• Korean Circulation Journal
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• 제48권11호
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• pp.951-963
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• 2018

HMG-CoA reductase inhibitors, i.e. statins, are effective in reducing cardiovascular disease events but also in cardiac-related and overall mortality. Statins are in general well-tolerated, but currently the concerns are raised if statins may increase the risk of new-onset diabetes mellitus (NOD). In this review, the possible effects of statins on organs/tissues being involved in glucose metabolism, i.e. liver, pancreas, adipose tissue, and muscles, had been discussed. The net outcome seems to be inconsistent and often contradictory, which may be largely affected by in vitro experimental settings or/and in vivo animal conditions. The majority of studies point out statin-induced changes of regulations of isoprenoid metabolites and cellassociated cholesterol contents as predisposing factors related to the statin-induced NOD. On the other hand, it should be considered that dysfunctions of isoprenoid pathway and mitochondrial ATP production and the cholesterol homeostasis are already developed under (pre)diabetic and hypercholesterolemic conditions. In order to connect the basic findings with the clinical manifestation more clearly, further research efforts are needed.

• Reproductive and Developmental Biology
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• 제41권1호
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• pp.17-23
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• 2017

The oocyte undergoes various events during in vitro maturation (IVM) and subsequence development. One of the events is production of reactive oxygen species (ROS) that is a normal process of cell metabolism. But imbalances between ROS production and antioxidant systems induce oxidative stress that negatively affect to mammalian reproductive process. In vitro environments, in vitro matured oocytes have many problems, such as excessive production of ROS and imperfect cytoplasmic maturation. Therefore, in vitro matured oocytes still have lower maturation rates and developmental competence than in vivo matured oocytes. In order to improve the IVM and in vitro culture (IVC) system, antioxidants, vitamins were added to the IVM, IVC medium. Antioxidant supplementation was effective in controlling the production of ROS and it continues to be explored as a potential strategy to overcome mammalian reproductive disorders. Based on these studies, we expect that the use of antioxidants in porcine oocytes could improved maturation and development rates.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.214.2-214.2
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• 2003

Eupatilin (5,7-dihydroxy-3",4",6-trimethoxyflavone) is an active ingredient of an ethanol extract of Artemisia asiatica (DA-9601) that is used in the treatment of gastritis. In vitro and in vivo metabolism of eupatilin in the rats has been studied by LC- electrospray mass spectrometry. Rat liver microsomal incubation of eupatilin in the presence of NADPH and UDPGA resulted in the formation of four metabolites (M1-M4). M1, M2, M3 and M4 were tentatively identified as 3"- or- 4"-O-demethyl-eupatilin glucuronide, eupatilin glucuronide, 6-O-demethyleupatilin and 3"-or 4"-O-demethyl- eupatilin glucuronide, eupatilin glucuronide, 6-O-demethyleupatilin and 3"-or 4"-O- demethyl-eupatilin glucuronide, eupatilin glucuronide, 6-O demethyleupatilin and 3"-or 4"-O-demethyl-eupatilin glucuronide, respectively. (omitted)

• Journal of Microbiology and Biotechnology
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• 제34권4호
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• pp.795-803
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• 2024

Microorganisms usually coexist as a multifaceted polymicrobial community in the natural habitats and at mucosal sites of the human body. Two opportunistic human pathogens, Pseudomonas aeruginosa and Staphylococcus aureus commonly coexist in the bacterial infections for hospitalized and/or immunocompromised patients. Here, we observed that autolysis of the P. aeruginosa quorum-sensing (QS) mutant (lasRmvfR) was suppressed by the presence of the S. aureus cells in vitro. The QS mutant still displayed killing against S. aureus cells, suggesting the link between the S. aureus-killing activity and the autolysis suppression. Independent screens of the P. aeruginosa transposon mutants defective in the S. aureus-killing and the S. aureus transposon mutants devoid of the autolysis suppression revealed the genetic link between both phenotypes, suggesting that the iron-dependent metabolism involving S. aureus exoproteins might be central to both phenotypes. The autolysis was suppressed by iron treatment as well. These results suggest that the interaction between P. aeruginosa and S. aureus might be governed by mechanisms that necessitate the QS circuitry as well as the metabolism involving the extracellular iron resources during the polymicrobial infections in the human airway.

