• YAKHAK HOEJI
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• v.46 no.3
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• pp.179-184
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• 2002

The abuse of dextromethorphan has been prevalent for 15 years in Korea and its fatal cases were reported even though it has proved to be very safe. In this study, to investigate the safety and tolerance assessment of dextromethorphan, the metabolic phenotyping and genotype of dextromethorphan were studied. After a single 30 mg of dextromethorphan oral administration to 74 volunteers, concentration of dextromethorphan and its metabolites, dextrorphan, hydroxymorphinan and methoxymorphinan were measured in urine which collected during 8hrs after the drug administration. CYP2D6 phenotype was determined from the ratio of dextromethorphan to dextrorphan. GC/MS was used to quantify dextromethorphan and its metabolites. For genotyping, mutant alleles of the CYP2D6 gene were identified. 24 subjects (32.4％) were homozygous for CYP2D6＊10B, 29 subjects (39.2％) were heterozygous for this allele, while in 21 subjects (28.4％) no exon 1 mutation could be found. The frequency of CYP2D6＊10B-allele containing the 188C T mutation was 54％ of total subjects studied.

• Journal of Plant Biotechnology
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• v.48 no.3
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• pp.139-147
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• 2021

Since whole-genome duplication (WGD) of diploid Chrysanthemum nankingense and de novo assembly whole-genome of C. seticuspe have been obtained, they have afforded to perceive the diversity evolution and gene discovery in the improved investigation of chrysanthemum breeding. The robust tools of high-throughput identification and analysis of gene function and expression produce their vast importance in chrysanthemum genomics. However, the gigantic genome size and heterozygosity are also mentioned as the major obstacles preventing the chrysanthemum breeding practices and functional genomics analysis. Nonetheless, some of technological contemporaries provide scientific efficient and promising solutions to diminish the drawbacks and investigate the high proficient methods for generous phenotyping data obtaining and system progress in future perspectives. This review provides valuable strategies for a broad overview about the high-throughput identification, and molecular analysis of gene function and expression in chrysanthemum. We also contribute the efficient proposition about specific protocols for considering chrysanthemum genes. In further perspective, the proper high-throughput identification will continue to advance rapidly and advertise the next generation in chrysanthemum breeding.

• BMB Reports
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• v.55 no.12
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• pp.633-638
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• 2022

Liver regeneration is a well-known systemic homeostatic phenomenon. The N⁶-methyladenosine (m⁶A) modification pathway has been associated with liver regeneration and hepatocellular carcinoma. m⁶A methyltransferases, such as methyltransferase 3 (METTL3) and methyltransferase 14 (METTL14), are involved in the hepatocyte-specific-regenerative pathway. To illustrate the role of METTL14, secreted from non-parenchymal liver cells, in the initiation phase of liver regeneration, we performed 70% partial hepatectomy (PH) in Mettl14 heterozygous (HET) and wild-type (WT) mice. Next, we analyzed the ratio of liver weight to body weight and the expression of mitogenic stimulators derived from non-parenchymal liver cells. Furthermore, we evaluated the expression of cell cycle-related genes and the hepatocyte proliferation rate via MKI67-immunostaining. During regeneration after PH, the weight ratio was lower in Mettl14 HET mice compared to WT mice. The expressions of hepatocyte growth factor (HGF) and tumor necrosis factor (TNF)-α, mitogens derived from non-parenchymal liver cells that stimulate the cell cycle, as well as the expressions of cyclin B1 and D1, which regulate the cell cycle, and the number of MKI67-positive cells, which indicate proliferative hepatocyte in the late G1-M phase, were significantly reduced in Mettl14 HET mice 72 h after PH. Our findings demonstrate that global Mettl14 mutation may interrupt the homeostasis of liver regeneration after an acute injury like PH by restraining certain mitogens, such as HGF and TNF-α, derived from sinusoidal endothelial cells, stellate cells, and Kupffer cells. These results provide new insights into the role of METTL14 in the clinical treatment strategies of liver disease.

