• Title/Summary/Keyword: CYP51

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Early Life Stage Toxicity for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Crucian Carp (Carassius auratus) (붕어 수정란을 이용한 다이옥신의 초기발생단계 독성평가)

  • Park, Yong-Joo;Kim, Ha-Ryong;Lee, Min-Jee;Lee, Wan-Ok;Lee, Jung-Sick;Chung, Kyu-Hyuck;Oh, Seung-Min
    • Environmental Analysis Health and Toxicology
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    • v.25 no.3
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    • pp.241-251
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    • 2010
  • Crucian carp (Carassius auratus) has been used as the sentinel species for POPs (Persistent Organic Pollutants) monitoring in aquatic environment. However, there is little information for dioxin toxicity and especially, early life stage toxicity in crucian carp have been never carried out. In this study, we investigated several toxic effects for 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) in fertilized egg obtained by natural fertilization from crucian carp. The embryos at 3 h post-fertilization (hpf) were treated with 0.039, 0.156, 0.625, and 2.5 (${\mu}g/L$) TCDD by waterborne exposure for 60 minutes and changed with fresh water 2 times per day. Fertilized eggs started hatching at 51 hpf and TCDD exposed embryo showed decrease of hatching rate in a dose-dependent manner at 75 hpf. Pericardial edema was continuously observed in larvae exposed to TCDD from hatching start time (51 hpf), followed by the onset of mortality. In addition, AhR-related gene, CYP1A was clearly increased by TCDD in a dose dependent manner. These results indicated that fertilized eggs obtained from crucian carp have the TCDD related gene regulation and a distinct TCDD developmental toxicity syndrome by TCDD exposure. Therefore, we suggested that early life stage test in crucian carp could be used as test methods on dioxins toxicity.

Effect of methyl jasmonate on the glucosinolate contents and whole genome expression in Brassica oleracea (유묘기 양배추류에서 메틸자스모네이트에 의한 글루코시놀레이트 함량 변화 및 전사체 발현 분석)

  • Lee, Jeongyeo;Min, Sung Ran;Jung, Jaeeun;Kim, HyeRan
    • Journal of Plant Biotechnology
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    • v.46 no.3
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    • pp.189-204
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    • 2019
  • In this study, we analyzed the changes in glucosinolate content and gene expression in TO1000DH3 and Early big seedling upon methyl jasmonate (MeJA) treatment. Analysis of glucosinolate contents after MeJA treatment at $200{\mu}M$ concentration showed that the total glucosinolate content increased by 1.3-1.5 fold in TO1000DH3 and 1.3-3.8 fold in Early big compared to those before treatment. Aliphatic glucosinolates, progoitrin and gluconapin, were detected only in TO1000DH3, and the changes in the content of neoglucobrassicin were the greatest at 48 hours after MeJA treatment in TO1000DH3 and Early big. The transcriptomic analysis showed that transcripts involved in stress or defense reactions, or those related to growth were specifically expressed in TO1000DH3, while transcripts related to nucleosides or ATP biosynthesis were specifically expressed in Early big. GO analysis on transcripts with more than two-fold change in expression upon MeJA treatment, corresponding to 12,020 transcripts in TO1000DH3 and 13,510 transcripts in Early big, showed that the expression of transcripts that react to stimulus and chemical increased in TO1000DH3 and Early big, while those related to single-organism and ribosome synthesis decreased. In particular, the expression increased for all transcripts related to indole glucosinolate biosynthesis, which is associated with increase in glucobrassicin and neoglucobrassicin contents. Upon MeJA treatment, the expression of AOP3 (Bo9g006220, Bo9g006240), TGG1 (Bo14804s010) increased only in TO1000DH3, while the expression of Dof1.1 (Bo5g008360), UGT74C1 (Bo4g177540), and GSL-OH (Bo4g173560, Bo4g173550, Bo4g173530) increased specifically in Early big.

Assessment of Flavin-containing Monooxygenase (FMO) Activity by Determining Urinary Ratio of Theobromine and Caffeine in a Korean Population after Drinking a Cup of Coffee