• Molecules and Cells
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• 제40권2호
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• pp.123-132
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• 2017

Insulin signaling is coordinated by insulin receptor substrates (IRSs). Many insulin responses, especially for blood glucose metabolism, are mediated primarily through Irs-1 and Irs-2. Irs-1 knockout mice show growth retardation and insulin signaling defects, which can be compensated by other IRSs in vivo; however, the underlying mechanism is not clear. Here, we presented an Irs-1 truncated mutated mouse ($Irs-1^{-/-}$) with growth retardation and subcutaneous adipocyte atrophy. $Irs-1^{-/-}$ mice exhibited mild insulin resistance, as demonstrated by the insulin tolerance test. Phosphatidylinositol 3-kinase (PI3K) activity and phosphorylated Protein Kinase B (PKB/AKT) expression were elevated in liver, skeletal muscle, and subcutaneous adipocytes in Irs-1 deficiency. In addition, the expression of IRS-2 and its phosphorylated version were clearly elevated in liver and skeletal muscle. With miRNA microarray analysis, we found miR-33 was down-regulated in bone marrow stromal cells (BMSCs) of $Irs-1^{-/-}$ mice, while its target gene Irs-2 was up-regulated in vitro studies. In addition, miR-33 was down-regulated in the presence of Irs-1 and which was up-regulated in fasting status. What's more, miR-33 restored its expression in re-feeding status. Meanwhile, miR-33 levels decreased and Irs-2 levels increased in liver, skeletal muscle, and subcutaneous adipocytes of $Irs-1^{-/-}$ mice. In primary cultured liver cells transfected with an miR-33 inhibitor, the expression of IRS-2, PI3K, and phosphorylated-AKT (p-AKT) increased while the opposite results were observed in the presence of an miR-33 mimic. Therefore, decreased miR-33 levels can up-regulate IRS-2 expression, which appears to compensate for the defects of the insulin signaling pathway in Irs-1 deficient mice.

• International Journal of Oral Biology
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• 제32권1호
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• pp.23-34
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• 2007

We performed the present study to investigate whether Rehmannia glutinosa Libosch (RG) extracts (RGX) and Eleutherococcus senticosus Max (ES) extracts (ESX) play any roles in bone metabolism. We examined cellular activities of bone cells by measurement of osteoblastic cell viability, osteoprotegerin (OPG) secretion from osteoblasts, osteoclastogenesis, and osteoclastic activity. There is no cytotoxicity from osteoblasts after treatment with RGX and ESX. The secretion of OPG from the osteoblasts showed marked increases after treatment with RGX and ESX. In addition, RGX and ESX treatment decreased the number of tartrate-resistant acid phosphatase-positive multinucleated cells and the resorption areas. RGX and ESX, when mixed at optimal ratios, induced synergic effects, in vitro. OPB, which showed synergic effects, is the extract of natural ingredients RG and ES mixed at a raw material weight ratio of 4 : 1. It can be suspected that extracts of RG and ES mixtures contains active ingredients involved in bone tissue metabolism and may be effective in improving osteoporosis.

• 한국식품영양과학회지
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• 제23권2호
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• pp.187-191
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• 1994

The present stduy was undertaken to investigate the possible effect of Puffer fish skin extract (Pf) on the heptic acetaldehyde metabolism . It was obsrved that PF markedly decreased the acetaldehyde levels in blood and liver. The activity of mitochondrial aldehyde dehydrogenase (Ald DH) increased by induction of acute intoxicatiion of alcohol (5 g/kg) was further increased through pretreatment with PF for 2 weeks. When PF was given to rat fed with 25% alcohol solution instead of water for 6 weeks. the activity of Ald DH in mitochondrial fraction decreased to about 28% compared with sucrose-treated group. But after pretreatemnt of PF, the activity was restored to the normal level. By the treatment with disulfiram (300 mg/kg, once a day for 3days) was restored to the control after the pretreatment with PF. And also mitochondrial Ald DH activity in vitro was not changed. All these observations suggest that reduction of acetaldehyde levels are partly due to increase activity of mitochondrial Ald DH. Therefore, the recovery from intoxication of acetaldehyde may be enhanced by treatment with PF.

