Interpretation of toxicological activity of ionic liquids to acetylcholinesterase inhibition via in silico modelling

Cho, C.W.,Yun, Y.S. Pergamon Press 2016 Chemosphere Vol.159 No.-

For designing environmentally friendly ionic liquids (ILs), their structural effects on the toxicity should be interpreted via modelling based on the quantitative-structure-activity-relationship (QSAR) concept. For the purpose, QSAR models for predicting IL toxicity in acetylcholinesterase activity were developed by using linear free-energy relationship (LFER) descriptors, whose chemical meanings are well defined. These are excess molar refraction (E<SUB>c or a</SUB>), dipolarity/polarizability (S<SUB>c or a</SUB>), H-bonding acidity (A<SUB>c or a</SUB>), H-bonding basicity (B<SUB>c or a</SUB>), McGowan volume (V<SUB>c or a</SUB>), and ionic interactions of cation (J<SUP>+</SUP>) and anion (J<SUP>-</SUP>). Since the experimentally determined LFER descriptors are not available, we calculated them based on density functional theory, conductor-like screening model and the open-source software, obprop. The toxicity values of imidazolium- and pyridinium-based ILs could be predicted by a combination of four descriptors (A<SUB>c</SUB>, B<SUB>c</SUB>, V<SUB>c</SUB> and S<SUB>a</SUB>) with an R<SUP>2</SUP> of 0.828, and (E<SUB>c</SUB>, A<SUB>c</SUB>, E<SUB>a</SUB> and S<SUB>a</SUB>) with an R<SUP>2</SUP> of 0.879, respectively. In prediction study using the overall dataset containing various IL structures, the six calculated terms (E<SUB>c</SUB>, S<SUB>c</SUB>, A<SUB>c</SUB>, J<SUP>+</SUP>, E<SUB>a</SUB>, and S<SUB>a</SUB>) were selected and correlated with the observed toxicity values in R<SUP>2</SUP> of 0.748 for the training set, R<SUP>2</SUP> of 0.711 for the test set and R<SUP>2</SUP> of 0.655 for external validation set. And this study explains how the selected terms are contributing to the prediction models, and their chemical meanings were understood.

TmSR-C, scavenger receptor class C, plays a pivotal role in antifungal and antibacterial immunity in the coleopteran insect Tenebrio molitor

Kim, S.G.,Jo, Y.H.,Seong, J.H.,Park, K.B.,Noh, M.Y.,Cho, J.H.,Ko, H.J.,Kim, C.E.,Tindwa, H.,Patnaik, B.B.,Bang, I.S.,Lee, Y.S.,Han, Y.S. Pergamon Press ; Elsevier Science Ltd 2017 Insect biochemistry and molecular biology Vol.89 No.-

Scavenger receptors (SRs) constitute a family of membrane-bound receptors that bind to multiple ligands. The SR family of proteins is involved in removing cellular debris, oxidized low-density lipoproteins, and pathogens. Specifically, class C scavenger receptors (SR-C) have also been reported to be involved in phagocytosis of gram-positive and -negative bacteria in Drosophila and viruses in shrimp. However, reports are unavailable regarding the role of SR-C in antifungal immune mechanisms in insects. In this study, a full-length Tenebrio molitor SR-C (TmSR-C) sequence was obtained by 5'- and 3'-Rapid amplification of cDNA ends-polymerase chain reaction (RACE-PCR). The TmSR-C full-length cDNA comprised 1671 bp with 5'- and 3'-untranslated regions of 23- and 107-bp, respectively. TmSR-C encodes a putative protein of 556 amino acid residues that is constitutively expressed in all tissues of late instar larvae and 2-day-old adults, with the highest transcript levels observed in hemocytes of larvae and adults. TmSR-C mRNA showed a 2.5-fold and 3-fold increase at 24 and 6 h after infection with Candida albicans and β-glucan, respectively. Immunoassay with TmSR-C polyclonal antibody showed induction of the putative protein in the cytosols of hemocytes at 3 h after inoculation of C. albicans. RNA interference (RNAi)-based gene silencing and phagocytosis assays were used to understand the role of TmSR-C in antifungal immunity. Silencing of TmSR-C transcripts reduced the survivability of late instar larvae at 2 days post-inoculation of C. albicans, Escherichia coli, or Staphylococcus aureus. Furthermore, in TmSR-C-silenced larvae, there was a decline in the rate of microorganism phagocytosis. Taken together, results of this study suggest that TmSR-C plays a pivotal role in phagocytosing not only fungi but also gram-negative and -positive bacteria in T. molitor.