  • Chung, Woon-Gye;Kang, Ju-Hee;Roh, Hyung-Keun;Lee, Kyung-Hoon;Park, Chang-Shin;Cha, Young-Nam
    • The Korean Journal of Physiology and Pharmacology
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    • v.3 no.2
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    • pp.207-213
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    • 1999
  • To examine individual variation in drug metabolism catalyzed by flavin-containing monooxygenase (FMO), 179 Korean volunteers' urinary molar concentration ratio of theobromine (TB) and caffeine (CA) was determined. Their urine was collected for 1 hr (between 4 and 5 hrs) after they drank a cup of coffee containing 115 mg CA and analyzed by an HPLC system. The lowest TB/CA ratio obtained was 0.40, the highest ratio was 15.17 (38-fold difference), and the median ratio for all subjects was 1.87. The mean was 2.66 with 2.36 S.D.. In 134 nonsmokers, the mean ratio was $2.35{\pm}1.93,$ that of 51 males was $2.30{\pm}2.26$ and 83 females was $2.37{\pm}1.85,$ respectively. There was no significant gender difference in the obtained TB/CA ratio (Mann-Whitney test; p=0.518). There were no smokers among the 83 female volunteers. In the remaining 96 male subjects, the ratio obtained in 51 nonsmokers was $2.30{\pm}2.06$ and that of 45 smokers was $3.62{\pm}3.19.$ This indicated that the TB/CA ratio was increased significantly in smokers (p=0.007). However, when the TB/CA ratios (FMO activity) obtained in all 179 Korean volunteers are compared with the urinary concentration ratios of paraxanthine (PX) plus 1,7-dimethylurate (17U) to CA (CYP1A2 activity), there was a weak but significant correlation (Pearson's correlation coefficient test; $r^2=0.28,$ p<0.0001). This indicates that, although the urinary TB/CA ratio mostly represents FMO activity, minor contribution by CYP1A2 activity cannot be ignored. In conclusion, the FMO activity measured by taking the urinary TB/CA ratio from normal healthy Korean volunteers shows marked individual variations without significant gender differences and the increased TB/CA ratio observed in cigarette smokers may have been caused by the increased CYP1A2 activity.

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Cross Resistance of Cypermethrin-and Methomyl-Resistance and Linkage Group Analysis on Cypermethrin Resistance in House Fly(Musca domestica L.) (Cypermethrin과 Methomyl 저항성 집파리의 교처저항성과 Cypermethrin 저항성에 대한 연관군 분석)

  • Yoo, Ju;Park, Chung-Gyoo;Lee, Si-Woo;Choi, Byeong-Ryeol
    • Korean journal of applied entomology
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    • v.40 no.4
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    • pp.337-344
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    • 2001
  • The house fly (Musca domestica L.) strains were derived from the Yumenoshima III strain by selecting with cypermethrin and methomyl for 19 and 16 generations, respectively. The resulting strains, cypermethrin resistance strain (Cyp-R19) and methomyl resistance strain (Met-R16), showed high level of resistance by 12906 and 51 times, respectively, comparing with the susceptible SRS strain. The Cyp-R19 strain was resistant to synthetic pyrethroids such as deltamethrin, esfenvalerate, fenpropathrin, $\beta$-cyfluthrin, showing > 11000, 1231, 103, 292 times higher $LD_{50}$ values than the SRS strain, respectively. It was also resistant to 3 organophosphates and 2 carbamates such as fenitrothion, profenofos, pyridaphenthion, benfuracarb, methomyl, showing resistance ratios fo 51, 17, 49, 39 and 62 comparing to SRS strain. The Met-R16 strain was resistant to synthetic carbamate benfuracarb, showing 6 times higher $LD_{50}$ value than SRS strain. It was also resistant to 4 organophosphates such as acephate, fenitrothion, profenofos and pyridaphenthion, showing > 40, 103, 19, 60 times higher $LD_{50}$ value. It was also resistant to 5 pyrethroids and a pyrrole such as cypermethrin, deltamethrin, esfenvalerate, fenpropathrin, $\beta$-cyfluthrin and chlorfenapyr, showing 3030, 249, 4063, 34, 330 and 86 times higher $LD_{50}$ values than the SRS strain. Cyp-R14 strain which was selected for 14 generations by cypermethrin and developed 11014 times higher resistance to the SRS strain was used in the dominance and linkage group analysis. Cypermethrin resistance inheritance was incompletely dominant in house fly as judged by the reciprocal cross between the resistant and susceptible strains. The linkage group analysis for the major factors responsible for this resistance was carried out by the$ F_1$male-backcross method, using susceptible multi-chromosomal marker aabys strain. The major factors for cypermethrin resistance were located on the 1st, the 3rd and the 4th chromosomes, and the effect of the 3rd chromosome was most prominent.

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The Anticancer Effects and Drug Metabolic Enzyme Change by Oral Intake of Agrimonia Pilosa Ledeb (선학초(짚신나물) 경구투여시 항암효과 탐색 및 약물 대사효소의 변화)

