• Title/Summary/Keyword: CYP3A1

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Experimental Study on the Effects of GamiSamgieum (SGMX) on Hyperlipidemia

  • Kim, Hun;An, Joung-Jo;Jo, Hyun-Kyung;Yoo, Ho-Rhyong;Seol, In-Chan;Kim, Yoon-Sik
    • The Journal of Korean Medicine
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    • v.30 no.3
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    • pp.86-97
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    • 2009
  • Objectives : This study was aimed to investigate the effects of GamiSamgieum (SGMX) on hyperlipidemia using an animal model. Additionally, the underlying mechanisms were investigated by determination of gene expressions related with lipid metabolism. Methods : Forty mice were selected for use in this experiment, and then divided into five groups; Naive, Induced, SGMX 100, SGMX 200, and Lovastatin group as positive control with 8 mice each, and their blood was collected for analysis of blood and serum parameters. Results : Administration of SGMX significantly inhibited the increase of liver weight and the macrovacuolar cytoplasmic alterations in histopathologic finding. SGMX administration significantly protected the liver from pathologic elevation of AST and ALT and from lipid peroxidation. SGMX administration significantly lowered total cholesterol levels and TG, and partially upregulated the gene expression of LCAT, CYP7A1 and LDL-R receptor. Conclusion : SGMX is suggested to possess hypolipidemic effect, and thus could be a potential candidate for herbal hypolipidemic via further studies.

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Toxicogenomic Analysis and Identification of Estrogen Responsive Genes of Di (n-ethylhexyl) Phthalate in MCF-7 Cells

  • Kim, Youn-Jung;Yun, Hye-Jung;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.1 no.3
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    • pp.149-156
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    • 2005
  • Di (n-ethylhexyl) phthalate (DEHP) is thought to mimic estrogens in their action, and are called endocrine disrupting chemicals. DEHP is used in numerous consumer products, especially those made of flexible polyvinyl chloride and have been reported to be weakly estrogenic. In this study, DEHP were tested for estrogenic properties in vitro models and with microarray analysis. First, the E-screen assay was used to measure the proliferation of DEHP in MCF-7 cells, a human breast cancer cell line. DEHP induced an increase in MCF-7 cell proliferation at concentration of $10^{-4}M$. Second, we carried out a microarray analysis of MCF-7 cells treated with DEHP using human c-DNA microarray including 401 endocrine system related genes. Of the genes analyzed, 60 genes were identified showing significant changes in gene expression resulting from DEHP. Especially, 4 genes were repressed and 4 genes were induced by DEHP compared to $17{\beta}-estradiol$. Among these genes, trefoil factor 3 (intestinal), breast cancer 1, early onset and CYP1B1 are involved in estrogen metabolism and regulation. Therefore it suggests that these genes may be associated with estrogenic effect of the DEHP on transcriptional level. The rationale is that, as gene expression is a sensitive endpoint, alterations of these genes may act as useful biomarkers to define more precisely the nature and level of exposure to kinds of phthalates.

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.

Combined application of rapamycin and atorvastatin improves lipid metabolism in apolipoprotein E-deficient mice with chronic kidney disease

