• Title/Summary/Keyword: $S_N1$ mechanism

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Inhibitory Effects of Functional Sujeonggwa Drinks on Hepatic Lipid Accumulation in Hypercholesterolemic ApoE Knockout Mice (고콜레스테롤혈증 ApoE Knockout Mice에서 기능성 수정과의 간지질 축적 억제 효과)

  • Baek, Aran;Kim, Mijeong;Jung, Koeun;Kim, Seulki;Lee, Jeehyun;Song, Yeong Ok
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.11
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    • pp.1648-1657
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    • 2014
  • In this study, the hepatic lipid-lowering effects and related mechanism of action of sujeonggwa were examined in hypercholesterolemia-induced apoprotein E knockout (apo E ko) mice. Sujeonggwa drink was prepared with cinnamon, ginger, and sugar by modifying the traditional recipe of sujeonggwa. Sugar was partially substituted with either stevia or short chain fructooligosaccharide (scFOS) in order to reduce the calorie content of sujeonggwa, which was measured by descriptive analysis. Apo E ko mice (n=42) were induced to have hypercholesterolemia (plasma total cholesterol concentration >1,000 mg/dL) by administration of a high cholesterol diet for 4 weeks, followed by division into six groups. Experimental groups were orally administered water as a vehicle (normal group), sugar solution (control group), commercially available 'V' sujeonggwa drink (positive control group), or three different types of sujeonggwa drinks (S-sugar, S-stevia, and S-scFOS group) for 6 weeks while high cholesterol diet was provided to all animals. Compared to the control group, concentrations of hepatic triglycerides, total cholesterol, thiobarbituric acid reactive substances, and reactive oxygen species in S-sugar, S-stevia, S-scFOS were significantly reduced (P<0.05), indicating that sujeonggwa had inhibitory effects on hepatic lipid accumulation. Protein expression levels of fatty acid synthase (FAS) and its transcription factor, sterol regulatory element-binding protein (SREBP)-1 responsible for triglyceride synthesis, as well as 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and its transcription factor, SREBP-2 responsible for cholesterol synthesis, were also reduced in S-sugar, S-stevia, and S-scFOS groups (P<0.05). These benefits of sujeonggwa were even greater in S-stevia and S-scFOS compared to S-sugar. The beneficial effects of S-stevia on regulation of hepatic lipid metabolism were slightly greater than those of S-scFOS although the differences were not significant. In conclusion, sujeonggwa drinks, especially functional sujeonggwa drinks in which sugar was partially substituted with stevia or scFOS, inhibited hepatic lipid accumulation via suppressing FAS and HMGCR protein expression through down-regulation of SREBP-1 and 2.

Upregulation of Connexin43 Expression in Mitral Valves in a Rabbit Model of Hypercholesterolemia (고콜레스테롤혈증을 유발한 토끼의 승모판막에서 Connexin43 발현의 증가)

  • Kwon, Jong-Bum;Park, Chan-Beom;Sa, Young-Jo;Kim, Young-Du;Moon, Seok-Whan;Kim, Chi-Kyung
    • Journal of Chest Surgery
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    • v.43 no.4
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    • pp.356-363
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    • 2010
  • Background: Connexin 43-mediated gap junctional communication plays an important role in atherosclerosis. Numerous studies have demonstrated a correlation between mitral valve annular calcification and atherosclerotic disease. However, the relevance of connexin 43 to mitral valve disease remains unclear. We hypothesized that the mechanism contributing to mitral valve disease is associated with alterations in cell-to-cell communication mediated by changes in Connexin 43 expression. Material and Method: Twenty male New Zealand rabbits were divided into two groups: animals in group 1 (n=10) were fed a normal chow diet, whilst those in group 2 (n=10) received a diet containing 1% cholesterol for 12 weeks. After sacrificing the animals, the mitral valves were excised and analyzed with immunohistochemical staining and Real-time Reverse Transcriptase polymerase chain reaction (real time RT-PCR). Result: Myofibroblasts and macrophages were found concentrated within the endothelial layer on the ventricular side of the leaflet in the cholesterol diet group. Immunohistochemial staining showed elevated expression of connexin43 in the cholesterol diet group. Real-time RT-PCR revealed increased connexin43 mRNA levels in mitral valves from hypercholesterolemic animals. Conclusion: Our finding that connexin43 expression is increased in mitral valves of hypercholesterolemic rabbits suggests that alterations in cell-to-cell communication via connexin43 containing gap junctions play a role in the development of mitral valve disease in hypercholesterolemia.