• Proceedings of the Korean Society of Crop Science Conference
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• 2017.10a
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• pp.15-15
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• 2017

• Proceedings of the PSK Conference
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• 2000.04a
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• pp.130.2-131
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• 2000

• 대한임상약리학회:학술대회논문집
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• 1996.12a
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• pp.32-32
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• 1996

• BMB Reports
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• v.52 no.4
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• pp.289-294
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• 2019

The present study evaluated the role of AHNAK in Bartonella henselae infection. Mice were intraperitoneally inoculated with $2{\times}10^8$ colony-forming units of B. henselae Houston-1 on day 0 and subsequently on day 10. Blood and tissue samples of the mice were collected 8 days after the final B. henselae injection. B. henselae infection in the liver of Ahnak-knockout and wild-type mice was confirmed by performing polymerase chain reaction, with Bartonella adhesion A as a marker. The proportion of B. henselae-infected cells increased in the liver of the Ahnak-knockout mice. Granulomatous lesions, inflammatory cytokine levels, and liver enzyme levels were also higher in the liver of the Ahnak-knockout mice than in the liver of the wild-type mice, indicating that Ahnak deletion accelerated B. henselae infection. The proportion of CD4+interferon-${\gamma}$ ($IFN-{\gamma}^+$) and $CD4^+$ interleukin $(IL)-4^+$ cells was significantly lower in the B. henselae-infected Ahnak-knockout mice than in the B. henselae-infected wild-type mice. In vitro stimulation with B. henselae significantly increased $IFN-{\gamma}$ and IL-4 secretion in the splenocytes obtained from the B. henselae-infected wild-type mice, but did not increase $IFN-{\gamma}$ and IL-4 secretion in the splenocytes obtained from the B. henselae-infected Ahnak-KO mice. In contrast, $IL-1{\alpha}$, $IL-1{\beta}$, IL-6, IL-10, RANTES, and tumor necrosis $factor-{\alpha}$ secretion was significantly elevated in the splenocytes obtained from both B. henselae-infected wild-type and Ahnak-knockout mice. These results indicate that Ahnak deletion promotes B. henselae infection. Impaired $IFN-{\gamma}$ and IL-4 secretion in the Ahnak-knockout mice suggests the impairment of Th1 and Th2 immunity in these mice.

• 대한임상약리학회:학술대회논문집
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• 1994.12a
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• pp.28-28
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• 1994

• Proceedings of the Korean Society of Crop Science Conference
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• 2021.10a
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• pp.179-179
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• 2021

• Toxicological Research
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• v.17
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• pp.127-133
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• 2001

Together with cytochrome P450 (CYP), flavin-containing monooxygenase (FMO) present in liver microsomes oxidizes various endogenous and exogenous chemicals. In an effort to determine the human FMO activity, we have developed two non-invasive urine analysis methods using caffeine (CA) and ranitidine (RA) as the probe compounds. As the production of theobromine (TB) and ranitidine N-oxide (RANO) from CA and RA is catalyzed primarily by the hepatic FMO, we have assigned the urinary molar ratios of TB/CA and RA/RANO as the in vivo FMO activity. In 200 age-matched Korean volunteers, the obtained TB/CA ratio ranged from 0.4 to 15.2 (38-fold difference) and the RA/RANO ratio from 5.7 to 27.2 (4.8-fold). The FMO activity of 20's, determined by caffeine metabolism, was the highest (2.5$\pm$l.9) and those of 30's, 40's, 50's, 60's and 70's were 40%, 50%, 24%, 39% and 36% of the 20's, respectively. Intake of grapefruit juice, known to contain flavonoids, inhibited the in vivo FMO (TB/CA) activity by 79%. Addition of the flavonoids like naringin, quercitrin and kaempferol, present in grapefruit juice, to the in vitro microso-mal FMO assay, thiobenzamide S-oxidation, produced 75%, 70% and 60% inhibition, respectively. Obtained Ki values of quercitrin, kaempferol and naringin on the in vitro FMO activity were 6.2, 12.0 and 13.9 $\mu\textrm{M}$, respectively. This suggested that the dose of drug should need to be adjusted to suit the individual FMO activities when the drugs metabolized by FMO are given to patients. As the intake of grapefruit juice has been identified to inhibit the FMO as well as CYP3A4 and lA2 activities, patients taking drugs metabolized by these enzymes should not drink grapefruit juice as the carrier.