  • Song, Eun Ju;Ahn, Sanghyun;Min, Seung-Kee;Ha, Jongwon;Oh, Goo Taeg
    • BMB Reports
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    • v.54 no.3
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    • pp.170-175
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    • 2021
  • Atherosclerosis arising from the pro-inflammatory conditions associated with chronic kidney disease (CKD) increases major cardiovascular morbidity and mortality. Rapamycin (RAPA) is known to inhibit atherosclerosis under CKD and non-CKD conditions, but it can cause dyslipidemia; thus, the co-application of lipid-lowering agents is recommended. Atorvastatin (ATV) has been widely used to reduce serum lipids levels, but its synergistic effect with RAPA in CKD remains unclear. Here, we analyzed the effect of their combined treatment on atherosclerosis stimulated by CKD in apolipoprotein E-deficient (ApoE-/-) mice. Oil Red O staining revealed that treatment with RAPA and RAPA+ ATV, but not ATV alone, significantly decreased the atherosclerotic lesions in the aorta and aortic sinus, compared to those seen in the control (CKD) group. The co-administration of RAPA and ATV improved the serum lipid profile and raised the expression levels of proteins involved in reverse cholesterol transport (LXRα, CYP7A1, ABCG1, PPARγ, ApoA1) in the liver. The CKD group showed increased levels of various genes encoding atherosclerosispromoting cytokines in the spleen (Tnf-α, Il-6 and Il-1β) and aorta (Tnf-α and Il-4), and these increases were attenuated by RAPA treatment. ATV and RAPA+ATV decreased the levels of Tnf-α and Il-1β in the spleen, but not in the aorta. Together, these results indicate that, in CKD-induced ApoE-/- mice, RAPA significantly reduces the development of atherosclerosis by regulating the expression of inflammatory cytokines and the co-application of ATV improves lipid metabolism.

Therapeutic effect of Ferula assa-foetida oleo-gum resin in rats with letrozole-induced polycystic ovary syndrome

  • Amir Shieh;Seyyed Majid Bagheri;Maryam Yadegari;Davoud Javidmehr;Zeinab Farhadi
    • Clinical and Experimental Reproductive Medicine
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    • v.49 no.4
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    • pp.239-247
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    • 2022
  • Objective: Asafoetida is a gum derived from Ferula assa-foetida, which is used in traditional Iranian medicine to treat some reproductive system disorders. The effects of asafoetida on ovarian tissue, expression of certain genes associated with polycystic ovary syndrome (PCOS), and levels of liver, kidney, and blood cell factors after treatment in a rat model were investigated. Methods: Thirty rats were divided into five groups: normal, polycystic, and treatment with three doses of asafoetida (12.5, 25, and 50 mg/kg for 3 weeks after PCOS induction). PCOS was induced by letrozole at a dose of 1 mg/kg administered orally for 3 weeks. Blood samples were taken, and the ovaries were removed and prepared for histomorphometric examination. Liver and kidney parameters were measured. The mRNA expression levels of luteinizing hormone receptor, CYP11A1, adenosine monophosphate-activated protein kinase, adiponectin, and adiponectin receptors 1 and 2 were also measured by real-time polymerase chain reaction. Results: The levels of liver, kidney, and blood parameters did not significantly differ between the treatment groups and the control group. At doses of 25 and 50 mg/kg, ovarian histopathology, especially the thicknesses of the theca and granulosa layers, was significantly improved relative to the PCOS group. The expression of target genes also improved in the 25 and 50 mg/kg treatment groups. Conclusion: Asafoetida can be used to treat PCOS as a complementary approach to conventional therapies. Asafoetida appears to act by regulating and activating metabolic and ovarian cycle enzymes.

Discovery of a Novel 2,6-Difunctionalized 2H-Benzopyran Inhibitors Toward Sphingosylphosphorylcholine Synthetic Pathway as New Anti-inflammatory Target

  • Lee, Gee-Hyung;Lee, Seong Jin;Jeong, Dae Young;Kim, Ha-Young;Lee, Doohyun;Lee, Taeho;Hwang, Jong-Yeon;Park, Woo Kyu;Kong, Jae-Yang;Cho, Heeyeong;Gong, Young-Dae
    • Bulletin of the Korean Chemical Society
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    • v.35 no.8
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    • pp.2385-2390
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    • 2014
  • Novel 2,6-difuctionalized 2H-benzopyrans were synthesized and evaluated for a sphingosylphosphorylcholine(SPC) inhibitor. The synthetic 2H-benzopyrans 1c and 3a showed high potency in SPC-induced cell proliferation assay ($IC_{50}$ < 20 nM). Neither hERG $K^+$ channel binding (> $10{\mu}M$) nor CYP inhibitions (> $10{\mu}M$) were observed. Also, the simple structure-activity relationship (SAR) results were obtained from analysis of 2H-benzopyran derivatives 1-3 and the anti-SPC effect of 2H-benzopyran 1c was confirmed by a HUVEC tube formation assay.