Data Build-up for the Construction of Korean Specific Greenhouse Gas Emission Inventory in Livestock Categories

Won, S.G.,Cho, W.S.,Lee, J.E.,Park, K.H.,Ra, C.S. Asian Australasian Association of Animal Productio 2014 Animal Bioscience Vol.27 No.3

Many studies on methane ($CH_4$) and nitrous oxide ($N_2O$) emissions from livestock industries have revealed that livestock production directly contributes to greenhouse gas (GHG) emissions through enteric fermentation and manure management, which causes negative impacts on animal environment sustainability. In the present study, three essential values for GHG emission were measured; i.e., i) maximum $CH_4$ producing capacity at mesophilic temperature ($37^{\circ}C$) from anaerobically stored manure in livestock category ($B_{0,KM}$, Korean livestock manure for $B_0$), ii) $EF_{3(s)}$ value representing an emission factor for direct $N_2O$ emissions from manure management system S in the country, kg $N_2O-N$ kg $N^{-1}$, at mesophilic ($37^{\circ}C$) and thermophilic ($55^{\circ}C$) temperatures, and iii) $N_{ex(T)}$ emissions showing annual N excretion for livestock category T, kg N $animal^{-1}$ $yr^{-1}$, from different livestock manure. Static incubation with and without aeration was performed to obtain the $N_2O$ and $CH_4$ emissions from each sample, respectively. Chemical compositions of pre- and post- incubated manure were analyzed. Contents of total solids (% TS) and volatile solid (% VS), and the ratio of carbon to nitrogen (C/N) decrease significantly in all the samples by C-containing biogas generation, whereas moisture content (%) and pH increased after incubation. A big difference of total nitrogen content was not observed in pre- and post-incubation during $CH_4$ and $N_2O$ emissions. $CH_4$ emissions (g $CH_4$ kg VS-1) from all the three manures (sows, layers and Korean cattle) were different and high C/N ratio resulted in high $CH_4$ emission. Similarly, $N_2O$ emission was found to be affected by % VS, pH, and temperature. The $B_{0,KM}$ values for sows, layers, and Korean cattle obtained at $37^{\circ}C$ are 0.0579, 0.0006, and 0.0828 $m^3$ $CH_4$ kg $VS^{-1}$, respectively, which are much less than the default values in IPCC guideline (GL) except the value from Korean cattle. For sows and Korean cattle, $N_{ex(T)}$ values of 7.67 and 28.19 kg N $yr^{-1}$, respectively, are 2.5 fold less than those values in IPCC GL as well. However, $N_{ex(T)}$ value of layers 0.63 kg N $yr^{-1}$ is very similar to the default value of 0.6 kg N $yr^{-1}$ in IPCC GLs for National greenhouse gas inventories for countries such as South Korea/Asia. The $EF_{3(s)}$ value obtained at $37^{\circ}C$ and $55^{\circ}C$ were found to be far less than the default value.

