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      • Molecular basis involved in the blocking effect of antidepressant metergoline on C-type inactivation of Kv1.4 channel

        Bai, Hyoung-Woo,Eom, Sanung,Yeom, Hye Duck,Nguyen, Khoa V.A.,Lee, Jaeeun,Sohn, Sung-Oh,Lee, Jun-Ho Elsevier 2019 NEUROPHARMACOLOGY - Vol.146 No.-

        <P><B>Abstract</B></P> <P>Voltage-gated potassium channels (VGKCs) are transmembrane ion channels specific for potassium. Currently there are nine kinds of VGKCs. Kv1.4 is one of shaker-related potassium channels. It is a representative alpha subunit of potassium channels that can inactivate A type-currents, leading to N pattern inactivation. Inactivation of Kv channels plays an important role in shaping electrical signaling properties of neuronal and muscular cells. The shape of N pattern inactivation can be modified by removing the N-terminal (NT) domain which results in non-inactivated currents and C pattern inactivation. In a previous work, we have reported the regulatory effect of metergoline on Kv1.4 and Nav1.2 channel activity. In the present study, we constructed a mutant of deleted 61 residues from NT of Kv1.4 channels (Kv1.4 Δ2-61) and found that it induced an outward peak and steady-state currents We also studied the modulation effect of metergoline on the activity of this Kv1.4 Δ2-61 mutant channel without having the N-terminal quick inactivation domain. Our results revealed that treatment with metergoline inhibited NT deleted Kv1.4 mutant channel activity in a concentration-dependent manner which was reversible. Interestingly, metergoline treatment induced little effects on the outward peak current in the deleted Kv1.4 mutant channel. However, metergoline treatment conspicuously inhibited steady state currents of Kv1.4 Δ2-61 channels with acceleration current mode. The acceleration of steady-state current of deleted Kv1.4 mutant channel occurred in a concentration-dependent manner. This means that metergoline can accelerate C pattern inactivation of Kv1.4 Δ2-61 channel by acting as an open state dependent channel blocker. We also performed site-directed mutations in V561A and K532Y, also known as C-type inactivation sites. V561A, K532Y, and V561A + K532Y substitution mutants significantly attenuated the acceleration effect of metergoline on C pattern inactivation of hKv1.4 channel currents. In docking modeling study, predicted binding residues for metergoline were analyzed for six amino acids. Among them, the K532 residue known as the C-type inactivation site was analyzed to be a major site of action. Then various mutants were constructed. K532 substitution mutant significantly abolished the effect of metergoline on Kv1.4 currents among various mutants whereas other changes had slight inhibitory effects. Furthermore, we found that metergoline had specificity for Kv1.4, but not for Kv1.5 currents. In addition, the A type current in rat neuronal cell was inhibited and accelerated of inactivation. This result further shows that metergoline might interact with Lys532 residue and then accelerate C pattern inactivation of Kv1.4 channels with channel type specificity. Taken together, these results demonstrate the molecular basis involved in the effect of metergoline, an ergot alkaloid, on human Kv1.4 channel, providing a novel interaction ligand.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Metergoline, ergot-derived psychoactive drug, produced inhibition on steady state current of Kv1.4 channel currents. </LI> <LI> Treatment of metergoline on Kv1.4 Δ2-61 channel currents produced significant inhibitions of the non-inactivating plateau than peak currents. </LI> <LI> Metergoline interacted predominantly with residues at channel pore region of Kv1.4 channel. </LI> <LI> Metergoline is more selective for Kv1.4 channels and is shown the effects as open channel blocker. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

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        Degradation of Limonene by Gamma Radiation for Improving Bioethanol Production

        Bai, Hyoung-Woo,Hong, Sung Hyun,Park, Chul-Hong,Jang, Dong Min,Kim, Tae Hoon,Chung, Byung Yeoup The Korean Society for Applied Biological Chemistr 2014 Applied Biological Chemistry (Appl Biol Chem) Vol.57 No.1

        Use of orange peel as a raw material for bioethanol production requires removal of its limonene content, which inhibits fermentation. Orange peel was pretreated using electron beam or gamma ray irradiation. Limonene content decreased in a dose-dependent manner, with approximately 60% reduction compared to the control after gamma irradiation at a dose of 800 kGy. However, electron beam irradiation did not demonstrate the same effectiveness. Therefore, gamma irradiation was deduced to be a promising pretreatment method for removing limonene from orange peel.