Mechanism of Decrease in Lung Injury by Low Dose of Endotoxin During Hyperoxia in the Rats (저용량의 내독소가 쥐에서 고농도의 산소에 의한 급성폐손상을 경감시키는 기전)

  • Song, Jeong-Sup;Yoon, Hyung-Kyu;Kim, Young-Kyoon;Kim, Kwan-Hyung;Moon, Hwa-Sik;Park, Sung-Hak
    • Tuberculosis and Respiratory Diseases
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    • v.53 no.2
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    • pp.148-160
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    • 2002
  • 배 경 : 쥐를 고농도의 산소에 60시간 이상 노출시켰을 때 급성 폐손상이 유발되지만 내독소를 저용량으로 투여시에는 이러한 폐손상이 경감된다고 알려져 있으나 그 기전에 대하여는 확실히 밝혀지지 않고 있다. 산화질소(nitric oxide, NO)는 내독소나 염증성 사이토카인(cytokine) 등의 자극에 의해서 폐내 여러 염증세포에서 만들어지며 이 산화질소는 경우에 따라 우리 몸에 이롭거나 해로운 양면성을 지니고 있다. 저자들은 쥐에서 고농도의 산소에 의한 폐손상이 저농도의 내독소 투여로 경감되는 기전에, 산화질소가 중요한 역할을 하는지 또는 황산화효소나 다른 항염증성 사이토카인이 중요한 역할을 하는지를 규명하고자 하였다. 방 법 : 총 120마리의 쥐 (Sprague-Dawley rat)를 24마리씩 5군으로 나누어 대조군은 실내 공기를, 고농도 산소군은 100%의 산소를 100%의 산소를 60시간 투여하였고 내독소군은 100% 산소 투여시 2일간 저용량의 내독소를 투여하였다. 다른 두 군은 산화질소 합성 억제물인 aminoguanidine(AG)과 N-nitro-L-arginine methyl ester (L-NAME)를 각각 2일간 고농도 산소와 내독소에 더하여 투여하였다. 각각의 군에서 폐손상의 정도와 사망률을 관찰하고 superoxide dismutase(SOD), catalase, nitric oxide, IL-6, IL-11을 기관지폐포세척액에서 측정하고, 고농도산소 투여군의 폐조직에서 iNOS synthase rnRNA의 발현을 비교하였다. 결 과: 1. 100%의 산소에 60시간 노출시켰을 때 쥐의 사망률은 8.3% 이었고 내독소 투여군은 4.2%, NAME 투여군이 37.5%, AG 투여군이 25%로 산화질소 합성 억제제에 의하여 사망률의 증가가 관찰되었다. 2. 폐의 손상 정도를 나타내는 폐의 wet/dry 중량비와 늑막액도 100%의 산소에 노출된 군에서 증가되었고 내독소 투여에 의하여 감소되었으며 NAME나 AG 투여군에서는 오히려 증가되었다. 3. 이러한 내독소에 의한 폐손상 억제효과가 항산화효소인 SOD나 catalase, 또는 protective cytokine인 IL-6나 IL-11등의 증가와 관련이 있는지를 관찰하였으나 이들 모두에서 유의한 변화를 관찰하지 못하였다. 4. 산화질소는 100% 산소에 노출시킨 군에서도 증가하였으나 내독소 투여군에서 유의하게 더욱 증가하였고 이는 L-NAME 나 aminoguanidine의 투여시 감소하였다. 5. iNOS mRNA의 발현도 내독소 투여군에서 유의하게 증가하였다. 결 론 : 쥐의 고농소 산소 투여에 의한 폐손상은 저용량의 내독소 투여로 경감되며, 이는 주로 내독소 투여에 의한 iNOS mRNA의 발현을 유도하여 생성된 산화질소의 증가에 기인하는 것으로 생각된다.

