• The Journal of Korean Medicine
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• v.42 no.4
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• pp.10-24
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• 2021

Objectives: Yongdamsagan-tang (YST) and Paljung-san (PJS) in traditional medicine and finasteride in modern medicine are used to treat benign prostatic hyperplasia (BPH). In recent, the use of combination herbal remedies with conventional drugs has been increasing. Therefore, we investigated the anti-inflammatory effects of these drugs to treat BPH and the influence of herbal formulas on finasteride metabolism. Methods: The inhibitory effects of the herbal formulas and finasteride on the production of inflammatory mediators and cytokines were determined in lipopolysaccharide (LPS)-treated RAW 264.7 cells. Additionally, the influence of herbal formulas on activities of human drug metabolizing enzymes (DMEs) was assessed using human microsomal enzymes. Results: We observed that YST, PJS and finasteride inhibited the production of nitric oxide (NO), prostaglandin E₂ (PGE₂) and interleukin-6 (IL-6) in RAW 264.7 cells. The half maximal inhibitory concentration (IC₅₀) of YST on PGE₂ production was calculated to be below 25 ㎍/mL. YST inhibited the activity of uridine diphosphate-glucuronosyltransterase (UGT) 1A4 with an IC₅₀ value of 49.35 ㎍/mL. The activities of cytochrome P450 (CYP) 1A2, CYP2B6, CYP2C19, CYP3A4, and UGT1A1 were inhibited by PJS (IC₅₀ < 100 ㎍/mL, each). Although PJS and YST inhibited the activities of CYP3A4 and UGT1A4, respectively, these formulas may not influence the metabolism of finasteride because the IC₅₀ values of herbal formulas on DMEs are too high to affect metabolism. Conclusions: Our results suggest that the combination of finasteride and YST or PJS might not influence their drug metabolism and that the drugs may have synergistic effects against BPH.

• Journal of Preventive Medicine and Public Health
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• v.36 no.2
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• pp.93-100
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• 2003

Objectives : Because shipyard workers are involved with various manufacturing process, they are exposed to many kinds of hazardous materials. Welders especially, are exposed to bisphenol-A (BPA) during the welding and flame cutting of coated steel, This study was conducted to assess the exposure status of the endocrine disrupter based on the job-exposure matrix. The effects of the genetic polymorphism of xenobiotic enzyme metabolisms involved in the metabolism of BPA on the levels of urinary metabolite were investigated. Methods : The study population was recruited from a shipyard company in the f province. A total of 84 shipbuilding workers 47 and 37 in the exposed and control groups, respectively, were recruited for this study. The questionnaire variables included, age, sex, use of personal protective equipment, smoking, drinking and work duration. The urinary metabolite was collected in the afternoon and correction made for the urinary creatinine concentration. The of the CYP1A1, CYP2E1 and UGT1A6 genotypes were investigated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods with the DNA extracted from venous blood. Results : The urinary BPA level in the welders group was significantly higher than in the control group (p<0.05). The urinary BPA concentration with the wild type UGT1A6 was higher than the other UGT1A6 genotypes, but with no statistical significant. From themultiple regression analysis of the urinary BPA, the regression coefficient for job grade was statistically significant (p<0.05). Conclusions : The grade of exposure to BPA affected the urinary BPA concentration was statistically significant. However, the genetic polymorphisms of xenobiotics enzyme metabolism were not statistically significant. Further investigation of the genetic polymorphisms with a larger sample size is needed.

• Journal of Ginseng Research
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• v.44 no.6
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• pp.757-769
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• 2020

Background: Panax quinquefolius and Panax notoginseng are widely used and well known for their pharmacological effects. As main pharmacological components, saponins have different distribution patterns in the root tissues of Panax plants. Methods: In this study, the representative ginsenosides were detected and quantified by desorption electrospray ionization mass spectrometry and high-performance liquid chromatography analysis to demonstrate saponin distribution in the root tissues of P. quinquefolius and P. notoginseng, and saponin metabolite profiles were analyzed by metabolomes to obtain the biomarkers of different root tissues. Finally, the transcriptome analysis was performed to demonstrate the molecular mechanisms of saponin distribution by gene profiles. Results: There was saponin distribution in the root tissues differed between P. quinquefolius and P. notoginseng. Eight-eight and 24 potential biomarkers were detected by metabolome analysis, and a total of 340 and 122 transcripts involved in saponin synthesis that were positively correlated with the saponin contents (R > 0.6, P < 0.05) in the root tissues of P. quinquefolius and P. notoginseng, respectively. Among them, GDPS1, CYP51, CYP64, and UGT11 were significantly correlated with the contents of Rg1, Re, Rc, Rb2, and Rd in P. quinquefolius. UGT255 was markedly related to the content of R1; CYP74, CYP89, CYP100, CYP103, CYP109, and UGT190 were markedly correlated with the Rd content in P. notoginseng.

