137
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    • 2013
  • Vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), P- and E-selectin play a pivotal role for initiation of atherosclerosis. Ginsenoside, a class of steroid glycosides, is abundant in Panax ginseng root, which has been used for prevention of illness in Korea. In this study, we investigated the mechanism(s) by which ginsenoside Rg2 may inhibit VCAM-1 and ICAM-1 expressions stimulated with lipopolysaccharide (LPS) in human umbilical vein endothelial cell (HUVEC). LPS increased VCAM-1 and ICAM-1 expression. Ginsenoside Rg2 prevented LPS-mediated increase of VCAM-1 and ICAM-1 expression. On the other hand, JSH, a nuclear factor kappa B (NF-${\kappa}B$) inhibitor, reduced both VCAM-1 and ICAM-1 expression stimulated with LPS. SB202190, inhibitor of p38 mitogen-activated protein kinase (p38 MAPK), and wortmannin, phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, reduced LPS-mediated VCAM-1 but not ICAM-1 expression. PD98059, inhibitor of mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) did not affect VCAM-1 and ICAM-1 expression stimulated with LPS. SP600125, inhibitor of c-Jun N-terminal kinase (JNK), reduced LPS-mediated ICAM-1 but not VCAM-1 expression. LPS reduced IkappaB${\alpha}$ ($I{\kappa}B{\alpha}$) expression, in a time-dependent manner within 1 hr. Ginsenoside Rg2 prevented the decrease of $I{\kappa}B{\alpha}$ expression stimulated with LPS. Moreover, ginsenoside Rg2 reduced LPS-mediated THP-1 monocyte adhesion to HUVEC, in a concentration-dependent manner. These data provide a novel mechanism where the ginsenoside Rg2 may provide direct vascular benefits with inhibition of leukocyte adhesion into vascular wall thereby providing protection against vascular inflammatory disease.

Triglyceride Up-regulates Expression of ABCG1 in PMA-induced THP-1 Macrophages Through Activation of JNK and p38 MAPK Pathways

  • Lim, Jaewon;Kim, Sung Hoon;Kang, Yeo Wool;Jung, Byung Chul;Kim, Hyun-Kyung;Lee, Juyeon;Lee, Dongsup;Rhee, Ki-Jong;Kim, Yoon Suk
    • Biomedical Science Letters
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    • v.20 no.4
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    • pp.237-243
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    • 2014
  • Triglyceride (TG) can cause death of macrophages and formation of foam cells thereby increasing inflammation in atherosclerotic plaques. Accumulation of cholesterol in macrophages is another critical event that promotes development of inflammatory cardiovascular diseases. Several proteins are known to transport intracellular cholesterol outside of the cell and these proteins are thought to be protective against atherosclerosis pathogenesis. It is unknown whether TG can affect cholesterol efflux in macrophages. In the current study, we examined mRNA expression levels of genes that promote efflux of cholesterol (ABCA1, ABCG1 and SR-B1). We found that TG treated THP-1 macrophages exhibited an increase in ABCG1 expression in a dose- and time-dependent manner. In contrast, the expression of ABCA1 and SR-B1 remained unchanged. To identify cell signaling pathways that participate in up-regulation of ABCG1, THP-1 macrophages were treated with various cell signaling inhibitors. We found that inhibition of the JNK and p38 MAPK pathway completely abrogated up-regulation of ABCG1 whereas inhibition of MEK1 further enhanced ABCG1 expression in TG treated THP-1 macrophages. Also, TG induced phosphorylation of JNK and p38 MAPK in THP-1 macrophages. These results suggest that TG may potentially influence cholesterol efflux in macrophages.

Application of Biofilter Using Fibril-form Matrix for Odor Gas Removal

  • Lee, Gwang-Yeon;Jeong, Gwi-Taek;Lee, Kyoung-Min;Snuwoo, Chang-Shin;Lee, Woo-Tae;Cha, Jin-Myoung;Jang, Young-Seon;Park, Don-Hee
    • 한국생물공학회:학술대회논문집
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    • 2005.04a
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    • pp.247-251
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    • 2005
  • This research was performed for developing of biological treatment process of odor gas such as MEK, $H_{2}S$, and toluene, which is generated from the food waste recycling process. To establish the operational conditions of odor gas removal by small-scale biofiltration equipment, it was continuously operated by using toluene as a treating odor object. When the odor treating microorganisms were adhered to fibril form biofilter, high removal efficiency over 93% was obtained by biofilm formation. At 400 ppm of inlet odor gas concentration and 10 sec of retention time, the removal efficiency was 76% and 93% in 1st stage reactor and 2nd stage reactor, respectively. However, the removal efficiency remained over 97% at the operational conditions above 15 sec of retention time.

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