Effect of different levels of protein concentrates supplementation on the growth performance, plasma amino acids profile and mTOR cascade genes expression in early-weaned yak calves

  • Peng, Q.H.;Khan, N.A.;Xue, B.;Yan, T.H.;Wang, Z.S.
    • Asian-Australasian Journal of Animal Sciences
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    • v.31 no.2
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    • pp.218-224
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    • 2018
  • Objective: This study evaluated the effects of different levels of protein concentrate supplementation on the growth performance of yak calves, and correlated the growth rate to changes occurring in the plasma- amino acids, -insulin profile, and signaling activity of mammalian target of rapamycin (mTOR) cascade to characterize the mechanism through which the protein synthesis can be improved in early weaned yaks. Methods: For this study, 48 early (3 months old) weaned yak calves were selected, and assigned into four dietary treatments according to randomized complete block design. The four blocks were balanced for body weight and sex. The yaks were either grazed on natural pasture (control diet) in a single herd or the grazing yaks was supplemented with one of the three protein rich supplements containing low (17%; LP), medium (19%; MP), or high (21%; HP) levels of crude proteins for a period of 30 days. Results: Results showed that the average daily gain of calves increased (0.14 vs 0.23-0.26 kg; p<0.05) with protein concentrates supplementation. The concentration of plasma methionine increased (p<0.05; 8.6 vs $10.1-12.4{\mu}mol/L$), while those of serine and tyrosine did not change (p>0.05) when the grazing calves were supplemented with protein concentrates. Compared to control diet, the insulin level of calves increased (p<0.05; 1.86 vs $2.16-2.54{\mu}IU/mL$) with supplementation of protein concentrates. Addition of protein concentrates up-regulated (p<0.05) expression of mTOR-raptor, mammalian vacuolar protein sorting 34 homolog, the translational regulators eukaryotic translation initiation factor 4E binding protein 1, and S6 kinase 1 genes in both Longissimus dorsi and semitendinosus. In contrast, the expression of sequestosome 1 was down-regulated in the concentrate supplemented calves. Conclusion: Our results show that protein supplementation improves the growth performance of early weaned yak calves, and that plasma methionine and insulin concentrations were the key mediator for gene expression and protein deposition in the muscles.

High $K^+$-Induced Relaxation by Nitric Oxide in Human Gastric Fundus

  • Kim, Dae-Hoon;Kim, Young-Chul;Choi, Woong;Yun, Hyo-Young;Sung, Ro-Hyun;Kim, Hun-Sik;Kim, Heon;Yoo, Ra-Young;Park, Seon-Mee;Yun, Sei-Jin;Song, Young-Jin;Xu, Wen-Xie;Lee, Sang-Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.5
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    • pp.297-303
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    • 2012
  • This study was designed to elucidate high $K^+$-induced relaxation in the human gastric fundus. Circular smooth muscle from the human gastric fundus greater curvature showed stretch-dependent high $K^+$ (50 mM)-induced contractions. However, longitudinal smooth muscle produced stretch-dependent high $K^+$-induced relaxation. We investigated several relaxation mechanisms to understand the reason for the discrepancy. Protein kinase inhibitors such as KT 5823 (1 ${\mu}M$) and KT 5720 (1 ${\mu}M$) which block protein kinases (PKG and PKA) had no effect on high $K^+$-induced relaxation. $K^+$ channel blockers except 4-aminopyridine (4-AP), a voltage-dependent $K^+$ channel ($K_V$) blocker, did not affect high $K^+$ -induced relaxation. However, N(G)-nitro-L-arginine and 1H-(1,2,4)oxadiazolo (4,3-A)quinoxalin-1-one, an inhibitors of soluble guanylate cyclase (sGC) and 4-AP inhibited relaxation and reversed relaxation to contraction. High $K^+$-induced relaxation of the human gastric fundus was observed only in the longitudinal muscles from the greater curvature. These data suggest that the longitudinal muscle of the human gastric fundus greater curvature produced high $K^+$-induced relaxation that was activated by the nitric oxide/sGC pathway through a $K_V$ channel-dependent mechanism.