Hepatoprotective effect of vitamin C on lithocholic acid-induced cholestatic liver injury in Gulo(-/-) mice

Yu, S.J.,Bae, S.,Kang, J.S.,Yoon, J.H.,Cho, E.J.,Lee, J.H.,Kim, Y.J.,Lee, W.J.,Kim, C.Y.,Lee, H.S. North-Holland ; Elsevier Science Ltd 2015 european journal of pharmacology Vol.762 No.-

<P>Prevention and restoration of hepatic fibrosis from chronic liver injury is essential for the treatment of patients with chronic liver diseases. Vitamin C is known to have hepatoprotective effects, but their underlying mechanisms are unclear, especially those associated with hepatic fibrosis. Here, we analyzed the impact of vitamin Con bile acid induced hepatocyte apoptosis in vitro and lithocholic acid (LCA) induced liver injury in vitamin C-insufficient Gulo(-/-) mice, which cannot synthesize vitamin C similarly to humans. When Huh BAT cells were treated with bile acid, apoptosis was induced by endoplasmic retiiculum stress related JNK activation but vitamin C attenuated bile acid induced hepatocyte apoprosis in vitro. In our in vivo experiments. LCA feeding increased plasma marker of cholestasis and resulted in more extensive liver damage and hepatic fibrosis by more prominent apoptotic cell death and recruiting more intrahepatic inflammatory CD11b(+) cells in the liver of vitamin C-insufficient Gulo(-/-) mice compared to wild type mice which have minimal hepatic fibrosis. However, when vitamin C was supplemented to vitamin C-insufficient Gulo(-/-) mice, hepatic fibrosis was significantly attenuated in the liver of vitamin C-sufficient Gulo(-/-) mice like in wild type mice and this hepatoprotective effect of vitamin C was thought to be associated with both decreased hepatic apoptosis and necrosis. These results suggested that vitamin C had hepatoprotective effect against cholestatic liver injury. (C) 2015 Elsevier B.V. All rights reserved.</P>

한우 비육에 관한 연구 1 . Methylthiouracil 첨가 및 Estradiol 17β - Cypionate 주사가 약령 모우 비육에 미치는 효과

김창기 ( C K Kim ),이택원 ( T W Lee ),김종욱 ( J W Kim ),배대식 ( D S Bae ),오선균 ( S K Oh ),조지훈 ( C H Cho ),김법회 ( B H Kim ),김상렬 ( S Y Kim ),배신석 ( S S Bae ) 한국축산학회 1971 한국축산학회지 Vol.13 No.1

This study was performed to affirm any effects of methylthiouracil and estradiol 17β-cypionate administered to young bulls for short term fattening. Eighteen bulls of Korean native breed, approximately 1.5 to 2 years of age and 260㎏ to 360㎏ in weight, were used in this study. All bulls had received a basal ration of soiling corn and concentrate made up of 55% grains, 40% brans and 5% others, in a period of 40 days. Bulls were divided into six groups as follows: group C was not treated, group M-2 received 2g of methylthiouracil per day, group M-3 received 3g of methylthiouracil per day, group EM-0 was injected intramusculary with 25㎎ of estradiol 17β-cypionate in the neck region 10 days after the beginning of the fattening period, group EM-2 was injected with estradiol 17β-cypionate as above mentioned and simultaneously received 2g of methylthiouracil per day, and group EM-3 was injected with estradiol 17β-cypionate as above mentioned and simultaneously received 3g of methylthiouracil per day. The results obtained were summarized as follows. 1. The average daily gain was for group C: 0.83㎏, group M-2: 1.07㎏, group M-3: 1.40㎏, group EM-0, 0.93㎏, group EM-2: 0.95㎏, and group EM-3: 1.18㎏. The M-3 group gained significantly(P$lt;0.05) more weight than C and EM-0 group. There were no significant differences in the average daily gain between the groups injected with estradiol 17β-eypionate and the control group. 2. The average daily concentrate intake was as follows: group C: 5.47㎏, group M-2: 5.00㎏, group M-3: 4.52㎏, group EM-0: 5.21㎏, group EM-2: 4.35㎏, and group EM-3: 4.61㎏. The consumption of concentrate was decreased by 17% in the M-3 group compared with the C group. There was no significant difference in the soiling corn intake among these groups. 3. Feed consumed for 1㎏ gain were decreased by the supplementation of methylthiouracil. The consumption of DCP for 1㎏ gain was in group C: 0.82㎏, group M-2: 0.59㎏, group M-3: 0.41㎏, group EM-0: 0.70㎏, group EM-2: 0.59㎏, and group EM-3: 0.50㎏. The amounts of TDN required were; group C: 6.57㎏, group M-2: 4.76㎏, group M-3: 3.39㎏, group EM-0: 5.67㎏, group EM-Z: 4.87㎏, and group EM-3: 4.08㎏. The consumption of DCP and TDN for 1㎏ gain in the M-3 group was about a half of that in the C group. 4. There was not any significant difference in the increase in body measurements among the various groups. 5. The average margins in the fattening period of 40 days were for group C: 2,950won, group M-2: 5,327won, group M-3: 9,158won, group EM-0: 3,310won, group EM-2: 3,623won, and group EM-3: 5,575won. The margin of group M-3 was about three times higher than that of group C. In short, this experiment demonstrated that methylthiouracil when fed to young native Korean bulls at the proper level 40 days before slaughter would bring a noticeable effect on weight gain, feed efficiency and economic advantage. There were no advantages from the simultaneous injecting estradiol 17β-cypionate with methylthiouracil. The proper supplementation level of methylthiouracil would appear to be 3g per head per day in this experiment.