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      • Novel Radiolytic Rotenone Derivative, Rotenoisin B with Potent Anti-Carcinogenic Activity in Hepatic Cancer Cells

        Badaboina, Srilatha,Bai, Hyoung-Woo,Na, Yun Hee,Park, Chul-Hong,Kim, Tae Hoon,Lee, Tae-Hoon,Chung, Byung Yeoup MDPI 2015 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.16 No.8

        <P>Rotenone, isolated from roots of derris plant, has been shown to possess various biological activities, which lead to attempting to develop a potent drug against several diseases. However, recent studies have demonstrated that rotenone has the potential to induce several adverse effects such as a neurodegenerative disease. Radiolytic transformation of the rotenone with gamma-irradiation created a new product, named rotenoisin B. The present work was designed to investigate the anticancer activity of rotenoisin B with low toxicity and its molecular mechanism in hepatic cancer cells compared to a parent compound, rotenone. Our results showed rotenoisin B inhibited hepatic cancer cells’ proliferation in a dose dependent manner and increased in apoptotic cells. Interestingly, rotenoisin B showed low toxic effects on normal cells compared to rotenone. Mitochondrial transmembrane potential has been decreased, which leads to cytochrome c release. Down regulation of anti-apoptotic Bcl-2 levels as well as the up regulation of proapoptotic Bax levels were observed. The cleaved PARP (poly ADP-ribose polymerase) level increased as well. Moreover, phosphorylation of extracellular signal regulated kinase (ERK) and p38 slightly up regulated and intracellular reactive oxygen species (ROS) increased as well as cell cycle arrest predominantly at the G<SUB>2</SUB>/M phase observed. These results suggest that rotenoisin B might be a potent anticancer candidate similar to rotenone in hepatic cancer cells with low toxicity to normal cells even at high concentrations compared to rotenone.</P>

      • SCISCIESCOPUS

        Clinical Significance of the Prognostic Nutritional Index for Predicting Short- and Long-Term Surgical Outcomes After Gastrectomy : A Retrospective Analysis of 7781 Gastric Cancer Patients

        Lee, Jee Youn,Kim, Hyoung-Il,Kim, You-Na,Hong, Jung Hwa,Alshomimi, Saeed,An, Ji Yeong,Cheong, Jae-Ho,Hyung, Woo Jin,Noh, Sung Hoon,Kim, Choong-Bai Williams & Wilkins Co 2016 Medicine Vol.95 No.18

        <P><B>Abstract</B></P><P>To evaluate the predictive and prognostic significance of the prognostic nutritional index (PNI) in a large cohort of gastric cancer patients who underwent gastrectomy.</P><P>Assessing a patient's immune and nutritional status, PNI has been reported as a predictive marker for surgical outcomes in various types of cancer.</P><P>We retrospectively reviewed data from a prospectively maintained database of 7781 gastric cancer patients who underwent gastrectomy from January 2001 to December 2010 at a single center. From this data, we analyzed clinicopathologic characteristics, PNI, and short- and long-term surgical outcomes for each patient. We used the PNI value for the 10th percentile (46.70) of the study cohort as a cut-off for dividing patients into low and high PNI groups.</P><P>Regarding short-term outcomes, multivariate analysis showed a low PNI (odds ratio [OR] = 1.505, 95% CI = 1.212–1.869, <I>P</I> <0.001), old age, male sex, high body mass index, medical comorbidity, total gastrectomy, and combined resection to be independent predictors of postoperative complications. Among these, only low PNI (OR = 4.279, 95% CI = 1.760–10.404, <I>P</I> = 0.001) and medical comorbidity were independent predictors of postoperative mortality. For long-term outcomes, low PNI was a poor prognostic factor for overall survival, but not recurrence (overall survival: hazard ratio [HR] = 1.383, 95% CI = 1.221–1.568, <I>P</I> < 0.001; recurrence-free survival: HR = 1.142, 95% CI = 0.985–1.325, <I>P</I> = 0.078).</P><P>PNI can be used to predict patients at increased risk of postoperative morbidity and mortality. Although PNI was an independent prognostic factor for overall survival, the index was not associated with cancer recurrence.</P>

      • Gamma irradiation improves the antioxidant activity of <i>Aloe vera</i> (<i>Aloe barbadensis</i> miller) extracts

        Mi Lee, Eun,Bai, Hyoung-Woo,Sik Lee, Seung,Hyun Hong, Sung,Cho, Jae-Young,Yeoup Chung, Byung Elsevier 2012 Radiation physics and chemistry Vol.81 No.8

        <P><B>Abstract</B></P><P>Aloe has been widely used in food products, pharmaceuticals, and cosmetics because of its aromatic and therapeutic properties. In the present study, the ethanolic extracts of aloe gel were gamma-irradiated from 10 to 100kGy. After gamma irradiation, the color of the ethanolic extracts of aloe gel changed to red; this color persisted up to 40kGy but disappeared above 50kGy. Liquid chromatography/mass spectrometry analysis demonstrated the production of a new, unknown compound (<I>m</I>/<I>z</I>=132) after gamma irradiation of the ethanolic extracts of aloe gel. The amount of this unknown compound increased with increasing irradiation up to 80kGy, and it was degraded at 100kGy. Interestingly, it was found that gamma irradiation significantly increased the antioxidant activity, as measured by the 1,1-diphenyl-2-picrylhydrazyl-radical scavenging capacity. The antioxidant activity of aloe extract was dramatically increased from 53.9% in the non-irradiated sample to 92.8% in the sample irradiated at 40kGy. This strong antioxidant activity was retained even at 100kGy. These results indicate that gamma irradiation of aloe extract can enhance its antioxidant activity through the formation of a new compound. Based on these results, increased antioxidant activity of aloe extracts by gamma rays can be applied to various industries, especially cosmetics, foodstuffs, and pharmaceuticals.</P>