  • Rhee, Si-Hyung;Jung, Hee;Lee, Ju-Ah;Go, Ho-Yeon;Choi, Yu-Kyung;Park, Jong-Hyung;Kim, Ji-Hye;Ko, Seong-Kyu;Jun, Chan-Yong
    • Journal of Society of Preventive Korean Medicine
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    • v.13 no.2
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    • pp.51-64
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    • 2009
  • Objective : This research was aimed to investigate the anti-tumor effect, safety, mechanism and metabolizing enzyme of Agrimonia pilosa LEDEB(APL) in female C57B/L mouse. Methods : At first, to evaluate the anti-tumor activity of APL, we divided into four groups, normal, control, APL100(100mg/kg), APL150(150mg/kg). LLC obtained American Type Culture Collection was used. LLC had been inoculated to induce tumor. To measure the anti-tumor effect of APL, we calibrate tumor size and weight. To study for mechanism of anti-tumor in APL, we used western blotting and to know metabolizing enzyme in APL we used to real-time PCR. Results : APL100, APL150 inhibited tumor growth after medicine injected. APL did not only induced caspase-dependent apoptosis in LLC-bearing mouse tumor. In APL100, it were decreased 72% in CYP3A11. In APL150, it were decreased 62%, 75% in CYP3A11 and MRP1a respectively. Conclusion : These results suggests that APL has some anti-tumor effects in female C57B/L mouse tumor. APL should be careful use with other drugs related with CYP3A11 or MRP1a.

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Metabolites of Latilactobacillus curvatus BYB3 and Indole Activate Aryl Hydrocarbon Receptor to Attenuate Lipopolysaccharide-Induced Intestinal Barrier Dysfunction

  • Wang, Xing;Yong, Cheng Chung;Oh, Sejong
    • Food Science of Animal Resources
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    • v.42 no.6
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    • pp.1046-1060
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    • 2022
  • This study aimed to investigate the effects of the metabolites of Latilactobacillus curvatus BYB3 and indole-activated aryl hydrocarbon receptor (AhR) to increase the tight junction (TJ) proteins in an in vitro model of intestinal inflammation. In a Western blot assay, the metabolites of L. curvatus BYB3 reduced the TJ demage in lipoploysaccharide (LPS) stimulated-Caco-2 cells. This reduction was a result of upregulating the expression of TJ-associated proteins and suppressing the nuclear factor-κB signaling. Immunofluorescence images consistently revealed that LPS disrupted and reduced the expression of TJ proteins, while the metabolites of L. curvatus BYB3 and indole reversed these alterations. The protective effects of L. curvatus BYB3 were observed on the intestinal barrier function when measuring transepithelial electrical resistance. Using high-performance liquid chromatography analysis the metabolites, the indole-3-latic acid and indole-3-acetamide concentrations were found to be 1.73±0.27 mg/L and 0.51±0.39 mg/L, respectively. These findings indicate that the metabolites of L. curvatus BYB3 have increasing mRNA expressions of cytochrome P450 1A1 (CYP1A1) and AhR, and may thus be applicable for therapy of various inflammatory gut diseases as postbiotics.

Lipid-lowering Effect of Chunggantang in Poloxamer-407 induced Hyperlipidemia Model in Rat (Poloxamer-407로 유발시킨 고지혈증에 대한 청간탕의 효과)

  • Park, Hong-Hak;Cho, Jung-Hyo;Shin, Jang-Woo;Lee, Yeon-Weol;Yoo, Hwa-Seung;Lee, Nam-Heon;Yun, Dam-Hee;Cho, Chong-Kwan;Son, Chang-Gue
    • The Journal of Internal Korean Medicine
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    • v.26 no.4
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    • pp.820-827
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    • 2005
  • 연구목적: 본 연구는 Poloxamer-407로 유발시킨 고지혈증에 대한 청간탕의 효과를 알아보기 위해 수행되어졌다. 실험방법: Poloxamer-407로 쥐에 고지혈증을 유발시킨후 청간탕과 Lipidil을 경구 투여하여 혈청 cholesterol, 고밀도 지단백, 중성지질을 측정하였으며, 지질대사와 관련된 ACAT, DGAT, $CYP7{\alpha}H$, LDL receptor의 gene expression을 RT-PCR를 통해 비교 분석하였다. 실험결과: 청간탕 투여군은 혈청 콜레스테롤을 각각 32% 와 65% (p<0.05)로, 혈청 중성지방을 각각 21% 와 51% (p<0.05)로 감소시켰다. 또한, 청간탕은 LDL 수용체와 $CYP7{\alpha}H$ 유전자 발현을 증가시켰다. 결론: 이상의 연구로부터 우리는 청간탕이 지질의 흡수, 저장을 억제하고 콜레스테롤의 분비를 촉진함으로써 고지혈증에 일정한 효과가 있음을 알 수 있었다.