One-year experience of oral substrate reduction therapy in three patients with Gaucher disease type I

  • Sohn, Young Bae;Kim, Yewon;Moon, Ji Eun
    • Journal of Genetic Medicine
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    • v.17 no.2
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    • pp.62-67
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    • 2020
  • Purpose: Eliglustat is an oral substrate reduction therapy (SRT) approved for adults with Gaucher disease type I (GD1) who are extensive, intermediate, or poor CYP2D6 metabolizers. Here we report one-year experience of eliglustat switch therapy from long-term enzyme replacement therapy (ERT) in three adult patients with GD1. Materials and Methods: Medical history, clinical (hemoglobin concentration, platelet count, and bone mineral density) and biochemical parameters (angiotensin converting enzyme, total acid phosphatase, and lyso-gb1) of the patients were collected and evaluated by retrospective review of medical records at every 3, 6, or 12 month after switch to SRT. Results: Patient 1 was a 43-year old female diagnosed GD1 and her clinical and biochemical parameters were stabilized for more than 20 years by ERT. Due to the burden of regular hospital visit, she switched to SRT. During one-year of SRT, clinical parameters and biomarkers were maintained stable. However, after suffering acute febrile illness during SRT, she decided to re-switch to ERT due to concerns about drug interaction. Patient 2 was 41-year old male, younger brother of patient 1 and Patient 3 was 31-year old male. They switched to SRT in clinically stable condition with long-term ERT. The one-year SRT was tolerable without specific safety issue and the clinical parameters were maintained stable. Conclusion: One-year eliglustat therapy in three adult patients with GDI was generally tolerable and effective for maintaining the clinical parameters and biomarkers. However, the drug compliance, concurrent drug interactions, and long-term safety of eliglustat should be carefully monitored.

Association Analysis of the Essential Hypertension Susceptibility Genes in Adolescents: Kangwha Study (청소년 고혈압 관련 유전자의 연관성 분석: Kangwha Study)

  • Suh, Il;Nam, Chung-Mo;Kim, Sung-Joo;Shin, Dong-Jik;Hur, Nam-Wook;Kang, Dae-Ryong
    • Journal of Preventive Medicine and Public Health
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    • v.39 no.2
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    • pp.177-183
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    • 2006
  • Objectives : In this study we examined the association between the genetic markers ACE (A-240T, C-93T, I/D, A2350G), AGT (M235T), AT1R (A1166C), CYP11B2 (T344C, V386A), REN (G2646A), ADRB2 (G46A, C79G, T47C, T1641), GNB3 (C825T) and ADD1 (G460W) and the presence of essential hypertension in adolescents. Methods : The Kangwha Study is an 18-year prospective study that is aimed at elucidating the determinants of the blood pressure level from childhood to early adulthood. For this study, we constructed a case-control dataset of size of 277 and 40 family trios data from the Kangwha Study. For this purpose, we perform a single locus-based case-control association study and a single locus-based TDT (transmission/disequilibrium test) study. Results : In the case-control study, the single locus-based association study indicated that the ADD1 (G460W) (p=0.0403), AGT (M235T) (p=0.0002), and REN (G2646A) (p=0.0101) markers were significantly associated with the risk of hypertension. These results were not confirmed on the TDT study. This study showed that genetic polymorphisms of the ADD1, AGT and REN genes might be related to the hypertension in Korean adolescents. Conclusions : This study provided useful information on genetics markers related to blood pressure. Further study will be needed to confirm the effect of the alpha adducin gene, the angiotensinogen gene and the renin gene on essential hypertension.

