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Assessment of the Abuse Liability of Synthetic Cannabinoid Agonists JWH-030, JWH-175, and JWH-176

  • Tampus, Reinholdgher;Yoon, Seong Shoon;Pena, June Bryan de la;Botanas, Chrislean Jun;Kim, Hee Jin;Seo, Joung-Wook;Jeong, Eun Ju;Jang, Choon Gon;Cheong, Jae Hoon
    • Biomolecules & Therapeutics
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    • v.23 no.6
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    • pp.590-596
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    • 2015
  • The emergence and use of synthetic cannabinoids have greatly increased in recent years. These substances are easily dispensed over the internet and on the streets. Some synthetic cannabinoids were shown to have abuse liability and were subsequently regulated by authorities. However, there are compounds that are still not regulated probably due to the lack of abuse liability studies. In the present study, we assessed the abuse liability of three synthetic cannabinoids, namely JWH-030, JWH-175, and JWH-176. The abuse liability of these drugs was evaluated in two of the most widely used animal models for assessing the abuse potential of drugs, the conditioned place preference (CPP) and self-administration (SA) test. In addition, the open-field test was utilized to assess the effects of repeated (7 days) treatment and abrupt cessation of these drugs on the psychomotor activity of animals. Results showed that JWH-175 (0.5 mg/kg), but not JWH-030 or JWH-176 at any dose, significantly decreased the locomotor activity of mice. This alteration in locomotor activity was only evident during acute exposure to the drug and was not observed during repeated treatment and abstinence. Similarly, only JWH-175 (0.1 mg/kg) produced significant CPP in rats. On the other hand, none of the drugs tested was self-administered by rats. Taken together, the present results indicate that JWH-175, but not JWH-030 and JWH-176, may have abuse potential. More importantly, our findings indicate the complex psychopharmacological effects of synthetic cannabinoids and the need to closely monitor the production, dispensation, and use of these substances.

Transcriptional and Mycolic Acid Profiling in Mycobacterium bovis BCG In Vitro Show an Effect for c-di-GMP and Overlap between Dormancy and Biofilms

  • Cruz, Miguel A. De la;Ares, Miguel A.;Rodriguez-Valverde, Diana;Vallejo-Cardona, Alba Adriana;Flores-Valdez, Mario Alberto;Nunez, Iris Denisse Cota;Aceves-Sanchez, Michel de Jesus;Lira-Chavez, Jonahtan;Rodriguez-Campos, Jacobo;Bravo-Madrigal, Jorge
    • Journal of Microbiology and Biotechnology
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    • v.30 no.6
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    • pp.811-821
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    • 2020
  • Mycobacterium tuberculosis produces mycolic acids which are relevant for persistence, recalcitrance to antibiotics and defiance to host immunity. c-di-GMP is a second messenger involved in transition from planktonic cells to biofilms, whose levels are controlled by diguanylate cyclases (DGC) and phosphodiesterases (PDE). The transcriptional regulator dosR, is involved in response to low oxygen, a condition likely happening to a subset of cells within biofilms. Here, we found that in M. bovis BCG, expression of both BCG1416c and BCG1419c genes, which code for a DGC and a PDE, respectively, decreased in both stationary phase and during biofilm production. The kasA, kasB, and fas genes, which are involved in mycolic acid biosynthesis, were induced in biofilm cultures, as was dosR, therefore suggesting an inverse correlation in their expression compared with that of genes involved in c-di-GMP metabolism. The relative abundance within trehalose dimycolate (TDM) of α-mycolates decreased during biofilm maturation, with methoxy mycolates increasing over time, and keto species remaining practically stable. Moreover, addition of synthetic c-di-GMP to mid-log phase BCG cultures reduced methoxy mycolates, increased keto species and practically did not affect α-mycolates, showing a differential effect of c-di-GMP on keto- and methoxy-mycolic acid metabolism.

The Stimulatory Effect of Essential Fatty Acids on Glucose Uptake Involves Both Akt and AMPK Activation in C2C12 Skeletal Muscle Cells