• Journal of fish pathology
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• v.36 no.2
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• pp.337-348
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• 2023

This study was undertaken to evaluate the effect of amprolium hydrochloride on detoxification process of olive flounder Paralichthys olivaceus. A series of two experiment was performed based on the LD₅₀ value obtained for amprolium. First, thirty flounder (average weight 230.27 g; average length 27.99 cm) was randomly allocated into five groups. Treatment was carried out using intra-muscular injection of amprolium at the dose levels of 4, 8, 16, and 32 mg/kg body weight. At 8, 24 and 48 h post injection, liver and kidney were collected for expression assay of drug metabolizing enzymes and pro-inflammatory cytokine genes. We found that the interleukin-1β (IL-1β) mRNA level were induced at 32 mg/kg and CYP1A genes showed the opposite pattern, while UDP-glucuronosyl-transferase (UGT1A7) and GST were significantly reduced in the liver. Moreover, the suppression of drug metabolizing enzymes and cytokine gene in the kidney was observed after treatment. Another treatment was carried out using intramuscular injection with 4, 8, 16, and 32 mg/kg and 60, 80, 100, 120 mg/kg body weight. At 6 days post injection, liver was collected. The IL-1β expression was markedly induced in the experimental group treated with 4 mg/kg. In addition, glutathione S-transferase (GST) mRNA level was higher in the group with 4 mg/kg. In conclusion, our data suggests that amprolium seem to cause direct or indirect physical, or biological toxicity of flounders, although this drug is considered one of the safest synthetic anticoccidial drugs of the livestock industry.

• Journal of Ginseng Research
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• v.43 no.1
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• pp.116-124
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• 2019

Background: Ginsenosides are known as the principal pharmacological active constituents in Panax medicinal plants such as Asian ginseng, American ginseng, and Notoginseng. Some ginsenosides, especially the 20(R) isomers, are found in trace amounts in natural sources and are difficult to chemically synthesize. The present study provides an approach to produce such trace ginsenosides applying biotransformation through Escherichia coli modified with relevant genes. Methods: Seven uridine diphosphate glycosyltransferase (UGT) genes originating from Panax notoginseng, Medicago sativa, and Bacillus subtilis were synthesized or cloned and constructed into pETM6, an ePathBrick vector, which were then introduced into E. coli BL21star (DE3) separately. 20(R)-Protopanaxadiol (PPD), 20(R)-protopanaxatriol (PPT), and 20(R)-type ginsenosides were used as substrates for biotransformation with recombinant E. coli modified with those UGT genes. Results: E. coli engineered with $GT95^{syn}$ selectively transfers a glucose moiety to the C20 hydroxyl of 20(R)-PPD and 20(R)-PPT to produce 20(R)-CK and 20(R)-F1, respectively. GTK1- and GTC1-modified E. coli glycosylated the C3-OH of 20(R)-PPD to form 20(R)-Rh2. Moreover, E. coli containing $p2GT95^{syn}K1$, a recreated two-step glycosylation pathway via the ePathBrich, implemented the successive glycosylation at C20-OH and C3-OH of 20(R)-PPD and yielded 20(R)-F2 in the biotransformation broth. Conclusion: This study demonstrates that rare 20(R)-ginsenosides can be produced through E. coli engineered with UTG genes.

• Toxicological Research
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• v.17
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• pp.299-304
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• 2001

Xenobiotics and their reactive intermediates bind to cellular macromolecules and/or generate oxidative stress. which provoke deleterious effects on the cell function. Induction of xenobiotic-biotrans-forming enzymes and antioxidant molecules is an important defense mechanism against such insults. A group of genes involved in the defense mechanism. e.g. genes encoding glutathione S-transferases. NAD(P)H: quinone oxidoreductase, UDP-glucuronosyltransferase (UDP-GT) and ${\gamma}$-glutamylcysteine synthetase (GGCS). have a common regulatory sequence, Antioxidant or Electrophile Responsive Element (ARE/EpRE). Recently. Nrf2. discovered as a homologue of erythroid transcription factor p45 NF-E2, was shown to bind ARE/EpRE and induce the expression of these defense genes. Mice that lack Nrf2 show low basal levels of expression and/or impaired induction of these genes. which makes the animals highly sensitive to xenobiotic toxicity. Indeed. we show here that nrf2-deficient mice had a higher mortality than did the wild-type mice when exposed to acetaminophen (APAP). Detailed analyses of APAP hepatotoxicity in the nrf2 knockout mice indicate that a large amount of reactive APAP metabolites was generated in the livers due to the impaired basal expression of two detoxifying enzyme genes, UDP-GT (Ugt1a6) and GGCS. while the cytochrome P450 content was unchanged. Thus. the studies using the nrf2 knockout mice clearly demonstrate significance of the expression of Nrf2-regulated enzymes in protection against xenobiotic toxicity.