韓國 低所得層의 小兒結核症에 對한 臨床 및 統計的 考察

金晟澤,裵鍾三,趙宗大,金大成,趙璋濟,金贊榮 金原出版 1969 小兒科 Vol.10 No.5

<i>CYP2A6</i> and <i>ERCC1</i> polymorphisms correlate with efficacy of S-1 plus cisplatin in metastatic gastric cancer patients

Park, S R,Kong, S-Y,Nam, B-H,Choi, I J,Kim, C G,Lee, J Y,Cho, S J,Kim, Y W,Ryu, K W,Lee, J H,Rhee, J,Park, Y-I,Kim, N K Nature Publishing Group 2011 The British journal of cancer Vol.104 No.7

<P><B>Background:</B></P><P>We evaluated the association between polymorphisms of cytochrome P450 2A6 (<I>CYP2A6</I>)/excision repair cross-complementation group 1 (<I>ERCC1</I>)/X-ray repair cross-complementing group 1(<I>XRCC1</I>) and treatment outcomes of metastatic gastric cancer (MGC) patients treated with S-1/cisplatin.</P><P><B>Methods:</B></P><P>Among MGC patients (<I>n</I>=108), who received S-1 (40 mg m<SUP>−2</SUP> b.i.d., days 1–14) and cisplatin (60 mg m<SUP>−2</SUP>, day 1) every 3 weeks, we analysed the wild-type allele (<I>W</I>) and variants (<I>V</I>) of <I>CYP2A6</I> (<I>*4</I>, <I>*7, *9, *10</I>), and the polymorphisms of <I>ERCC1</I> (rs11615, rs3212986) and <I>XRCC1</I> (rs25487).</P><P><B>Results:</B></P><P>Patients having fewer <I>CYP2A6</I> variants had better response rates (<I>W</I>/<I>W vs W</I>/<I>V</I> other than <I>*1/*4 vs V</I>/<I>V</I> or <I>*1/*4</I>=66.7 <I>vs</I> 58.3 <I>vs</I> 32.3% <I>P</I>=0.008), time to progression (TTP) (7.2 <I>vs</I> 6.1 <I>vs</I> 3.5 months, <I>P</I>=0.021), and overall survival (23.2 <I>vs</I> 15.4 <I>vs</I> 12.0 months, <I>P</I>=0.004). <I>ERCC1 19442C</I>><I>A</I> (rs3212986) was also associated with response rate (<I>C/C</I>, 46.7% <I>vs C/A</I>, 55.3% <I>vs A/A</I>, 87.5%) (<I>P</I>=0.048) and TTP (4.4 <I>vs</I> 7.6 <I>vs</I> 7.9 months) (<I>P</I>=0.012). Patients carrying both risk genotypes of <I>CYP2A6</I> (<I>V</I>/<I>V</I> or <I>1/*4</I>) and <I>ERCC1 19442C</I>><I>A</I> (<I>C/C</I>) <I>vs</I> those carrying none showed an adjusted odds ratio of 0.113 (<I>P</I>=0.004) for response, and adjusted hazard ratios of 3.748 (<I>P</I>=0.0001) for TTP and 2.961 (<I>P</I>=0.006) for death.</P><P><B>Conclusion:</B></P><P>Polymorphisms of <I>CYP2A6</I> and <I>ERCC1 19442C</I>><I>A</I> correlated with the efficacy of S-1/cisplatin.</P>