  • Park, So Yeon;Kim, Min Hye;Ahn, Joung Hoon;Lee, Su Jin;Lee, Jong Ho;Eum, Won Sik;Choi, Soo Young;Kwon, Hyeok Yil
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.3
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    • pp.255-261
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    • 2014
  • Essential fatty acid (EFA) is known to be required for the body to function normally and healthily. However, the effect of EFA on glucose uptake in skeletal muscle has not yet been fully investigated. In this study, we examined the effect of two EFAs, linoleic acid (LA) and ${\alpha}$-linolenic acid (ALA), on glucose uptake of C2C12 skeletal muscle cells and investigated the mechanism underlying the stimulatory effect of polyunsaturated EFAs in comparison with monounsaturated oleic acid (OA). In palmitic acid (PA)-induced insulin resistant cells, the co-treatment of EFAs and OA with PA almost restored the PA-induced decrease in the basal and insulin-stimulated 2-NBDG (fluorescent D-glucose analogue) uptake, respectively. Two EFAs and OA significantly protected PA-induced suppression of insulin signaling, respectively, which was confirmed by the increased levels of Akt phosphorylation and serine/threonine kinases ($PKC{\theta}$ and JNK) dephosphorylation in the western blot analysis. In PA-untreated, control cells, the treatment of $500{\mu}M$ EFA significantly stimulated 2-NBDG uptake, whereas OA did not. Phosphorylation of AMP-activated protein kinase (AMPK) and one of its downstream molecules, acetyl-CoA carboxylase (ACC) was markedly induced by EFA, but not OA. In addition, EFA-stimulated 2-NBDG uptake was significantly inhibited by the pre-treatment of a specific AMPK inhibitor, adenine 9-${\beta}$-D-arabinofuranoside (araA). These data suggest that the restoration of suppressed insulin signaling at PA-induced insulin resistant condition and AMPK activation are involved at least in the stimulatory effect of EFA on glucose uptake in C2C12 skeletal muscle cells.

Station Keeping Maneuver Planning Using COMS Flight Dynamic Software

  • Kim, Hae-Yeon;Lee, Byoung-Sun;Hwang, Yoo-La;Shin, Dong-Suk;Kim, Jae-Hoon
    • Journal of Satellite, Information and Communications
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    • v.2 no.2
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    • pp.16-21
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    • 2007
  • Various perturbations by the sun, the moon and the earth itself cause a continuous change in nominal position of a geostationary satellite. In order to maintain the satellite within a required window, north-south station keeping for controlling inclination and right ascension of ascending node, and east-west station keeping for controlling eccentricity and longitude are required. In this paper, station keeping maneuver simulation for Communication, Ocean and Meteorological Satellite (COMS) was performed using COMS Flight Dynamics Software(FDS) and the results were analyzed. COMS performs weekly based east-west/north-south station keeping to maintain satellite within ${\pm}0.05^{\circ}$ at the nominal longitude of $128.2^{\circ}E$. In addition, COMS performs wheel off-loading maneuver twice a day to eliminate attitude error caused by one-solar wing in the south panel of the satellite. In this paper, station keeping maneuver considering wheel off-loading maneuver was performed and the results showed that COMS can be maintained well within ${\pm}0.05^{\circ}$ window using COMS FDS.

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Spatial-Temporal Distribution Characteristics of Bigeye and Yellowfin Tunas in Kiribati Waters

  • Taanga, Aketa Mature;Cai, Yi-Hui;Lu, Hsueh-Jung;Ni, I-Hsun
    • Proceedings of the KSRS Conference
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    • v.1
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    • pp.174-179
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    • 2006
  • Information on the distribution characteristics of tuna resources in Kiribati EEZ waters in three zones (Zone 1: west Gilbert region, Zone 2: central Phoenix region, and Zone 3: east Line region) as well as their relationship with the ocean environment is critical for sustainable managing the migratory tuna resource and fishing practices in this region. Therefore, this study is designed to investigate the spatial and temporal distribution and concentration of bigeye (BET) and yellowfin tuna (YFT) in Kiribati EEZ waters in relation to sea surface temperature (SST) and thermocline depth so as to better understand the tuna resources management basis in Kiribati waters. The geographic and temporal distribution and concentration were first displayed. Paired t-test was utilized to compare the distribution between the two tuna species based on Catch per Unit Effort (CPUE) derived from the Korean longliners during 1996 to 2004, and also among the three zones of Kiribati EEZ waters. Environmental conditions of the three zones were then compared and correlated with the CPUE of YFT and BET. In addition, the effect of ENSO phenomena on the environmental conditions and the distribution of YFT and BET within the three zones were also examined. The BET was relatively higher in the Zone 3 whereas YFT predominate in the Zone 1 and the Zone 2 due to oceanographic differences among the three zones and the ecological habitats of the two tuna species. It was suggested that El Ni?o/Southern Oscillation (ENSO) phenomena altered the oceanographic conditions of the three zones that in turn change the distribution of the two tuna species. During El Ni?o, the warm phase of ENSO, resulted in having more BET in all the three zones and the opposite observed during La Ni?a (cold phase) replacing by having relatively higher catch rate for YFT, particularly in the Zone 2. Although the results of the study are from short periods (1996 to 2004) in considering oceanographic anomality, these environmental variations should be considered into sustainable fisheries management of tuna fisheries in Kiribati EEZ waters.