Sensing Properties of ZrO2-added SnO2 for Nerve and Blister Agent (ZrO2 첨가된 SnO2를 이용한 신경 및 수포작용제 검지에 대한 연구)

  • Yun, Ky-Youl;Cha, Gun-Young;Choi, Nak-Jin;Lee, Duk-Dong;Kim, Jae-Chang;Huh, Jeung-Soo
    • Journal of Sensor Science and Technology
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    • v.13 no.5
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    • pp.323-328
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    • 2004
  • N-type semi-conducting oxides such as $SnO_{2}$, ZnO, and $ZrO_{2}$ have been known for the detecting materials of inflammable or toxic gases. Of those materials, $SnO_{2}$-based sensors are well known as high sensitive materials to detect toxic gases. And the sensitivity is improved if catalysts are added. Detecting toxic gases, especially DMMP (di-methyl-methyl-phosphonate) and DPGME (Dipropylene glycol methyl ether), was performed by a mixture of Tin oxide ($SnO_{2}$) and Zirconia ($ZrO_{2}$). The films consist of each three different mass% of Zr (from 1 mass% to 5 mass%), and they were tested by XRD, SEM, TEM, BET. Nano-structure, pore and particle size was controlled to verify the sensor's sensing mechanism. The sensors was evaluated at five different degrees (from $200^{\circ}C$ to $400^{\circ}C$) and three different concentrations (from 500 ppb to 1500 ppb). The sensors had good sensitivity of both simulants, and high selectivity of DMMP.

DESIGN OF A SINGLE MODE VARIABLE BRIDGE TYPE SPLIT-POWERED CVT WITH AN INNER-SPHERICAL CONTINUOUSLY VARIABLE UNIT

  • Seong, S.H.;Lee, H.W.;Choi, J.H.;Park, N.G.
    • International Journal of Automotive Technology
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    • v.8 no.6
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    • pp.799-806
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    • 2007
  • One method for improving the torque capacity of the CVT is to use a split-powered CVT(SPCVT) to reduce the power transmitted into a continuously variable unit(CVU). A variable bridge SPCVT with two planetary gear units(PGUs), which are composed of a sun gear, a ring gear, and carrier and planetary gears, can minimize the power to the CVU. However, a SPCVT with a conventional CVT should possess a dual mode, which would allow the conventional CVT to be used at high speeds and an additional gear train to be used at low speeds. The inner-spherical CVU(ISCVU) with an inner and outer spherical contact mechanism developed in this study can cover the range from low to high speeds. The rated power and the overall speed ratios were 100 kW and $0.09{\sim}0.36$, respectively. Power efficiency was numerically calculated to be over 90% over the speed ratio range of $0.1{\sim}0.29$. The maximum shear stress at the two contact areas of the rotor pairs, the minimum life and the overall size were estimated to be 700 MPa, 276 kh and $350{\times}350{\times}400mm^3$, respectively. This study shows that an ISCVU and a variable bridge type PGU can realize the SPCVT with a single mode for a vehicle.

Nitric Oxide Prevents the Bovine Cerebral Endothelial Cell Death Induced by Serum-Deprivation

  • Kim, Chul-Hoon;Ahn, Young-Soo
    • The Korean Journal of Physiology and Pharmacology
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    • v.1 no.5
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    • pp.515-521
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    • 1997
  • Endothelial cells play a central role in the inflammatory processes, and activation of nuclear factor kappa B ($NF-_{\kappa}B$) is a key component in that inflammatory processes. Previously, we reported that tumor necrosis factor alpha($TNF{\alpha}$) had protective effect of cell death induced by serum deprivation and this protection was related to $NF-_{\kappa}B$ activation. Inducible nitric oxide synthase (iNOS) is a member of the molecules which transcription is regulated mainly by $NF-_{\kappa}B$. And the role of nitric oxide (NO) generated by iNOS on cell viability is still controversial. To elucidate the mechanism of $TNF{\alpha}$ and $NF-_{\kappa}B$ activation on cell death protection, we investigate the effect of NO on the cell death induced by serum- deprivation in bovine cerebral endothelial cells in this study. Addition of $TNF{\alpha}$, which are inducer of iNOS, prevented serum-deprivation induced cell death. Increased expression of iNOS was confirmed indirectly by nitrite measurement. When selective iNOS inhibitors were treated, the protective effect of $TNF{\alpha}$ on cell death was partially blocked, suggesting that iNOS expression was involved in controlling cell death. Exogenously added NO substrate (L-arginine) and NO donors (sodium nitroprusside and S-nitroso-N-acetylpenicillamine) also inhibited the cell death induced by serum deprivation. These results suggest that NO has protective effect on bovine cerebral endothelial cell death induced by serum-deprivation and that iNOS is one of the possible target molecules by which $NF-_{\kappa}B$ exerts its cytoprotective effect.