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Complete Recovery of Oxysterol 7α-Hydroxylase Deficiency by Living Donor Transplantation in a 4-Month-Old Infant: the First Korean Case Report and Literature Review

  • Hong, Jeana;Oh, Seak Hee;Yoo, Han-Wook;Nittono, Hiroshi;Kimura, Akihiko;Kim, Kyung Mo
    • Journal of Korean Medical Science
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    • v.33 no.51
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    • pp.324.1-324.6
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    • 2018
  • Oxysterol $7{\alpha}$-hydroxylase deficiency is a very rare liver disease categorized as inborn errors of bile acid synthesis, caused by CYP7B1 mutations. As it may cause rapid progression to end-stage liver disease even in early infancy, a high index of suspicion is required to prevent fatal outcomes. We describe the case of a 3-month-old boy with progressive cholestatic hepatitis and severe hepatic fibrosis. After excluding other etiologies for his early liver failure, we found that he had profuse urinary excretion of $3{\beta}$-monohydroxy-${\Delta}^5$-bile acid derivatives by gas chromatography/mass spectrometry analysis with dried urine spots on filter paper. He was confirmed to have a compound heterozygous mutation (p.Arg388Ter and p.Tyr469IlefsX5) of the CYP7B1 gene. After undergoing liver transplantation (LT) from his mother at 4 months of age, his deteriorated liver function completely normalized, and he had normal growth and development until the current follow-up at 33 months of age. We report the first Korean case of oxysterol $7{\alpha}$-hydroxylase deficiency in the youngest infant reported to undergo successful living donor LT to date.

Prescribing Patterns of Codeine among Children under Aged 12 in Korea (건강보험자료를 이용한 12세 미만 소아에서 코데인 처방양상평가)

  • Park, Hyo-Ju;Shin, Han-Na;Shin, Ju-Young
    • Korean Journal of Clinical Pharmacy
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    • v.25 no.4
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    • pp.273-279
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    • 2015
  • Objective: Codeine may result in death or respiratory depression in children, particularly who are rapid metabolizer of CYP2D6, therefore it should be used cautiously among children under 12 years of age. This study was to investigate the prescribing pattern of codeine among children according to the age group, prescribed diagnosis, type of medical service and medical specialties. Method: We used Korea Health Insurance Review and Assessment Service-National Patient Sample (HIRA-NPS) database. Study subjects included inpatients or outpatients, who were prescribed codeine between January, 1, 2011 and December, 31, 2011. Contraindicated use of codeine was defined as the use of codeine at least one times under aged 12. Age groups were subclassified according to the <2 years, 2-4 years, 5-8 years, and 9-11 years. Frequently prescribed diagnosis (ICD-10), type of medical service, and medical specialties were also described among codeine users under aged 12. Results: Codeine users were 6,411 inpatients (9,958 prescriptions), and 3,397 outpatients (6,258 prescriptions), respectively. Codeine prescription under 12 years of age were 2.1% (210 prescriptions) among inpatients, and 12.3% (776 prescriptions) among outpatients (p-value<0.05). Outpatient prescriptions of codeine under 12 aged were issued mostly from primary care clinics and frequent diagnosis were unspecified bronchopneumonia (51.6%), and vasomotor rhinitis (23.7%). Conclusion: This study found prescribing of codeine under 12 aged is common in outpatient and primary clinics. Nationwide and community-based efforts should be needed to reduce inappropriate prescribing among children.

Transcriptome sequencing revealed the inhibitory mechanism of ketoconazole on clinical Microsporum canis

  • Wang, Mingyang;Zhao, Yan;Cao, Lingfang;Luo, Silong;Ni, Binyan;Zhang, Yi;Chen, Zeliang
    • Journal of Veterinary Science
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    • v.22 no.1
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    • pp.4.1-4.13
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    • 2021
  • Background: Microsporum canis is a zoonotic disease that can cause dermatophytosis in animals and humans. Objectives: In clinical practice, ketoconazole (KTZ) and other imidazole drugs are commonly used to treat M. canis infection, but its molecular mechanism is not completely understood. The antifungal mechanism of KTZ needs to be studied in detail. Methods: In this study, one strain of fungi was isolated from a canine suffering with clinical dermatosis and confirmed as M. canis by morphological observation and sequencing analysis. The clinically isolated M. canis was treated with KTZ and transcriptome sequencing was performed to identify differentially expressed genes in M. canis exposed to KTZ compared with those unexposed thereto. Results: At half-inhibitory concentration (½MIC), compared with the control group, 453 genes were significantly up-regulated and 326 genes were significantly down-regulated (p < 0.05). Quantitative reverse transcription polymerase chain reaction analysis verified the transcriptome results of RNA sequencing. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the 3 pathways of RNA polymerase, steroid biosynthesis, and ribosome biogenesis in eukaryotes are closely related to the antifungal mechanism of KTZ. Conclusions: The results indicated that KTZ may change cell membrane permeability, destroy the cell wall, and inhibit mitosis and transcriptional regulation through CYP51, SQL, ERG6, ATM, ABCB1, SC, KER33, RPA1, and RNP genes in the 3 pathways. This study provides a new theoretical basis for the effective control of M. canis infection and the effect of KTZ on fungi.