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Novel pH/Temperature Sensitive Hydrogels of Poly (ethylene glycol)-Poly (caprolactone) -Poly (${\beta}-amino\;ester$) (PAE-PCLA-PEGPCLA-PAE) Biodegradable Polyester Block Copolymer

  • Huynh Dai Phu;Lee Doo-Sung
    • Proceedings of the Polymer Society of Korea Conference
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    • 2006.10a
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    • pp.263-263
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    • 2006
  • Poly (ethylene glycol)(PEG) - Poly (${\varepsilon}-caprolactone(CL)$) - Poly (D,L lactide(LA) (PCLA-PEG-PCLA) was synthesized by ring-opening polymerization to form temperature sensitive hydrogel triblock copolymer. The triblock copolymer was acrylated by acryloyl chloride. ${\beta}-amino$ ester was used as a pH sensitive moiety, in this study ${\beta}$- amino ester obtained from 1,4-butandiol diacrylate, and 4, 4' trimethylene dipiperidine, it have pKb around 6.6. pH/temperature sensitive penta-block copolymer (PAE-PCL-PEG-PCL-PAE) was synthesized by addition polymerization from acrylated triblock copolymer, 1,4-butandiol diacrylate, and 4, 4' trimethylene dipiperidine. Their physicochemical properties of triblock and penta-block copolymers were characterized by $^1H-NMR$ spectroscopy and gel permeation spectroscopy. Sol-gel phase transition behavior of PAE-PCL-PEG-PCL-PAE block copolymers were investigated by remains stable method. Aqueous media of the penta-block copolymer (at 20 wt%) changed from a sol phase at pH 6.4 and $10^{\circ}C$ to a gel phase at pH 7.4 and $37^{\circ}C$. The sol-gel transition properties of these block copolymers are influenced by the hydrophobic/hydrophilic balance of the copolymers, block length, hydrophobicity, stereo-regularity of the hydrophobic of the block copolymer, and the ionization of the pH function groups in the copolymer depended on the changing of environmental pH, respectively. The degradation and the stabilization at pH 7.4 and $37^{\circ}C$, and the stabilization at pH 6.4 and $10^{\circ}C,\;5^{\circ}C,\;0^{\circ}C$, of the gel were determined. The results of toxicity experiment show that the penta block copolymer can be used for injection drug delivery system. The sol?gel transition of this block copolymer also study by in vitro test ($200{\mu}l$ aqueous solution at 20wt% polymer was injected to mouse). Insulin loading and releasing by in vitro test was investigated, the results showed that insulin can loading easily into polymer matrix and release time is around 14-16days. The PAE-PCL-PEG-PCL-PAE can be used as biomaterial for drug, protein, gene loading and delivery.

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Quality characteristics of meat seasoning sauce containing fermented Oenothra biennis juice (달맞이꽃 발효액을 이용한 양념육 소스의 품질 특성)

  • Ahn, Yoo-Bok;Park, La-Young;Lee, Shin-Ho
    • Food Science and Preservation
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    • v.23 no.4
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    • pp.516-521
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    • 2016
  • The characteristics and quality changes of sauces containing different concentrations (5, 10, and 15%) of fermented Oenothra biennis juice (FOBJ) were studied for its potential as a new meat seasoning suace. pH of the seasoning sauce was ranged from 5.23 to 5.37. Sugar content of seasoning sauces increased decreasing on increase of FOBJ concentration while the color (L, a, b) decreased. DPPH radical scavenging ability and TBARS values of the seasoning sauce was increased significantly by the addition of FOBJ (p<0.05). The total bacteria number of the seasoning sauces was approximately 3 log CFU/g while coliform bacteria were not detected in all tested sauces. The sauce containing 5% FOBJ showed the highest value in taste, color, overall acceptability among all tested sauces. The pH and titratable acidity of the meat seasoning sauces was not changed significantly during 25 days at $10^{\circ}C$. The total bacteria number of the seasoning sauces was steadly 3.62~3.83 log CFU/g for 25 days at $10^{\circ}C$. The number of coliform was not detected during storage periods. These results suggested the possibility of development of new meat seasoning sauce containing FOBI.