      • Method of Reconstruction Governs Iron Metabolism After Gastrectomy for Patients With Gastric Cancer

        Lee, Joong Ho,Hyung, Woo Jin,Kim, Hyoung-Il,Kim, Yoo-Min,Son, Taeil,Okumura, Naoki,Hu, Yanfeng,Kim, Choong-Bai,Noh, Sung Hoon by Lippincott Williams Wilkins. 2013 Annals of surgery Vol.258 No.6

        OBJECTIVE:: Anemia after gastrectomy is commonly neglected by clinicians despite being an important and frequent long-term metabolic sequela. We hypothesized that the incidence and timing of the occurrence of iron deficiency after gastrectomy is closely associated with the extent of gastrectomy and the reconstruction method, and we investigated the treatment outcomes of iron supplementation to understand iron metabolism and determine the optimal reconstruction method after gastrectomy. PATIENTS AND METHODS:: Using a prospective gastric cancer database, we identified 381 patients with early gastric cancer with complete hematologic parameters who underwent gastrectomy between January 2004 and May 2008. Kaplan-Meier methods, Cox regression, and logistic regression were used to evaluate the associations of the extent of gastrectomy and reconstruction method with iron metabolism. RESULTS:: The prevalence of iron deficiency 3 years after gastrectomy was 69.1%, and iron-deficiency anemia was observed in 31.0% of patients. Iron deficiency developed in 64.8% and 90.5% of patients after distal gastrectomy and total gastrectomy within 3 years after surgery (P < 0.0001), respectively. Iron deficiency was significantly more frequent in women than in men (P < 0.0001) and after gastrojejunostomy than after gastroduodenostomy (P < 0.0001). Serum ferritin levels were different according to the extent of gastrectomy and reconstruction method. The proportion of patients treated for iron-deficiency anemia was also significantly different according to the extent of gastrectomy (P = 0.020). CONCLUSIONS:: Iron deficiency occurs in most patients with gastric cancer after gastrectomy, and its incidence was different according to the extent of gastrectomy and reconstruction method. To improve iron metabolism after distal gastrectomy, gastroduodenostomy would be the method of reconstruction whenever possible.

      • Stress-induced increase in the amounts of maysin and maysin derivatives in world premium natural compounds from centipedegrass

        Lee, Eun Mi,Bai, Hyoung-Woo,Lee, Seung Sik,Hong, Sung Hyun,Cho, Jae-Young,Lee, In-Chul,Chung, Byung Yeoup Elsevier 2012 Radiation physics and chemistry Vol.81 No.8

        <P><B>Abstract</B></P><P>The red leaves of centipedegrass are known to produce compounds with stronger antibiotic effects than those produced by green leaves. Therefore, the aim of this study was to identify if stress methods (e.g., gamma irradiation, UV-B irradiation, and wounding) could effectively convert green leaves to red leaves, and thereby increase the production of maysin and maysin derivatives that have been known for antibiotic properties. Our results showed differential concentration changes for different compounds using these stress methods. The concentrations of luteolin increased from 0.014% to 0.019%, 0.022%, and 0.028% following gamma irradiation, UV-B irradiation, and wounding, respectively. The concentration of isoorientin increased from 0.898% to 1.938% and 2.538%, while the concentration of mixed rhamnosylisoorientin and orientin increased from 0.303% to 0.474% and 0.690%, following UV-B irradiation and wounding, respectively. Gamma irradiation produced concentrations of isoorientin, rhamnosylisoorientin, and orientin similar to those found in red leaves. The concentrations of derhamnosylmaysin increased from 0.004% to 0.009%, 0.015%, and 0.024% by gamma irradiation, UV-B irradiation, and wounding, respectively. The concentration of maysin increased from 0.515% to 0.714%, 0.583%, and 0.777% by gamma irradiation, UV-B irradiation, and wounding, respectively, while the concentration of luteolin-6-<I>C</I>-boivinopyranoside increased from 0.324% to 0.834%, 0.979%, and 1.493% by gamma irradiation, UV-B irradiation, and wounding, respectively. According to these results, wounding and gamma irradiation are promising methods for increasing the concentrations of maysin and maysin derivatives.</P> <P><B>Highlights</B></P><P>► The contents of maysin and its derivatives were increased by changing leaf color. ► The contents of maysin and its derivatives were increased by various treatments. ► Gamma irradiation and wounding increase the content of maysin in centipedegrass.</P>

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