• Journal of Plant Biotechnology
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• v.42 no.3
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• pp.245-256
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• 2015

In the agricultural industries, LEDs are used as supplementary, as well as main lighting sources in closed cultivation systems. In cultivation using artificial light sources, various light qualities have been tried to supplement fluorescent lamps to promote plant growth and metabolism. Microarray analysis of Brassica rapa seedlings under blue and fluorescent mixed with blue light conditions identified changes in three genes of the glucosinolate pathway. This attracted attention as functional materials highly expressed 3.6-4.6 fold under latter condition. We selected four more genes of the glucosinolate pathway from the Brassica database and tested their expression changes under fluorescent light mixed with red, green, and blue, respectively. Some genes increased expression under red and blue mixed conditions. The Bra026058, Bra015379, and Bra021429; the orthologous genes of CYP79F1, ST5a, and FMOGS-OX1 in Arabidopsis, are highly expressed in Brassica rapa under fluorescent mixed with blue light conditions. Further, Bra029355, Bra034180, Bra024634, and Bra022448; the orthologous genes of MAM1, AOP3, UGT74B1, and BCAT4 in Arabidopsis, are highly expressed in Brassica rapa under fluorescent mixed with red light conditions. The various light conditions had unique effects on the varieties of Brassica, resulting in differences in glucosinolate synthesis. However, in some varieties, glucosinolate synthesis increased under mixed blue light conditions. These results will help to construct artificial light facilities, which increase functional crops production.

• Toxicological Research
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• v.31 no.2
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• pp.173-180
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• 2015

Extract from Gryllus bimaculatus crickets inhibits oxidation at the DNA level, with reduced production of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Microarray analyses were performed with a rat 28K cDNA clone set array to identify the gene expression profiles of aged (10 months old) Wistar Kyoto rats treated for one month with 100 mg/kg G. bimaculatus ethanol extract to assess the effects. The extract produced a meaningful anti-edema effect, evident by the inhibition of creatinine phosphokinase activity. The weights of abdominal and ovarian adipose tissues were reduced and the proportion of unsaturated fatty acids in adipose tissues was increased in an extract dose-dependent manner. Compared with untreated control rats, rats treated with the extract displayed the upregulation of 1053 genes including Fas (tumor necrosis factor receptor superfamily, member 6), Amigo3 (adhesion molecule with an immunoglobulin-like domain), Reticulon 4, 3-hydroxy-3-methylglutaryl-coenzyme (Hmgcr; a reductase), related anti-fatigue (enzyme metabolism), and Rtn antioxidant, and the downregulation of 73 genes including Ugt2b (UDP glycosyltransferase 2 family), Early growth response 1, and Glycoprotein m6a. Data suggest that G. bimaculatus extract may have value in lessening the effects of aging, resulting in a differential gene expression pattern indicative of a marked stress response and lower expression of metabolic and biosynthetic genes.

• The Plant Pathology Journal
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• v.36 no.6
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• pp.558-569
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• 2020

Fusarium head blight (FHB) is a devastating fungal disease of wheat (Triticum aestivum L.). The lack of genetic resources with stable FHB resistance combined with a reliable and rapid screening method to evaluate FHB resistance is a major limitation to the development of FHB resistant wheat germplasm. The present study utilized an immature wheat spike culture method to screen wheat spike culture derived variants (SCDV) for FHB resistance. Mycotoxin concentrations determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) correlated significantly (P < 0.01) with FHB severity and disease progression during in vitro spike culture. Selected SCDV lines assessed for FHB resistance in a Fusarium field disease nursery in Carman, Manitoba, Canada in 2016 showed significant (P < 0.01) correlation of disease severity to the in vitro spike culture screening method. Selected resistant SCDV lines were also crossed with an elite cv. CDC Hughes and the progeny of F₂ and BC₁F₂ were screened by high resolution melt curve (HRM) analyses for the wheat UDP-glucosyl transferase gene (TaUGT-3B) single nucleotide polymorphism to identify resistant (T-allele) and susceptible (G-allele) markers. The progeny from the crosses were also screened for FHB severity using the immature spike culture method and identified resistant progeny grouped according to the HRM genotyping data. The results demonstrate a reliable approach using the immature spike culture to screen for FHB resistance in progeny of crosses in early stage of breeding programs.

• 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.