CASE REPORTS OF TREATMENT OF ERUPTION-DISTURBED MX. FIRST MOLAR BY SURGICAL EXPOSURE (맹출 장애를 가진 상악 제1대구치의 외과적 노출을 이용한 치험례)

  • Seok, Choong-Ki;Nam, Dong-Woo;Kim, Hyun-Jung;Kim, Young-Jin;Nam, Soon-Hyeun
    • Journal of the korean academy of Pediatric Dentistry
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    • v.31 no.1
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    • pp.11-18
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    • 2004
  • The eruption of permanent teeth represents the movement in the alveolar bone before appearance in oral cavity, to the occlusal plane after appearance in oral cavity, and additive movement after reaching th the occlusal plane. Tooth eruption is mostly controlled by genetic signals. The eruption stage is divided to preeruptive alveolar stage, alveolar bone stage, mucosal stage according to the process of growth and development. If the disturbance is occured in any stage of eruption, tooth does not erupt. The cause of eruption disturbance are ectopic position of the tooth germ, obstruction of the eruption path and defects in the follicle or PDL. In the treatment of eruption disturbance, surgical procedures are commonly used. There are three kind of surgical procedure ; surgical exposure, surgical repositioning, surgical exposure and traction Surgical exposure is basic procedure. This involves removal of mucosa, bone, lesion that are surrounding the teeth, dental sac when necessary to maintain a patent channel between the crown and the normal eruptive path into the oral cavity. To ensure this patency, many techniques including cementation of a celluloid crown, packing with gutta-percha or zinc oxide-eugenol, or a surgical pack, are used. When surgical exposure is conducted, operators should not expose any part of cervical root cement and not injure periodontium or root of adjunct tooth. After surgical exposure, tooth should be surrounded by keratinized gingiva. There is direct relationship between the extent of development of pathophysiologic aberrations and the intensity of the manipulative injury inflicted on the tooth by surgical treatment, so operator should consider this thing. In these cases, surgical exposure is conducted on Maxillary 1st milars that have a eruption disturbance and improve the eruption disturbance effectively.

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INHIBITORY EFFECT OF Er:YAG LASER ON THE GROWTH OF STREPTOCOCCUS MUTANS (Er:YAG 레이저 조사가 Streptococcus mutans의 증식억제에 미치는 효과)

  • Song, Gwang-Chul;Lee, Chang-Seop;Lee, Sang-Ho;Lee, Nan-Young
    • Journal of the korean academy of Pediatric Dentistry
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    • v.30 no.1
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    • pp.15-24
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    • 2003
  • The purpose of this study is to investigate the sterilization effect of Er:YAG laser against the intraoral acid producing bacterium, S. mutans, by irradiating the culture solution containing S. mutans KCTC 3065 with Er:YAG laser having a $650{\mu}m$ diameter beam through the non-contact method. We obtained the following results after examining the temperature changes of the culture solution, numbers of bacterial colonies, and acid-producing ability and attaching ability on teeth by measuring the amount of extracellular polysaccharide produced by S. mutans. The number of bacterial colony was decreased in $10{\mu}l$ culture solution irradiated with laser in overall compared to the control solution. The number decreased as the irradiation intensity and pulse repetition rate were larger and as the exposure time was increased. However, it did not change significantly in $100{\mu}l$ culture solution compared to the control solution. Although the acid-producing ability of S. mutans was inhibited for a certain duration after laser irradiation in 10r1 bacterial culture solution, it did not change in $100{\mu}m$ solution compared with the control solution. The amount of extracellular polysaccharide synthesized by S. mutans was partially decreased through laser irradiation in $10{\mu}m$ culture solution but did not change in $100{\mu}m$ culture solution. Based on these findings, we concluded that Er:YAG laser has an sterilization effect on S. mutans in which we presume that the mechanism is through the heat effect rather than the mechanical effect from development of ultrasound.

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