• Archives of Pharmacal Research
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• 제11권4호
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• pp.292-300
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• 1988

Metabolism of tranylcypromine (TCP) in rat liver microsomes was studied in vitro using fortified microsomal preparations. As well as unlabeled TCP, two deuterium labeled analogs, TCP-phenyl-$d_{5}$ and TCP-cyclopropyl-$d_{2}$ were used and GC/MS employed which was then metabolized to cinnamaldehyde and hydrocinnamyl alcohol. Schiff bases of TCP with hydrocinnamaldehyde and acetaldehyde were detected and possibility of the metabolic formation of N-ethylidene TCP was proposed. In addition, acetophenone (benzoylacetic acid), benzaldehyde, benzoic acid, and benzyl alcohol were detected as the metabolites. Chemical decomposition studies suggested that parts of the oxidized products might be derived by air oxidation processes. A potential metabolite assumed to be N-ethylidene-1, 2-dihydroxy-3-phenylpropanamine oxide was also detected.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.153-163
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• 1994

P450s are a superfamily of heme-containing monooxygenases and important in the metabolism of numerous physiological substrates and foreign compounds. It has been established that tilers are at least 30 distinct human isoforms of P450. Four families containing numerous individual P450s are mainly responsible for metabolizing foreign compounds, A cDNA expression system in which individual human P450s are synthesized in cultured human hepatoma (Hep G2) cells infected with a recombinant vaccinia virus containing human P450 cDNA has been constructed.

• Journal of Ginseng Research
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• 제44권4호
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• pp.664-671
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• 2020

Background: Ginsenoside compound-Mc1 (Mc1) is a member of the deglycosylated ginsenosides obtained from ginseng extract. Although several ginsenosides have a cardioprotective effect, this has not been demonstrated in ginsenoside Mc1. Methods: We treated H9c2 cells with hydrogen peroxide (H₂O₂) and ginsenoside Mc1 to evaluate the antioxidant effects of Mc1. The levels of antioxidant molecules, catalase, and superoxide dismutase 2 (SOD2) were measured, and cell viability was determined using the Bcl2-associated X protein (Bax):B-cell lymphoma-extra large ratio, a cytotoxicity assay, and flow cytometry. We generated mice with high-fat diet (HFD)-induced obesity using ginsenoside Mc1 and assessed their heart tissues to evaluate the antioxidant effect and the fibrosis-reducing capability of ginsenoside Mc1. Results: Ginsenoside Mc1 significantly increased the level of phosphorylated AMP-activated protein kinase (AMPK) in the H9c2 cells. The expression levels of catalase and SOD2 increased significantly after treatment with ginsenoside Mc1, resulting in a decrease in the production of H₂O₂-mediated reactive oxygen species. Treatment with ginsenoside Mc1 also significantly reduced the H₂O₂-mediated elevation of the Bax:Bcl2 ratio and the number of DNA-damaged cells, which was significantly attenuated by treatment with an AMPK inhibitor. Consistent with the in vitro data, ginsenoside Mc1 upregulated the levels of catalase and SOD2 and decreased the Bax:B-cell lymphoma-extra large ratio and caspase-3 activity in the heart tissues of HFD-induced obese mice, resulting in reduced collagen deposition. Conclusion: Ginsenoside Mc1 decreases oxidative stress and increases cell viability in H9c2 cells and the heart tissue isolated from HFD-fed mice via an AMPK-dependent mechanism, suggesting its potential as a novel therapeutic agent for oxidative stress-related cardiac diseases.