In vitro antibacterial activity and major bioactive components of Cinnamomum verum essential oils against cariogenic bacteria, Streptococcus mutans and Streptococcus sobrinus

Choi, O.,Cho, S.K.,Kim, J.,Park, C.G.,Kim, J. China Humanity Technology Publishing House 2016 Asian Pacific journal of tropical biomedicine Vol.6 No.4

Objective: To evaluate the antibacterial activity of Cinnamomum verum (C. verum) from 32 different essential oils against cariogenic bacteria, Streptococcus mutans (S. mutans) and Streptococcus sobrinus (S. sobrinus). Methods: The antibacterial activities of each essential oil were individually investigated against S. mutans and S. sobrinus. The essential oil of C. verum was selected for further evaluation against S. mutans and S. sobrinus. Gas chromatography mass spectrometry was used to determine the major constituents of C. verum essential oil. In addition, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration of the most effective constituent was investigated. Results: The essential oil from C. verum exhibited the greatest antibacterial activity. Gas chromatography mass spectrometry analysis revealed that the major components of C. verum essential oil were cinnamaldehyde (56.3%), cinnamyl acetate (7.1%) and β-phellandrene (6.3%). The MIC of cinnamaldehyde was measured using broth dilution assays. The MIC of cinnamaldehyde was 0.02% (v/v) against both bacterial strains tested. The minimum bactericidal concentration of cinnamaldehyde against S. mutans and S. sobrinus were 0.2% and 0.1% (v/v), respectively. Conclusions: The essential oil of C. verum and its major component cinnamaldehyde possessed considerable in vitro antibacterial activities against cariogenic bacteria, S. mutans and S. sobrinus strains. These results showed that the essential oil of C. verum and its bioactive component, cinnamaldehyde, have potential for application as natural agents for the prevention and treatment of dental caries.

Production of soluble truncated spike protein of porcine epidemic diarrhea virus from inclusion bodies of Escherichia coli through refolding

Piao, D.C.,Lee, Y.S.,Bok, J.D.,Cho, C.S.,Hong, Z.S.,Kang, S.K.,Choi, Y.J. Academic Press 2016 Protein expression and purification Vol.126 No.-

The emergence of highly pathogenic variant porcine epidemic diarrhea virus (PEDV) strains, from 2013 to 2014, in North American and Asian countries have greatly threatened global swine industry. Therefore, development of effective vaccines against PEDV variant strains is urgently needed. Recently, it has been reported that the N-terminal domain (NTD) of S1 domain of PEDV spike protein is responsible for binding to the 5-N-acetylneuraminic acid (Neu5Ac), a possible sugar co-receptor. Therefore, the NTD of S1 domain could be an attractive target for the development of subunit vaccines. In this study, the NTD spanning amino acid residues 25-229 (S25-229) of S1 domain of PEDV variant strain was expressed in Escherichia coli BL21 (DE3) in the form of inclusion bodies (IBs). S25-229 IBs were solubilized in 20 mM sodium acetate (pH 4.5) buffer containing 8 M urea and 1 mM dithiothreitol with 95% yield. Solubilized S25-229 IBs were refolded by 10-fold flash dilution and purified by one-step cation exchange chromatography with >95% purity and 20% yield. The CD spectrum of S25-229 showed the characteristic pattern of alpha helical structure. In an indirect ELISA, purified S25-229 showed strong reactivity with mouse anti-PEDV sera. In addition, immunization of mice with 20 μg of purified S25-229 elicited highly potent serum IgG titers. Finally, mouse antisera against S25-229 showed immune reactivity with native PEDV S protein in an immunofluorescence assay. These results suggest that purified S25-229 may have potential to be used as a subunit vaccine against PEDV variant strains.