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K+ Ion Catalysis in Nucleophilic Displacement Reaction of Y-Substituted-Phenyl Picolinates with Potassium Ethoxide: Effect of Substituent Y on Reactivity and Transition State Structure

  • Im, Hyun-Ju;Lee, Jieun;Kim, Mi-Yeon;Um, Ik-Hwan
    • Bulletin of the Korean Chemical Society
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    • v.35 no.6
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    • pp.1749-1753
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    • 2014
  • Pseudo-first-order rate constants ($k_{obsd}$) have been measured spectrophotometrically for the nucleophilic substitution reaction of Y-substituted-phenyl picolinates (7a-f) with potassium ethoxide (EtOK) in anhydrous ethanol at $25.0{\pm}0.1^{\circ}C$. The plot of $k_{obsd}$ vs. [EtOK] curves upward while the plot of $k_{obsd}/[EtO^-]_{eq}$ vs. $[EtO^-]_{eq}$ is linear with a positive intercept in all cases. Dissection of $k_{obsd}$ into $k_{EtO^-}$ and $k_{EtOK}$ (i.e., the second-order rate constants for the reactions with the dissociated $EtO^-$ ion and ion-paired EtOK, respectively) has revealed that the ion-paired EtOK is more reactive than the dissociated $EtO^-$. The ${\sigma}^{\circ}$ constants result in a much better Hammett correlation than ${\sigma}^-$ constants, indicating that the reaction proceeds through a stepwise mechanism in which departure of the leaving group occurs after the rate-determining step (RDS). $K^+$ ion catalyzes the reaction by increasing the electrophilicity of the reaction center through formation of a cyclic transition state (TS). The catalytic effect decreases as the substituent Y becomes a stronger electron-withdrawing group (EWG). Development of a positive charge on the N atom of the picolinyl moiety through resonance interactions is responsible for the decreasing $K^+$ ion catalysis.

In Vivo Antitumor Activities and Pharmacokinetics of DW2282 Depending on Vehicles (DW2282의 용매의존성 항암효과 및 약동력학)

  • Moon, Eun-Yi;Choi, Chung-Ha;Seong, Seung-Kyoo;Lee, Jin;Ryu, Jei-Man;Lee, Moon-Sun;Jung, Sang-Hun;Chung, Yong-Ho;Lee, Dog-Keun;Yoon, Sung-June
    • Biomolecules & Therapeutics
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    • v.6 no.4
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    • pp.395-399
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    • 1998
  • DW2282, (S)- (+)-4-phenyl -1-[N-(4-am mob enzoyl) -indolin-5- sulfonyl]-4,5- dihydro-2-imidazolone hydrochloride, is a novel anticancer agent thought to have an unique mechanism of action on the inhibition of tumor growth. In this study, we estimated in vivo antitumor activities and pharmacokinetics of Dw2282 depending on various vehicles. The inhibition rate of tumor growth was increased by 50, 100 and 200 mg/kg of Dw2282 in a dose-dependent manner. When Dw2282 dissolved in 4 sorts of vehicles was orally single dosed to rats at 50 mg/kg, Cmax of Dw2282 in 0.5% CMC.Na was a half as high as those in PG, PG+CP and PG+CP+DW. When Dw2282 was orally administered to mice for 5 days, antitumor activity of 130 mg/kg suspended in 0.5% CMC.Na was as effective as that of 65 mg/kg dissolved in the rest of vehicles. Taken together, it is thought that antitumor activities of Dw2282 are resulted from the absorption extent of it and related to the vehicle used.

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