Effect of Scutellaria baicalensis Georgi on Shelf Life of Tofu (황금첨가 농도가 두부의 저장성에 미치는 영향)

  • Woo, In-Taeck;Park, La-Young;Park, Geum-Soon;Lee, Shin-Ho
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.36 no.4
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    • pp.458-463
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    • 2007
  • This study was carried out to investigate potential use of Scutellaria bicalensis Georgi (SBG) as an ingredient for extending the shelf life of tofu. The spore of Bacillus sp. KN-4 was isolated from commercial tofu and inoculated to soybean milk to prepare artificially contaminated tofu. The contaminated tofu was stored in the presence of 0.05 and 1% of SBG extract at $25^{\circ}C$ for 72 hrs. The pH changes of contaminated tofu with SBG extract was slower than those of control during storage. The degree of pH change decreased as the concentration of SBG extract was increased from 0.05% to 0.1%. The change of titratable acidity of the tofu showed the same tendency as pH change during storage. Total cell number of the SBG extract added tofu was lower about $1{\sim}2$ log cycle (0.05% SBG extract) or $2{\sim}3$ log cycle (0.1% SBG extract) than that of control after storage for 12 hrs at $25^{\circ}C$. The color changes of the tofu did not show any difference with and without SBG during storage at $25^{\circ}C$. The strength and hardness of the tofu was improved by the addition of SBG extract. Especially, the strength and hardness of tofu in the Presence of 0.1% SBG extract did not change during storage time. The sensory Qualify of SBG extract added tofu was better than control in texture, but not in taste and color. The overall acceptability of the SBG extract added tofu was similar to control.

Comparison between denture wearer's evaluation and clinician's rating for complete denture (총의치 사용에 대한 환자와 술자간 평가 비교)

  • Byun, Jin-Soo;Huh, Yoon-Hyuk;Cho, Lee-La;Park, Chan-Jin
    • The Journal of Korean Academy of Prosthodontics
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    • v.54 no.4
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    • pp.364-369
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    • 2016
  • Purpose: The aim of this study was to compare denture wearer's evaluation and clinician's technical rating for complete denture used on edentulous patients. Materials and methods: Total 43 edentulous patients who had complete denture fabricated more than one year ago were recalled. The questionnaire based on the various literatures was modified and applied to patients for subjective assessments. Functional aspects related to retention, stability, occlusion and denture condition were included in operator's evaluation. In addition, correlations were evaluated between patient's subjective and operator's objective assessments. Friedman test and Cohen's Kappa value were used for statistical analysis. Results: It was found that denture wearers' evaluations were slightly or fairly agree to clinician's rating for complete denture. More differences were found in maxillary denture than mandibular denture and moderate difference was found in esthetic, occlusion aspects. Conclusion: There were slightly or fairly agreement between subjective and objective evaluations.

Five miRNAs as Novel Diagnostic Biomarker Candidates for Primary Nasopharyngeal Carcinoma

  • Tang, Jin-Feng;Yu, Zhong-Hua;Liu, Tie;Lin, Zi-Ying;Wang, Ya-Hong;Yang, La-Wei;He, Hui-Juan;Cao, Jun;Huang, Hai-Li;Liu, Gang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.18
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    • pp.7575-7581
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    • 2014
  • MicroRNAs (miRNAs) play an essential role in the development and progression of nasopharyngeal carcinomas (NPC). Despite advances in the field of cancer molecular biology and biomarker discovery, the development of clinically validated biomarkers for primary NPC has remained elusive. In this study, we investigated the expression and clinical significance of miRNAs as novel primary NPC diagnostic biomarkers. We used an array containing 2, 500 miRNAs to identify 22 significant miRNAs, and these candidate miRNAs were validated using 67 fresh NPC and 25 normal control tissues via quantitative real-time PCR (qRT-PCR). Expression and correlation analyses were performed with various statistical approaches, in addition to logistic regression and receiver operating characteristic curve analyses to evaluate diagnostic efficacy. qRT-PCR revealed five differentially expressed miRNAs (miR-93-5p, miR-135b-5p, miR-205-5p and miR-183-5p) in NPC tissue samples relative to control samples (p<0.05), with miR-135b-5p and miR-205-5p being of significant diagnostic value (p<0.01). Moreover, comparison of NPC patient clinicopathologic data revealed a negative correlation between miR-93-5p and miR-183-5p expression levels and lymph node status (p<0.05). These findings display an altered expression of many miRNAs in NPC tissues, thus providing information pertinent to pathophysiological and diagnostic research. Ultimately, miR-135b-5p and miR-205-5p may be implicated as novel NPC candidate biomarkers, while miR-93-5p, miR-650 and miR-183-5p may find application as relevant clinical pathology and diagnostic candidate biomarkers.