산란계 사료내 CLA 함유 Oil (CLAzen 80) 첨가가 난황내 지방산 조성에 미치는 영향

황보종,장종수,정일병,이병석,김동운,조성백,김희도,배해득,손진혁,홍의철,최낙진,Hwangbo J.,Chang J. S.,Chung I. B.,Lee B. S.,Kim D. U.,Cho S. B.,Kim H. D.,Bae H. D.,Son J. H.,Hong U. C.,Choi N. J. 한국가금학회 2005 韓國家禽學會誌 Vol.32 No.1

본 연구는 oil 형태의 conjugated linoleic acid(CLAzen 80)를 산란계 사료에 수준별로 첨가 급여하였을 때 산란율과 난황내 지방산 조성의 변화를 조사하기 위하여 수행하였다. 59주령의 산란계 72수를 완전임의배치법으로 4개 처리구에 6주간 공시하였다. 처리구는 CLAzen 80를 첨가하지 않은 대조구와 각각 1, 2 및 $3\%$를 첨가구를 두었다. 연구 결과를 살펴보면 산란율은 처리구별 통계적 유의차가 없었지만, 난황내 지방산 조성은 CLAzen 80 첨가에 의하게 크게 영향을 받았다. 난황내 C16:0과 C18:0과 같은 포화 지방산 함량은 CLAzen 80 첨가에 의하여 증가하였으나, 일가불포화지방산인 C18:1 함량은 오히려 감소하였다. 한편, 난황내 C18:2와 C18:3와 같은 다가불포화지방산은 CLAzen 80 급여 2$\~$4주사이에는 모든처리구들에 있어서 그 함량이 일정하게 유지되었다. 그러나, 대조구와 비교하여 CLAzen 80 급여 6주 째에는 난황내 C18:2 함량이 감소하였다. 불포화지방산:포화지방산 비율과 n-6:n-3 불포화지방산 비율은 2$\~$4주 사이에는 처리구별간에 통계적 유의차가 없었고, 6주째 불포화지방산:포화지방산 비율이 CLAzen 80 첨가에 의하여 감소하였다. 한편, 난황내 CLA 함량은 CLAzen 80 첨가수준에 비례하여 증가하였다. 따라서, 산란계 사료 내 CLAzen 80 첨가는 난황내 CLA 함량을 증진시키는 것으로 요약할 수 있다. The objectives of the present study were to investigate the effects of varying levels of dietary oil containing conjugated linoleic acid (CLA) on the egg production and fatty acid composition of egg yolk. Seventy-two 59-wk-old ISA Brown laying hens were randomly allotted to four dietary treatments, each consisting of three replicates with six birds per replicate. There were four treatments that consist of diets containing 0, 1, 2, or $3\%$ commercial CLA-containing oil. Egg production was not significantly different among the dietary treatments at 0, 2, 4, and 6 week. The proportion of saturated fatty acids such as C16:0 and C18:0 in egg yolk were increased, but that of monounsaturated fatty acid C18:1 was decreased by feeding CLA-containing oil supplementation. However, the proportion of polyunsaturated fatty acids such as C18:2 and C18:3 in egg yolk were not different among dietary treatments at 2 and 4 wk of the experiment. At 6 week, the proportion of C18:2 in egg yolk was decreased by feeding CLA-containing oil compared with the control. Polyunsaturated fatty acid:saturated fatty acid (P:S) ratio and n-6:n-3 polyunsaturated fatty acid ratio were similar across the treatments between 2 and 4 week. The P:S ratio was decreased by dietary CLA-containing oil supplementation at 6 week. The proportion of CLA in egg yolk was linearly increased with increasing levels of CLA-containing oil supplementation. In conclusion, dietary supplementation of CLA-containing oil to laying hens increased beneficially increased CLA content in their egg yolk.